Drug Regulatory Authority of Pakistan T.F. Complex, Mauve

Minutes of 294th Meeting of Registration Board | 1

MINUTES OF 294th MEETING OF REGISTRATION BOARD

HELD ON 9th April, 2020. *=*=*=*=*

Item No. Detail of Item Pages

I. Confirmation of Minutes of 293rd meeting of Registration Board 04

II. Division of Pharmaceutical Evaluation & Registration.

Pharmaceutical Evaluation Cell (PEC) .... ...... ...... .........

Registration-I .......... ............. ............. ............. ......... …

Import & Vet-I-II ……………………………………....

Post Registration-I.……………………………………..

5 – 408

5-347

348-349

350-352

353-355

III. Division of Biological Evaluation & Research 356 – 359

IV. Division of Quality Assurance & Laboratory Testing 360 – 369

Drug Regulatory Authority of Pakistan

T.F. Complex, Mauve Area, G-9/4

Islamabad.


294th meeting of Registration Board was held on 9th April, 2020 in the Committee Room,

Drug Regulatory Authority of Pakistan, G-9/4, Islamabad. The meeting was chaired by

Dr.Obaidullah, Director, Pharmaceutical Evaluation & Registration Division, DRAP. The meeting

started with recitation of the Holy Verses.

The Chairman apprised that like rest of the world, Pakistan is also facing various challenges

due to Pandemic COVID-19. Government of Pakistan is striving to provide the best possible relief

to the public in general and COVID-19 patients in particular. In this regard, functional and

operational DRAP has been stressed from the highest level under this existing situation of Force

Majoure. DRAP has decided to convene various meetings viz. Central Licensing Board,

Registration Board, Clinical Study Committee, Enlistment Committee, Coordination with

provincial governments and stakeholders on priority through video link to address matter of public

health importance. Accordingly, instant meeting of Registration Board has been convened.

Following members attended the meeting.

1. Maj.Gen. (R) Dr. Tahir Mukhtar Sayed,

Inspector General (Hospitals), Fauji Foundation, Rawalpindi

Member

2. Dr. Qurban Ali, Ex-Director General,

National Veterinary Laboratories, Islamabad

Member

3. Dr. Muhammad Khalid Jawed, Director,

Drugs Testing Laboratory,Peshawar Government of Khyber Pakhtunkhwa

Member

4. Mr. Muhammad Aslam, Deputy Draftsman-II,

Representative of Ministry of Law & Justice, Islamabad

Member

5. Mr. Ghulam Mujtaba, Deputy Director (Patent)

Representative of IPO, Islamabad.

Member

6. Dr. Noor-us-Saba, Director,

Biological Evaluation & Research Division, DRAP

Member

7. Mr. Abdullah,

Additional Director (PE&R), DRAP.

Member/

Secretary

Following members attended the meeting via video link.

8. Dr. Rafeeq Alam Khan, Meritorious Professor,

Faculty of Pharmacy, Ziauddin University, Karachi.

Member

9. Lt.Gen.(R) Prof.Dr. Karamat Ahmed Karamat (HI-M, SI-M)

Former Surgeon General Pakistan

Member

10. Mr. Iftikhar A.Choudhary,

Hospital Pharmacist, Lahore

Member

11. Dr. Amanullah Khan, Director,

Drugs Testing Laboratory, Quetta. Government of Balochistan

Member


12. Syed Adnan Rizvi, Director,

Drugs Testing Laboratory, Karachi. Government of Sindh

Member

13. Mr. Muzammil Waheed, Director,

Drugs Testing Laboratory, Faisalabad, Government of Punjab

Member

14. Dr. Hafsa Karam Ellahi, Additional Director,

Representative of QA&LT Division, DRAP

Member

Mr. Asif Jalil, Incharge PEC with respective Assistant Directors presented the agenda of

PE&R Division. Director, BE&R assisted by respective Assistant Directors presented the agenda

of BE&R Division. Mr. Kashif Khan and Shahid Nawaz Assistant Director presented the agenda

of QA & LT Division.

Mr. Hamid Raza, Mr.Tipu Sultan Akram (PPMA), Mr. Nadeem Alamgir (Pharma Bureau)

and Mr. Khalid Saeed (PCDA) attended the meeting as observers on behalf of their respective

associations.


Item No. I: Confirmation of Minutes of 293rd Meeting of Registration Board.

293rd meeting of Registration Board was held on 6th – 8th 2020. Initially partial draft

minutes were circulated among the members on 9th January, 2020 & 3rd February, 2020. All

members agreed and approved the said minutes. Two members commented on the minutes as

under:

Comments of Syed Adnan Rizvi

Dear Sir,

Futher permission of furhter 30 months for contract manufacturing of M/s. Novartis Pharma is the

sheer violation of rule 20 A (1) (c) of the Drugs (LRA) Rules 1976. Previously permission was

granted on special case to the Novartis Pharma which has been expired, according to law no

permission could be granted. Therefore no question of consideration of fresh application and

dealing as fresh application.

There is a need of amendment in Rule 20 A (1)(c) of the Drugs(LRA) Rules 1976 otherwise this

application for further extension could not be proceeded. It is worth mentioning that none of all 39

products are life saving drugs and there are several me too products are available in the market

manufacturing by national pharmaceuticals companies.

I disagree with the approval of contract manufacturing, as it is a sheer violation of Drugs (LRA)

Rules 1976.

Regards

Syed Adnan Rizvi

Member RB/ Director

Drug Testing Laboratory Sindh

Karachi

Comments of Iftikhar Ahmed

Asslamo allikum.

Thanks for sending partial draft minutes of above meeting.

For Novartis case, my opinion is that they should be given further chance to have contract

manufacturing for the requested period with the condition that they are bound to inform the board

about the progress on the manufacturing facility.

Agreed on the decision of all other cases as you have suggested.

Iftikhar ch

It is pertinent to mention that Syed Adnan Rizvi was not present in the meeting, the day on

which Novartis case was discussed. Further, all present approved the partial draft minutes so fair

minutes were approved by the Chairman Registration Board and circulated to all concerned for

implementation.

After that complete draft minutes of the meeting of Registration Board were circulated

among the members of the Board on 11th February, 2020 for perusal/approval and comments (if

any) within five days.

None of the members disagreed the complete draft minutes. Accordingly, fair minutes were

approved by the Chairman Registration Board and circulated to all concerned for implementation.

Decision: Registration Board confirmed minutes of 293rd meeting


Item No. II Division of Pharmaceutical Evaluation & Registration

Pharmaceutical Evaluation Cell (PEC)

Item No. 1: Priority approval / registration of drugs during the COVID-19 Pandemic

Agenda of Evaluator PEC-I (Mr. Farooq Aslam)

Agenda of Evaluator PEC-II (Mr. Ammar Ashraf Awan)

Agenda of Evaluator PEC-III (Mr. Muhammad Haseeb Tariq)

Agenda of Evaluator PEC-IV (Ms. Farzana Raja)

Agenda of Evaluator PEC-V (Ms. Iqra Aftab)

Agenda of Evaluator PEC-VI (Mr. Umar Latif)

Agenda of Evaluator PEC-VIII (Ms. Haleema Sharif)

Agenda of Evaluator PEC-IX (Mr. Hanifullah)

Agenda of Evaluator PEC-XI (Mr. Farhadullah)

Agenda of Evaluator PEC-XIV (Mr. Muhammad Ahsan Hafiz)


Item No. II Division of Pharmaceutical Evaluation & Registration.

Item No. I: Priority approval / registration of drugs during the COVID-19 Pandemic.

Background:

The world is currently facing one of the biggest public health outbreak of coronavirus disease

2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-

CoV-2). The outbreak was first identified in Wuhan, Hubei, China, in December 2019. The World

Health Organization (WHO) declared the outbreak to be a Public Health Emergency of

International Concern on 30th January 2020 and recognized it as a pandemic on 11th March

2020. More than 723,500 cases of COVID-19 have been reported in over 190 countries and

territories, resulting in approximately 34,000 deaths till date.

Many clinical trials are under way for treatment / prevention of COVID-19 which uses different

type of pharmaceutical / biological drugs. Many drugs have been allowed for investigational use

in hospitals under medical care for the COVID-19 patients.

The authorities from all over the world have considered the use of several drugs under their

respective national emergency management plans. Clinical Management Guidelines for COVID-

19 Infections issued by Ministry of National Health Services, Regulation & Coordination

(available at http://covid.gov.pk/guideline) also recommends the use of these drugs in the

management of mild to moderate and severe cases of COVID-19 patients. Further, USFDA has

also given Emergency Use Authorization for chloroquine and hydroxychloroquine tablets for

COVID-19 patients (available at: https://www.fda.gov/media/136534/download). Further Centers

for disease control and prevention (CDC) USA also issued Information for Clinicians on

Therapeutic Options for Patients with COVID-19(available at:

https://www.cdc.gov/coronavirus/2019-ncov/hcp/therapeutic-options.html).Similarly Italian

Medicines Agency (AIFA) considers it essential to provide clinical elements useful to guide the

prescription and to define, for each drug used, a relationship between benefits and risks for the

individual patient. Off-label use is only permitted under the national emergency management plan

for treatment of COVID-19 by using Lopinavir / ritonavir (available at:

https://www.aifa.gov.it/emergenza-covid-19).

Keeping in view the above information, Drug Regulatory Authority of Pakistan (DRAP),

exercising its powers under Rule 26of Drugs (LRA) Rules amended via SRO 713(1)/2018 dated

8th June, 2018, has made following decision in its meeting dated 3rd April, 2020.

1. Allowed to submit registration application on form 5, form 5A, form 5D or form 5E instead

of form 5F for following formulations as approved by the reference regulatory authorities;

a. Chloroquine Phosphate

b. Hydroxychloroquine Sulfate

c. Lopinavir/Ritonavir

d. Oseltamivir

e. Ascorbic Acid

2. The applicant can submit their application till 2nd May 2020.

3. These applications will be considered out of queue.

http://covid.gov.pk/guideline

https://www.fda.gov/media/136534/download

https://www.cdc.gov/coronavirus/2019-ncov/hcp/therapeutic-options.html

https://www.aifa.gov.it/emergenza-covid-19


4. The validity of registration period for above mentioned drugs registered during this time

will be one year only.

5. The registration holder will submit data of product development of 3 and 6 months within

one year. The data will be considered by Registration Board for extension of validity period

of registration for further period.

6. Applicant shall submit affidavit for compliance of point 4 and 5 above.

Discussion:

Registration Board deliberated upon the current situation of Covid-19 pandemic and realized the

extraordinary circumstances where in no treatment therapy has yet been approved by any of the

reference regulatory authorities while several drugs have been recommended by various agencies

for investigational use in hospitals under medical care for the management of Covid-19 patients.

Registration Board was also apprised regarding the various regulatory waivers which have been

granted by reference regulatory authorities at national level to make these investigational drugs

readily available. Considering the situation of public health emergency where in getting the

potentially life-saving investigational medicines to the patients is of paramount importance,

Registration Board deliberated upon various regulatory flexibilities offered in the above cited

decision of Drug Regulatory Authority of Pakistan and considering the dire need of ensuring

timely availability of possible treatment options for Covid-19 patients the Board decided as under:

Decision:

a. The registration applications of following formulations, as approved by Reference

Regulatory Authorities, will be considered out of queue on priority basis:

Chloroquine Phosphate

Hydroxychloroquine Sulfate

Lopinavir/Ritonavir

Oseltamivir

Ascorbic Acid

b. As present, registration applications are without product development and stability

data, thus registration shall be valid for 01 year only and the registration holder shall

perform product development including stability studies for 6 months as per

intervals and data requirements decided by Registration Board in 293rd meeting and

shall submit to PE&R Division within one year time for consideration by

Registration Board for extension of validity period of registration for further period.

The same shall be applicable for the 5D applications of above formulations.

c. Registration Board also clarified that no therapeutic claim regarding treatment of

COVID-19 shall be made for above formulations until unless approved by any

Reference Regulatory Authority and the same is approved by Registration Board as

well. Presently above formulations shall only be used as part of the clinical trials or

its management of COVID-19 under strict supervision of relevant medical experts.

d. Registration Board further directed to issue an advisory wherein self-medication

and other related matters related to COVID-19 shall be addressed.


With reference to the decision of Drug Regulatory Authority of Pakistan, following

applications were received and evaluated by PEC and now presented before the Board.

Registration Board considered these applications in light of its above cited decision:

1. Hydroxychloroquine sulfate Tablet 200mg:

Composition: Each Film Coated Tablet contains:

Hydroxychloroquine sulfate……200mg

Reference Regulatory Authority status: PLAQUENIL 200mg film coated tablet by M/s Concordia, USFDA Approved.

Generic status: HCQ 200 Tablets by M/s Getz Pharma, Reg. No. 45471

Specifications: USP Specification Sr.

No.

Name of applicant Brand Name composition Diary no. /

Date / fee /

form

Pack

Size /

Price

Remarks/GMP status

1. M/s Ferozsons

Laboratories Ltd. P.O

Ferozsons,Amangarh,

Nowshera-Khyber

Pakhtunkhwa

Quinovid

200mg tablet

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy.No. 5221

224/03/2020

Rs. 20,000/-

Form 5

30’s,

price

Rs.

11.50/-

per

tablet

Panel inspection dated

25-01-2019 concluded

that panel recommends

the grant of GMP

certificate.

2. M/s Genix pharma

Private Limited,

Karachi.

Oxyquine

tablet 200mg

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy.No. 5231

24/03/2020

Rs. 20,000/-

Form 5

As per

SRO

Last inspection report

dated 10/04/2019,

acceptable level of

compliance GMP

guidelines.

3. M/s Standpharm

Pakistan (Pvt) Ltd.

Lahore.

Acron

Tablet

200mg

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy.No. 5230

24/03/2020

Rs. 20,000/-

Form 5

As per

SRO

Last GMP inspection

was conducted on 19-

10-2017 and the report

concludes a satisfactory

level of GMP

compliance.

4. M/s Aries

Pharmaceuticals 1-W,

Industrial Estate

Hayatabad Peshawar.

H-quin

200mg tablet

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy. No. 5771

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO


dated 10/3/17, panel

recommended for grant

of GMP certificate.

5. M/s Briel

Pharmaceuticals (Pvt)

Ltd. 538-C, Sundar

Industrial Estate

Lahore.

Hydroquin

200mg tablet

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy. No. 5771

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO


dated 24/05/2019, firm

was found to be

operated at satisfactory

level of GMP

compliance.

6. M/s Seraph

Pharmaceuticals,

Plot# 210, Industrial

Triangle, Kahuta

Road, Islamabad.

S-Chlor

Tablet

200mg

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy.No. 5283

25/03/2020

Rs. 20,000/-

Form 5

As per

SRO

GMP certificate issued

on the basis of

inspection conducted

on 11/07/2019.

7. M/s Caliph

Phrmaceuticals (pvt)

Ltd. Plot No. 17,

special industrial zone

(EPZ), Risalpur,

KPK.

HC-CAL

Tablet

200mg

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy.No. 5850

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO


dated 06/11/2018, the

panel recommended

renewal of DML.


8. M/s Quaper pvt. Ltd.

26-A Samll industrial

estate Lahore road

Sargodha.

Hy-Quine

tablet 200mg

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy.No. 5882

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO


dated 28/01/2019, the

panel recommends the

renewal of DML.

9. M/s Focus & Rules

Pharmaceuticasl (pvt)

Ltd. 44-industrial

triangle Kahuta Road,

Islamabad.

FoQuin

tablet 200mg

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy.No. 5294

26/03/2020

Rs. 20,000/-

Form 5

As per

SRO


on 18/03/2019.

10. M/s Aulton

Phamraceutical, plot #

84/1, Block A, Phase

V, Industrial Estate

Hattar.

Aultaquil

200mg tablet

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy. No. 5942

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO

The firm was last

inspected on

13.02.2018, the firm

was operating at good

level of compliance

with cGMP guidelines

11. M/s Glitz Pharma,

plot No. 265,

industrial triangle

Kahuta Road

Islamabad.

Quinglit

tablet 200mg

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy.No. 5298

26/03/2020

Rs. 20,000/-

Form 5

As per

SRO

Last inspection report,

16th Jan, 2019, the panel

recommended issuance

of GMP certificate.

12. M/s Bio-Mark

Pharmaceuticals, plot

No. 527-sundar

industrial estate,

Lahore.

Bio-HCQ

200mg tablet

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy.No. 5320

27/03/2020

Rs. 20,000/-

Form 5

As per

SRO

The firm was GMP

compliant on the day of

inspection dated

13/02/2020

13. M/s Genetics

Pharmacetuicasl (Pvt)

Ltd, 539-A, Sundar

Industrial Estate,

Raiwind, Lahore.

Coviquine-H

200mg tablet

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy.No. 5367

30/03/2020

Rs. 20,000/-

As per

SRO



was operation at

satisfactory level of

GMP compliance.

14. M/s Scotmann

Pharmaceuticasl, 5-D,

I-10/3, Industrial

Area, Islamabad.

Hystat tablet

200mg

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy.No. 5256

30/03/2020

Rs. 20,000/-

Form 5

As per

SRO

Last Inspection report

dated 17-18/11/2018,

panel recommended

regularization of

revised layout & grant

of renewal of license.

15. M/s Navegal

Laboratoriesd, 41/1-

A2, Phase-I,

Industrial Estate

Hattar.

Navequin-H

200mg tablet

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy.No. 5409

31/03/2020

Rs. 20,000/-

Form 5

As per

SRO


dated 11/03/2017, GMP

was satisfactory.

16. M/s Polyfine

Chempharma, 51

Industrial Estate,

Hayatabad Peshawar.

Malaquine-

H 200mg

Tablet

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy.No. 541

31/03/2020

Rs. 20,000/-

Form 5

As per

SRO



is consider4ed to be

operating at satisfactory

level of GMP

compliance.

17. M/s Scilife Pharma

(pricate) Limited,

Plot#FD-57/58-A2,

Korangi Creek

Industrial Park,

(KCIP) Karachi.

Hydroxychl

oroquine

200mg tablet

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy.No. 5407

31/03/2020

Rs. 20,000/-

Form 5

As per

SRO


dated 24/4/19,

Acceptable level of

good compliance with

GMP guidelines.


18. M/s Honig

Pharmaceuticals

Laboratories, 14km

Adyala Road,

Rawalpindi.

MCQ

200mg

Tablet

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy.No. 5412

31/03/2020

Rs. 20,000/-

Form 5

As per

SRO


on 15th

April, 2019.

19. M/s Cher Wel

Pharmacetuicals, Plot

No.20 Phase 4, Hattar

Industrial Estate,

Hattar KPK.

Quinoline

200mg tablet

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy.No. 5421

01/04/2020

Rs. 20,000/-

Form 5

As per

SRO


on 26th March, 2019 on

the basis of inspection

conducted on

04/02/2019.

20. M/s Pharmix

Laboratories (pvt)

Ltd. 21km Ferozpur

Road Lahore.

Cydro

200mg tablet

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy.No. 5423

01/04/2020

Rs. 20,000/-

Form 5

As per

SRO


dated 13/09/2019, The

panel recommended

renewal of DML.

21. M/s Dyson Research

Laboratories Pvt Ltd.

28 km Ferozepur

Road Lahore

Dyquin

Tablets

200mg

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200 mg

Dy.No 41779

07-12-2018

Rs.20,000/-

Form 5

As per

SRO

11-01-2019 satisfactory

level of GMP

compliance, hence

panel recommended

issuance of GMP

certificate to the firm.

Some advises were also

given in the report to the

firm for further up

gradations.

22. M/s Wnsfeild

Pharmaceuticals,

Plot#122, Phase V,

Block A, Industrial

Estate Hattar.

Hydroqin

200mg tablet

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy.No 39683

03-12-2018

Rs.20,000/-

Form 5

As per

SRO

Last GMP inspection

conducted on

18/01/2018 wherein

renewal of DML was

recommended.

23. M/s Pharm Evo Pvt

Ltd, A-29, North

West Industrial Zone,

Light Industrial Zone,

Port Qasim, Karachi

Evoquin

plus 200mg

tablet

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy.No 5589

06-04-2020

Rs.20,000/-

Form 5

As per

SRO


07-02-02019


of GMP certificate.

24. M/s Vision

Pharmaceuticals, Plot

No.22-23, Industrial

Triangle, Kahuta

Road, Islamabad

Visoquin-H

200mg tablet

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy.No 5561

06-04-2020

Rs.20,000/-

Form 5

As per

SRO

Last inspection dated


GMP compliance

25. M/s Paramount

Pharma, Plot No.36,

Indus. Triangle

Kahuta Road,

Islamabd.

Paraquin

tablet

Each film coated

tablet contains:

Hydroxychloroquine

sulfate..….200mg

Dy. No 5573

06-04-2020

Rs.20,000/-

Form 5

As per

SRO


08-02-19 concluded

keeping in view the

observations noticed

during inspection as

narrated above, the

panel is of opinion that

firm may be allowed to

start manufacturing in

the light of GMP

guidelines

26. M/s Invictus


No.21,26, NS2,

RCCI, Rawat,

Islamabad

I-Quin

200mg tablet

Each film coated

tablet contains:

Hydroxychloroquine

sulfate..….200mg

Dy. No 5571

06-04-2020

Rs.20,000/-

Form 5

As per

SRO

Issuance of DML on

08-01-2019


27. M/s Davis

Pharmaceutical Labs

121 Industrial

Triangle Area, Kahuta

Road, Islamabad.

Coronaquine

tablet

Each film coated

tablet contains:

Hydroxychloroquine

sulfate ..…. 200mg

Dy. No 5553

06-04-2020

Rs.20,000/-

Form 5

As per

SRO


on basis of inspection

conducted on 01-10-

2019

28. M/s Global


No 204-205, Kahuta

Triangle, Industrial

Area, Islamabad.

Quinex

200mg tablet

Each film coated

tablet contains:

Hydroxychloroquine


Dy. No 5557

06-04-2020

Rs.20,000/-

Form 5

As per

SRO


on basis of inspection

conducted on 01-10-

2019

29. M/s Sapient Pharma,

123-S Industrial Area

, Kot Lakhpat, Lahore

Sadroxi

200mg tablet

Each film coated

tablet contains:

Hydroxychloroquine


Dy. No 5784

07-04-2020

Rs.20,000/-

Form 5

As per

SRO


19-9-2019 & 18-11-

2019 recommended

renewal of DML.

30. M/s Cunningham


Ltd. Plot#81 Sundar

Industrial Estate

Raiwind Road,

Lahore

H-Curine

200mg tablet

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy.No. 5545

Dated

06/04/2020

Rs. 20,000/-

As per

SRO

Firm has maintained

conformance to GMP

compliance as per

inspection report dated

01/04/2019.

31. M/s Metro

Pharmaceuticals

Plot#14, St.No. SS-2,

National Industrial

Zone, Rawat,

Islamabad.

M-Quin

200mg tablet

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy. No. 5581

Dated

06/04/2020

Rs. 20,000/-

As per

SRO

The panel

recommended renewal

of DML, inspection

date 17/05/2019

32. M/s Wimits Pharma

(Pvt) Ltd. Plot#129,

Sundar Industrial

Estate (PIE) Raiwind

Road Lahore.

COV-HCQ

200mg tablet

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy.No. 5542

Dated

06/04/2020

Rs. 20,000/-

As per

SRO

GMP Certificate issued

on 10-12-2018.

33. M/s Aims

Pharmaceuticals,

Plot#291 Industrial

Triangle Kahuta

Road, Islamabad.

Hydro-Q

tablet 200mg

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy.No. 5531

Dated

06/04/2020

Rs. 20,000/-

As per

SRO

Panel recommended

renewal of DML, dated

31/05/2018.

34. M/s MartinDow Ltd,

Plot#37, Sector 19,

Korangi Industrial

Area Karachi.

Clordow-H

tablet 200mg

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy.No. 5533

06/04/2020

Rs. 20,000/-

As per

SRO

Firm was operating at

good level of

compliance with GMP

as per inspection report

dated 06/12/2018.

35. M/s Don valley

Pharmaceuticasl (Pvt)

Ltd. 31-KM Main

Ferozpur Road

Lahore.

DV-Quine

tablet 200mg

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy.No. 5516

02/04/2020

Rs. 20,000/-

As per

SRO

Good compliance of

GMP, inspection date

13/02/2020.

36. M/s Zafa

Pharmaceuticals

Laboratories (Pvt)

Ltd., L1/B Block-22

federal B Industrial

area, Karachi.

Hydroquin

tablet 200mg

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy.No.5529

Dated

06/04/2020

Rs. 20,000/-

As per

SRO


on 05/09/2019.


37. M/s The Searle

company Limited, F-

319 SITE Karachi,

Pakistan

Qoroze-H

200mg tablet

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy.No.55278

06/04/2020

Rs. 20,000/-

As per

SRO


on 22/07/2019.

38. M/s Tabros Pharma

(Pvt) Ltd, L-20/B,

Sector-22 Federal B

Industrial Area,

Karachi.

Coronaz

200mg

Tablet

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy.No.55280

Dated

06/04/2020

Rs. 20,000/-

As per

SRO


dated 28/8/19, current

GMP compliance level

is rated as good.

39. M/s Crystolite

Pharmaceuticals,

Plot#1&2, St.#S-2,

National Industrial

Zone, Rawat,

Islamabad.

Quenil

200mg

tablets

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy.No.

11228 dated

07/03/2019

Rs. 20,000/-

Form 5

As per

SRO

DML renewed vide

letter No.F.1-54/2009-

Lic (Vol-I) dated 6th

March 2019.

40. M/s Bio-Labs (Pvt)

Ltd., Plot No. 145

Industrial Triangle

Kahuta Road,

Islamabad.

Hydro-Q

200 tablet

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy.No. 5440

dated

01/04/2019

Rs. 20,000/-

Form 5

As per

SRO


on 21/05/2019.

41. M/s Linear Pharma,

Plot No. 18, Street #S-

4, National Industrial

Zone (RCCI) Rawat

Islamabad.

Malaram

200mg tablet

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy.No. 5439

dated

01/04/2019

Rs. 20,000/-

Form 5

As per

SRO


dated 30/01/2019,


GMP compliance.

42. M/s MartinDow

Marker Ltd. (formerly

Meck (Pvt) Ltd) 7,

Jail Road, Quetta.

Covoquin-H

tablets

200mg

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy.No. 5779

Dated

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO

The firm’s GMP

compliance level is

rated as good as pe the


12/07/2019.

43. M/s Neutro Pharma

(Pvt) Ltd. 9.5 KM,

Sheikhupura Road,

Lahore.

Neudrox

Tablets

200mg

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy.#13978

07/03/2019

Rs. 20,000/-

Form 5

As per

SRO


dated 18/7/17, fair

levelof GMP

compliance.

44. M/s Medisynth


Ltd. Plot#55 St.S-5,

NIZ, Rawat.

Marquin

200mg tablet

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy.No.5788

07/04/2019

Rs. 20,000/-

Form 5

As per

SRO


01/03/2019,


GMP.

45. M/s Medpharm

Research Lab, 28 km,

Ferozpur Road,

Lahore.

MED-HC

tablet 200mg

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy.No. 6181

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO

DML issued on

26/02/2018.

46. M/s Masfa Industries

17km, Sheikhupura

Road, Lahore.

MSQ 200mg

tablet

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy.No. 6173

08/04/2020

Rs. 20,000/-

(20,000×2)

One challan

of Rs.

40,000/- is

attached in

Masfaquine

tablet.

Form 5

As per

SRO


dated 29/03/2019, good

level of GMP

compliance.


47. M/s Hygeia

Pharmaceuticals,

Industrial Triangles

Kahuta Road

Islamabad.

Hysul

200mg tablet

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy.No. 5864

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO


21/09/2017,


GMP compliance.

48. M/s Aurik

Pharmaceuticals,

Plot#6&7, St#S-9

National Industrial

Zone, Rawat

Islamabad.

Coronil-H

200mg

Tablet

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy.No. 5795

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO


dated 05/09/2018, the

firm was complying

with GMP standards.

49. M/s CKD

Pharmaceuticals

Pakistan (Pvt),

Karachi.

Daraquine-

OX Tablet

200mg

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy.No. 6165

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO


dated 11/10/2019, good

compliance

50. M/s Hiranis


Ltd. Plot#E-145 to E-

149, North Western

Industrial Zone, PQ,

Karachi.

Coviquine

Tablet

200mg

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy.No. 5770

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO


dated 29/01/2019, the

firm is overall GMP

compliant.

51. M/s Rasco Pharma,

5.5 KM Raiwind

Road, Lahore.

Hydrovid

tablet 200mg

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy.No. 5802

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO



recommended renewal

of DML.

52. M/s Next

Pharmaceutical

Products (Pvt) Ltd.,

Plot No.44 A-B,

Sundar Industrial

Estate, Lahore.

Chloronext

200mg tablet

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy.No. 6154

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO


on 08/07/2019.

53. M/s Qintar

Pharmaceutical, 14-

A, Small Industrial

Estate, Lahore Road,

Sargodha.

H-Queen

200mg tablet

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy.No. 5849

07-04-2020

Rs. 20,000/-

Form 5

As per

SRO

GMP inspection dated

24-5-2019 which

concludes as:

Firm has improved a lot

of observations and

showed Good intention

to improve further.

54. M/s Biogen Pharma,

8-KM, Rawat Chak

Beli Road,

Rawat, Rawalpindi.

Q-gen

200mg tablet

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy. No. 5873

dated 07-04-

2020 Rs.

20,000/-

Form 5

As per

SRO


18-08-2017 which

concludes as:

Keeping in view the

above facts, overall

GMP compliance found

GOOD as of today

management has been

advised to continue the

process of up gradation

and submit compliance

report on observations

made within two weeks

positively especially

sterile area.


55. M/s Munawar

Pharma. Pvt Ltd, 31-

Km, Multan Road,

Lahore.

Hydroxyqui

n tablet

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy.No. 5890

07-04-2020

Rs. 20,000/-

Form 5

As per

SRO


based on the inspection

dated 7-11-2017

56. M/s EG

Pharmaceuticals,

Industrial Triangle

Kahuta Road,

Islamabad.

Oxychloro

200mg tablet

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy.No. 5924

07-04-2020

Rs. 20,000/-

Form 5

As per

SRO

Renewal of DML

recommended in the

inspection dated 13-02-

2019

57. M/s Pharmasol (Pvt)

Ltd. Plot No. 549,

Sundar Industrial

Estate, Raiwind Road,

Lahore.

Quinovid-H

tablet 200mg

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy.No. 6137

08-04-2020

Rs. 20,000/-

Form 5

As per

SRO


08-07-2019 & 25-07-

2019 concluding

satisfactory level GMP

compliance.

58. M/s. Athan

Pharmaceuticals,

Plot#84/1, Block B,

Phase V, Industrial

Estate, Hattar.

Athquin

200mg tablet

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy. No. 5955

07-04-2020

Rs. 20,000/-

Form 5

As per

SRO

New DML issued on 5-

03-2019.

59. M/s Albro Pharma

Private Limited.

340-S Industrial state,

Kot Lakhpat, Lahore,

Pakistan.

Quinbro

200mg tablet

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy. No. 6230

08-04-2020

Rs. 20,000/-

Form 5

As per

SRO

Last GMP dated 30-05-

2019 concluding that

firm is complying most

of the GMP guidelines.

60. M/s Sami

Pharmaceuticals, S-

95, SITE, Karachi.

Quinco

200mg tablet

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy. No. 6168

08-04-2020

Rs. 20,000/-

Form 5

As per

SRO


on 14-6-2018.

61. M/s MKB

Pharmaceutical Pvt.

Ltd. 66-Hayatabad

Industrial Estate,

Jamrud Road,

Peshawar.

Covigon

200mg tablet

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy. No. 6166

08-04-2020

Rs. 20,000/-

Form 5

As per

SRO

Last GMP inspection

conducted on 01-2-

2018 & report

concludes that overall

the firm was working at


GMP compliance."

62. M/s Horizon Health

Care Pvt Ltd, Plot

No.35-A, Small

Industrial Estate,

Taxila, Rawalpindi.

Hydrozon

200mg tablet

Each film coated

tablet contains:

Hydroxychloroquine

sulfate ……. 200mg

Dy. No. 6174

08-04-2020

Rs. 20,000/-

Form 5

As per

SRO

Last GMP inspection



concludes that company

has shown good

response and rectified

problems & has shown

good compliance as per

schedule B-II.

63. M/s Fresh

Pharmaceuticals,

Plot# 07, Street S-6

National Industrial

Zone Rawat,

Islamabad

Cronofate

Tablet

200MG

Each film coated

tablet contains:

Hydroxychloroquine

sulfate…….200mg

Dy.No. 5905

dated

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO

GMP inspection report

dated 02-10-2019 is

complying satisfactory

level of cGMP as of

today.

64. M/s Valor

Pharmaceuticals,

124/A, Triangle

Industrial Estate,

QUIT

TABLET

200mg

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy.No. 5889

dated

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO


dated 20-04-2018

recommended renewal

of DML.


Kahuta Road,

Islamabad.

65. M/s Winlet

Pharmaceuticals, 30-

km, Lahore Sargodha

Road, Lahore.

WIN-CQ

TABLET

200mg

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy.No. 6126

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO

The firm is granted

New DML based on


2017.

66. M/s. Sayyed

Pharmaceutical

Industries (Pvt) Ltd.,

Plot#67/2, Phase 3,

Industrial Estate,

Hattar

CRONOSY

D TABLET

200mg

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy.No. 5796

dated

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO

Inspection conducted

on 04-09-2019, firm

operates at satisfactory

level of GMP

guidelines.

67. M/s HIMARK

Laboratories (Pvt.)

Ltd., Plot#37-A,

Sundar Industrial

Estate, Lahore

QUINMAR

K TABLET

200mg

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy.No. 5780

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO

New License

68. M/s Hamaz

Pharmaceuticals

(Pvt.) Ltd. 13-Km,

Bosan Road,

Lutfabad, Multan

HYDRO-Q

TABLET

200mg

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy.No.5911

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO

Firm is granted GMP

certificate based on


on 28-09-2019.

69. M/s Kaizen

Pharmaceuticals

(Pvt) Ltd., E-127-

129, North Western

Industrial Zone, Bin

Qasim, Karachi

Hydroquin

TABLET

200mg

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy.No.5868

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO

Firm is granted GMP



on 28-8-2019.

70. M/s Linta Pharma

(Pvt) Ltd. Plot # 03,

St#S-5, Rawat

Industrial Estate,

Islamabad

LCQ

TABLET

200mg

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy.No.5869

dated

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO

GMP inspection was

conducted on 12-06-18

and the report

concludes the firm to be

GMP complaint.

71. M/s Gray’s

Pharmaceutical,

Plot#2,St.#N-3,

National Industrial

Zone, Rawat

HIQUIN

TABLET

200mg

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy. No. 5866

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO


on 23-05-2019 overall

GMP compliance

graded as Good.

72. M/s Moringa


A Sundar Industrial

Estate, Lahore

HCQ Tablet

200mg

Each film coated

tablet contains:

Hydroxychloroquine

sulfate….200mg

Dy. No. 6277

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO

The firm is granted

GMP certificate based

on inspection

conducted on 30-5-

2019.

73. M/S Pulse

Pharmaceuticlas (Pvt)

Ltd. Raiwind Road

Lahore.

Qunodrox

200mg

Tablet

Each Film Coated

Tablet contains:

Hydroxychloroquine

sulfate……200mg

Dy.No. 5226

24/03/2020

Rs. 20,000/-

Form 5

As per

SRO

Certificate of cGMP is

issued to the firm based

on evaluation conducted

on 10th May, 2017

74. M/s Searle IV

Solutions (Pvt) Ltd.

1.5km, Manga Raiwind

Road, Lahore

Macdoquine

200mg

Tablet

Each Film Coated

Tablet contains:

Hydroxychloroquine

sulfate……200mg

Dy.No. 6135

24/03/2020

Rs. 20,000/-

Form 5

As per

SRO

27-02-2018. GMP

Certificate issued on 15-

03-2018.


75. M/s Olive

Laboratories, 52-56

National Industrial

Zone, Rawat,

Rawalpindi

Hydroquine

200mg

Tablet

Each Film Coated

Tablet contains:

Hydroxychloroquine

sulfate……200mg

Dy.No. 6133

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO

Inspection report dated

05-03-2019 confirms

firm is operating in

compliance with GMP

76. M/s NabiQasim

Industries (Pvt) Ltd.

17/24, Korangi

Industrial Area,

Karachi.

Miniquin-H

Tablets

200mg

Each Film Coated

Tablet contains:

Hydroxychloroquine

sulfate……200mg

Dy.No. 6140

dated

24/03/2020

Rs. 20,000/-

Form 5

As per

SRO


dated 02/08/2018

concludes that GMP

compliance as good.

77. M/s Saibins

Pharmaceuticals,

Plot#316, Industrial

Triangle, Kahuta Road,

Islamabad

H Quine

Tablets

Each Film Coated

Tablet contains:

Hydroxychloroquine

sulfate……200mg

Dy.No. 6142

dated

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO

GMP certificat4e issued

on 17/01/2019 on the

basis of inspection

conducted on

24/12/2018.

78. M/S Indus Pharma

(Pvt) Ltd., Plot No. 26,

27,63, 64, 65, 66 & 67,

Sector-27, Korangi

Industrial Area,

Karachi.

Doquine-S

200mg

Tablet

Each Film Coated

Tablet contains:

Hydroxychloroquine

sulfate……200mg

Dy.No. 6146

dated

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO

Last inspection was


& report concludes that

firm was considered to be

operating at an

acceptable level of GMP

compliance.

79. M/s Prays

Pharmaceuticals,

Plot#10, St.#SS-4,

National Industrial

Zone (RCCI) Rawat,

Islamabad

Prayquine

200mg

Tablet

Each Film Coated

Tablet contains:

Hydroxychloroquine

sulfate……200mg

Dy.No. 5858

dated

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO

Overall Evaluation of the

Inspection Report is

rated as Good.

80. M/s Wenovo

Pharmaceuticals

Plot#31& 32 Punjab

Small Industrial Estate

Taxila Pakistan

Hydroqin

200mg

Tablet

Each Film Coated

Tablet contains:

Hydroxychloroquine

sulfate……200mg

Dy.No. 6291

dated

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO

Last GMP inspection


& 29-10-2018 and report

concludes that Firm is

compliant to current

GMP

81. M/s Reliance Pharma

Plot No. 8, Street No.

S-8 Rawat Islamabad.

Reliquine

200mg

tablet

Each Film Coated

Tablet contains:

Hydroxychloroquine

sulfate……200mg

Dy.No. 6265

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO


dated 09/01/2020, the

basic elements of GMP

compliance are in place.

82. M/s Saaf


No. 15, Special

Industrial Zone,

Risalpur, KPK

Hydquin

Tablet

200mg

Each Film Coated

Tablet contains:

Hydroxychloroquine

sulfate……200mg

Dy.No. 6270

dated

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO


20-2-2019, the panel

recommended the

resumption of

production.

83. M/s Islam

Pharmaceuticals, 7km,

Pasrur Road, Sialkot

Clorox

Tablet

200mg

Each Film Coated

Tablet contains:

Hydroxychloroquine

sulfate …… 200mg

Dy.No. 6225

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO

New License (letter

issuance date: 29th

August 2018)

84. M/s Medera

Pharmaceuticals Pvt

Ltd, Plot #2, Street #4,

National Industrial

Zone, Rawat,

islamabad

Medoxiquin

e 200mg

Tablet

Each Film Coated

Tablet contains:

Hydroxychloroquine

sulfate……200mg

Dy.No. 6229

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO

Last GMP inspection

conducted on 07-11-

2018 and report


GMP compliance is

found Good of today.


85. M/s Amros

Pharmaceuticals, A-96,

S.I.T.E. Super

Highway, Karachi.

Amroxy Q

200mg

Tablet

Each Film Coated

Tablet contains:

Hydroxychloroquine

sulfate……200mg

Dy.No. 6247

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO


dated 18/07/2018

confirms current

compliance level as

Good.

86. M/s Allmed Pvt Ltd.

Plot No. 590, Sundar

Industrial Estate,

Lahore, Pakistan

Oxyquin

tablet

200mg

Each film coated tablet

contains:

Hydroxychloroquine

sulfate ……. 200mg

Dy.No.6235

08-04-2020

Rs. 20,000/-

Form 5

As per

SRO

Last GMP inspection

conducted on 01-01-

2020 and report

concludes GMP

compliance.

87. M/s Welwrd


#03, Block A, PhaseI-

II, Industrial Estate,

Hattar

QLORON

200mg

tablet


contains:

Hydroxychloroquine

sulfate……200mg

Dy.No. 6281

dated

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO


on 12-11-2018 the firm

is operating at


GMP.

88. M/s Winbrains

Research Labs, Plot#

69/1, Block B, Phase I-


Hattar

Hydrowin

200mg

Tablet


contains:

Hydroxychloroquine

sulfate…….200mg

Dy.No. 6279

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO

The firm is granted


on inspection

conducted on 20-05-

2019.

89. M/s Benson

Pharmaceuticals,

Plot# 3, Main Road,

National Industrial

Zone, Rawat

Hydroxychl

oroquine

200mg

Tablet


contains:

Hydroxychloroquine

sulfate…….200mg

Dy.No. 6271

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO


on 08-11-2019,


GMP compliance.

90. M/s MTI Medical

(Pvt) Ltd, 586-587,

Sundar Industrial

Estate, Lahore

Hydroquine

200mg

Tablet


contains:

Hydroxychloroquine

sulfate…….200mg

Dy.No. 6261

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO

Firm is granted GMP



on 25-9-2019.

91. M/s Mass Pharma

(Pvt) Ltd., 17Km,

Ferozpur Road,

Lahore

H-Masquine

Tablet

200mg


contains:

Hydroxychloroquine

sulfate…….200mg

Dy.No. 6259

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO

Inspection report

conducted on 04-09-

2018, firm has good

compliance of GMP.

92. M/s Friends pharma,

(pvt) ltd, 31-km

ferozepur road lahore.

Malaquine

tablet

200mg

Each Film Coated

Tablet contains:

Hydroxychloroquine


Dy.No. 6386

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO



recommended renewal

of DML.

93. M/s Uni-Tiech


Ltd. Plot#4/116,

Sector 21 Korangi

Industrial Area,

Karachi.

Hydroxychl

oroquine

200mg

tablet

Each Film Coated

Tablet contains:

Hydroxychloroquine


Dy.No. 6464

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO


dated 08/10/2019

Satisfactory level of

GMP

94. M/s Fynk


Ltd. 19-km, GT Road

Kalashah Kaku,

Lahore.

Hydroquine

200mg

tablet

Each Film Coated

Tablet contains:

Hydroxychloroquine


Dy.No. 6787

15/02/2019

Rs. 20,000/-

Form 5

As per

SRO


dated 21/11/2017, fair

level of GMP

compliance.

Decision: Registration Board approved registration of above applications from Serial No. 1 to 94.

Conditions regarding validity of registration and data requirement will be same as decided by the

Board in its general decision recorded above.


2. Chloroquine Phosphate 250mg Tablet:

Composition: Each Film Coated Tablet contains:

Chloroquine phosphate……..250mg

Reference Regulatory Authority status: Chloroquine phosphate (250mg & 500mg) film coated tablet by M/s Hima Pharma, USFDA

Approved.

While the product approved in MHRA is uncoated.

Generic status: 1. RESOCHIN 250MG TAB by M/s Bayer Karachi, Reg. No. 25

Specifications: USP Specification

Sr.

No.

Name of applicant Brand Name Composition Diary no. /

Date / fee /

Form

Pack

Size /

Price

Remarks/GMP status

95. M/s Ferozsons

Laboratories Ltd.

P.O Ferozsons,

Amangarh,

Nowshera-KPK

Chlroquine

Phosphate

250mg tablet


contains:

Chloroquine

phosphate……..250mg

Dy.No. 5222

dated

24/03/2020

Rs. 20,000/-

Form 5

As per

SRO



that the panel

recommends grant of

GMP certificate.

96. M/s Metro

Pharmaceuticals,

Plot#14, St.#SS-2,

National Industrial

Zone, Rawat,

Islamabad.

M-Cloquin

tablet 250mg


contains:

Chloroquine


Dy.No.5853

Dated

07/04/2020

Rs. 20,000/-

As per

SRO

The panel

recommended

renewal of DML,

inspection date

17/05/2019

97. M/s Genix pharma

Private Limited.

Geclo tablet

250mg


contains:

Chloroquine


Dy.No. 5232

24/03/2020

Rs. 20,000/-

Form 5

As per

SRO


dated 10/4/19,

acceptable level of

compliance GMP

guidelines.

98. M/s Briel

Pharmaceuticals

(Pvt) Ltd. 538-C,

Sundar Industrial

Estate Lahore.

B-quine

250mg tablet


contains:

Chloroquine


Dy.No. 5929

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO


dated 24/05/2019, the

firm was found to be

operated at


GMP compliance.


Plot# 265, Industrial

Triangle Kahuta

Road, Islamaad.

Chloroglit

tablet 250mg


contains:

Chloroquine


Dy.No. 5297

26/03/2020

Rs. 20,000/-

Form 5

As per

SRO


16th Jan, 2019, the

panel recommended

issuance of GMP

certificate.


Pharmaceuticasl (Pt)

Ltd. 44-Industrial

Triangle Kahuta

Road, Islamabad.

M-Quit

Tablet 250mg


contains:

Chloroquine


Dy.No. 5293

26/03/2020

Rs. 20,000/-

Form 5

As per

SRO

GMP certificate

issued on 18/03/2019.

101. M/s Bio-Mark

Pharmaceuticals,

Plot No. 527-Sundar

Industrial Estate,

Lahore.

Clokit 250mg

tablet


contains:

Chloroquine


Dy.No. 5323

27/03/2020

Rs. 20,000/-

Form 5

As per

SRO

The firm was GMP

compliant on the day

of inspection dated

13/02/2020


102. M/s Crystolite

Pharmaceuticals,

Plot#1&2, St.#S-2,

National Industrial

Zone, Rawat,

Islamabad.

Quinfex

250mg tablet

Each tablet contains:

Chloroquine


Dy.No. 5319

dated

27/03/2020

Rs. 20,000/-

Form 5

As per

SRO

DML renewed vide



march 2019.

103. M/s Quaper (Pvt.)

Ltd. 26-A Samll

Industrial Estate

Lahore Road,

Sargodha.

Chloroquine

250mg tablet


Chloroquine


Dy.No. 5884

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO



recommends renewal

of DML.

104. M/s Scotmann

Pharmaceuticasl, 5-

D, I-10/3, Industrial

Area, Islamabad.

Costat DS

Tablet 250mg


contains:

Chloroquine


Dy.No. 5257

dated

30/03/2020

Rs. 20,000/-

Form 5

As per

SRO


dated 17-18/11/18,

panel recommended

regularization of

revised layout & grant

of renewal of license.

105. M/s Genetics

Pharmacetuicasl

(Pvt) Ltd, 539-A,

Sundar Industrial

Estate, Raiwind,

Lahore.

Coviquine

250mg tablet


contains:

Chloroquine


Dy.No. 5365

dated

30/03/2020

Rs. 20,000/-

Form 5

As per

SRO


dated 29/03/2019,

firm was operation at


GMP compliance.

106. M/s Genome

Pharmaceuticals Pvt.

Lt., Plot # 16/I-phase

IV, Industrial Estate

Hattar KPK,.

Genoquine

250mg tablet


contains:

Chloroquine


Dy.No. 5420

01/04/2020

Rs. 20,000/-

Form 5

As per

SRO


dated 03/05/2019.

Firm was operating

under good level

GMP.

107. M/s Nabiqasim

Industries (Pvt) Ltd.

17/24, Korangi

Industrial Area,

Karachi.

Miniquine

Tablet 250mg


contains:

Chloroquine


Dy.No.5411

31/03/2020

Rs. 20,000/-

Form 5

As per

SRO

GMP certificate

issued on 30th August,

2019.

108. M/s PharmEvo (Pvt)

Ltd, A-29, North

West Industrial Zone,

Light Industrial

Zone, Port Qasim,

Karachi.

Evoquin

250mg tablet


contains:

Chloroquine phosphate ...

250mg

Dy. No.

5588 dated

06/04/2020

Rs. 20,000/-

Form 5

As per

SRO


07-02-02019

recommended

issuance of GMP

certificate

109. M/s Vision

Pharmaceuticals,

Plot#22-23,

Industrial Triangle,

Kahuta Road,

Islamabad

Visoquine

250mg tablet


contains:

Chloroquine phosphate

….. 250mg

Dy. No.

5559 dated

06/04/2020

Rs. 20,000/-

Form 5

As per

SRO



good level of GMP

compliance.

110. M/s Invictus

Pharmaceuticals,

Plot No.21,26, NS2,

RCCI, Rawat,

Islamabad

Malaquin-P

250mg tablet


contains:


……..250mg

Dy.No. 5570

06/04/2020

Rs. 20,000/-

Form 5

As per

SRO

Issuance of DML on

08-01-2019

111. M/s Global

Pharmaceuticals,

Plot No 204-205,

Kahuta Triangle,

C-Quin

250mg tablet


contains:


……..250mg

Dy.No. 5556

dated

06/04/2020

Rs. 20,000/-

Form 5

As per

SRO


11 & 24-10-2018

recommended

issuance of GMP

certificate


Industrial Area,

Islamabad.

112. M/s Global

Pharmaceuticals,

Plot No 204-205,

Kahuta Triangle,

Industrial Area,

Islamabad.

C-Quin

250mg tablet


contains:


……..250mg

Dy.No. 5556

dated

06/04/2020

Rs. 20,000/-

Form 5

As per

SRO


11 & 24-10-2018

recommended

issuance of GMP

certificate

113. M/s the Searle

company limited, F-

319 SITE Karachi,

Pakistan

Qoroza

250mg tablet


contains:

chloroquine


Dy.No. 5577

Dated

06/04/2020

Rs. 20,000/-

As per

SRO

GMP certificate

issued on 22/07/2019.

114. M/s Zafa

Pharmaceuticals

Laboratories (Pvt)

Ltd., L1/B Block-22

Federal B Industrial

Area, Karachi.

Zafquin table

250mg


contains:

chloroquine


Dy.No. 5530

Dated

06/04/2020

Rs. 20,000/-

Form 5

As per

SRO

GMP certificate

issued on 05/09/2019.

115. M/s Cunningham

Pharmaceuticals

(Pvt) Ltd. Plot # 81

Sundar Industrial

Estate Raiwing Road,

Lahore.

Curine

250mg tablet


contains:

chloroquine


Dy.No. 5544

06/04/2020

Rs. 20,000/-

Form 5

As per

SRO

The firm has

maintained

conformance to GMP

compliance as per

inspection report

dated 01/04/2019.

116. M/s Wimits

Pharmaceuticals

(Pvt) Ltd. Plot#129,

Sundar Industrial


Road, Lahore.

Covlor-P

250mg tablet


contains:

chloroquine


Dy.No. 5541

Dated

06/04/2020

Rs. 20,000/-

Form 5

As per

SRO

GMP Certificate

issued on 10-12-2018.

117. M/s Aims

Pharmaceuticals,


Triangle Kahuta

Road, Islamabad.

H0chlor

tablet 250mg


contains:

chloroquine


Dy.No. 5532

Dated

06/04/2020

Rs. 20,000/-

Form 5

As per

SRO

Panel recommended

renewal of DML,

dated 31/05/2018.

118. M/s MartinDow

Limited, Plot no. 37,

sector 19, Korangi

Industrial Area

Karachi.

Clordow

Tablet 250mg


contains:

chloroquine


Dy.No. 5534

Dated

06/04/2020

Rs. 20,000/-

Form 5

As per

SRO

The firm was

operating at good

level of compliance

with GMP as per

inspection report

dated 06/12/2018.

119. M/s Reko Pharmacal

Pvt. Limited, 13km,

Multan road Lahore.

Requine

tablet 250mg


contains:

chloroquine


Dy.No. 5528

Dated

06/04/2020

Rs. 20,000/-

Form 5

As per

SRO

The panel

recommended

renewal of DML

except Liquid

injectable section on

the basis of inspection

dated 02/05/2017.

120. M/s MartinDow

Marker Ltd.

(formerly Meck (pvt)

ltd) 7, jail road

Quetta.

Covoquin

tablet 250mg


contains:

chloroquine


Dy.No. 5777

Dated

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO

The firm’s GMP

compliance level is

rated as good as per

the inspection report

dated 12/07/2019.


121. M/s Medpharm

research Lab, 28 km

ferozpur road

Lahore.

Medochin

tablet 250mg

Each Film Coated Tablet

contains:

Chloroquine


Dy.No.6180

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO

DML issued on

26/02/2018.

122. M/s Masfa Industries

17km, Sheikhupura

Road, Lahore.

Masfaquine

250mg tablet


contains:

Chloroquine


Dy.No.6172

08/04/2020

Rs. 20,000/-

(20,000×2)

Form 5

As per

SRO


dated 29/03/2019,

good level of GMP

compliance

123. M/s Standpharm

Pakistan (pvt) Ltd.

Lahore.

Coren Tablet

250mg


contains:

Chloroquine


Dy.No. 6197

dated

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO

Last GMP inspection


10-2017 & the report

concludes a


GMP compliance.

124. M/s Hygeia

Pharmaceuticals

Industrial Triangles

Kahuta Road

Islamabad.

H-Quin

250mg tablet


contains:

Chloroquine


Dy.No. 5863

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO


21/09/2017,


GMP compliance.

125. M/s Aurik

Pharmaceuticals,

Plot # 6&7, St #S-9

National Industrial

Zone, Rawat

Islamabad.

Coronil

250mg tablet


contains:

Chloroquine


Dy.No. 5794

dated

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO


dated 05/9/18, the firm

was complying with

GMP standards.

126. M/s Fresh

Pharmaceutical, Plot

No. 07, Street No. S-


Zone, RCCI, Rawat,

Rawalpindi.

Chloro

250mg tablet


contains:

Chloroquine


Dy. No.

5908 dated

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO


02-10-2019

complying

satisfactory level

cGMP.

127. M/s Pharmasol (Pvt)

Ltd. Plot#549,

Sundar Industrial

Estate, Raiwind

Road, Lahore.

Quinovid

250mg tablet


contains:

Chloroquine


Dy.No. 6130

dated

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO


08-07-2019 & 25-07-

2019 concluding

satisfactory level

GMP compliance.


Private Limited.

340-S Industrial

state, Kot Lakhpat,

Lahore.

Malabro

250mg tablet


contains:

Chloroquine


Dy. No.

6234 dated

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO

Last GMP dated 30-

05-2019 concluding

that firm is complying

most of the GMP

guidelines

129. M/s Sami

Pharmaceuticals, S-

95, SITE, Karachi.

Samochin

250mg tablet


contains:


…….. 250mg

Dy.No.6167

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO

GMP certificate

issued on 14-06-2018.

130. M/s Macter

International

Limited, F-216,

S.I.T.E, Karachi

Macvid

250mg tablet


contains:


…….. 250mg

Dy.No. 6128

dated

07/04/2020

Rs. 20,000/-

Form 5

30’s,

price

Rs.

11.50/-

per

tablet


on 23-01-2019

concludes the firm is

considered to be

operating at good

level of GMP.


131. M/s Winlet


km, Lahore Sargodha

Road, Lahore

Winquin

250mg Tablet


contains:


…….. 250mg

Dy.No. 6128

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO

The firm is granted

New DML based on

inspection dated 05-

12-2017.

132. M/s. Sayyed

Pharmaceutical

Industries (Pvt) Ltd.,

Plot#67/2, Phase-3,

Industrial Estate,

Hattar

Chlorsyd

250mg tablet


contains:


…….. 250mg

Dy.No. 5797

dated

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO


on 04-09-2019 the

firm operates at


GMP guidelines.

133. M/s HIMARK

Laboratories (Pvt.)

Ltd., Plot#37-A,

Sundar Industrial

Estate, Lahore

Marquin-CP

250mg tablet


contains:


…….. 250mg

Dy.No.5782

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO

New License

134. M/s Linta

Pharmaceutical (Pvt)

Ltd. Plot # 03, St# S-

5, Rawat Industrial

Estate, Islamabad

Lintque

250mg tablet


contains:


…….. 250mg

Dy.No.5870

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO

GMP inspection was

conducted on 12-06-

18 and the report

concludes the firm to

be GMP complaint.

135. M/s Gray’s


# 2, Street No N-3,

national industrial

Zone, Rawat

Grayquin

250mg tablet


contains:


…….. 250mg

Dy.No.5865

dated

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO


on 23-05-2019 overall

GMP compliance

graded as Good.

136. M/s Pulse

Pharmaceutical (Pvt)

Ltd. Raiwind Road

Lahore.

Queenchlor

250mg Tablet


Chloroquine

phosphate…..250mg

Dy.No. 6125

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO


issued to the firm

based on evaluation

conducted on 10th

May, 2017

137. M/s Searle IV

Solutions (Pvt) Ltd.

1.5km, Manga

Raiwind Road,

Lahore

Macquine

250mg Tablet


Chloroquine

phosphate…..250mg

Dy.No. 6134

24/03/2020

Rs. 20,000/-

Form 5

As per

SRO

27-02-2018. GMP

Certificate issued on

15-03-2018.

138. M/s Saibins

Pharmaceuticals,


Triangle, Kahuta

Road, Islamabad

Quine Tablets Each tablet contains:

Chloroquine

phosphate…..250mg

Dy.No. 6143

dated

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO

GMP certificate

issued on 17/1/2019

on the basis of


on 24/12/2018.

139. M/S Indus Pharma

(Pvt) Ltd, Plot No.

26, 27,63, 64, 65, 66

& 67, Sector-27,

Korangi Industrial

Area, Karachi.

Indoquine-P

250mg Tablet


Chloroquine

phosphate…..250mg

Dy.No. 6145

dated

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO

Last inspection was


& report concludes

that firm was

considered to be

operating at an

acceptable level of

GMP compliance

140. M/s Wnsfeild

Pharmaceuticals,

Plot No. 122, Phase

V,

Block A, Industrial

Estate Hatter, KPK

Chlorwin

250mg Tablet


Chloroquine

phosphate…..250mg

Dy.No. 6285

dated

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO


18-01-2018

unanimously

recommends renewal

of DML No. 000610

by way of formulation


141. M/s Wenovo

Pharmaceuticals

Plot#31 & 32, Punjab

Small Industrial

Estate Taxila

Pakistan

Kalqin

250mg Tablet


Chloroquine

phosphate…..250mg

Dy.No. 6289

dated

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO

Last GMP inspection

conducted on 30-09-

2018 & 29-10-2018

and report concludes

that Firm is compliant

to current GMP

142. M/s Saaf

Pharmaceuticals,

Plot#15, Special

Industrial Zone,

Risalpur, KPK

F-Quin

250mg Tablet


contains:

Chloroquine


Dy.No. 6266

dated

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO

Inspection report

dated 20-2-2019, the

panel recommended

the resumption of

production.

143. M/s Medera

Pharmaceuticals Pvt

Ltd, Plot#2, St.#4,

National Industrial

Zone, Rawat,

Islamabad

Queen 250mg

Tablet


contains:

Chloroquine


Dy.No. 6227

dated

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO

Last GMP inspection

conducted on 07-11-

2018 & report


GMP compliance is

found Good of today.

144. M/s Amros

Pharmaceuticals, A-

96, S.I.T.E. Super

Highway, Karachi.

Amro Quine

250mg Tablet


contains:

Chloroquine


Dy.No. 6249

dated

08/04/2020

Rs. 20,000/-

Form 5


dated 18/7/18

confirms the current

compliance level as

Good.



Industrial Estate,

Lahore, Pakistan

Chlorogen

Tablet 250mg


contains:


…….. 250mg

Dy. No. 6236

dated

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO

Last GMP inspection

conducted on 01-01-

2020 and report

concludes GMP

compliance.

146. M/s MTI Medical

(Pvt) Ltd, 586-587,

Sundar Industrial

Estate, Lahore

Qonine

250mg

Tablet


Chloroquine

phosphate…….250mg

Form 5

Dy.No. 6262

08/04/2020

Rs. 20,000/-,

Form 5

As per

SRO

The firm is granted


on inspection

conducted on 25-9-

2019.

147. M/s Mass Pharma

(Pvt) Ltd., 17Km,

Ferozpur Road,

Lahore

MASOQUI

NE Tablet

250mg


Chloroquine


Form 5

Dy.No. 6258

08/04/2020

Rs. 20,000/-,

Form 5

As per

SRO

Inspection report

conducted on 04-9-

2018, the firm has

good compliance of

GMP.

Decision: Registration Board approved registration of above applications from Serial No. 95 to

147. Conditions regarding validity of registration and data requirement will be same as decided

by the Board in its general decision recorded above.


3. Chloroquine Phosphate 500mg Tablet: Composition:

Each Film Coated Tablet contains:

Chloroquine phosphate……..500mg

Reference Regulatory Authority status:

Chloroquine phosphate (250mg & 500mg) film coated tablet by M/s Hima Pharma, USFDA

Approved.

While the product approved in MHRA is uncoated.

Generic status: not registered


Sr.

No.

Name of applicant Brand

Name

Composition Diary no. /

Date / fee /

Form

Pack

Size /

Price

Remarks/GMP

status


Private Limited.

Geclo tablet

500mg


contains:

Chloroquine


Dy.No.5233

24/03/2020

Rs. 20,000/-

Rs. 30,000/-

07/04/2020

Form 5D

As per

SRO


dated 10/04/2019,

acceptable level of

compliance GMP

guidelines.

149. M/s Scotmann

Pharmaceuticasl, 5-D,

I-10/3, Industrial

Area, Islamabad.

Costat DS

Tablet

500mg


contains:

Chloroquine

phosphate…..500mg

Dy.No. 5258

dated

30/03/2020

Rs. 50,000/-

Form 5D

As per

SRO


dated 17-18/11/2018,

panel recommended

regularization of

revised layout and

grant of renewal of

license.

150. M/s Genetics

Pharmacetuicasl pvt

limited, 539-A,

Sundar Industrial

Estate, Raiwind,

Lahore.

Coviquine

500mg

tablet


contains:

Chloroquine


Dy.No. 5364

dated

30/03/2020

Rs. 20,000/-

Rs. 30,000/-

17/04/2020

Form 5D

As per

SRO


dated 29/03/2019,

firm was operation at


GMP compliance

151. M/s MartinDow


Meck (Pvt) Ltd) 7, jail

road Quetta.

Covoquin

tablet

500mg


contains:

Chloroquine


Dy.No. 5778

Dated

07/04/2020

Rs. 50,000/-

Form 5D

As per

SRO

The firm’s GMP

compliance level is


the inspection report

dated 12/07/2019.

Decision: Registration Board approved registration of above applications from S No. 148 to 151.

Conditions regarding validity of registration and data requirement will be same as decided by

Board in its general decision


4. Chloroquine Phosphate Syrup: Composition: Each 5ml contains:

Chloroquine Phosphate eq. to Chloroquine …… 50mg


Malarivon Syrup 50mg /5ml approved by MHRA of UK

Generic status: Malaquin syrup of M/s Rakaposhi Pharmaceutical Ltd., Peshawar having registration no. 034687


Sr.

No.


Date / fee /

Form

Pack

Size /

Price

Remarks/GMP status

152. M/s Metro

Pharmaceuticals Plot#

14, St.No. SS-2,

National Industrial

Zone, Rawat,

Islamabad.

M-Cloquin

syrup

50mg/5ml

Each 5ml contains:


eq. Chloroquine..50mg

Dy. No. 5852

Dated

07/04/2020

Rs. 20,000/-

As per

SRO

The panel

recommended renewal

of DML, inspection

date 17/05/2019

153. M/s Global


No 204-205, Kahuta

Triangle, Industrial

Area, Islamabad.

C-Quin

50mg/5ml

Syrup

Each 5ml contains:


eq. Chloroquine …...

50mg

Dy. No. 5554

06-04-2020

Rs. 20,000/-

Form 5

As per

SRO


11 & 24-10-2018


of GMP certificate

154. M/s Glitz Pharma, plot

No. 265, industrial

triangle Kahuta Road

Islamabad.

Chloroglit

syrup

50mg/5ml

Each 5ml contains:


eq. Chloroquine ......

50mg

Dy. No. 5296

06-04-2020

Rs. 20,000/-

Form 5

As per

SRO


16th jan, 2019, the

panel recommended

issuance of GMP

certificate.


Pharmaceuticasl (pvt)

Ltd. 44-industrial

triangle kahuta road,

Islamabad.

M-Quit

syrup

50mg/5ml

Each 5ml contains:


eq. Chloroquine ......

50mg

Dy. No. 5292

06-04-2020

Rs. 20,000/-

Form 5

As per

SRO


on 18/03/2019.

156. M/s Care

Pharmaceuticals, 8 Km,

Thokar Raiwind Road,

Lahore

Carequin

Oral

Suspension

50mg/5ml

Each 5ml contains:



50mg

Dy. No. 5801

07-04-2020

Rs. 20,000/-

Form 5

As per

SRO

The firm was granted


on inspection

conducted on 13-03-

2019.

157. M/s HIMARK

Laboratories Pvt. Ltd.,

Plot # 37-A, Sundar

Industrial Estate,

Lahore

Marquin- CP

50mg/5ml

Each 5ml contains:



50mg

Dy. No. 5781

07-04-2020

Rs. 20,000/-

Form 5

As per

SRO

New license

158. Saaaf Pharmaceuticals,

plot No. 15, Special

Industrial Zone,

Risalpur, KPK

F-Quin

Syrup

50mg/5ml

Each 5ml contains:


eq. to Chloroquine

…… 50mg

Dy.No. 6267

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO


20-2-2019, the panel

recommended the

resumption of

production.

159. M/s Amros

Pharmaceuticals, A-96,

S.I.T.E. Super

Highway, Karachi.

Amro Quine

Syrup

50mg/5ml

Each 5ml contains:


eq. to Chloroquine

…… 50mg

Dy.No. 6248

dated

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO


dated 18/07/2018

confirms current

compliance level as

Good.




Industrial Estate,

Lahore, Pakistan

Chlorogen

Syrup

50mg/5ml

Syrup

Each 5ml contains:

Chloroquine

phosphate eq.

Chloroquine….50mg

Dy. No. 6237

06-04-2020

Rs. 20,000/-

Form 5

As per

SRO

Last GMP inspection

conducted on 01-1-

2020 & report

concludes GMP

compliance.


160. Conditions regarding validity of registration and data requirement will be same as decided by

the Board in its general decision recorded above.

5. Lopinavir/Ritonavir (200mg/50mg) Tablet:

Composition: Each film Coated Tablet contains:

Lopinavir……..200mg

Ritonavir……..50mg


Kaletra (200mg/50mg & 100mg/25mg) Film coated tablet by M/s Abbvie, USFDA Approved.

Generic Status: 1. Lopinavir/Ritonavir Tablets 200mg/50mg by M/S Scitech Health (Private)

Limited, Reg. No. 62250


Sr.

No.


Date / fee /

Form

Pack

Size /

Price

Remarks

161. M/s Martin Dow

Limited, Plot No.37,

Sector 19, Korangi

Industrial Area

Karachi.

Ritolop tablet

200mg/50mg


contains:

Lopinavir…200mg

Ritonavir…50mg

Dy. No. 5861

Dated

07/04/2020

Rs. 20,000/-

As per

SRO

The firm was operating

at good level of

compliance with GMP

as per inspection report

dated 06/12/2018.

162. M/s Aulton

Phamraceutical, plot

# 84/1, Block A,

Phase V, Industrial

Estate Hattar.

Kalaulta

200mg/50mg

tablets


contains:

Lopinavir…200mg

Ritonavir…50mg

Dy. No. 5945

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO

The firm was last

inspected on

13.02.2018, the firm

was operating at good

level of compliance


163. M/s Seraph

Pharmaceuticals,


Triangle, Kahuta

Road, Islamabad.

NT-Cor tablet

200mg/50mg


contains:

Lopinavir…200mg

Ritonavir…50mg

Dy.No. 5282

dated

25/03/2020

Rs. 20,000/-

Form 5

As per

SRO


on the basis of


on 11/07/2019


Private Limited.

Loprit Tablet

200mg/50mg


contains:

Lopinavir……200mg

Ritonavir……50mg

Dy.No. 5524

03/04 /2020

Rs. 20,000/-

Form 5

As per

SRO


dated 10/4/19,

acceptable level of

compliance GMP

guidelines.

165. M/s Bio-Mark


No.527-Sundar

Industrial Estate,

Lahore.

Ritopin tablet

200mg/50mg


contains:


Ritonavir……50mg

Dy.No. 5324

27/03/2020

Rs. 20,000/-

Form 5

As per

SRO

The firm was GMP


inspection dated

13/02/2020.

166. M/s Genome


Lt., Plot # 16/I-phase

IV, Industrial Estate

Hattar KpK,.

Lopirit

200mg/50mg

tablet


contains:


Ritonavir……50mg

Dy.No. 5419

dated

01/04/2020

Rs. 20,000/-

Form 5

As per

SRO


dated 03/05/2019. Firm

was operating under

good level GMP.


167. M/s Crystolite

Pharmaceuticals,

Plot#1&2, St.S-2,

National Industrial

Zone, Rawat,

Islamabad.

Loretra

Tablet

200mg/50mg


contains:


Ritonavir……50mg

Dy.No. 5414

dated

27/03/2020

Rs. 20,000/-

Form 5

As per

SRO

DML renewed vide



March 2019.


123-S Industrial Area

, Kot Lakhpat, Lahore

Pinrit Tablet

200mg/50mg


contains:


Ritonavir……50mg

Dy. No. 5787

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO


19-9-2019 & 18-11-

2019 recommended

renewal of DML.

169. M/s Wimits

Pharmaceuticals(Pvt)

Ltd. Plot No. 129,

Sundar Industrial


Road Lahore.

Lorit

200mg/50mg

tablet


contains:


Ritonavir……50mg

Dy. No. 5539

Dated

06/04/2020

Rs. 20,000/-

Form 5

As per

SRO


on 10-12-2018.

170. M/s MartinDow

Marker Ltd.

(formerly Meck (Pvt)

ltd) 7, Jail Road

Quetta.

Covolor

Tablet

200mg/50mg


contains:


Ritonavir……50mg

Dy. No. 5776

Dated

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO

The firm’s GMP

compliance level is



12/07/2019.



estate Lahore road

Sargodha.

Qlatra tablet

200mg/50mg


contains:


Ritonavir……50mg

Dy.No. 5888

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO


dated 28/1/2019, the


renewal of DML.

172. M/s the Searle

Company Limited, F-

319, S.I.T.E.,

Karachi.

Ritohi tablet

200mg/50mg

Each film Coated Tablet

contains:



Dy. No. 5800

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO


on 22/07/2019.

173. M/s Next

Pharmaceutical

Products (Pvt) Ltd.,

Plot No. 44 A-B,

Sundar Industrial

Estate, Lahore.

Loritanext

200mg/50mg

tablet


contains:



Dy.No. 6156

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO


on 08/07/2019.


Plot No 265,

Industrial Triangle,

Kahuta Road,

Islamabad.

Loprit tablet Each film coated tablet

contains:


Ritonavir……50mg

Dy.No. 5879

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO

Issuance of GMP

certificate dated 16-01-

2019


(Pvt.) Ltd Plot No.L-

20/B, Karachi

Industrial Area,

Sector-22, Federal B

Area, Karachi.

Rotana tablet

200/50


contains:


Ritonavir……50mg

Dy. No. 5893

dated

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO

Last GMP inspection

conducted on 07/02/18

& report

concludes on the basis

of current inspection it

was observed that firm

rectified all

observations noted

during last GMP

Inspection.

176. M/s EG

Pharmaceutical,

Industrial Triangle

KR, Islamabad.

Loritivar

tablet 200/50


contains:


Ritonavir……50mg

Dy. No. 5926

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO

Renewal of DML

recommended in the


2019.


177. M/s. Athan

Pharmaceuticals

Plot#84/1, Block B,

Phase V industrial

Estate, Hattar

Kalath tablet

200/50


contains:


Ritonavir……50mg

Dy. No. 5951

dated

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO


03-2019.


Private Limited.



Pakistan

Albetra tablet

200/50


contains:


Ritonavir……50mg

Dy.No.6232

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO

Last GMP dated 30-

05-2019 concluding

that firm is complying

most of the GMP

guidelines

179. M/s Linear Pharma,

Plot No. 18, S. No. S-


Zone, RCCI, Rawat,

Islamabad.

Lipivir tablet

200/50


contains:

Lopinavir …… 200mg

Ritonavir …… 50mg

Dy.No.6183

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO



firm is operating at


compliance with GMP

standards

180. M/s Pharmix Lab. 21-

Km Ferozepur Road,

Lahore.

Lipivir tablet

200/50


contains:



Dy.No.6221

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO


dated 13/09/2019,

panel recommended

renewal of DML.

181. M/s Shrooq


Ltd, 21-Km,

Ferozepur Road, Near

Masjid Ibrahim,

Lahore.

Lipivir tablet

200/50


contains:



Dy.No.6196

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO


dated 07-06-2017 &

30-08-2017

recommended renewal

of DML.

182. M/s Horizon Health

Care Pvt Ltd, Plot 35

A, Small Industrial

Estate, Taxila.

Lopira tablet

200/50


contains:



Dy.No.6176

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO

Last GMP inspection



concludes that

company has shown

good response and

rectified the problems

and has shown good

compliance as per

schedule B-II.

183. M/s Macter

International Limited,

F-216, S.I.T.E,

Karachi.

Macletra

tablet

200mg/50mg


contains:


Ritonavir……50mg

Dy.No.5904

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO


on 23-01-2019

concludes the firm is

considered to be

operating at good level

of GMP.

184. M/s Fresh

Pharmaceuticals,

Plot#07, Street S-6

National Industrial

Zone Rawat,

Islamabad

Lopirivirt

tablet

200mg/50mg


contains:


Ritonavir……50mg

Dy.No.5906

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO


dated 02-10-2019 is

complying satisfactory

level of cGMP as of

today.

185. M/s Hamaz

Pharmaceuticals

(Pvt.) Ltd. 13-Km,

Bosan Road,

Lutfabad, Multan

NOVAPIR

tablet

200mg/50mg


contains:


Ritonavir……50mg

Dy.No.5918

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO

The firm is granted


on inspection

conducted on 28-09-

2019.


186. M/s CCL

Pharmaceuticals

(Pvt.) Ltd., 62-

Industrial Estate, Kot

Lakhpat, Lahore

Corovir

tablet

200mg/50mg


contains:


Ritonavir……50mg

Dy.No.

5938 dated

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO



on inspection dated 24-

04-2018.

187. M/s PharmEvo (Pvt).

Limited Plot # A-29,

North Western

Industrial Zone Port

Qasim Karachi

EVOKAL

Tablet

200mg/50mg


contains:


Ritonavir……50mg

Dy.No. 5871

dated

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO


23-02-2018 the firm

was operating at an

acceptable level of

compliance with GMP

standards.

188. M/s Wnsfeild


No. 122, Phase V,

Block A, Industrial

Estate Hatter, KPK

Letnova

200/50mg

Tablet

Each film Coated

Tablet contains:



Dy.No. 6286

dated

08/04/2020

Rs. 50,000/-

Form 5

As per

SRO


18-1-2018

unanimously

recommends the

renewal of DML no.

000610 by way of

formulation.

189. M/s Wenovo

Pharmaceuticals

Plot # 31& 32 Punjab

Small Industrial

Estate Taxila

Pakistan

Lopirit

200/50mg

Tablet


contains:



Dy.No. 6294

dated

08/04/2020

Rs. 50,000/-

Form 5

As per

SRO

Last GMP inspection

conducted on 30-09-

2018 & 29-10-2018


that Firm is compliant

to current GMP

190. M/s Polyfine

Chempharma.

51-Industrial Estate,

Hayatabad,

Peshawar, Pakistan

Petala

200/50mg

Tablet


contains:



Dy.No. 6297

dated

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO

Last GMP inspection

conducted on 07-02-

2018 & report

concludes that Based

on the area inspected

the people met &

document reviewed &

considering findings of

inspection firm was

considered to be

operated at acceptable

level of compliance

with GMP guideline.

191. M/s Sami

Pharmaceuticals, S-

95, SITE, Karachi.

Opna tablet

200/50


contains:



Dy. No. 6253

08/04/2020

Rs. 20,000/-,

Rs. 30,000/-

Form 5D

As per

SRO


on 14-6-2018.



Industrial Estate,

Lahore.

Lorita tablet

200/50


contains:



Dy. No. 6241

08/04/2020

Rs. 50,000/-

Form 5D

As per

SRO

Last GMP inspection

conducted on 1-1-20 &

report concludes GMP

compliance.

193. M/s Welwrd



II,Industrial Estate,

Hattar

RITLOP

200/50 mg

tablet


contains:


Ritonavir……50mg

Dy.No. 6282

dated

08/04/2020

Rs. 50,000/-

Form 5

As per

SRO


on 12-11-2018 the firm

is operating at


GMP.


(Pvt) Ltd, 586-587,

Sundar Industrial

Estate, Lahore

Lopivir

200/50 mg

tablet


contains:


Ritonavir……50mg

Dy.No. 6260

08/04/2020

Rs. 50,000/-

Form 5D

As per

SRO

Firm is granted GMP



on 25-9-2019.


195. M/s English

Pharmaceutical

Industries, Link

Kattar Bund Road

Thokar Niaz Baig

Multan Road, Lahore

Loretra

200mg/50m

g tablet


contains:

Lopinavir…..200mg


Dy.No. 6477

dated

09/04/2020

Rs. 20,000/-

Form 5

As per

SRO


date 17& 18/01/2019,

fair compliance

196. M/s Briel


Ltd. 538-C, Sundar

Industrial Estate

Lahore.

Bellet

200mg/50m

g tablet


contains:

Lopinavir…..200mg


Dy. No. 5931

dated

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO


dated 24/5/19, the firm

was found to be

operated at satisfactory

level of GMP

compliance.


Conditions regarding validity of registration and data requirement will be same as decided by the Board in

its general decision recorded above.


Import:

197. Name and address of Applicant M/s AGP LimitedB-23, S.I.T.E., Karachi-75700, Pakistan.

Detail of Drug Sale License Address: AGP Limited, B-23-C, S.I.T.E, Karachi.

Validity: 21 September, 2021

Status: Valid

Name and address of manufacturer M/s Mylan Laboratories Limited, F-4 & F-12, MIDC, Malegaon,

TAL, Sinnar, Nashik 422113 Maharashtra State, India.

Name and address of marketing

authorization holder

M/s Mylan Laboratories Limited, F-4 & F-12, MIDC, Malegaon,

TAL, Sinnar, Nashik 422113 Maharashtra State, India.

Name of exporting country India

Type of Form Form 5-F

Diary No. & Date of R& I Dy. No. 5527 Dated 06-10-2018

Fee including differential fee Rs. 100,000/- Dated 05-10-2018

Brand Name+Dosage Form+Strength Lopinavir/Ritonavir Tablets 200mg/50mg

Composition Each film coated tablet contains:


Ritonavir……50mg

Finished Product Specification USP

Pharmacological Group Anti viral

Shelf life 24 months

Demanded Price As per SRO

Pack size HDPE bottle of 120tablets

Me too Lopinavir/Ritonavir Tablets 200mg/50mg By M/S Scitech Health

(Private) LIMITED, Rweg No. 62250

Detail of certificates attached Copy of CoPP:

Certificate No:

COPP/CERT/NKD/74692/2018/11/24108/125666

Certifying Authority: Food & Drug Administration M.S

Valid upto: 12th June, 2021

Free sale in exporting country: Yes

Applicant of certificate:

GMP: Facilities and operation conform to WHO GMP as per

COPP

Applicant of certificate: M/s Mylan Laboratories Limited, F-4

& F-12, MIDC, Malegaon, TAL., Sinnar, Nashik 422113

Maharashtra State, India.

1. The manufacturer complies with the principles and guidelines

of GMP as per the certificate of GMP (EudraGMDP).

Remarks of the Evaluator:

Decision: Registration Board approved registration of above application as per Policy of inspections

of manufacturer abroad. As application was made on Form 5-F along with the product development

and stability studies data hence validity of registration shall be 5 years. Firm shall provide legalized

version of CoPP in 3 months time.


6. Lopinavir/Ritonavir Oral Solution: Composition: Each ml contains:




Kaletra Oral Solution 80mg/20mg by M/s Abbvie, USFDA Approved.

Me too: Kaletra Oral Solution 80mg/20mg By M/S Abbott, Reg. No. 28427

Specifications: USP Specification Sr.

No.


Date / fee /

Form

Pack

Size /

Price

Remarks/GMP status

198. M/s Bio-Mark

Pharmaceuticals,

plot No. 527-sundar

industrial estate,

Lahore.

Ritopin Oral

Solution

80mg/20mg

Each ml contains:



Dy. No. 5325

dated

27/03/2020

Rs. 20,000/-

Form 5

As per

SRO

The firm was GMP


inspection dated

13/02/2020

199. M/s Sapient

Pharma, 123-S

Industrial Area, Kot

Lakhpat, Lahore.

Pinrit Oral

Solution

80mg/20mg

Each ml contains:



Dy. No. 5786

dated

27/03/2020

Rs. 20,000/-

Form 5

As per

SRO


19-9-2019 & 18-11-2019

recommended renewal of

DML.

200. M/s Pharmix Lab.

21-Km Ferozepur

Road, Lahore.

Lopnit Oral

Solution

80mg/20mg

Each ml contains:



Dy. No. 6220

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO


dated 13/09/2019,

The panel recommended

renewal of DML.

201. M/s Shrooq

Pharmaceuticals Pvt

Ltd, 21-Km,

Ferozepur Ropad,

Near Masjid

Ibrahim, Lahore.

Lipton Oral

Solution

80mg/20mg

Each ml contains:



Dy. No. 6195

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO


dated 07-06-2017 and 30-

08-2017 recommended

renewal of DML.

202. M/s Macter

International

Limited, F-216,

S.I.T.E, Karachi.

MACLETR

A 80mg

+20mg/ml

oral solution

Each ml contains:



Dy.No. 5901

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO

Inspection conducted on

23-01-2019 concludes

the firm is considered to

be operating at good level

of GMP.

203. M/s Hamaz

Pharmaceuticals

(Pvt.) Ltd. 13-Km,

Bosan Road,

Lutfabad, Multan

NOVAPIR

80mg/20mg

oral Solution

Each ml contains:



Dy.No. 5916

dated

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO

The firm is granted GMP


inspection conducted on

28-09-2019.

204. M/s Sami

Pharmaceuticals, S-

95, SITE, Karachi.

Opna Oral

Solution

80mg/20mg

Each ml contains:

Lopinavir…..80mg

Ritonavir…..20mg

Dy. No. 6252

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO


on 14-06-2018.

205. M/s Ipram

International

Pharmaceuticals

Plot#26, Street#

S.S-3 National

Industrial Zone,

(RCCI) Rawat,

Islamabad.

Ipraviz

powder for

oral

suspension

80mg/20mg

Each ml contains:

Lopinavir…..80mg

Ritonavir…..20mg

Dy.No. 6392

dated

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO



on inspection conducted

on 20th December, 2018.


206. M/s English

Pharmaceutical

Industries Link

Kattar Bund Road

Thokar Niaz Baig

Multan Road

Lahore.

Loretra

80mg/20mg

syrup

Each ml contains:

Lopinavir…..80mg

Ritonavir…..20mg

Dy.No. 6476

dated

09/04/2020

Rs. 20,000/-

Form 5

As per

SRO


date 17-18/01/2019, fair

compliance


Conditions regarding validity of registration and data requirement will be same as decided by Board in its

general decision.

7. Lopinavir/Ritonavir (100mg/25mg) Tablet:

Composition:

Each film Coated Tablet contains:




Kaletra (100mg/25mg) Film coated tablet by M/s Abbvie, USFDA Approved.

Generic status: Not registered


Sr.

No.

Name of

applicant

Brand Name composition Diary no. /

Date / fee /

Form

Pack

Size /

Price

Remarks/GMP status

207. M/s Horizon

Health Care Pvt

Ltd, Plot 35 A,

Small Industrial

Estate, Taxila.

Lopira film

coated tablet

100/25mg

Each film Coated

Tablet contains:



Dy. No.

6175 dated

08/04/2020

Rs. 20,000/-

+ 30,000/-

Form 5D

As per

SRO

Last GMP inspection was

conducted on 25-06-

2018 and the report

concludes that company

has shown good response

and rectified problems

and has shown good

compliance as per

schedule B-II.

208. M/s Allmed (pvt)

Ltd. Plot no. 590,

sundar Industrial

Estate Lahore.

Orita

100+25mg

tablet

Each film Coated

Tablet contains:



Dy.No. 6175

08/04/2020

Rs. 50,000/-

Form 5D

As per

SRO


dated 01/01/2020, GMP

compliant.



by Board in its general decision.


8. Oseltamivir Phosphate capsule 75mg: Composition: Each capsule conatins: Oseltamivir as phosphate…….75mg Reference Regulatory Authority status: Tamiflu 75mg capsule (oseltamivir as phosphate) by M/s Roche, USFDA Approved. Generic status status: Tamiflu 75mg capsule by M/s Roche. Specifications: USP Specification

Sr.

No.

Name of applicant Brand

Name

composition Diary no. /

Date / fee /

Form

Pack

Size /

Price

Remarks

209. M/s MartinDow Limited, Plot no. 37, sector 19, Korangi Industrial Area Karachi.

Dowflu Capsules

75mg

Each capsule contains: Oseltamivir as phosphate ….. 75mg

Dy.No.5859 Dated 07/04/2020 Rs. 20,000/-

As per SRO

The firm was operating at good level of compliance with GMP as per inspection report dated 06/12/2018.

210. M/s Aulton Phamraceutical, plot # 84/1, Block A, Phase V, Industrial Estate Hattar.

Aultaflu 75mg

Capsule


Dy.No.5948 dated 07/04/2020 Rs. 20,000/- Form 5

As per SRO

The firm was last inspected on 13.02.2018, the firm was operat\ing at good level of compliance with cGMP guidelines

211. M/s Sapient Pharma, 123-S Industrial Area, Kot Lakhpat, Lahore contract manufacturing by M/s Bio-Mark Pharmaceuticals, Plot#527-sundar industrial estate, Lahore

Salmivir 75mg

capsule



As per SRO

The firm was GMP compliant on the day of inspection dated 13/02/2020

212. M/s Briel Pharmaceuticals (Pvt) Ltd. 538-C, Sundar Industrial Estate, Lahore.

Ostavir 75mg

capsule



As per SRO

Last inspection report 24/05/2019, firm was found to be operated at satisfactory level of GMP compliance.

213. M/s Seraph Pharmaceuticals, Plot#210, Industrial Triangle, Kahuta Road, Islamabad.

Osmivir capsule 75mg


Dy.No.5574 06/04/2020 Rs. 20,000/- Form 5

As per SRO

GMP certificate issued on the basis of inspection conducted on 11/07/2019.

214. M/s Wimits Pharmaceuticals (pvt) Ltd. Plot No. 129, sundar Industrial Estate (PIE) Raiwind Road, Lahore.

Osmir 75mg capsule


Dy. No. 5538 Dated 06/04/2020 Rs. 20,000/- Form 5

As per SRO

GMP Certificate issued on 10-12-2018.

215. M/s Bio-Mark Pharmaceuticals, plot No. 527-sundar industrial estate, Lahore.

Boselta 75mg

capsule


Dy.No. 5322 dated 27/03/2020 Rs. 20,000/- Form 5

As per SRO

Firm was GMP compliant on inspection day dated 13/02/2020. Method of manufacturing is not as per innovator’s product.


216. M/s Crystolite Pharma, Plot#1&2, St.S-2, National Industrial Zone, Rawat, Islamabad

Flulite 75mg Capsule



As per SRO

DML renewed vide letter No.F.1-54/2009-Lic (Vol-I) dated 6th March 2019.

217. M/s Invictus Pharmaceuticals Plot No.21, 26, Street No. NS-2, National Industrial Zone (RCCI) Rawat Rawalpindi.

Oseflu 75mg capsule


Dy.No.10104 04/03/2019 Rs. 20,000/- Form 5

As per SRO

Last inspection report 13.11.18 & 17/12/2018, the panel recommends the grant of DML for tablet (general) & Capsule (General) section.

218. M/s MartinDow Marker Ltd. (formerly Meck (pvt) ltd) 7, jail road Quetta.

Covoflu Capsule 75mg


Dy. No. 5774 07/04/2020 Rs. 20,000/- Form 5

As per SRO

The firm’s GMP compliance level is rated as good as per inspection report dated 12/07/2019.

219. M/s Neutro Pharma (Pvt) Ltd. 9.5 KM, Sheikhupura Road, Lahore.

Selvir 75mg capsules

Each capsule conatins: Oseltamivir as phosphate…….75mg

Dy.No.11337 05/03/2019 Rs. 20,000/- Form 5

As per SRO

Last inspection report dated 18/07/2017, fair level of GMP compliance.

220. M/s The Searle Company Ltd,F-319,SITE., Karachi.

Seflu 75mg capsule


Dy. No. 5798 07/04/2020 Rs. 20,000/- Form 5

As per SRO

GMP certificate issued on 22/07/2019.

221. M/s Life Pharmaceutical Company, 24-III, Industrial Estate, Multan.

Miviron Capsule 75mg


Dy. No. 6171 Dated 08/04/2020 Rs. 20,000/- Form 5

As per SRO

Last inspection report dated 15/01/2018, satisfactory level of GMP compliance.

222. M/s Medpharm research Lab, 28 km ferozpur road Lahore.

Medflu 75mg

Capsule


Dy. No. 6182 08/04/2020 Rs. 20,000/- Form 5

As per SRO

DML issued on 26/02/2018.

223. M/s Aurik Pharmaceuticals, Plot#6&7,St #S-9 national industrial zone, Rawat Islamabad.

Selta-75mg Capsule



As per SRO

Last inspection report dated 05/09/2018, the firm was complying with GMP standards.

224. M/s Next Pharmaceutical Products (Pvt) Ltd.,Plot#44 A-B, Sundar Industrial Estate, Lahore.

Oseltanext 75mg

capsule



As per SRO

GMP certificate issued on 08/07/2019.

225. M/s Tabros Pharma (Pvt.) Ltd Plot No.L-20/B, Karachi Industrial Area, Sector-22, Federal B Area, Karachi.

Flunor 75mg capsule

Each capsule: Oseltamivir as phosphate ….. 75mg

Dy. No. 5892 07-04-2020 Rs. 20,000/- Form 5

As per SRO

Last GMP inspection conducted on 07/02/18 & report concludes on the basis of current inspection it was observed that the firm rectified all observations noted during last GMP Inspection


226. M/s Navegal Laboratories 41/1-A2, Phase-1, Industrial Estate Hattar

Oslu 75mg Capsule


Dy.No.39117 28-11-2018 Rs. 20,000/- Form 5

As per SRO

The firm was inspected on 31.12.16, wherein renewal of DML was recommended.

227. M/s. Athan Pharmaceuticals Plot No 84/1, block B, Phase V industrial Estate, Hattar

Athflu 75mg Capsule


Dy. No. 5954 07-04-2020 Rs. 20,000/- Form 5

As per SRO

New DML issued on 5-03-2019


(Pvt) Ltd.



Sytavir

75mg

Capsule

Each capsule:

Oseltamivir as

phosphate ….. 75mg

Dy. No. 6231

08-04-2020

Rs. 20,000/-

Form 5

As per

SRO



firm is complying most

of GMP guidelines.

229. M/s. Shaigan Pharma,

14 Km Adyala Road,

Rawalpindi.

Tamivir

75mg

Capsule

Each capsule:

Oseltamivir as


Dy. No. 6189

08-04-2020

Rs. 20,000/-

Form 5

As per

SRO

Last GMP 30-5-19

concluding that firm is

complying 25-9-19

Panel recommended

renewal of DML most

of GMP Guidelines.

230. M/s. Linear Pharma,

Plot#18, St.#S-4,

National Industrial

Zone, RCCI, Rawat,

Islamabad.

Oslivir

75mg

Capsule

Each capsule:

Oseltamivir as


Dy. No. 6187

08-04-2020

Rs. 20,000/-

Form 5

As per

SRO





compliance with GMP

standards

231. M/s Sami

Pharmaceuticals, S-

95, SITE, Karachi.

Flunar 75mg

Capsule

Each capsule:

Oseltamivir as


Dy. No. 6169

08-04-2020

Rs. 20,000/-

Form 5

As per

SRO


on 14-06-2018.

232. M/s Pharmix Lab. 21-

Km Ferozepur Road,

Lahore.

Ostam 75mg

Capsule

Each capsule:

Oseltamivir as


Dy. No. 6219

08-04-2020

Rs. 20,000/-

Form 5

As per

SRO





compliance with GMP

standards

233. M/s Shrooq

Pharmaceuticals Pvt

Ltd, 21-Km,

Ferozepur Ropad,

Near Masjid Ibrahim,

Lahore.

Onnil 75mg

Capsule

Each capsule:

Oseltamivir as


Dy. No. 6194

08-04-2020

Rs. 20,000/-

Form 5

As per

SRO


dated 07-06-2017 & 30-

08-2017 recommended

renewal of DML.

234. M/s Macter

International Limited,

F-216, S.I.T.E,

Karachi.

Macflu

75mg

capsule

Each capsule

Contains:

Oseltamivir as


Form 5

Dy. No. 5900

07/04/2020

Rs.20,000/-

As per

SRO


23-1-2019 concludes

that firm is considered to

be operating at good

level of GMP.

235. M/s. GLITZ Pharma,

Plot No. 265,

Industrial Triangle

Kahuta Road,

Islamabad

Glitflu 75mg

capsule

Each capsule

Contains:

Oseltamivir as


Form 5

Dy. No. 5877

07/04/2020

Rs.20,000/-

As per

SRO

Panel inspection

conducted on 16-01-

2019 recommended

issuance of GMP

certificate.


236. M/s Winlet

Pharmaceuticals. 30-

km, Lahore Sargodha

Road, Lahore

WINFLU

75mg

capsule

Each capsule

Contains:

Oseltamivir as


Form 5

Dy. No. 6129

07/04/2020

Rs.20,000/-

As per

SRO

The firm is granted New

DML based on


2017.

237. M/s Hamaz

Pharmaceuticals

(Pvt.) Ltd. 13-Km,

Bosan Road,

Lutfabad, Multan

OSELTA

75mg

Capsule

Each capsule

Contains:

Oseltamivir as


Form 5

Dy. No. 5923

dated

07/04/2020

Rs.20,000/-

As per

SRO




28-09-2019.

238. M/s CCL

Pharmaceuticals

(Pvt.) Ltd., 62-


Lakhpat, Lahore

Temevir

75mg

Capsule

Each capsule

Contains:

Oseltamivir as


Form 5

Dy. No. 5941

dated

07/04/2020

Rs.20,000/-

As per

SRO


GMP certificate based on


2018.

239. M/s Moringa


A Sundar Industrial

Estate, Lahore

OMEVIR

Capsule

75mg

Each capsule

Contains:

Oseltamivir as


Dy. No. 6278

dated

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO




30-05-2019.

240. Pulse Pharmaceuticlas

(Pvt) Ltd. Raiwind

Road Lahore.

Pulsevir

75mg

Capsule

Each capsule

conatins:

Oseltamivir as


Dy.No. 6124

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO



on evaluation

conducted on 10th May,

2017

241. M/s Genome

Pharmaceuticals Pvt

Ltd. Plot # 16/I-Phase

IV, Industrial Estate,

Hattar.

Flugen

75mg

Capsule

Each capsule

conatins:

Oseltamivir as


Dy.No. 6148

dated

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO

The inspection report

dated 12.5.18

concluded that overall

firm was operating

under good level of

cGMP

242. M/s Searle IV Solutions

Pvt Ltd. 1.5 km, Manga

Raiwind Road, Lahore

Macmivir

75mg

Capsule

Each capsule

conatins:

Oseltamivir as


Dy.No. 6136

24/03/2020

Rs. 20,000/-

Form 5

As per

SRO

27-02-2018. GMP


03-2018.

243. M/s NabiQasim

Industries (PVT)

Limited. 17/24,

Korangi Industrial

Area, Karachi.

Onzir

Capsule

75mg

Each capsule

conatins:

Oseltamivir as


Dy.No. 6139

24/03/2020

Rs. 20,000/-

Form 5

As per

SRO


dated 02/8/18 concludes

the GMP compliance as

good.

244. M/S Indus Pharma (Pvt)

Ltd., Plot No. 26, 27,63,

64, 65,66&67, Sector-

27, Korangi Industrial

Area. Karachi.

Iveltar

75mg

Capsule

Each capsule

conatins:

Oseltamivir as


Dy.No. 6147

dated

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO

Last inspection on 16-8-

2017 & report

concludes that firm was

considered to be

operating at an

acceptable level of

GMP compliance

245. M/s Wnsfeild


No. 122, Phase V,

Block A, Industrial

Estate Hatter, KPK

Osimavir

75mg

Capsule

Each capsule

conatins:

Oseltamivir as


Dy.No. 6288

dated

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO


18-01-2018

unanimously

recommends renewal of

DML no. 000610 by

way of formulation.

246. M/s Wenovo

Pharmaceuticals

Ozwir

75mg

Capsule

Each capsule

conatins:

Dy.No. 6293

dated

As per

SRO

Last GMP inspection on

30-09-2018 & 29-10-

2018 and report




Taxila Pakistan

Oseltamivir as


08/04/2020

Rs. 20,000/-

Form 5

concludes that Firm is

compliant to current

GMP

247. M/s Polyfine

Chempharma.


Hayatabad, Peshawar,

Pakistan

Ozelta

75mg

Capsule

Each capsule

conatins:

Oseltamivir as


Dy.No. 6300

dated

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO

Last GMP inspection on

7-2-18 & report

concludes that Based on

the area inspected the

people met, document

reviewed and

considering the findings

of inspection firm was

considered to be


level of compliance

with GMP guideline

248. M/s Pearl

Pharmaceuticals.

Plot No. 204, Street

No.1, I-10/3, Islamabad

Coniflu

75mg

Capsule

Each capsule

conatins:

Oseltamivir as


Dy.No. 6301

dated

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO

23-7-2018, Firm was

found in satisfactory

compliance with GMP

guidelines.

249. M/s Allmed Pvt Ltd. Plot No. 590, Sundar Industrial Estate, Lahore, Pakistan

Ostavir

75mg

capsule

Each capsule:

Oseltamivir as


Dy. No. 6239

08-04-2020

Rs. 20,000/-

Form 5

As per

SRO

Last GMP inspection

conducted on 01-1-20 &

report concludes GMP

compliance.

250. M/s MTI Medical (Pvt) Ltd, 586-587, Sundar Industrial Estate, Lahore

Osetavir

75mg

capsule

Each capsule

Contains:

Oseltamivir as


Form 5

Dy. No. 6263

08/04/2020

Rs.20,000/-

As per

SRO

The firm is granted


on inspection

conducted on 25-9-19.

251. M/s Himark Pharma (Pvt) Ltd. Plot#37-A, Sundar Industrial Estate, Lahore

Osemark

75mg

Capsules

Each capsule

Contains:

Oseltamivir as


Form 5

Dy. No. 6274

08/04/2020

Rs.20,000/-

As per

SRO

New license

252. M/s Ipram International Pharma Plot#26, St.#S.S-3 National Industrial Zone, (RCCI) Rawat, Islamabad.

Covi-flu

75mg

capsule

Each capsule

conatins:

Oseltamivir as

phosphate….75mg

Dy.No. 6394

dated

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO


issued to the firm

based on inspection

conducted on 20th

december, 2018.

253. M/s English Pharmaceutical Industries, Link Kattar Bund Road Thokar Niaz Baig Multan Road Lahore.

Osevir

75mg

capsule

Each capsule

conatins:

Oseltamivir as


Dy.No. 6475

dated

09/04/2020

Rs. 20,000/-

Form 5

As per

SRO


date 17-18/01/2019,

fair compliance


Conditions regarding validity of registration and data requirement will be same as decided by Board in

its general decision.


9. Oseltamivir Phosphate dry suspension : Composition:

Each ml of reconstituted suspension contains:

Oseltamivir as phosphate……..12mg


Tamiflu 12mg/ml for Suspension (oseltamivir as phosphate) by M/s Roche, Italy AIFA Approved.

Generic status:

Ozenta 12mg Dry Suspensin by M/s Hilton, reg. No. 42219

Specifications: Innovator’s Sr.

No.


Date / fee /

Form

Pack

Size /

Price

Remarks/GMP status

254. M/s Goodman Laboratories (Pvt) Ltd, Plot#5 St.#S-5, National Industrial Zone Rawat.

Tamivir dry suspension

Each ml of reconstituted suspension contains: Oseltamivir as phosphate…..12mg

Dy. No.13489 07/04/2020 Rs. 20,000/- Form 5

As per SRO

GMP certificate issued on the basis of inspection conducted on 08/08/2018.

Decision: Registration Board approved registration of above application while conditions regarding validity of registration and data requirement will be same as decided by Board in its general decision.

10. Ascorbic acid chewable tablet 500mg:

Composition:

Each chewable tablet contains:

Ascorbic acid……..500mg

Reference Regulatory Authority status: Ascorbic acid chewable tablet 500mg

Generic status: Cecon 500mg tablet by M/s Abbott.

Specifications: USP

Sr.

No.


Date / fee /

Form

Pack

Size /

Price

Remarks/GMP status

255. M/s Metro

Pharmaceuticals Plot #

14, Street No. SS-2,

National Industrial

Zone, Rawat,

Islamabad.

Meta-C tablet

500mg

Each chewable tablet

contains:

Ascorbic

acid…500mg

Dy. No.

5854

Dated

07/04/2020

Rs. 20,000/-

As per

SRO

The panel recommended

renewal of DML,

inspection date

17/05/2019

256. M/s Aulton

Phamraceutical, plot #

84/1, Block A, Phase

V, Industrial Estate

Hattar.

Ascort 500mg

tablet


contains:

Ascorbic acid …….

500mg

Dy. No.

5943

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO

The firm was last

inspected on 13.02.2018,

the firm was operating at

good level of compliance


257. M/s Aries

Pharmaceuticals 1-W,

Industrial Estate

Hayatabad Peshawar.

C 500 tablet Each chewable tablet

contains:


500mg

Dy.No.5772

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO



recommended for grant

of GMP certificate.

258. M/s Briel

Pharmaceuticals (pvt)

Ltd. 538-C, Sundar

Industrial Estate

Lahore.

B-Quine

500mg

chewable

tablet


contains:


500mg

Dy.#5932

dated

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO



was found to be operated

at satisfactory level of

GMP compliance.

259. M/s Martin Dow

Limited, Plot no. 37,

sector 19, Korangi

Dow-C tablet

500mg


contains:

Dy.No.5860

07/04/2020

Rs. 20,000/-

As per

SRO

The firm was operating

at good level of

compliance with GMP as


Industrial Area

Karachi.


500mg

per inspection report

dated 06/12/2018.

260. M/s Wimits

Pharmaceuticals (pvt)

Ltd. Plot#129, sundar

Industrial Estate (PIE)

Raiwind road Lahore.

Vita-C 500mg

tablet


contains:


500mg

Dy.No.5773

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO


on 10-12-2018.


Private Limited.

Karachi

Carb-C

tablets 500mg


contains:


500mg

Dy.No.

5768

7/04/2020

Rs. 20,000/-

Form 5

As per

SRO


dated 10/4/19,

acceptable level of

compliance GMP

guidelines.


123-S Industrial Area,

Kot Lakhpat, Lahore.

Sapsi tablet

500mg


contains:


500mg

Dy. No.

5783

27/03/2020

Rs. 20,000/-

Form 5

As per

SRO


19-9-2019 & 18-11-

2019 recommended

renewal of DML.

263. M/s Caliph

Phrmaceuticals (Pvt)

Ltd. Plot#17, special

industrial zone (EPZ),

Risalpur, KPK.

Cecal

Chewable

tablet


contains:


500mg

Dy.No.

5851 dated

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO


dated 06/11/2018, the

panel recommended

renewal of DML.

264. M/s Bio-Mark

Pharmaceuticals, plot

No. 527-sundar

industrial estate,

Lahore.

Bio-scorb

tablet 500mg


contains:

Ascorbic

acid……500mg

Dy.No.

5321 dated

27/03/2020

Rs. 20,000/-

Form 5

As per

SRO

The firm was GMP


inspection dated

13/02/2020. Method of

manufacturing is not as

per innovator’s product.

265. M/s Crystolite

Pharmaceuticals,

Plot# 1&2, Street

No.S-2, National

Industrial Zone,

Rawat, Islamabad.

Ascon-C

500mg tablet


contains:

Ascorbic

acid……500mg

Dy.No.

5569 dated

06/04/2020

Rs. 20,000/-

Form 5

As per

SRO

DML renewed vide letter

No.F.1-54/2009-Lic

(Vol-I) dated 6th march

2019.

266. M/s Seraph

Pharmaceuticals,


Triangle, Kahuta

Road, Islamabad.

C-lime

chewable

tablet 500mg


contains:

Ascorbic

acid……500mg

Dy.No.

5575 dated

06/04/2020

Rs. 20,000/-

Form 5

As per

SRO


on the basis of inspection

conducted on

11/07/2019.

267. M/s MartinDow


Meck (Pvt) Ltd) 7, jail

road Quetta.

Cevion

chewable

tablet 500mg


contains:

Ascorbic

acid……500mg

Dy. No.

5775

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO

The firm’s GMP

compliance level is rated

as good as pe the


12/07/2019.

268. M/s Medisynth


Ltd. Plot#55 Street S-

5, NIZ, Rawat.

Calsynth

500mg tablets


contains:

Ascorbic

acid……..500mg

Dy.No.

5789

07/04/2019

Rs. 20,000/-

Form 5

As per

SRO


01/03/2019, satisfactory

level of GMP.

269. M/s The Searle

Company Limited, F-

319 SITE., Karachi.

Sorby 500mg

tablet


contains:

Ascorbic

acid……..500mg

Dy.No.5799

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO


on 22/07/2019.


270. M/s Medpharm

research Lab, 28 km

ferozpur road Lahore.

Med C-500

Chewable

tablet


contains:

Ascorbic

acid……..500mg

Dy.No.6179

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO

DML issued on

26/02/2018

271. M/s Cunningham


Ltd. Plot#81 Sundar

Industrial Estate

Raiwing Road,Lahore

C-Rise

500mg

Chewable

tablet


contains:

Ascorbic

acid……..500mg

Dy.No.6198

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO

The firm has maintained

conformance to GMP

compliance as per


01/04/2019.

272. M/s Hygeia

Pharmaceuticals

industrial triangles

kahuta road

Islamabad.

C-Quic

500mg Tablet


contains:

Ascorbic

acid……..500mg

Dy.No.5862

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO


21/09/2017, satisfactory

level of GMP

compliance.

273. M/s Davis

Pharmaceutical

Laboratories,Plot#121

Industrial Triangle

Area, Kahuta Road

Islamabad.

Daily C 500

tablet


contains:

Ascorbic

acid……..500mg

Dy.No.6170

dated

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO


01/10/2019, Renewal of

DML.

274. M/s Werrick


217, I-10/3, Industrial

Area, Islamabad.

Werrick’s

vitamin C

500mg

chewable

tablet


contains:

Ascorbic

acid……..500mg

Dy.No.

6161

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO



recommended grant of

GMP certificate.

275. M/s Next

Pharmaceutical

Products (Pvt)Ltd

Plot#44 A-B, Sundar

Industrial Estate,

Lahore.

C-Mext

500mg tablet


contains:

Ascorbic

acid……..500mg

Dy.No.

6152

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO


on 08/07/2019.

276. M/s Genetics Pharma

(Pvt) Ltd, 539-A,

Sundar Industrial

Estate, Raiwind,

Lahore.

Cascor

500mg

chewable

tablet


contains:

Ascorbic

acid……..500mg

Dy.No.

6302

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO



was operation at


GMP compliance.


(Pvt.) Ltd Plot No.L-

20/B, Karachi

Industrial Area,

Sector-22, Federal B

Area, Karachi.

Sensit-C

500mg

Chewable

tablet


contains:


500mg

Dy. No.

5894 dated

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO

Last GMP inspection

conducted on

07/2/18and report

concludes on the basis of

current inspection it was

observed that the firm

rectified all observations

noted during last GMP

Inspection.


278. M/s Fresh


No. 07, Street No. S-6,

National Industrial

Zone, RCCI, Rawat,

Rawalpindi.

Ascor 500mg

Chewable

tablet


contains:

Ascorbic

acid…500mg

Dy.No.5910

dated

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO


02-10-2019 complying

satisfactory level

cGMP

279. M/s Glitz Pharma, Plot

No 265, Industrial

Triangle, Kahuta

Road, Islamabad.

Vita-C 500mg

Chewable

tablet


contains:

Ascorbic

acid…500mg

Dy.No.5881

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO

Issuance of GMP

certificate dated 16-01-

2019

280. M/s EG

Pharmaceuticals,

Industrial Triangle

Kahuta road,

Islamabad.

Cec Cec

500mg

Chewable

tablet


contains:

Ascorbic

acid…500mg

Dy.No.5927

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO

Renewal of DML

recommended in the


2019

281. M/s. Athan

Pharmaceuticals

Plot#84/1, Block B,

Phase-V industrial

Estate, Hattar.

Athanart

500mg tablet


contains:

Ascorbic

acid…500mg

Dy.No.5949

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO


03-2019

282. M/s. Shaigan Pharma,

14 Km Adyala Road,

Rawalpindi.

Ascomin

Chewable

tablets 500mg


contains:


500mg

Dy.No.6791

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO

25-9-2019 Panel

recommended the

renewal of DML

283. M/s. Wilson’s


388, I-9, Sector,

Industrial Area,

Islamabad.

Wilson’s

Vitamin-C

Chewable

tablets 500mg


contains:


500mg

Dy.No.6212

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO

24-01-2018 Good level

of CGMP Compliance

284. M/s. Pharmix Lab. 21-

Km Ferozepur Road,

Lahore.

Cemax

Chewable

tablets 500mg


contains:


500mg

Dy.No.6218

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO


dated 13/09/2019. The

panel recommended

renewal of DML.


Private Limited.



Pakistan.

Ascobro

tablets 500mg


contains:


500mg

Dy.No.6233

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO


2019 concluding that firm

is complying most of the

GMP guidelines.

286. M/s CCL

Pharmaceuticals

(Pvt.) Ltd., 62-


Lakhpat, Lahore

C-VIT Tablet

500mg


contains:


500mg

Dy. No.

5934 dated

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO


GMP certificate based on


2018.

287. M/s Winlet

Pharmaceuticals. 30-

km, Lahore Sargodha

Road, Lahore

SCORBLET

Tablet 500mg


contains:


500mg

Dy. No.

6127 dated

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO


Drug Manufacturing

License

based on inspection

Dated 05-12-2017.

288. M/s Hiranis


Ltd. Plot# E-145 to E-

149, North Western

Industrial Zone, Port

Qasim, Karachi

Hawk-C

Tablet 500mg


contains:


500mg

Dy. No.

5769 dated

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO


Drug Manufacturing

License

based on inspection

Dated 05-12-2017.


289. M/s Hamaz

Pharmaceuticals

(Pvt.) Ltd. 13-Km,

Bosan Road,

Lutfabad, Multan

Vita-C

Chewable

500mg Tablet


contains:


500mg

Dy. No.

5913 dated

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO




28-09-2019.

290. M/s SNB Pharma

(Pvt) Ltd. 142,

Industrial Estate,

Hayatabad, Peshawar

SN-C500mg

Tablet


contains:


500mg

Dy. No.

6222 dated

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO




10-10-2019.

291. M/s Gray’s

Pharmaceutical, Plot #

2, Street No N-3,

national industrial

Zone, Rawat

C-Gain

500mg Tablet


contains:


500mg

Dy. No.

5867 dated

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO


23-05-2019 overall GMP

compliance graded as

Good.

292. M/s Moringa


A Sundar Industrial

Estate, Lahore

C-MOR

500mg

Tablet


contains:


500mg

Dy. No.

6276 dated

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO




30-05-2019.

293. M/s Searle IV Solutions

Pvt Ltd. 1.5 km, Manga

Raiwind Road, Lahore

Macorbic

500mg

chewable

Tablet


contains:

Ascorbic

acid……..500mg

Dy.No. 6138

24/03/2020

Rs. 20,000/-

Form 5

As per

SRO

27-02-2018. GMP


03-2018.

294. M/s Genome

Pharmaceuticals Pvt

Ltd.

Plot # 16/I-Phase IV,

Industrial Estate,

Hattar, KPK

Ascarb-C

chewable

500mg

Tablet


contains:

Ascorbic

acid……..500mg

Dy.No. 6149

dated

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO

The inspection report

dated 12.05.2018

concluded that overall the

firm was operating under

good level of cGMP.

295. M/s Olive Laboratories,

52-56 National

Industrial Zone, Rawat,

Rawalpindi

C-Live

500mg

Tablet


contains:

Ascorbic

acid……..500mg

Dy.No. 6132

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO


05-03-2019 confirms the

firm is operating in

compliance with GMP.

296. M/s Invictus

Pharmaceuticals.

Plot No. 21,26, Street

No.NS-2, National

Industrial Zone, Rawat,

Rawalpindi

Vit-C 500mg

Chewable

Tablet


contains:

Ascorbic

acid……..500mg

Dy.No. 5855

dated

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO

13-11-2018, The panel

recommended the grant of

DML

297. M/s Wnsfeild


No. 122, Phase V,

Block A, Industrial

Estate Hatter, KPK

VIT-C

500mg

Tablet


contains:

Ascorbic

acid……..500mg

Dy.No. 6284

dated

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO


18-01-2018 unanimously

recommends renewal of

DML no. 000610 by way

of formulation.

298. M/s Wenovo

Pharmaceuticals



Taxila Pakistan

Azbic

500mg

Tablet


contains:

Ascorbic

acid……..500mg

Dy.No. 6290

dated

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO

Last GMP inspection


& 29-10-2018

and report concludes that

Firm is compliant to

current GMP


299. M/s Polyfine

Chempharma.


Hayatabad, Peshawar,

Pakistan

Ascon

Chewable

Tablet

500mg


contains:

Ascorbic

acid……..500mg

Dy.No. 6295

dated

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO

Last GMP inspection

conducted on 07-02-

2018 and report

concludes that Based on

the area inspected the

people met

and document reviewed

and considering the

findings of

inspection firm was

considered to be


level of compliance with

GMP guideline

300. M/s Islam

Pharmaceuticals,7 km,

Pasrur Road, Sialkot

Life-C

500mg

Chewable

Tablet


contains:

Ascorbic

acid……..500mg

Dy.No.6226

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO

New License (letter

issuance date: 29th

August 2018)

301. M/s Amros

Pharmaceuticals, A-

96, S.I.T.E. Super

Highway, Karachi.

AMRO-C

Chewable

Tablet

500mg


contains:

Ascorbic

acid……..500mg

Dy.No.6250

08/04/2020

Rs. 20,000/-

Form 5

As per

SRO


dated 18/07/2018

confirms thecurrent

compliance level as

Good.



estate Lahore road

Sargodha.

Vitamin C

500mg tablet


contains:

Ascorbic

acid……..500mg

Dy.No.5885

07/04/2020

Rs. 20,000/-

Form 5

As per

SRO


dated 28/01/2019, the


renewal of DML.



Industrial Estate,

Lahore, Pakistan

Acogen

tablet 500mg


contains:

Ascorbic acid….

500mg

Dy.No. 6244

dated

08/04/2020

Rs. 20,000/-

Form 5

As

per

SRO

Last GMP inspection



GMP compliance.

304. M/s Welwrd




Hattar

AZBIK

Tablet

500mg


contains:


500mg

Dy.No. 6283

dated

08/04/2020

Rs. 20,000/-

Form 5

As

per

SRO


12-11-2018 the firm is


level of GMP.

305. M/s Welwink

Pharmaceuticals, G.T.

Road, Industrial

Estate, Gujranwala

Cantt

ASCO-C

Tablet

500mg


contains:


500mg

Dy.No. 6280

08/04/2020

Rs. 20,000/-

Form 5

As

per

SRO


20-12-2017 the firm is


level of GMP.


(Pvt) Ltd, 586-587,

Sundar Industrial

Estate, Lahore

BOOST

Tablet

500mg


contains:


500mg

Dy.No. 6264

08/04/2020

Rs. 20,000/-

Form 5

As

per

SRO




25-09-2019.

307. M/s Himark


Ltd. Plot # 37-A,

Sundar Industrial

Estate, Lahore

Mark C

Tablet

500mg


contains:


500mg

Form 5

Dy. No. 6275

dated

08/04/2020

Rs.20,000/-

As

per

SRO

New license

308. M/s Fiends pharma,

(pvt) ltd, 31-km

ferozepur road lahore.

Vitafen

tablet 500mg


contains:

Ascorbic

acid……..500mg

Dy.No. 6388

08/04/2020

Rs. 20,000/-

Form 5

As

per

SRO


dated 08/03/2019,panel

recommended renewal of

DML.




by Board in its general decision.

Item No. 2: Agenda of Evaluator PEC-I

Vet New Section

M/s Medi-Excel Pharmaceutical, Plot No. 282, Industrial Triangle, Kahuta Road, Islamabad was granted

additional sections vide letter no. F.1-2/2001-Lic (Vol-I) dated 29/09/2019. The firm has applied for

following products against relevant sections as under.

Liquid Antibiotic Injectable Section-1 (VET)

Number of products: 05

Number of molecules: 03

1. Name and address of manufacturer /

Applicant

"M/s Mediexcel Pharmaceuticals Islamabad. Plot # 282 Industrial

Triangle, Kahuta Road, Humak, Islamabad 45700"

Brand Name +Dosage Form+ Strength Extragent CT Injection

Composition "Each 100ml Injection contains:

Tylosin Tartrate …….….10gm

Gentamicin Sulphate....…05gm

Colistin Sulphate………..20 MIU"

Diary No. Date of R& I & fee Dy. No 32404 dated 31-01-2020 Rs. 20,000/- 18-12-2019

Pharmacological Group Antibacterial

Type of Form Form-5

Finished product Specifications Innovator’s Specification

Pack size & Demanded Price 100ml/ Decontrolled

Me-too status (with strength & dosage

form)

Combigent Injection of M/s Selmore Pharmaceuticals Pvt Ltd,

(Reg.# 088086)

GMP status GMP certificate issued on the basis of inspection conducted on

08/10/2019.

Remarks of the Evaluator

Decision: Approved.


Applicant



Brand Name +Dosage Form+Strength Genta XL 5 Injection

Composition Each ml Injection contains:

Gentamicin Sulphate....…50mg"


Pharmacological Group Antibacterial/Antibiotic

Type of Form Form-5

Finished product Specifications USP


Me-too status (with strength and dosage

form)

Gentasel-5 Injection of M/s Selmore Pharmaceuticals Pvt Ltd,

(Reg.# 046516)


08/10/2019.


Decision: Approved.


Applicant


Triangle, Kahuta Road Humak, Islamabad 45700"

Brand Name +Dosage Form+ Strength Genta XL 10 Injection

Composition Each 100ml Injection contains:

Gentamicin Sulphate (eq.to Gentamicin base 10gm)..…15.9gm




Type of Form Form-5


Pack size & Demanded Price 100ml/ decontroled


form)

Gentasel-10 Injection of M/s Selmore Pharmaceuticals Pvt Ltd,

(Reg.# 034594)


08/10/2019.


Decision: Approved.


Applicant

M/s Mediexcel Pharmaceuticals Islamabad. Plot # 282 Industrial

Triangle, Kahuta Road Humak, Islamabad 45700.

Brand Name +Dosage Form+ Strength Genta XL Forte Injection


Gentamicin Sulphate…….110 mg"



Type of Form Form-5




form)

Hi-Gent Injection of M/s Selmore Pharma (Reg.# 046517)


08/10/2019.


Decision: Approved.


Applicant

"M/s Mediexcel Pharmaceuticals Islamabad. Plot # 282

Industrial Triangle, Kahuta Road Humak, Islamabad 45700"

Brand Name +Dosage Form+ Strength T-Gent XL Injection


Tylosin Tartrate …….100 mg

Gentamicin………….50mg



Type of Form Form-5

Finished product Specifications Mfg specs

Pack size & Demanded Price 100ml / Decontrolled


form)

Tygent Injection of M/s Selmore Pharmaceuticals Pvt Ltd,

(Reg.# 049636)


08/10/2019.


Decision: Approved with innovator’s specification.

Liquid Antibiotic Injectable Section-2 (VET)




Applicant



Brand Name +Dosage Form + Strength Coliexcel Forte Injection


Colistin Sulphate…….500,000 IU



Type of Form Form-5




Me-too status Coliforte Injection of M/s Selmore Pharma (Reg.# 071086)


08/10/2019.




Applicant



Brand Name +Dosage Form+ Strength Coliexcel Injection

Composition Each 100ml Injection contains:

Colistin Sulphate…….20M IU



Type of Form Form-5




form)

Colisel Injection of M/s Selmore Pharmaceuticals Pvt Ltd,

(Reg.# 043535)


08/10/2019.




Applicant



Brand Name +Dosage Form+ Strength Marbo XL 10 Injection

Composition Each ml contains:

Marbofloxacin…….100mg



Type of Form Form-5




form)

Marboflox Injection of M/s Selmore Pharmaceuticals Pvt Ltd,

(Reg.# 088088)


08/10/2019.




Applicant



Brand Name +Dosage Form+ Strength Oxy XL 5 Injection


Oxytetracycline…….50mg



Type of Form Form-5




form)

B.G Oxy-50 Injection of M/s Biogen Pharma, (Reg.# 072698)


08/10/2019.


Decision: Approved.



Applicant



Brand Name +Dosage Form+ Strength Oxy XL LA Injection

Composition Each 100ml contains:

Oxytetracycline…….20gm



Type of Form Form-5




form)

Oxy-La Injection of M/s Selmore Pharmaceuticals Pvt Ltd,

(Reg.# 035014)


08/10/2019.


Decision: Approved.


Applicant



Brand Name +Dosage Form+ Strength Oxy XL PVP Injection


Oxytetracycline HCl…….100mg


Pharmacological Group Antibacterial/ Antibiotic

Type of Form Form-5




form)

B.G Oxy-100 Injection of M/s Biogen Pharma (Reg.# 075615)


08/10/2019.




Applicant



Brand Name +Dosage Form+ Strength Tetrafen LA Injection


Oxytetracycline…….200mg

Ketoprofen…………30mg


Pharmacological Group Antibacterial/NSAID

Type of Form Form-5




form)

Oxyfen La Injection of M/s Selmore Pharmaceuticals Pvt Ltd,

(Reg.# 071091)


08/10/2019.


Decision: Registration Board referred the case to expert working group on veterinary drugs for

review of formulation.


Applicant



Brand Name +Dosage Form+ Strength Tylo XL 20 Injection



Tylosin Tartrate…….200mg



Type of Form Form-5




form)

Tylosel Injection of M/s Selmore Pharmaceuticals Pvt Ltd,

(Reg.# 043534)


08/10/2019.



General Injectable Section (Vet)




Applicant



Brand Name +Dosage Form+ Strength Atrowin Injection 1mg


Atropine Sulphate…….1mg


Pharmacological Group Antimuscarinic

Type of Form Form-5




form)

Atrovet Injection of M/s Selmore Pharmaceuticals Pvt Ltd,

(Reg.# 034577)


08/10/2019.


Decision: Approved.

Penicillin Powder Injectable Section (Vet)




Applicant



Brand Name +Dosage Form+ Strength Penstop 2.5 GM Injection

Composition Each Dry Powder Vial contains:

Benzyl Penicillin………….500,000 IU

Procaine Penicillin………..1,500,000 IU

Streptomycin Sulphate……2.5gm



Type of Form Form-5


Pack size & Demanded Price 1’s, Decontrolled


form)

Biopen 2.5 GM Injection of M/s Selmore Pharmaceuticals Pvt

Ltd, (Reg.# 081717)


08/10/2019.





Applicant



Brand Name +Dosage Form+ Strength Penstop 5 GM Injection


Benzyl Penicillin…….500,000 IU

Procaine Penicillin…….1,500,000 IU

Streptomycin Sulphate……5gm



Type of Form Form-5


Pack size & Demanded Price 1’s Decontrolled


form)

Biopen 5 GM Injection of M/s Selmore Pharmaceuticals Pvt Ltd,

(Reg.# 081718)


08/10/2019.




Applicant



Brand Name +Dosage Form+ Strength Penstop Forte Injection


Penicillin G Procaine……………..3,000,000 IU

Penicillin G Sodium……………….1,000,000 IU

Dihydrostreptomycin Sulphate……5 gm



Type of Form Form-5


Pack size & Demanded Price 1’s / Decontrolled


form)

PG-Vet Injection of M/s Selmore Pharmaceuticals Pvt Ltd,

(Reg.# 080957)


08/10/2019.




Applicant



Brand Name +Dosage Form+ Strength Penstop 40 Dry Powder Injection


Benzyl Penicillin…..….1,000,000 IU

Procaine Penicillin…….3,000,000 IU



Type of Form Form-5


Pack size & Demanded Price 1’s / Decontrolled


form)

Penisel-40 Dry Powder Injection of M/s Selmore

Pharmaceuticals Pvt Ltd, (Reg.# 080956)


08/10/2019.




Penicillin Liquid Injectable Section (Vet)

Number of Products: 05

Number of Molecules: 05


Applicant



Brand Name +Dosage Form+ Strength Clamoxel Injection 140mg/35mg


Amoxicillin as Trihydrate…….140mg

Clavulanic Acid……………….35mg



Type of Form Form-5




form)

Clavet Injection of M/s Selmore Pharmaceuticals Pvt Ltd, (Reg.#

046519)


08/10/2019.




Applicant



Brand Name +Dosage Form+ Strength Moxigent XL Injection 50mg/25mg


Amoxicillin Trihydrate eq. to Amoxicillin…….50mg

Gentamicin Sulphate eq. to Gentamicin……….25mg



Type of Form Form-5

Finished product Specifications Innovator’s Specification



form)

Amoxygent Injection of M/s Selmore Pharmaceuticals Pvt Ltd,

(Reg.# 080953)


08/10/2019.




Applicant



Brand Name +Dosage Form+ Strength Moxivet LA Injection

Composition "Each ml contains:

Amoxicillin as Trihydrate …….150 mg"



Type of Form Form-5




form)

Novamox LA Injection of M/s Selmore Pharmaceuticals Pvt Ltd,

(Reg.# 043135)


08/10/2019.





Applicant



Brand Name +Dosage Form+ Strength Moxstil Injection


Amoxicillin as Trihydrate…….100mg

Colistin Sulphate…………..….250,000 IU



Type of Form Form-5




form)

Colimoxin Injection of M/s Selmore Pharmaceuticals Pvt Ltd,

(Reg.# 034576)


08/10/2019.




Applicant



Brand Name +Dosage Form+ Strength Panidex Liquid Injection


Benzyl Penicillin Procaine….…………125,000IU

Benzathine Penicillin G………………..125,000IU

Dihydrostreptomycin Sulphate…………0.25 gm

Dexamethasone Sodium Phosphate…….0.20 mg

Dexamethasone-21-Isonicotinate……….0.20 mg


Pharmacological Group Antibacterial/Steroid

Type of Form Form-5




form)

BDEX Liquid Injection of M/s Selmore Pharmaceuticals Pvt Ltd,

(Reg.# 080952)


08/10/2019.

Remarks of the Evaluator The firm has been granted with New Steroid Injectable Section

(Vet) as well.



Penicillin Oral Powder Section (Vet)




Applicant



Brand Name +Dosage Form+ Strength Medi PSZ Oral Powder

Composition Each kg contains:

Procaine Penicillin………...12 gm

Streptomycin Sulphate…….36 gm

Zinc Bacitracin 10%............52 gm


Pharmacological Group Antibacterial/

Type of Form Form-5


Pack size & Demanded Price 1kg, 5kg / Decontrolled



form)

Probac Oral Powder of M/s Selmore Pharmaceuticals Pvt Ltd,

(Reg.# 088099)


08/10/2019.




Applicant



Brand Name +Dosage Form+ Strength Pro PSZ Powder

Composition Each kg contains:

Procain Penicillin………….12 gm

Streptomycin Sulphate…….36 gm

Colistin Sulphate……….….60 MIU

Zinc Bacitracin 10%.............52 gm



Type of Form Form-5


Pack size & Demanded Price 500gm, 1000gm, 2.5kg, 5kg/ Decontrolled


form)

Zeptocol Powder of M/s Selmore Pharmaceuticals Pvt Ltd,

(Reg.# 080962)


08/10/2019.




Applicant



Brand Name +Dosage Form+ Strength Clamo XL Forte Oral Powder

Composition Each 100gm Powder contains:

Amoxicillin as Amoxicillin Trihydrate……..…16 gm

Clavulanic Acid as Potassium Clavulanate…….4gm

Bromhexine Hydrochloride…………………….0.5gm


Pharmacological Group Antibacterial / Expectorant

Type of Form Form-5


Pack size & Demanded Price 100gm, 250gm, 500gm, 1000gm & 5Kg / Decontrolled


form)

Clavicillin Plus Oral Powder of M/s Vetz Pharmaceuticals Pvt

Ltd, (Reg.# 085486)


08/10/2019.




Applicant



Brand Name +Dosage Form+ Strength Moxi Kol 10 Powder Oral

Composition Each gm Powder contains:

Amoxicillin………….100 mg

Colistin Sulphate…….500,000 IU



Type of Form Form-5


Pack size & Demanded Price 100gm, 250gm, 500gm, 1000gm / Decontrolled



form)

Colimoxin Powder of M/s Selmore Pharmaceuticals Pvt Ltd,

(Reg.# 034583)


08/10/2019.




Applicant



Brand Name +Dosage Form+ Strength Moxi Kol 15 Water Soluble Powder Oral


Amoxycillin Trihydrate equivalent to amoxycillin…….15gm

Colistin Sulphate…….50MIU



Type of Form Form-5




form)

Vety Moxil C Water Soluble Powder of M/s Leads



08/10/2019.




Applicant



Brand Name +Dosage Form+ Strength Moxi Kol 20 Oral Dry Powder


Amoxicillin Trihydrate…….20gm

Colistin Sulphate…….80 MIU



Type of Form Form-5




form)

Colimoxin Forte Oral Dry Powder of M/s Selmore



08/10/2019.




Applicant



Brand Name +Dosage Form+ Strength Moxi Kol Forte Oral Water Soluble Powder


Amoxicillin Trihydrate…….50gm

Colistin Sulphate…………..50 MIU



Type of Form Form-5




form)

ATC-Forte Oral Water Soluble Powder of M/s Sanna

Laboratories, (Reg.# 081695)



08/10/2019.



M/s Evergreen Pharmaceuticals, Lahore was granted New Liquid Injection (General) Section (Veterinary

vide letter NO.F.1-31/2010-Lic (Vol I) dated 13/02/2020. The firm has applied the following products

against the approved section.

Liquid Injection (General) Section (Veterinary)


Number of Molecules: 10


Applicant

M/s Evergreen Pharmaceuticals, 69-70/B, Main Glaxo Town,

Industrial Area,20th Km Ferozpur Road, Lahore

Brand Name +Dosage Form+Strength Flomax 300mg Injection

Composition Each ml Contains:

Florfenicol……………..………..300MG

Diary No. Date of R& I & fee Dy. No.32321 Dated 30-1-2020, RS 20,000/-

Pharmacological Group Anti-Biotics

Type of Form Form-5

Finished product Specifications Manufacturer's Specifications


Me-too status (with strength and

dosage form)

Rivaflor 300 Injection by M/s Mylab Pharma, Reg . no. 78205

GMP status New Section




Applicant



Brand Name +Dosage Form+Strength Enrocol-20 Injection

Composition Each ml contains:-

Enrofloxacin ………………. 200mg

Diary No. Date of R& I & fee Dy. No. 32320 Dated 30-1-2020, RS 20,000/-

Pharmacological Group Anti-Biotic

Type of Form Form-5




dosage form)

Enflox-20 injection by M/s SJG Fazal Elahi, Reg. No. 048153

GMP status New section




Applicant



Brand Name+Dosage Form+ Strength Enrocol-10 Injection


Enrofloxacin ………………. 100mg

Diary No. Date of R& I & fee Dy. No. 21635 Dated 23/10/2019, RS 20,000/-

Pharmacological Group Anti-Biotic

Type of Form Form-5



Me-too status Enrosal Injection by M/s Zakfas Pharma, Reg. No. 046658






Applicant



Brand Name+Dosage Form+ Strength Evermec 10mg Injection


Ivermectin………..10mg


Pharmacological Group Anthelminitic

Type of Form Form-5




dosage form)

Alfamec 1% Injection by M/s Alina Pharma, Reg. No. 048180



Decision: Approved.


Applicant



Brand Name+Dosage Form+ Strength V-12 250mcg Injection


Cyanacobalamin……….. 250mcg


Pharmacological Group Vitamin

Type of Form Form-5




dosage form)

Cynosel Injection by M/s Selmore Pharma, Reg. No. 94483





Applicant



Brand Name+Dosage Form+ Strength Oxytec Injection 300mg/20mg


Oxytetracycline as dihydrate………... 300mg

Flunixin meglumine…………..…...... 20Mmg


Pharmacological Group Anti-biotic, Anti inflammatory

Type of Form Form-5




dosage form)

Floxy Injection by M/s Alina Combine Pharma,, Reg. No.

048288





Applicant



Brand Name +Dosage Form+Strength Meloxi-G Injection 10mg


Meloxicam………10mg



Pharmacological Group Anti inflammatory

Type of Form Form-5




dosage form)

Loxicon Injection by M/s Vecton Pharma, Reg. No. 057187





Applicant



Brand Name +Dosage Form+Strength E-SULPHA Injection 333mg


Sulphadimidine sodium……..333mg


Pharmacological Group Anti-biotic

Type of Form Form-5




dosage form)

Could not be confirmed



Decision: Deferred for evidence of applied formulation/drug already approved by DRAP (generic

/ me-too status) alongwith registration number, brand name and name of firm.


Applicant



Brand Name +Dosage Form+Strength OXY-G Injection 50mg


Oxytetracycline .….…..50mg



Type of Form Form-5




dosage form)

Emivet-5 Injection by M/s Zakfas Pharma, Reg.No. 046543



Decision: Approved.


Applicant



Brand Name+Dosage Form+Strength E-GENTA Injection 100mg


Gentamicin Sulphate …….100mg



Type of Form Form-5



Me-too status Genta-10% Injection by M/s Symans Pharma, R.No. 046547



Decision: Approved.



Applicant



Brand Name+Dosage Form+ Strength TYLO-G Injection 50mg/100mg


Gentamicin (as sulphate)……………....50mg

Tylosin (as tartrate)………………..…..100mg



Type of Form Form-5




dosage form)

Genta-Tylosin Injection by M/s International Chempharma,

Reg. No. 31514



Decision: Approved.

M/s Vetz Pharmaceutical (Pvt) Ltd, Plot No. Q-1, S.I.T.E Kotri Sindh was granted Aerosol Spray

(Veterinary) Section vide letter No. F.2-8/2011-Lic dated 5th November, 2019. The firm has

applied following products against the approved section.

Aerosol Spray (veterinary) Section\



42.

Name and address of Manufacturer /

Applicant

M/s Vetz Pharmaceutical (Pvt) Ltd Plot # Q-1, S.I.T.E, Kotri,

Sindh

Brand Name +DosageForm+Strength Oxygent Aerosol Spray


Oxytetracycline HCl……..40 mg

Gentian Violet..…..………4 mg

Permetrin ………………. 10 mg

Citronella oil …………… 20 mg

Diary No. Date of R & I & fee Dy No. 24326 dated 19/11/2019 Rs. 20,000


Types of Form Form-5

Finished Product Specification Vetz Specs

Pack Size & Demanded Price 100 ml, 125 ml, 150 ml, 200 ml, 250 ml, 300 ml / Decontrolled

Me-too status Tetragent Plus By M/s Star Labs, Reg No. 63623

GMP status 26 & 27-7-2019

Conclusion: Based on the above observation their current GMP

compliance level is rated as good.

Remarks of Evaluator


43. Name and address of Manufacturer /

Applicant


Sindh

Brand Name +DosageForm+Strength Teravetz Aerosol Spray

Composition Each gm contains:

Oxytetracycline HCl…..40 mg

Gentian Violet..…..……4 mg





Pack Size & Demanded Price 100 ml, 125 ml, 150 ml, 200 ml, 250 ml, 300 ml

Decontrolled


Me-too status Could not be verified

GMP status 26 & 27-7-2019. Conclusion: Based on the above observation their

current GMP compliance level is rated as good.

Remarks of Evaluator Me too status vcould not be verified.

Decision: Deferred for evidence of applied formulation/drug already approved by DRAP (generic /

me-too status) alongwith registration number, brand name and name of firm.


Applicant


Sindh

Brand Name +DosageForm+Strength Vetasone Aerosol Spray

Composition() Each ml contains:

Oxytetracycline HCl…..5mg

Hdrocortisone..…..……1.6mg

Diary No. Date of R & I & fee Dy No. 24331 dated 19/11/2019; Rs. 20,000

Pharmacological Group Antibacterial, corticosteroid




Decontrolled

Me-too status Cortisel Spray By M/s Selmore, Reg. No. 071079

GMP status 26 & 27-7-2019

Conclusion: Based on the above observation their current GMP





Applicant

M/s Vetz Pharmaceutical (Pvt) Ltd., Plot#Q-1, S.I.T.E, Kotri,

Sindh

Brand Name +DosageForm+Strength Teravetz 2.5 % Aerosol Spray


Oxytetracycline …..…..25 mg

Gentian Violet..…..……5 mg






Decontrolled

Me-too status Teragen 2.5% Aerosol Spray of M/s Star Labs, R.No.043300






Applicant


Sindh

Brand Name +DosageForm+Strength Clorvetz Aerosol Spray

Composition() Each 200 ml contains:

Chloramphenicol…..…..3.25 gm

Nitrofurazone ………….0.15 gm

Gentian Violet..…..……0.15 gm

Diary No. Date of R & I & fee Dy No. 24329 dated 19/11/2019 ; Rs. 20,000

Pharmacological Group Antibacterial / antiseptic




Decontrolled


Me-too status Clonigent Spray By M/s Star Labs, Reg. No. 023419







Applicant


Sindh

Brand Name +DosageForm+Strength Oxyvetz Aerosol Spray

Composition() Each 300 ml contains:

Oxytetracycline HCl ………………1500 mg


Pharmacological Group Diuretic




Decontrolled

Me-too status Oxycort spray By M/s Star Labs, Reg. No. 014143

GMP status 26 & 27-7-2019

Conclusion : Based on the above observation their current GMP




Item No. 3: Agenda of Evaluator PEC-II

Case no. 01 Registration applications for local manufacturing of (Human) drugs

a. New cases

b. Deferred cases

Case no. 02 Registration applications of newly granted DML or New section (Human)

a. New DML

b. New/Additional section(s)

Central Licensing Board in its 270th meeting held on 23rd MAY, 2019 has considered and approved the

following 4 additional section of firm M/s Arreta Pharmaceuticals Pvt. Ltd. Plot No. 13, Street N-5, RCCI,

Industrial Estate, Rawalpindi. Accordingly the Secretary CLB has issued letter for grant of additional section

dated 27th June, 2019.

In 291st meeting below mentioned products have been considered on priority against new sections as detailed

below:

Sr. No Section Previously considered applications

Molecules Products

01 Sterile Dry powder for

Injection(Cephalosporin)

4 11

02 Dry powder for suspension

(Cephalosporin)

3 3

03 Capsule Section Cephalosporin 1 1

Now the remaining applications of the firm have been retrieved, which were applied in the same date and are

presented below for priority consideration, against the available balance for priority consideration.

Sterile Dry Powder for Injection (Cephalosporin)

2 Molecules/ 09 Products


Applicant

M/s Arreta Pharmaceuticals Pvt Ltd. Plot No. 13, Street N-5,

RCCI, Industrial Estate, Rawalpindi

Brand Name +Dosage Form + Strength C-Tri 1g IV Injection

Composition "Each Vial Contains:

Ceftriaxone Sodium Eq. to Ceftriaxone…1000mg"


Diary No. Date of R& I & fee Dy.No.13383 dated 07-03-2019 Rs20,000/- (07-3-2019)

Pharmacological Group Antibiotic

Type of Form Form 5


Pack Size & Demanded Price As per SRO

Approval Status of Product in

Reference Regulatory Authorities

Approved by USFDA

Me-too Status Rezone 1gm Injection IV by M/s Well Care

Pharmaceuticals, Islamabad. (Reg.#031980)

GMP Status Central Licensing Board in its 270th meeting held on 23rd

MAY, 2019 has approved additional section

Remarks of the Evaluator. The molecule has already been considered for Sterile Dry

Powder for Injection (Cephalosporin) in 291st meeting

Decision: Approved.


Applicant



Brand Name+Dosage Form+Strength Alzone 500mg/500mg Injection


Cefoperazone as Sodium …… 500mg

Sulbactam as Sodium ….… 500mg"

Diary No. Date of R& I & fee Dy. No 13392 dated 07-03-2019 Rs20,000/- (07-03-2019)


Type of Form Form-5

Finished Product Specification JP




Approved by PMDA-Japan

Me-too Status 2Sum Injection 1g of M/s Sami

Pharmaceuticals(R.#047002)


MAY, 2019 has approved additional section



Decision: Approved.


Applicant



Brand Name+Dosage Form+Strength Arretaz 1g Injection


Ceftazidime Pentahydrate with L-Arginine eq. to

Ceftazidime ….…1gm"



Type of Form Form-5





Approved by MHRA of UK

Me-too Status Cefcom by Barrett Hodgson Pharmaceuticals


May, 2019 has approved additional section



Decision: Approved.



Applicant



Brand Name +Dosage Form+Strength Arretaz 250mg Injection


Ceftazidime Pentahydrate With L-Arginine eq. to

Ceftazidime…250mg"



Type of Form Form-5






Me-too Status Ceplo Injection 250mg IM/IV of M/s Cirin Parma (Pvt.) Ltd,

(Reg.# 024415)





Decision: Approved.


Applicant



Brand Name +Dosage Form+Strength Bestax 250mg Injection


Cefotaxime as Sodium…250mg"



Type of Form Form-5





Claforan 250mg Injection by Sanofi Aventis

(Netherland Approved)

Me-too Status Palfotax 250mg Injection M/s Palpex Pharmaceuticals (Pvt)

Ltd, Karachi



Remarks of the Evaluator.

Decision: Approved.


Applicant



Brand Name +Dosage Form+Strength Bestax 1g Injection


Cefotaxime as Sodium…1gm"



Type of Form Form-5





Approved by USFDA

Me-too Status Getex Dry powder Injection 1gm by M/s Amarant

from Medicaid, Karachi (Reg#080279)





Decision: Approved.


Applicant



Brand Name +Dosage Form+Strength Arrepim 500mg Injection


Cefepime as HCl With L-Arginine Eq. to Cefepime..500mg



Type of Form Form-5





Approved by USFDA

Me-too Status Feldopim 500mg Injection of M/s Wnsfeild (Reg.#046970)




Decision: Approved.


Applicant



Brand Name +Dosage Form+Strength Arrepim 1g Injection


Cefepime as HCl With L-Arginine Eq. to Cefepime…1gm"



Type of Form Form-5



Approval Status of Product in Reference

Regulatory Authorities

Approved by USFDA

Me-too Status Nuxipim 1g Injection of Bosch




Decision: Approved.


Applicant



Brand Name +Dosage Form+Strength Bestax 500mg Injection


Cefotaxime as Sodium…500mg"



Type of Form Form-5






Me-too Status Getex Dry Powder Injection 500mg of M/s Amarant from

Medicaid Karachi (Reg.# 080278)




Decision: Approved.


Dry powder for suspension (Cephalosporin)

5 molecules/10 products


Applicant



Brand Name +Dosage Form+Strength Arrenir 250mg/5ml Dry Suspension

Composition "Each 5ml After Reconstitution Contains:

Cefdinir…………………………..250mg"



Type of Form Form-5





Approved by USFDA

Me-too Status Zefnir 250mg Dry Powder Suspension of M/s Genome

Pharmaceuticals (Pvt,) Ltd, Hattar. (Reg.# 075526)




Decision: Approved.


Applicant



Brand Name +Dosage Form+Strength Arrenir 125mg/5ml Suspension


Cefdinir…125mg"



Type of Form Form-5





Approved by USFDA

Me-too Status Zefnir 250mg Dry Powder Suspension of M/s Genome





Decision: Approved.


Applicant



Brand Name +Dosage Form+Strength Aphrine 250mg/5ml Dry Suspension


Cephradine Monohydrate Eq. to Cephradine…250mg"



Type of Form Form-5






Me-too Status Licef Dry Powder suspension 250mg/5ml by M/s Wisdom

Pharmaceuticals (Reg#078531)





Decision: Approved.


Applicant



Brand Name +Dosage Form+Strength Aphrine 125mg/5ml Dry Suspension





Type of Form Form-5






Me-too Status Licef Dry Powder suspension 125mg/5ml by M/s Wisdom

Pharmaceuticals (Reg#078532)




Decision: Approved.


Applicant



Brand Name +Dosage Form+Strength Arrelexin 125mg/5ml Dry Suspension


Cephalexin as Monohydrate…125mg"



Type of Form Form-5





Approved by USFDA

Me-too Status Xesafin Suspension 125mg/5ml by MM/s Himont Pharma

(Pvt.) Ltd. 17 Km Ferozpur Road, Lahore. (Reg#076889)




Decision: Approved.


Applicant



Brand Name +Dosage Form+Strength Arrelexin 250mg/5ml Suspension





Type of Form Form-5





Approved by USFDA

Me-too Status Xesafin Suspension 250mg/5ml by MM/s Himont Pharma

(Pvt.) Ltd. 17 Km Ferozpur Road, Lahore. (Reg#076880)





Decision: Approved.


Applicant



Brand Name +Dosage Form+Strength Arofixime 100mg/5ml Dry Suspension


Cefixime Trihydrate Eq. to Cefixime…100mg"



Type of Form Form-5





Approved by AEMPS of Spain

Me-too Status Fasxime 100mg Suspension of M/s Fassgen (R.# 053526)




Decision: Approved.


Applicant



Brand Name +Dosage Form+Strength Arofixime 200mg/5ml Dry Suspension


Cefixime Trihydrate Eq. to Cefixime…200mg”

Diary No. Date of R& I & fee Dy. No 13390 dated 07-03-2019 Rs20,000/- 07-03-2019

(yellow slip)


Type of Form Form-5 (Duplicate)





Approved by USFDA

Me-too Status Fasxime 200mg Suspension of M/s Fassgen (Reg#053527)




Decision: Approved. Board further decided that verification of fee challan shall be done as per

decision of 285th meeting of Registration Board.


Applicant



Brand Name +Dosage Form+Strength Afurox 250mg/5ml Dry Suspension


Cefuroxime as Axetil…250mg"



Type of Form Form-5





Approved by AEMPS of Spain

Me-too Status Cefuroscot Oral Suspension of M/s Scotmann (R.#029911)





Decision: Approved.


Applicant



Brand Name +Dosage Form+Strength Arrenir 125mg/5ml Dry Suspension


Cefdinir…125mg"



Type of Form Form-5





Approved by USFDA

Me-too Status Zefnir 125 mg Dry Powder Suspension of M/s Genome





Decision: Approved.

Capsule Section Cephalosporin

4 molecules/5 products


Applicant



Brand Name +Dosage Form+Strength Arrelexin 500mg Capsule

Composition "Each Capsule Contains:




Type of Form Form-5





Approved by USFDA

Me-too Status Halphix 500 mg Capsules of M/s Genome Pharmaceuticals

(Pvt,) Ltd, Hattar. (Reg.# 074521)




Decision: Approved.


Applicant



Brand Name +Dosage Form+Strength Arrelexin 250mg Capsule





Type of Form Form-5





Approved by USFDA


Me-too Status Halphix 250 mg Capsules of M/s Genome Pharmaceuticals

(Pvt,) Ltd, Hattar. (Reg.# 074520)




Decision: Approved.


Applicant



Brand Name +Dosage Form+Strength Aphrine 250mg Capsule





Type of Form Form-5





Cefradine 250mg Capsules by M/s Athlone Pharmaceuticals

Limited (MHRA Approved)

Me-too Status Zasinol 250mg capsule byM/s Martin Dow (Reg#080643)




Decision: Approved.


Applicant



Brand Name +Dosage Form+Strength Arrenir 300mg Capsule


Cefdinir…300mg"

Diary No. Date of R& I & fee Dy.No 13403 dated 07-03-2019 Rs20,000/- (07-03-2019)


Type of Form Form-5





USFDA approved

Me-too Status Salus 300mg Capsule by M/s The Schazoo Pharmaceuticals

Laboratories (Pvt) Ltd (Reg#069407)




Decision: Approved.


Applicant



Brand Name +Dosage Form+Strength Aphrine 500mg Capsule





Type of Form Form-5





MHRA Approved


Me-too Status Biocef Capsules 500mg by M/s International Brands

(Registration No.013508)




Decision: Approved.

Central Licensing Board in its 273rd meeting held on 15th January, 2020 has considered and approved the

following additional section of firm M/s Scilife Pharma (Pvt) Ltd, Plot No. FD-57/58-A-2, Korangi Creek,

Industrial Park (KCIP) Karachi. Accordingly the Secretary CLB has issued letter for grant of additional section

dated 12th February, 2020.

Dry Powder Inhaler (General)

The panel inspection report on Investigation of Authenticity / Genuineness of data submitted for registration of

B-Form Rotacaps 400mcg + 12mcg (Budesonide + Formoterol fumarate dehydate) by M/s. Scilife Pharma

(Pvt). Ltd., Karachi considered by Registration Board in its 291st meeting has already confirmed the following:

Precautionary measures adopted by the firm to control of cross contamination of the steroidal

preparation with the general products during the manufacturing of applied formulations

Availability of specialized mixing facility to ensure the required particle size of formulation blend

including multi-directional-mixer having 3D mixing capability to ensure the homogeneous mixing of

APIs.

Availability of necessary apparatus for the performance of uniformity of deliver dose and aerodynamic

particle size including dose Uniformity sampling apparatus and MSLI(Multistage Liquid Impinger) for

aerodynamic particle size distribution.

Now, the firm has requested for the priority consideration following applications

Dry Powder Inhaler (General)

1 Molecules/ 09 Products


Applicant

"M/s Scilife Pharma Pvt Ltd. Plot # FD-57/58-A2, Korangi

Creek Industrial Park, Karachi"

Brand Name +Dosage Form+Strength Captair 150mcg Capsule


Indacaterol Maleate eq to Indacaterol…150mcg"

Diary No. Date of R& I & fee Dy. No 10739 dated 05-03-2019 Rs.20,000/- (04-03-2019)

Pharmacological Group Selective beta-2-adrenoreceptor agonists

Type of Form Form 5

Finished Product Specification Manufacturer’s specifications




Onbrez Breezhaler 150 microgram inhalation powder, hard

capsules approved by HPRA of Ireland.

Me-too Status Onbrez Breezhaler 150 microgram inhalation powder, hard

capsules by M/s Novartis Pharma, Islamabad.

(Reg.#069586)

GMP Status 10-07-2018./ GMP compliance level is rated as GOOD




Applicant



Brand Name +Dosage Form+Strength Captair 300mcg Capsule


Indacaterol Maleate eq to Indacaterol…300mcg"


Pharmacological Group Selective beta-2-adrenoreceptor agonists

Type of Form Form 5






Onbrez Breezhaler 300 microgram inhalation powder, hard

capsules approved by HPRA of Ireland.

Me-too Status Onbrez Breezhaler 300 microgram inhalation powder, hard

capsules by M/s Novartis Pharma (Reg.#069587`)





Applicant



Brand Name +Dosage Form+Strength Indigo 110/50mcg Capsule

Composition "Each capsule contains

Indacaterol as maleate……110mcg

Glycopyrronium as bromide……50mcg"


Pharmacological Group Drugs for obstructive airway diseases, adrenergics in

combination with anticholinergics

Type of Form Form 5





Ultibro Breezhaler inhalation powder hard capsules approved by

EMA

Me-too Status Ultibro Breezhaler inhalation powder hard capsules by M/s

Novartis Pharma (Pakistan) Limited. (Reg.#088393)



Decision: Registration Board deliberated that since the referred me-too product “Ultibro Breezhaler

by M/s Novartis Pharma (Pakistan) Limited. (Imported) Reg. No. 088393” was first approved in

254th meeting of Registration Board, and the Board in its 240th meeting has already decided that

stability studies data will be required for new formulation and its subsequent generic, hence Board

deferred the case for submission of stability study data as per the guidelines provided in 278th and

293rd meeting of Registration Board as it’s a subsequent generic.


Applicant



Brand Name +Dosage Form+Strength Salme-F DPI 500/50mcg Capsule

Composition Each Capsule Contains:

Fluticasone Propionate…..500mcg

Salmeterol as Xinafoate……50mcg


Pharmacological Group β-2 agonists/long-acting corticosteroids

Type of Form Form-5


Pack Size & Demanded Price As per Drug pricing policy



Seretide Accuhaler 50 microgram/500microgram /dose

inhalation powder, pre-dispensed. Approved by MHRA.

Me-too status Oxytide-F50/500DPI capsule of M/s Werrick (R.#095348).

GMP status 10-07-2018./ GMP compliance level is rated as GOOD

Remarks of the Evaluator2 The firm has submitted details of label claim & product

specifications as recommended by Registration board in its 290th

meeting regarding the Manufacturing Requirements for

Rotacaps (Dry powder Inhaler)

Decision: Approved.


Applicant








Diary No. Date of R& I & fee Dy. No 23596 dated 08-12-2017 Rs. 20,000/- (08-12-2017)


Type of Form Form-5

Finished Product Specification Manufacturer specifications

Pack Size & Demanded Price As per Drug pricing policy



Seretide Accuhaler 50 microgram /250 microgram /dose


Me-too status Seretide Diskus 50/250mcg Powder For Inhalation of M/s

Glaxosmithkline Pakistan Limited, Karachi. (Reg. #074727).




meeting regarding the Manufacturing Requirements for Rotacaps

(Dry powder Inhaler)



Applicant







Diary No. Date of R& I & fee Dy. No 23597 dated 08-12-2017 Rs. 20,000 (08-12-2017)


Type of Form Form-5

Finished product Specification Manufacturer specifications

Pack size & Demanded Price As per Drug pricing policy

Approval status of product in

Reference Regulatory Authorities.

Seretide Accuhaler 50 microgram /100 microgram /dose


Me-too status Seretide Diskus 50/100mcg Powder For Inhalation of M/s

Glaxosmithkline Pakistan Limited, Karachi. (Reg. #074726).




meeting regarding the Manufacturing Requirements for

Rotacaps (Dry powder Inhaler)



Applicant

"M/s Scilife Pharma Pvt Ltd. Plot # FD-57/58-A2, Korangi Creek

Industrial Park, Karachi"

Brand Name+Dosage Form+ Strength B-Form Rotacaps 400mcg+12mcg


Each capsule contains:-

Budesonide…..400mcg

Formoterol fumarate dihydrate……. 12 mcg

Diary No. Date of R& I & fee Dy. No 07-04-2017 Rs. 20,000/-

Pharmacological Group Glucocorticosteroid/Selective β2 adrenoceptor agonist

Type of Form Form-5

Finished product Specification Manufacturer specifications

Pack size & Demanded Price As per Drug pricing policy



Symbicort Turbuhaler approved by Health Canada

Me-too status Venticort Rotacaps by M/s Macter Pharma (Reg. #089365).


GMP status 10-07-2018./ GMP compliance level is rated as GOOD.

Remarks of the Evaluator2 The case was presented in 291st meeting along with details

of stability studies data & report of on-site panel inspection

report which is reproduced as under:

STABILITY STUDY DATA

Drug B-Form Rotacaps 400mcg+12mcg

Name of Manufacturer M/s Scilife Pharma (Pvt.) Ltd., Karachi.

Manufacturer of APIs M/s Vamsi labs Ltd., Maharashtra, India

API Lot No. Formoterol fumarate dihydrate: FF-0030317

Budesonide: BDS-0100517

Description of Pack

(Container closure system) Alu –Alu blister with unit carton

Stability Storage Condition Real time : 30°C ± 2°C / 75% ± 5%RH

Accelerated: 40°C ± 2°C / 75% ± 5%RH

Time Period Real time: 6 months Accelerated: 6 months

Frequency Accelerated: 0,3,6 month Real Time: 0,3,6 month

Batch No. 210B17 211B17 212B17

Batch Size 26000 rotacaps 26000 rotacaps 26000 rotacaps

Manufacturing Date 28-12-2017 28-12-2017 28-12-2017

Date of Initiation 19-01-2018 19-01-2018 19-01-2018

No. of Batches 03

DOCUMENTS / DATA PROVIDED BY THE APPLICANT

Sr.# Documents To Be Provided Status

1. COAS of API Yes.

2. Approval of API by regulatory authority of country of

origin or GMP certificate of API manufacturer issued by

regulatory authority of country of origin.

Copy of GMP certificate (certificate# NEW-

WHO-GMP/CERT/PD/75003/2018/1/25587)

issued by Food and Drug Administration

Maharashtra to M/s Vamsi labs Ltd.,

Maharashtra, India valid till 02-11-2021

3. Protocols followed for conduction of stability study and

details of tests. Yes

4. Data of 03 batches will be supported by attested

respective documents like chromatograms, laboratory

reports, data sheets etc.

Yes

5. Documents confirming import of API etc. Copy of Form 6 & commercial invoice has been

submitted attested by Assistant Director (I & E)

DRAP, Karachi

6. All provided documents will be attested (name, sign and

stamp) for ensuring authenticity of data / documents. Yes

7. Commitment to continue real time stability study till

assigned shelf life of the product. Yes

8. Commitment to follow Drug Specification Rules, 1978. Yes

REMARKS OF EVALUATOR


Sr.# Observation Firm’s Response

i.

Evidence of approval of applied

formulation in similar dosage form as

applied, by reference regulatory

authorities/agencies, which were adopted

by the Registration Board in its 275th

meeting.

Firm has referred to product “Venticort” with similar

composition of Macter International Karachi, approved

by Registration Board in its 275th meeting.

Moreover firm has referred that applied dosage form is

a cost effective approach as compared to reference

product.

ii.

Label claim for delivered dose shall be

submitted, based upon the performance

tests identified by USP in its general

chapter <601>.

Firm has submitted results for “Uniformity of delivered

dose” by Dose Uniformity Sampling Apparatus at 9th

month long term stability time point.

On the basis of above performance test firm has

submitted following label claim:

“Each delivered dose (the dose that leaves the

mouthpiece) contains:

“Budesonide ……. 320mcg

Formoterol fumarate dehydrate….. 9mcg”

iii.

Following performance quality &

specific tests as identified by USP in its

general chapter <5> & <601> have not

been performed during stability studies:

Aerodynamic size distribution.

Microbial Enumeration test

Test for specified microorganisms

Foreign particulate matter.

Uniformity of delivered dose

Firm has submitted results for following tests at 9th

month long term stability time point:

Aerodynamic size distribution.

Microbial Enumeration test

Test for specified microorganisms

Foreign particulate matter.

Uniformity of delivered dose

Report on Investigation of Authenticity / Genuineness of data submitted for registration of B-Form

Rotacaps 400mcg + 12mcg (Budesonide + Formoterol fumarate dehydate) by M/s. Scilife Pharma (Pvt).

Ltd., Karachi.

Reference No: F.3-11/2017-PEC (Pt) dated 30th July, 2019.

Investigation Date and Time: 31st July, 2019 (Morning).

Investigation Site: Factory premises of M/s. Scilife Pharma (Pvt). Ltd., Korangi Creek, Industrial State,

Karachi.

Background:

Chairman Registration Board considered the applications of M/s. Scilife Pharma (Pvt). Ltd., Korangi Creeck,

Industrial State, Karachi for registration of B-Form Rotacaps 400mcg + 12mcg (Budesonide + Formoterol

fumarate dehydrate) and constituted a three-member panel to investigate the authenticity / genuineness of

data (import of raw material and stability data). Panel was advised to conduct inspection of the firm and to

submit report for further consideration.

Composition of Panel:

1. Director, Drug Testing Laboratory, Government of Sindh, Karachi.

2. Dr. Saif ur Rehman Khattak, Director, CDL, DRAP, Karachi.

3. Mr. Asfandyar Ajab Khan, Assistant Director, CDL, DRAP, Karachi.

Scope of investigation:

Investigation of the authenticity / genuineness of data (import of raw material and stability data),

manufacturing of stability batches and stability studies on these batches.

Tools for Investigation:

The investigation was conducted by using a structured questionnaire of DRAP. For objective evidence

physical inspection of the facilities for manufacturing and quality control, material used and retained,

personnel involved, ongoing studies, printed data and integrity and security of data in respective databases

were also audited. The details of investigation may be summarized as under:

B-FORM ROTACAPS 400MCG + 12MCG


Sr.# Question Observation by panel

1. Do you have documents confirming the

import of API?

The firm has imported:

50g Budesonide API (Batch no: BSD-0100517) and

10g Formoterol Fumarate dihydrate API (Batch No. FF no:

0030317) from Vamsi Labs Ltd. India. Proper approval taken

from DRAP dated 30.11.2017,

and respectively

2. What was the rationale behind selecting

the particular manufacturer of API?

There is proper vendor evaluation form being implemented by

the firm. The parameters included in this form are, DMF status,

GMP certificate, Stability data, provision of reference standard

of API and impurities standards etc. The firm has evaluated on

this criteria and has been selected accordingly.


import of reference standard and

impurity standards?

The firm has imported Budesonide + Formeterol Fumerate

dihydrate working standard from the API manufacturer Vamsi

Labs Ltd., India). Moreover the firm has imported reference

standards and impurity standards from Eur. Ph. for both APIs.

4. Do you have certificate of Analysis of

the API, reference standards and

impurity standards?

The firm has certificates of analysis of both the API, reference

standard and impurities standards.

5. Do you have any approval of API or

GMP certificate of API manufacturer

issued by regulatory authority of country

of origin?

Firm has valid GMP certificate of Budesonide API and

Formoterol Fumarate dihydrate API issued by regulatory

authority of their respective country of origin from Joint

Commissioner (HQ) & controlling Authority, FDA

administration, M.S. Bandra (E), Mumbai, Maharashtra state,

India.

6. Do you use API manufacturer method of

testing?

The Firm used Eur. Ph compendial method for API which is the

same as that of manufacturer`s

7. Do you have stability studies reports on

API?

The firm has stability studies report on APIs (Budesonide +

formeterol fumerate dihydrate) conducted by API

manufacturers.

8. If whether the stability testing has been

performed as per SIM method &

degradation products have been

quantified?

The manufacturer of both APIs has performed the stability

studies on APIs as per SIM method and the degradation

products have been quantified.

9. Do you have method for quantifying the

impurities in the API?

The firm has method for quantifying the impurities by Eur. Ph

in the APIs

10. Do you have some remaining quantities

of the API, its reference standard and

impurities standards?

The firm has remaining quantities of APIs, reference standards

and impurities standards.

11. Have you used pharmaceutical grade

excipients?

The firm has used pharmaceutical grade excipient Lactose

monohydrate (respitose).


import of the used excipients?

The firm has relevant documents confirming the import of the

used excipient. Proper approval taken from DRAP on invoice

9003327957 dated 07.11.2017.

13. Do you have test reports and other

records on the excipients used?

The firm has test reports and other records on the excipients

used.

14. Do you have written and authorized

protocols for the development of the

product?

The firm has written and authorized protocol for the

development of the product (Budesonide + formeterol fumerate

dihydrate) 400+12 rotacaps.


15. Have you performed Drug-excipients

compatibility studies?

The firm has not performed Drug-excipients compatibility

studies as their formulation is similar to that of the reference

product formulation.

16. Have you performed comparative

studies?

The firm has conducted comparative studies with leading

generic product of M/S. Incepta Pharma, Bangladesh (Budimat

inhaler). Both the products have comparative profiles. The firm

will also conduct studies with innovator product before

commercial manufacturing.

17. Do you have product development

(R&D) section

The firm has well equipped exclusive product development

(R&D) section.

18. Do you have necessary equipment’s

available in product development section

for development of the product?

The firm has necessary equipment’s for production of

(Budesonide + formeterol fumerate dihydrate) 400+12 rotacaps

in product development section.

19. Are the equipments in product

development section qualified?

The equipment in product development section are qualified.

20. Do you have proper maintenance /

calibration / re-qualification program for

the equipment used in PD section?

The firm has proper maintenance / calibration / re-qualification

program for the equipment used in PD section.

21. Do you have qualified staff in product

development section with proper

knowledge and training in product

development?

The firm has a team of 3 pharmacists and 4 chemist, 1

biotechnologist with a machine operator in product

development section with suitable knowledge and training in

product development.

22. Have you manufactured three stability

batches for the stability studies of the

product as required?

The firm has manufactured three stability batches as

follows;

1) 210B17, 2) 211B17 and 212B17

23. Do you have any criteria for fixing the

batch size of stability batches?

The criteria for fixing the batch size of stability batches, as

informed by the firm, was based on the quantity required for

stability study (i.e. number of capsules per testing frequency and

number of testing frequencies / intervals) and minimum

working Capacity of the equipment.

24. Do you have complete record of

production of stability batches?

Firm has complete record of production of stability batches.

25. Do you have protocols for stability

testing of stability batches?

The firm has detailed protocol for stability testing of stability

batches.

26. Do you have developed and validated the

method for testing of stability batches?

The firm has developed and validated method for testing of

stability batches of finish product i.e. B Form DS (Budesonide

+ formeterol fumerate dihydrate) 400/12 rotacaps. The method

is stability indicating.

27. Do you have method transfer studies in

case when the method of testing being

used by your firm is given by any other

lab?

Transfer studies not applicable.


qualification of equipments / instruments

being used in the test and analysis of API

and the finished drug?

The firm has proper documents confirming the qualification of

equipment / instruments being used in the test and analysis of

APIs and the finished product.

29. Do your method of analysis stability

indicating?

Firm’s method of analysis was stability indicating and the

record of testing of stability batches available.

30. Do your HPLC software is 21CFR

compliant?

The HPLC software is 21CFR Compliant as per record of the

firm. Audit trail was active on all HPLC systems used


throughout stability study. Individual user log in and IDs were

available.

31. Can you show Audit Trail reports on

product testing?

Audit trail reports were available and randomly checked.


of degradation products and stability

batches?

The firm has only remaining quantities of stability batches kept

on real-time stability testing.

33. Do you have stability batches kept on

stability testing?

The firm has completed the accelerated stability testing on the

three stability batches however the real time stability testing is

in progress on all the three stability batches. First three

validation batches to be kept on stability.

34. Do you have valid calibration status for

the equipment’s used in production and

analysis?

The Firm has valid calibration status for the equipment used in

production and analysis of the product.

35. Do proper and continuous monitoring

and control are available for stability

chamber?

Continuous power supply and monitoring are available for

stability chambers.

Sr.# Question Observation by panel

36. Observations of PEC?

a) Precautionary measures adopted to

control of cross contamination of the

steroidal preparation with the general

products during the manufacturing of

applied formulations

The firm has taken several steps to control the cross-

contamination for steroidal preparation as below,

i) Installed, Qualified and Maintained dedicated Sampling /

Dispensing booth in the separate area for the handling of

steroidal raw materials to avoid the cross contamination as

Starting point of manufacturing.

ii) Dedicated multi-directional mixer for mixing of steroidal

formulations available

iii) Dedicated change parts available for the encapsulation of

(Budesonide + Formoterol fumarate dihydrate) 400/12mcg

that will ensure and minimize the risk cross contamination

during filling process

iv) Dedicated change parts along with auto feeder is installed

and available for the blistering of (Budesonide + Formoterol

fumarate dihydrate) 400/12mcg that will further ensure the

control of cross contamination during blistering and primary

packaging process.

v) In addition to that, firm executed the PRE/POST cleaning

validation studies on approved protocol for steroidal

formulations based on worst-case scenario to make sure the

prevention of cross contamination.

vi) Isolation gowning has been provided for this product.

b) Availability of specialized mixing

facility to ensure the required particle

size of formulation blend

The firm has executed and maintained the following steps for the

obtaining required particle size of formulation blend as given

below,

i) The firm used both the APIs Budesonide and Formoterol

fumarate dihydrate having controlled and special particle size

required for inhaler preparation as less than 5µm.

ii) The firm has also used inhaler grade excipients Lactose i.e.

Respitose having required particle size.

iii) Design and developed the Two stage mixing mechanism on

multi-directional-mixer having 3D mixing capability to

ensure the homogeneous mixing of APIs in blended


formations having desired particle size. The same has been

qualified through approved qualification protocol.

iv) In addition to that the final blend of each batch will be tested

on 10 point sampling method and checked on HPLC to make

sure the equal and homogeneous distribution of both the APIs

in formulation blend before start next step.

c) Availability of necessary apparatus

for the performance of uniformity of

deliver dose and aerodynamic particle

size

The firm has necessary apparatus for the performance of

uniformity of deliver dose which is Dose Uniformity sampling

apparatus and aerodynamic particle size distribution which is

MSLI (Multistage Liquid Impinger) available and qualified to test

the product.

d) Detailed of the drug delivery device

(Inhaler) intended to be marketed

along with the applied formulation.

i) We are importing the DPI Device (SciAir) from TAIAN

DALU MEDICAL INSTRUMENT CO., LTD. CHINA

under import license ELI-00187 for importing the inhaler

device issue by Secretary Medical device board dated 19-10-

2018 having 5 years expiry.

ii) The device (DL-D02) bear the mark, showing

Compliance of the designated product with the Directive

93/42/EEC has been assessed and certified by the Notified

Body TÜV Rheinland LGA Products GmbH following the

procedure relating to the EC Declaration of Conformity set

out in Annex V of Directive 93/42/EEC.

iii) The SciAir device main structure and performance are as

following:

a. Protection cap: Contain and protect the inner parts and avoid

pollution.

b. Mouthpiece: For helping users to inhale the powder

medication effectively.

c. Capsule cavity: Contain capsule.

d. Push button: For users to puncture the capsule to inhale the

powder.

e. Back piece: For seal the device bottom and supporting

function.

iv) SciAir DPI device enlistment with MD board having

enlistment no. MDIE-0000028, dated

v) 12/07/2019

vi) How to use: patient information leaflet attached for review.

e) Results for uniformity of delivered

dose by dose uniformity sampling

apparatus performed at 9th month of

long term stability time point

Results for uniformity of delivered dose by dose uniformity

sampling apparatus performed at 9th month of long term stability

time point has been checked and verified. Results are satisfactory.

f) Results for the following tests

performed at the 9th month of long term

stability time point

i) Aerodynamic size distribution

ii) Micro enumeration test

iii) Test for specified microorganisms

iv) Foreign particulate matter

Results for the following tests performed at the 9th month of long

term stability time point has been checked and verified.

i) Aerodynamic size distribution

ii) Micro enumeration test

iii) Test for specified microorganism

iv) Foreign particulate matter

Results are satisfactory.

Conclusion and Recommendations:

1. On the basis of risk-based approach the genuineness / authenticity of stability data submitted by the firm

for registration of B-Form Rotacaps 400mcg + 12mcg (Budesonide/Formoterol Fumarate dehydrate) is

verifiable to satisfactory level.


2. The firm has provided a number of measures and arrangements to minimize the risk of cross-

contamination including specialized dedicated dispensing booth, 3D mixer, dedicated change parts on

capsules filling machine, pre and post operation cleaning validation, work station exposure studies and

special gowning in addition to effective HVAC system. All the above mentioned measures / arrangements

technically reduce the chances of cross-contamination to satisfactory level. The arrangements, controls

and studies being made by the firm for manufacturing B-Form Rotacaps 400mcg / 12mcg of desired

quality can be rated satisfactory. Any special arrangement or decision related to manufacturing of DPIs

may kindly be rechecked by the board for uniform and effective compliance.

3. Registration of the product (B-Form Rotacaps 400mcg / 12mcg) is recommended in the name of the

manufacturer.

Decision of 291st meeting: Registration Board deferred the case for the requirement of separate section of “Dry

powder Inhaler Capsules” as decided by Board in its 290th meeting.

Evaluation by PEC:

Now the Central Licensing Board in its 273rd meeting held on 15th January, 2020 has considered and approved

the additional section of “Dry Powder Inhaler (General)” in the name of M/s Scilife Pharma (Pvt.) Ltd, Plot No.

FD-57/58-A-2, Korangi Creek, Industrial Park (KCIP) Karachi.

Decision of 294th meeting: Registration Board decided to approve registration of B-Form

Rotacaps 400mcg+12mcgwith Innovator’s specifications by M/s Scilife Pharma (Pvt.) Ltd Plot

FD-57/58-A2 Korangi Creek Industrial Park Karachi. Manufacturer will place first three

production batches of the product on long term stability studies throughout proposed shelf life

and on accelerated studies for six months.

Case No. 07 Registration applications of drugs for which stability study data is submitted

a. Deferred cases


Applicant

M/s CCL Pharmaceuticals Pvt. Ltd, 62 Industrial Estate, Kot

Lakhpat, Lahore.

Brand Name+Dosage Form+ Strength Censipar tablet 60mg

Composition "Each film coated tablet Contains:

Cinacalcet as hydrochloride…..…60mg"

Diary No. Date of R& I & fee Dy.No.16788 (03-10-2017); Rs. 50,000/- (03-10-2017)

Pharmacological Group Calcimimetic

Type of Form Form-5D

Finished product Specifications Manufacturer’s speci fications

Pack size & Demanded Price As per PRC



Approved by USFDA


dosage form)

GMP status

Remarks of the EvaluatorII

Now the firm has submitted stability data detailed as under:


Drug Censipar tablet 60mg

Name of Manufacturer M/s CCL Pharmaceuticals Pvt. Ltd, 62 Industrial Estate, Kot Lakhpat, Lahore.

Manufacturer of API Cinacalcet hydrochloride: M/s Ind-Swift Laboratories Ltd., Punjab, India

API Lot No. 1233040001

Description of Pack

(Container closure system) Alu-Alu foil in unit carton





Frequency Real Time: 0,3,6 months Accelerated: 0,3,6 months

Batch No. CNB-T2-18 CNB-T3-18 CNB-T4-18

Batch Size 2000 tablets 2000 tablets 2000 tablets

Manufacturing Date 09-2018 09-2018 09-2018


No. of Batches 03

Date of Submission 03-06-2019 (Dy. No. 7864)


Documents To Be Provided Status

COA of API Yes

Approval of API by regulatory authority of country

of origin or GMP certificate of API manufacturer

issued by regulatory authority of country of origin.

Copy of GMP Certificate for M/s Ind-Swift Laboratories

Ltd., Punjab, India issued by Food & Drug

Administration, Punjab, India has been submitted, valid

upto 11-2019.

Protocols followed for conduction of stability

study and details of tests. Yes

Data of 03 batches will be supported by attested

respective documents like chromatograms,

laboratory reports, data sheets etc.

Yes

Documents confirming import of API etc. Copy of invoice for Cinacalcet hydrochloride, attested by

Assistant Director (I & E) DRAP, Lahore dated 13-04-

2018 has been submitted.

All provided documents will be attested (name,

sign and stamp) for ensuring authenticity of data /

documents.

Yes

Commitment to continue real time stability study

till assigned shelf life of the product. Yes

Commitment to follow Drug Specification Rules,

1978. Yes


The frequency of testing for accelerated stability studies is not as per recommendations of 278th meeting

of Registration Board i.e., 0, 1,2,3,4 & 6 month.

You have not performed uniformity of dosage unit by content uniformity, as recommended by USP

General Chapter <905> throughout stability studies. Justification shall be submitted in this regard.

Justification for value of Q=70% in the dissolution test shall be submitted since USP chapter <1092>

(The Dissolution Procedure; Development and Validation) recommends Q values in the range of 75% - 80% for

immediate release dosage forms.

In response to above observations, firm has submitted as under:

Regret to inform you that accelerated stability studies at 0,3 & 6 months were performed as per ICH

guidelines. We commit that we will perform accelerated stability studies at 0,1,2,3,4 & 6 months as per DRAP

guidelines from 1st August 2019 to onward for new products.

We commit to incorporate content uniformity of dosage unit by assay method in our product test method

and will analyse real time stability batches for content uniformity. You may verify the same during on-site

inspection.


As identified by your good office, we hereby agree to revise the limit of Q=-75% for Cinalcalcet in the

dissolution test.


Applicant

M/s CCL Pharmaceuticals Pvt. Ltd, 62 Industrial Estate, Kot

Lakhpat, Lahore.

Brand Name+Dosage Form+ Strength Censipar tablet 30mg

Composition "Each film coated tablet Contains:

Cinacalcet as hydrochloride…..…30mg"

Diary No. Date of R& I & fee Dy.No.16786 (03-10-2017); Rs. 50,000/- (03-10-2017)

Pharmacological Group Calcimimetic


Finished product Specifications Manufacturer’s specifications




Approved by USFDA


dosage form)

GMP status


Now the firm has submitted stability data detailed as under:


Drug Censipar tablet 30mg

Name of Manufacturer M/s CCL Pharmaceuticals Pvt. Ltd, 62 Industrial Estate, Kot Lakhpat, Lahore.

Manufacturer of API Cinacalcet hydrochloride: M/s Ind-Swift Laboratories Ltd., Punjab, India

API Lot No. 1233040001

Description of Pack

(Container closure system) Alu-Alu foil in unit carton




Frequency Real Time: 0,3,6 months Accelerated: 0,3,6 months

Batch No. CNA-T2-18 CNA-T3-18 CNA-T4-18




No. of Batches 03




COA of API Yes




Copy of GMP Certificate for M/s Ind-Swift Laboratories

Ltd., Punjab, India issued by Food & Drug Administration,

Punjab, India has been submitted, valid upto 11-2019.




respective documents like chromatograms, Yes



Documents confirming import of API etc. Copy of invoice for Cinacalcet hydrochloride, attested by

Assistant Director (I & E) DRAP, Lahore dated 13-04-2018

has been submitted.



documents.

Yes




1978. Yes


The frequency of testing for accelerated stability studies is not as per recommendations of 278th meeting

of Registration Board i.e., 0, 1,2,3,4 & 6 month.

You have not performed uniformity of dosage unit by content uniformity, as recommended by USP

General Chapter <905> throughout stability studies. Justification shall be submitted in this regard.

Justification for value of Q=70% in the dissolution test shall be submitted since USP chapter <1092>

(The Dissolution Procedure; Development and Validation) recommends Q values in the range of 75% - 80% for

immediate release dosage forms.

In response to above observations, firm has submitted as under:

Regret to inform you that accelerated stability studies at 0,3 & 6 months were performed as per ICH

guidelines. We commit that we will perform accelerated stability studies at 0,1,2,3,4 & 6 months as per DRAP

guidelines from 1st August 2019 to onward for new products.

We commit to incorporate content uniformity of dosage unit by assay method in our product test method

and will analyse real time stability batches for content uniformity. You may verify the same during on-site

inspection.

As identified by your good office, we hereby agree to revise the limit of Q=-75% for Cinalcalcet in the

dissolution test.

Report on Investigation of Authenticity / Genuineness of data submitted for registration of Censipar tablet

30mg & 60mg by M/s CCL Pharmaceuticals Pvt. Ltd, 62 Industrial Estate, Kot Lakhpat, Lahore.

Reference No: No.F.13-11/2017-PEC (Pt) dated 19-08-2019..

Investigation Date and Time: 12-11-2019.

Investigation Site: Factory premises of M/s CCL Pharmaceuticals (Pvt.) Ltd., 62 Industrial Estate,

KotLakhpat, Lahore


1. Mr. Shaheen Iqbal Director, DTL, Lahore.

2. Ms. Aisha Irfan Area FID, DRAP, Lahore.

3. Ms. Maham Misbah Assistant Director, DRAP, Lahore.

Focus of Inspection:

Inspection was focused on a thorough evaluation of data for stability studies of following products namely:

Sr. No. Name / Composition of Drugs

01 Censipar Tablet 30mg

Each film coated tablet contains:

Cinacalcet (as HCl)………………………30mg





Detail of investigation:

Q.# Questions Observation by panel

1. Do you have documents confirming the import of

Cinacalcet HCl including approval from DRAP?

The firm had imported Cinacalcet HCl raw material

vide invoice no. 9100016098 dated 21/02/2019 from

M/s.Ind-Swift Laboratories, India and got DRAP

approval vide letter No. 5114/2018 DRAP dated 13-

04-2018.

2. What was the rationale behind selecting the

particular manufacturer of API?

The firm informed that they selected M/s. Ind-Swift

Laboratories, India based on their vendor evaluation

mechanism.


reference standard and impurity standards?

The firm’s representative informed that they had

imported Cinacalcet HCl working standard and

impurities standards from API supplier. However,

firm did not have import NOC for the same.

4. Do you have certificate of Analysis of the API,

reference standards and impurity standards?

The firm had certificates of analysis for API, working

standard and impurities standards for impurity A, B,

I, J, K and L.

5. Do you have GMP certificate of API

manufacturer issued by regulatory authority of

country of origin?

The firm had provided valid GMP Certificate of

M/s.Ind Swift Laboratories, India issued by Food &

Drugs Administration, Punjab, India, valid till 27-11-

2019.

6. Do you use API manufacturer method of testing

for testing API?

The firm used API manufacturer’s method of testing.

However, firm had not tested the related substances

in the API.

7. Do you have stability studies reports on API? The firm had stability studies reports on APIs of raw

material manufacturers.

8. If yes, whether the stability testing has been

performed as per SIM method and degradation

products have been quantified?

No.



The firm had testing method to quantify the

impurities as provided by raw material manufacturer.

10. Do you have some remaining quantities of the

API, its reference standard and impurities

standards?

The firm had some remaining quantities of the

working standard and impurities standards.

11. Have you used pharmaceutical grade excipients? The firm had used pharmaceutical grade excipients

including Starch 1500, Avicel pH 102, Kollidon K-

30, Kollidon CL, Aerosil-200Magnesium stearate,

Opadry AMB Green.


the used excipients?

The firm had necessary documents confirming the

import of the used excipients.

13. Do you have test reports and other records on the

excipients used?

The firm had Certificates of Analysis of the

excipients used.

14. Do you have written and authorized protocols for

the development of Cinacalcet HCl Tablets?

The firm had written and authorized protocols for the

development of CensiparTablet 30mg and Censipar

Tablet 60mg.

15. Have you performed Drug-excipient


The firm had performed drug-excipients

compatibility studies under stress conditions of 60oC

± 2oC / 75% ± 5% RH.

16. Have you performed comparative dissolution

studies?

The firm had performed comparative dissolution

studies for Censipar Tablet 60mg with Mimpara

Tablet 60mg, manufactured by M/s. Amgen,


USAusing eight basket dissolution apparatus (708-

DS by Agilent.

17. Do you have product development (R&D)

section

The firm had product development (R&D) section.

18. Do you have necessary equipment available in

product development section for development of

Cinacalcet HCl Tablets?

Product development section had necessary

equipment to develop CensiparTablets.

19. Is the equipment in product development section

qualified?

The available equipment in product development

section was qualified.

20. Do you have proper maintenance / calibration /

re-qualification program for the equipment used

in PD section?

The firm had proper maintenance / calibration / re-

qualification program for the equipment used in

product development section.


development section with proper knowledge and

training in product development?

Yes.

22. Have you manufactured three stability batches

for the stability studies of Cinacalcet HCl Tablets

as required?

The firm had manufactured three stability batches for

the stability studies of CensiparTablets (30mg and

60mg) with batch numbers i.e. CNA-T2-18, CNA-

T3-18, CNA-T4-18 for 30mg strength and CNB-T2-

18, CNB-T3-18,CNB-T4-18 for 60mg strength.

The accelerated studies were done in Climatic test

chamber (Model: HPP-749; Making Memmert,

Germany) and long-term studies were done in

Climatic test chamber (Model: HPP-750, Making

Memmert, Germany).

23. Do you have any criteria for fixing the batch size

of stability batches?

The firm had followed in-house SOP for fixing the

batch size of stability batches in the light of DRAP

guidelines.

24. Do you have complete record of production of

stability batches?

The firm had record of production of stability

batches.

25. Do you have protocols for stability testing of

stability batches?

The firm had protocols for stability testing of stability

batches.

26. Do you have developed and validated the method

for testing of stability batches?

The firm had developed method of Censipar Tablet

30mg (RD-PTM-08 A)& CensiparTablet 60mg (RD-

PTM-09 A) and validated the test method (CCL-

AMVR-213)for testing ofstability batches.

27. Do you have method transfer studies in case

when the method of testing being used by your

firm is given by any other lab?

Not Applicable.


qualification of equipment / instruments being

used in the test and analysis of Cinacalcet HCl

API and the finished drug?

The firm had proper documents confirming the

qualification of equipment / instruments being used in

the test and analysis of CinacalcetHCl API and the

finished drug.

29. Do your method of analysis stability indicating? The firm had conducted stress testing of finished

product.

30. Do your HPLC software 21CFR Compliant? API testing, FPP testing and compatibility testing

had been conducted on HPLCs(Agilent 1260

&Infinity II, USA) which were not 21 CFR compliant.

However, the firm had procured 21 CFR part 11

compliant HPLC.


31. Can you show Audit trail reports on Cinacalcet

HCl testing?

The audit trail was not enabled. However, log of

data was available in the HPLCs. The data was also

checked through hard copies of chromatograms.

32. Do you have some remaining quantities of

degradation products and stability batches?

The firm had remaining quantities of stability batches

kept on stability testing.

33. Do you have stability batches kept on stability

testing?

The firm had stability batches kept on stability

testing.

34. Do you have valid calibration status for the

equipment used in CinacalcetHCl tablets

production and analysis?

The firm had valid calibration status for the

equipment used in Censipar Tablets production and

analysis.

35. Do proper and continuous monitoring and control

are available for stability chamber?

Adequate monitoring and control was available for

stability chamber. The firm was advised to improve

the alarm system.

36. Do related manufacturing area, equipment,

personnel and utilities be rated as GMP

compliant?

Requisite facilities were satisfactory and GMP

compliant (DRAP ref. no. 118/2019-DRAP (AD-

789112-762) dated 13-05-2019).

Clarification:

(i) The firm had performed content uniformity of dosage unit on stability batches and incorporated the test

for content uniformity in Product Test Method.

(ii) The firm had revised the value of Q=75% in Product Test Method and Stability Studies Protocol.

REMARKS:

Based on the area inspected, the technical personnel met and the documents reviewed, and considering the

findings of inspection, it seems that M/s. CCL Pharmaceuticals (Pvt.) Ltd., at 62 Industrial Estate, Kot Lakhpat,

Lahore, Pakistan have conducted stability studies of the following products:








Remarks of Evaluator:

The panel has reported following with respect to documents confirming the import of Cinacalcet HCl including

approval from DRAP:

“The firm had imported Cinacalcet HCl raw material vide invoice no. 9100016098 dated 21/02/2019 from M/s

Ind-Swift Laboratories, India and got DRAP approval vide letter No. 5114/2018 DRAP dated 13-04-2018.”

While the invoice submitted in PEC has same invoice number but is dated 21-02-2018. Also the quantity

mentioned in submitted invoice is 225gm while the required quantity for production of three batches (2000 tablets

each) of Cinacalcet 30mg & 60mg tablets is approximately 590gms.

Proceedings: The Registration Board was apprised that the panel has identified the above cited variation in the

date of commercial invoice as drafting error, moreover firm has presented another invoice (Invoice# 9100017019

dated 03-03-2018) for the import of 575gm of Cinacalcet HCl, while this invoice was not attested by DRAP office.

Decision of 293rd meeting: Registration Board deferred the applications of Censipar 30mgtablet & Censipar

60mg tablet for seeking clarification from the applicant regarding the import of 575gm of Cinacalcet vide Invoice#

9100017019 dated 03-03-2018, without prior approval of DRAP office.

Reply of firm:

“Initially CCL planned to develop Censipar tablet 30mg (Cinacalcet HCl) only and accordingly imported 225gm

vide invoice no. 9100016098 dated 21-02-2018 and the same was released by Assistant Director I7E, DRAP,

Lahore vide letter no. 5114/2018 DRAP dated 13-04-2018.

Later on our Marketing department also requested for Censipar tablet 60mg (Cinaclacet HCl) so we arranged

further said material i.e., 575gm vide invoice no. 9100017019 dated 03-03-2018 through Fed EX and missed the

approval of Assistant Director I&E, DRAP, Lahore.


We apologise for partial compliance of DRAP instructions & commit to comply with true letter & spirit in future.”

Upon inquiring about online verification of the FedEx shipment, the firm responded as under:

“We have contacted requested to FedEx to verify attached Fed Ex airway bill dated 10-03-2018 & fed Ex informed

that said shipment cant be tracked after 90days.”

Decision: Registration Board decided to approve registration of Censipar (Cinacalcet as HCl)

Tablet 30mg and Censipar (Cinacalcet as HCl) Tablet 60mg with Innovator’s specifications by

M/s CCL Pharmaceuticals (Pvt.) Ltd., at 62 Industrial Estate, Kot Lakhpat, Lahore.

Manufacturer will place first three production batches of both products on long term stability

studies throughout proposed shelf life and on accelerated studies for six months.

Sr.

No.

Name & Address of

Manufacturer /

Applicant

Brand Name

(Proprietary Name + Dosage Form

+ Strength), Composition,

Pharmacological Group,

Finished Product Specification

Type of Form,

Initial Diary &

Date, Fee (including

differential fee),

Demanded Price /

Pack size

International Availability /

Local Availability

GMP Inspection Report

Date & Remarks


(Pvt.) Ltd

Plot FD-57/58-A2

Korangi Creek

Industrial Park

Karachi

Eflozin-M 12.5/500 mg Tablet

"Each Film Coated Tablet

Contains:

Empagliflozin .…12.5mg

Metformin HCl …… 500mg"

(Anti-diabetic)

(Mfg. Specs)

Form 5-D

Dy. No 37404

12-11-2018

Rs.50,000/-

12-11-2018

Rs.50,000/-

As per PRC

Approved by USFDA


(Pvt.) Ltd

Plot FD-57/58-A2

Korangi Creek

Industrial Park

Karachi

Eflozin-M 12.5/1000 mg Tablet

"Each Film Coated Tablet

Contains:

Empagliflozin .…12.5mg

Metformin HCl …… 1000mg"

(Anti-diabetic)

(Mfg. Specs)

Form 5-D

Dy. No 37406

dated 12-11-2018

Rs.50,000/- Dated

12-11-2018

Rs.50,000/-

As per PRC

Approved by USFDA

REQUEST OF EXEMPTION ROM ON SITE INSPECTION

The firm has requested for Exemption from On-site Investigation of their submitted stability data and provided

the following documents in conjunction with the checklist approved by the Registration Board in its 278th Meeting:

Administrative Portion

1. Reference of last onsite panel

inspection for instant dosage form

conducted during last two years.

Registration Board approved Eflozin 10 & 25mg tablets in its 292nd

Meeting.

Date of Inspection: 27th September, 2019 (Morning).

The HPLC software is 21CFR Compliant as per record of firm.

Audit trail reports were available and randomly checked.

2. Documents for the procurement of

API with approval from DRAP (in

case of import).

Empagliflozin

i. Copy of Form 6 (License to Import drug) issued by Licensing

Authority (Karachi) dated 11-06-2018, for the import of

Empagliflozin from the M/s Zhejiang Hongyuan

Pharmaceutical Co., Ltd, Chem & API’s Industrial Zone,

Linhai, Zhejiang province, China has been submitted.

ii. Copy of Commercial Invoice

Invoice no. 30180190

Attested by Assistant Director (I&E) DRAP (Karachi) dated 11-06-

2018.

Batch No 20180401.

Quantity: 1 Kg

Metformin HCl


Copy of Form 6 (License to Import drug) issued by Licensing

Authority (Karachi) dated 23-12-2016, for the import of

Metformin HCl from the M/s Aarti Drugs Ltd. (Unit-II) Plot No.

211-213 Road No.2 Char Rasta GIDC Sarigma India. has been

submitted.

Copy of Commercial Invoice

Invoice no. 30180190

Attested by Assistant Director (I & E) DRAP (Karachi) dated 11-06-

2018.

Batch No 20180401.

Quantity: 1 Kg


reference standard and impurity

standards.

Empagliflozin

Copy of GMP certificate issued by Taizhuo Drug Administration to the

M/s Zhejiang Hongyuan Pharmaceutical Co., Ltd, Chem & API’s

Industrial Zone, Linhai, Zhejiang province, China valid upto 21-09-

2022.

Metformin HCl

Copy of GMP certificate issued by Food & Drugs Control

Administration to the M/s Aarti Drugs Ltd. (Unit-II) Plot No. 211-213

Road No.2 Char Rasta GIDC Sarigma India valid upto 09-01-2020.

4. Approval of API/ DML/GMP

certificate of API manufacturer

issued by regulatory authority of

country of origin.

Empagliflozin

The firm has provided copy of GMP certificate

(Certificate#ZJ20180032) issued by China Food & Drug

Administration for M/s Zhejiang Hongyuan Pharmaceutical Co., Ltd.

Valid Up to 14-03-2023.

Metformin HCl

Copy of GMP certificate issued by Food & Drugs Control

Administration to the M/s Aarti Drugs Ltd. (Unit-II) Plot#211-213

Road No.2 Char Rasta GIDC Sarigma India valid upto 09-01-2020.

5. Mechanism for Vendor pre-

qualification

The firm has submitted Memorandum Of Vendor Approval for both

APIs.

6. Certificate of analysis of the API,

reference standards and impurity

standards

Empagliflozin

API Batch. #

Empagliflozin 20180401

Empagliflozin WS 20180501WS

Empagliflozin WS 20180702WS

Impurity A IMPA20190107

Impurity C IMPC20190110

Metformin HCl

API Batch. #

Metformin HCl MEF/16111159

Metformin HCl Primary

reference standard

USP Lot No. R069H0


excipients used in product

development?

The firm has submitted commercial invoices & COAs of excipients

used in formulation from relevant manufacturers.

8. List of qualified staff involved in

product development with relevant

experience.

The firm has submitted copy of List of qualified staff along with their

training record involved in Research & Development.


Production Data

9. Authorized Protocols/SOP for the

development & stability testing of

trial batches.

The firm has submitted SOP of Product development and protocol for

stability studies specific to the product.

10. Complete batch manufacturing

record of three stability batches.

The firm has submitted copy of Batch Manufacturing Record and batch

packaging record of the following 03 Batches.

Eflozin-M 12.5/1000mg Tablet

Batch#: Batch size Mfg. date

135B18 500 tablets 07-2018

148B18 500 tablets 08-2018

149B18 500 tablets 08-2018

Eflozin-M 12.5/500mg Tablet

134B18 1000 tablets 07-2018

146B18 1000 tablets 08-2018

147B18 1000 tablets 08-2018

11. Record of remaining quantities of

stability batches. Description B.No:

135B18

B.No: 148B18

B.No: 149B18

Theoretical Batch

Size

500

tablets

500

tablets

500

tablets

Total produced 450 459 423

Kept On

30°C/RH75%

280 280 280

Kept On

40°C/RH75%

112 112 112

Remaining On

30° C/RH75%

154 154 154

Remaining On

40° C/RH75%

- - -

Total used for CDP 36 -

Remaining quantities

in R&D

28 N/A N/A

QA / QC DATA

12. Record of Digital data logger for

temperature and humidity

monitoring of stability chambers

(real time and accelerated)

Tabular record of Digital data logger for temperature and humidity

monitoring of stability chambers has been submitted.

13. Method used for analysis of API

along with COA.

Firm has provided copies of Method of analysis and COAs for both

APIs

14. Method used for analysis of FPP &

complete record of testing of

stability batches (i.e.

chromatograms, lab reports, raw

data sheets etc.)

The firm has submitted copy of Finished Product specification &

Test method.

Firm has submitted complete record of testing of stability batches

(i.e. chromatograms, lab reports, raw data sheets etc.)

15. Reports of stability studies of API

from manufacturer. Empagliflozin

The firm has submitted copies of reports of 06 Months Accelerated and

12 Months Real Time Stability Study Data of 03 Batches of API as per

Zone-IVA conditions

Metformin HCl

The firm has submitted copies of reports of 06 Months Accelerated and

60 Months Real Time Stability Study (30oC+2 oC, 65+5%) Data of 03

Batches of API.


16. Analysis reports for excipients

used.

The firm has submitted copies of its own Analytical reports for all

excipients used in product development.

17. Drug-excipients compatibility

studies.

Firm has not performed drug excipient compatibility studies as they

claim their qualitative composition is same as that of the innovator.

18. Record of comparative dissolution

data.

Firm has submitted protocol for comparative dissolution at pH 1.2, pH

4.5 and pH 6.8. The details of reference product & Sample product are

as follows: Feature Reference product Product of M/s

Scilife

Brand name Synjardy

12.5+1000mg tablet

Eflozin-M2.5/1000mg

tablet

Batch No. 744630 148B18

Exp. Date 06-2020

Feature Reference product of

Hilton pharma

Product of M/s

Scilife

Brand name Xenglumet

12.5/50012.5+500mg tablet

Eflozin-M2.5/500mg

tablet

Batch No. 131255 146B18

Exp. date 07-2021

F2 factor calculation is within acceptable range.

19. Compliance Record of HPLC

software 21CFR & audit trail

reports on product testing.

Firm has submitted audit trail reports for complete stability studies

analysis of three batches.


Significant change in the Assay results of various batches have been reported in the submitted data of

accelerated stability studies, detailed as under: Product Batch# API Assay value at

Initial time point

Significant change value

Eflozin-M

12.5/1000mg tablet

148B18 Empagliflozin 98.13% 106.05% (at 6th month

time point)

Eflozin-M

12.5/1000mg tablet

149B18 Metformin HCl 101.95% 96.775 (at 6th month

time point)

Justification shall be submitted for above reported significant changes for the grant of 2 years shelf life.

Firm’s response for Empagliflozin:

1. Batch number "149B18" showing the 5.18% difference in assay value which is slightly higher (0.18%)

from the initial time point while the rest of the batches "135B18" and "148B18" showing the satisfactory

insignificant change values 1.78% and 0.94% respectively.

2. Average results of each individual batch up to 6 month stability 99.65%, 98.43% and 100.16% which are

well within the limit having all values between 90% and 110% as a shelf life limit.

3. We have manufactured all the batches at 100% potency no results obtained at lower side less than 95%

which is satisfactory.

4. The consideration of the slightly lower results in one of the batch at 6 month at this stage while the results

are within limit between 90% - 110%

5. The results obtained at every time point of every batch well within shelf limit of 90% - 110% so consider

satisfactory and the only one result of one batch at single time point slightly lower so that could be considered

insignificant in general if we look the picture in broader way.

6. The 9 months at real time condition also completed and found satisfactory results which are 149B18=

96.94%, 135B18=96.66% and 97.90% for Metformin HCl well within the limit.

7. On the basis of above discussion and statistical evaluation the results need to be considered satisfactory

and reveals that the product will remains safe, effective and quality medicine and stable till 2 years shelf life.

Firm’s response for Metformin HCl:


1. Batch number "149B18" showing the 5.18% difference in assay value which is slightly higher (0.18%) from

the initial time point while the rest of the batches "135B18" and "148B18" showing the satisfactory insignificant

change values 1.78% and 0.94% respectively.

2. Average results of each individual batch up to 6 month stability 99.65%, 98.43% and 100.16% which are well

within the limit having all values between 90% and 110% as a shelf life limit.

3. We have manufactured all the batches at 100% potency no results obtained at lower side less than 95% which

is satisfactory.

4. The consideration of the slightly lower results in one of the batch at 6 month at this stage while the results are

within limit between 90% - 110%

5. The results obtained at every time point of every batch well within shelf limit of 90% - 110% so consider

satisfactory and the only one result of one batch at single time point slightly lower so that could be considered

insignificant in general if we look the picture in broader way.

6. The 9 months at real time condition also completed and found satisfactory results which are 149B18= 96.94%,

135B18=96.66% and 97.90% for Metformin HCl well within the limit.

7. The obtained results shows that the batch to batch and within batch variation which is acceptable because within

the limit 90-110% rather significant change however it will be further controlled and improved in future on full

scale validation.

8. On the basis of above discussion and statistical evaluation the results need to be considered satisfactory and

reveals that the product will remains safe, effective and quality medicine and stable till 2 years shelf life.

Decision of 293rd meeting: Registration Board deferred for further deliberation in light of above points.

Remarks of evaluator: Now the firm has submitted long term stability studies data of three batches each for both

Eflozin-M 12.5/1000mg tablet & Eflozin-M 12.5/500 mg Tablet till 12 month time point, wherein the results for

both Assay & Dissolution test are within the limits.

Decision: Registration Board decided to approve registration of Eflozin-M 12.5/500mg tablet &

Eflozin-M 12.5/1000 mg Tablet with Innovator’s specifications by M/s Scilife Pharma (Pvt.) Ltd

Plot FD-57/58-A2 Korangi Creek Industrial Park Karachi. Manufacturer will place first three

production batches of both products on long term stability studies throughout proposed shelf life

and on accelerated studies for six months.

b. Exemption from onsite verification of stability data 83. Name and address of manufacturer /

Applicant

M/s Getz Pharma Pvt. Ltd., Karachi

Brand Name +Dosage Form + Strength Glardin-M Tablets 5mg + 850mg

Composition Each film coated tablet contains:-

Empagliflozin …….5mg

Metformin HCl ….. 850mg

Diary No. Date of R& I & fee Dy. No 380 dated 18-03-2016, Rs.50,000/-

Pharmacological Group Anti-diabetic

Type of Form Form 5D

Finis`hed product Specifications Manufacturer specifications




Approved by EMA


dosage form)

GMP status



Applicant

M/s Getz Pharma Pvt. Ltd., Karachi

Brand Name +Dosage Form + Strength Glardin-M Tablets 5mg + 1000mg

Composition Each film coated tablet contains:-

Empagliflozin …. 5mg

Metformin HCl ….. 1000mg


Diary No. Date of R& I & fee Dy. No 378 dated 18-03-2016, Rs.50,000/-

Pharmacological Group Anti-diabetic


Finis`hed product Specifications Manufacturer specifications




Approved by EMA


dosage form)

GMP status


Now the firm has requested for Exemption from On-site Investigation of their submitted stability data of Glardin-

M tablet range tablets and provided the following documents in conjunction with the checklist approved by the

Registration Board in its 278th Meeting:





Firm has referred to onsite inspection report of their product “Arcox

(Etoricoxib) 90mg & 120mg”, which was conducted on 17th

September, 2018 and was presented in 286th meeting of Registration

Board held on 14-16th November, 2018.

Registration Board decided to approve registration of “Arcox

(Etoricoxib) 90mg & 120mg” by M/s Getz Pharma.

Following two observations were reported in the report:

i. The HPLC software is 21 CFR compliant as per record available

with the firm.

ii. Audit trail on the testing reports is available.

iii. Adequate monitoring and control are available for stability

chamber.



case of import).

Commercial invoice for Metformin Hydrochloride as per following

details Batch No. Invoice No. Quantity

Imported.

Date of approval by

DRAP

MT18731217

MT18741217

MT18751217

EXP/92001

511/1-7-18

500Kg 16-01-2018

Commercial invoice for Empagliflozin as per following details Batch

No.

Invoice#. Quantity

Imported.

Date of approval by

DRAP

20171108 CAVIR-

20171001AP

4Kg 23-11-2017



standards.

Empagliflozin:

Firm has submitted copy of commercial invoices from M/s Jiangsu

Yongan Pharmaceutical Co., ltd. China for the following reference

standards:

Reference Std. Batch# Quantity

Empagliflozin 20170303 10mg

Empagliflozin Impurity A EPG-ZA-160404 10mg

Empagliflozin Impurity B EPG-ZB-160408 10mg

Metformin HCl:

Firm has submitted copy of commercial invoices from M/s Lab

Sciences for the import of Metformin HCl 200mg USP reference

standard Cat# 1396309.





country of origin.

Empagliflozin:

The firm has provided copy of GMP certificate (Certificate#

JSHAHAQ2017005) issued by Huaian Market Supervision

Administration in the name of M/s Jiangsu Yongan Pharmaceutical

Co., Ltd. China Valid Up to 31-12-2020.

Metformin HCl: Copy of GMP certificate issued by DCA Andhra

Pradesh, India, issued for M/s Wanbury ltd., West Godavari District,

Andhra Pradesh, India issued on 06-02-2019.


qualification

The firm has submitted copy of Vendor Audit Questionnaire filled for

both Empagliflozin & Metformin HCl.



standards.

The firm has submitted certificate of analysis for API

& reference standards for both APIs.



development?

The firm has submitted copy of Purchase Order/Invoices for the

procurement of excipients used in product development



experience.

The firm has submitted copy of List of qualified staff involved in

product development & scientific Development and Analytical

services comprising of 19 technical members.

Production Data



trial batches.

The firm has submitted authorized copy of Product Development

Protocol & Stability protocols for applied products.



The firm has submitted copy of Batch Manufacturing Record and

Batch Packaging Record of three stability batches for the stability

studies of Empagliflozin + Metformin HCl tablet range such as. Empagliflozin/Metformin HCl (5mg + 1000mg Tablet)

Batch No. Date of Mfg. Batch Size

446DS01 09-2018 1500 Tablets

446DS02 09-2018 1500 Tablets

446DS03 09-2018 1500 Tablets

Empagliflozin/Metformin HCl (5mg + 850mg Tablet)



stability batches.

The firm has submitted reconciliation sheet mentioning details of the

remaining quantities of tablets kept at accelerated and real time

stability studies.

QA / QC DATA





The firm has submitted photocopies of digital printouts of graphical

charts for Real Time and Accelerated Conditions for complete stability

studies of applied formulations.


along with COA.

The firm has submitted copy of raw material specifications, raw

material testing procedures and report for Empagliflozin & Metformin

hydrochloride.


complete record of testing of



data sheets etc.)

The firm has submitted copy of Specification/Testing Method of

Finished Product for Glardin-M 5/1000 & 5/850 tablets along with

Stability Study Report of stability batches & chromatograms, lab

reports, raw data sheets etc. for both strengths of applied formulation.


from manufacturer.

The firm has submitted stability studies reports on Empagliflozin and

Metformin HCl.



used.

The firm has submitted photocopies of its own Analytical reports for

all excipients used in product development of Emazin-M tablet range.


studies. The firm has stated that they have similar qualitative formulation

as that of the innovator product.


data. Firm has submitted results for comparative dissolution results in

against the reference product “Synjardy tablet 12.5/850mg for

both the applied strength.

Dissolution results were above 85% in 15 minutes for both

reference and sample product.




Firm has submitted method audit trail reports of stability

studies of applied formulations.


This is to bring to your kind attention that our Empagliflozin + Metformin HCl tablets 5+850, 5+1000

& 12.5+850 are dose proportional in accordance with EMA guidelines on the investigation of Bioequivalence.

In view of the said guidelines we have benchmarked Synjardy tablets 12.5mg + 850mg as reference product for

all the strengths.

Discussion: Registration Board deliberated on the response of the firm and reiterated that the applicability of

biowaiver for an individual strength of a formulation applies in those conditions where bioequivalence have been

studied on the highest and lower strengths and is also not applicable for CDP. The Board further deliberated that

as the performance of Comparative Dissolution Profile (CDP) is optional for applications on Form 5D but is

mandatory for Form 5F.

Decision: Registration Board decided to approve registration of Glardin-M Tablets 5mg + 850mg

& Glardin-M Tablets 5mg + 1000mg by M/s Getz Pharma Pvt. Ltd., Karachi with Innovator’s

specifications. Manufacturer will place first three production batches of both products on long

term stability studies throughout proposed shelf life and on accelerated studies for six months.

Sr.

No.

Name &

Address of

Manufacturer /

Applicant

Brand Name

(Proprietary Name + Dosage

Form + Strength),

Composition,



Type of Form,

Initial Diary &

Date, Fee

(including

differential fee),

Demanded Price /

Pack size

International

Availability / Local

Availability

GMP Inspection

Report Date &

Remarks

Previous

DRB

Decision /

Remarks

(if any)

85. Genix Pharma

(Pvt.) Ltd.

Karachi

Vortex Tablets 5mg


contains: -

Vortioxetine

Hydrobromide………5mg

(Innovator’s Specifications)

Form 5D

18-04-2017,

Fee: 50,000/-

As per SRO

Approved by USFDA

Firm is operating

at acceptable

level of GMP

compliance as per

inspection dated

10-04-2019

-


Drug Vortex 5mg tablets

Name of Manufacturer Genix Pharma (Pvt.) Ltd.

Manufacturer of API M/s Jiangsu Yongan Pharmaceutical Co., Ltd. No. 18,237 provincial

highway, Jiangsu Huaian Economic development Zone, China

API Lot No. 3804-201803001

Description of Pack

(Container closure system) Alu-Alu Blister Pack

Stability Storage Condition Accelerated: 40°C ± 2°C / 75% ± 5%RH


Real Time: 30°C ± 2°C / 65% ± 5%RH

Time Period Accelerated: 06 months

Real Time: 12 months

Frequency Accelerated: 0, 1, 2,3,4 & 6 (Months)

Real Time: 3,6, 9 , 12 (Months)

Batch No. 18SB-118-01 18SB-119-02 18SB-120-03

Batch Size 1500 Tablets 1500 Tablets 1500 Tablets


Date of Initiation 07-2020 07-2020 07-2020

No. of Batches 03

DOCUMENTS / DATA PROVIDED BY THE APPLICANT INITIALLY

Documents to Be Provided Status

COA of API Yes




Yes

Protocols followed for conduction of stability study

and details of tests. Yes




Yes

Documents confirming import of API etc.

Copy of Form 6 (License to Import drug for clinical

trial examination, test or analysis) issued by

Assistant Director (I & E) DRAP (Karachi) dated

16-03-2018, for the import of Vortioxetine

hydrobromide (300g) from the M/s Suzhou Zhiyu

Biotechnology Co, Ltd., Manufactured by

M/sJiangsu Yongan Pharmaceutical Co. Ltd.,

China has been submitted.

Copy of Commercial Invoice (invoice no.

ZY18031601G/W) dated attested by Assistant

Director (I & E) DRAP (Karachi) dated 09-04-


All provided documents will be attested (name, sign

and stamp) for ensuring authenticity of data /

documents.

Yes

Commitment to continue real time stability study till



1978. Yes


(AD PEC-I)

The firm has provided 06 Months Accelerated and 12 Months Real Time Stability Data for 03 Lab Scale

Batches.

REQUEST OF EXEMPTION FROM ON SITE INSPECTION

Now the firm has requested for Exemption from On-site Investigation of their submitted stability data vide

Letter no. RA/224/19, dated 12-12-2019 and provided the following documents in conjunction with the

checklist approved by the Registration Board in its 278th Meeting:



1.

Reference of last onsite panel

inspection for instant dosage

form conducted during last two

years.

Firm has referred to onsite inspection report of their product “WYMLY

Tablets 25mg (Tenofovir Alafenamide)”, which was conducted on 06-

02-2018, and was presented in 281st meeting of Registration Board held

on 11-13th April, 2018.

Registration Board decided to approve registration of WYMLY Tablets

25mg (Tenofovir Alafenamide)”, by M/s. Genix Pharma (Pvt.) Ltd.,

Karachi. Manufacturer will place first three production batches on long

term stability studies throughout proposed shelf life and on accelerated

studies for 26 weeks.


i. The HPLC software is 21CFR complaint and having certificates of

compliance by USFDA.

ii. Audit trail on the testing reports of WYMLY Tablets 25mg (Tenofovir

Alafenamide) is available.

iii. Adequate monitoring and control are available for stability chamber.

Chamber are controlled and monitored through software having alarm

system for alerts as well.

2.

Documents for the procurement

of API with approval from

DRAP (in case of import).

Copy of Commercial Invoice (invoice no. ZY18031601G/W) dated

attested by Assistant Director (I & E) DRAP (Karachi) dated 09-04-2018

has been submitted for the batch number 3804-201803001.

3.


of reference standard and

impurity standards.

The firm has submitted copy of letters from

M/s Neon chemicals, in the name of M/s Genix Pharma (Pvt.) Ltd,

Karachi,

Particulars Batch no Qty

Vortioxetine hydrobromide 3804-201802001 (W/S) 3 gm

4.

Approval of API/ DML/GMP



country of origin.

Copy of GMP certificate (Certificate# JS 20160548) issued by Jiangsu

FDA in the name of M/s Jiangsu Yongan Pharmaceutical Co., Ltd, valid

upto 03-03-2021 has been submitted.

5.

Mechanism for Vendor pre-

qualification

The firm has submitted copy of “SOP for Selection of manufacturer for

API/Excipient and Procurement Procedure”,

SOP No: QA/SOP/SY/037 with effective date 07-10-2016.

Version no: 01

Copy of “Vendor’s Audit form” filled for M/s Jiangsu Yongan

Pharmaceutical Co. Ltd Co., Ltd, China.

6.

Certificate of analysis of the

API, reference standards and

impurity standards

Copy of COAs of Vortioxetine hydrobromide, working standards issued

by M/s Jiangsu Yongan Pharmaceutical Co. Ltd .is submitted. Detail is

as under

Particulars Batch no Quantity

Vortioxetine

hydrobromide

3804-201803001 300gm

Vortioxetine

hydrobromide

3804-201802001

(W/S)

3 gm

7.


of excipients used in product

development?



8.

List of qualified staff involved

in product development with

relevant experience.

The firm has submitted copy of List of qualified staff involved in product

development & regulatory affairs comprising of 4 members.


Production Data

9.

Authorized Protocols/SOP for

the development & stability

testing of trial batches.

The firm has submitted copy of Development Protocol for Lab scale

batch manufacturing of Vortex Tablets 5mg, 10mg, 15mg and 20mg. The

SOP mentions the details of master formulation & manufacturing method

for both Vortex Tablets 10mg,15mg and 20mg. Copies of stability

protocols have also been submitted for Vortex Tablets 5mg

10.

Complete batch manufacturing


The firm has submitted copy of Batch Manufacturing Record and Batch

Packaging Record of the following 03 Batches:

BATCH NO BATCH SIZE MFG DATE

18SB-118-01 1500 Tablets 07-2018

18SB-119-02 1500 Tablets 07-2018

18SB-120-03 1500 Tablets 07-2018

11.

Record of remaining quantities

of stability batches.

The firm has attached Record of remaining quantities of stability batches.

QA / QC DATA

12.

Record of Digital data logger

for temperature and humidity

monitoring of stability

chambers (real time and

accelerated)

The firm has submitted photocopies of digital record for Real Time and

Accelerated Conditions starting from 01-06-2018 to 31-08-2019.

13.

Method used for analysis of API

along with COA.

The firm has submitted copy of raw material specifications, raw material

testing procedures and report for Vortioxetine Hydrobromide (batch #

3804-201803001) along with COAs for Vortioxetine hydrobromide from

M/s Jiangsu Yongan Pharmaceutical Co. Ltd., China

14.

Method used for analysis of FPP

& complete record of testing of



data sheets etc.)

The firm has submitted copy of Finished Product Testing Procedure (QC-

FPNS-142 issued on 18-07-2018) for Vortex 5mg Tablet along with

Stability Study Report of stability batches.

15.

Reports of stability studies of

API from manufacturer.

The firm has submitted copy of 06 Months Accelerated and 12 Months

Real Time Stability Study (30oC+2 oC, 65+5%) Data of 03 Batches of

Vortioxetine from M/s Jiangsu Yongan PharmaceuticalCo. Ltd., China

16.

Analysis reports for excipients

used.

The firm has submitted photocopies of its own Analytical reports for all

excipients used in product development of Vortex tablets.

17.

Drug-excipients compatibility

studies.

The firm has not performed Drug-excipients compatibility studies and

stated that the qualitative composition of their product (Vortex Tablet) is

similar to that of innovator’s product i.e. Trintellix

Tablets and also stability studies have not shown any incompatibility or

significant degradation.

18.

Record of comparative

dissolution data.

Firm has submitted F2 factor protocol (QC/PRO/CD/30) & dated 11-

11-2019. feature Reference product Product of M/S Genix

Pharma

Brand name Trintellix tablet 5mg Vortex Tablets 5mg

Comparative dissolution studies have been performed in following

mediums:

i. pH 0.1N HCl buffer


ii. pH 4.5 Acetate buffer

iii. pH 6.8 Phosphate buffer

19.

Compliance Record of HPLC



Firm has submitted audit trail reports of stability studies of applied

formulation

Decision: Registration Board decided to approve registration of Vortex Tablets 5mg with

Innovator’s specifications by M/s Genix Pharma (Pvt.) Ltd. Karachi. Manufacturer will place

first three production batches on long term stability studies throughout proposed shelf life and

on accelerated studies for six months.

Sr.

No.

Name &

Address of

Manufacturer /

Applicant

Brand Name


Form + Strength), Composition,



Type of Form,

Initial Diary &

Date, Fee

(including

differential fee),

Demanded Price

/ Pack size

International


Availability

GMP Inspection

Report Date &

Remarks

Previous

DRB

Decision /

Remarks

(if any)

86. Genix

Pharma (Pvt.)

Ltd.

Karachi

Vortex Tablets 10mg


contains: -

Vortioxetine



Form 5D

26-12-2014,

Fee: 50,000/-

As per SRO

Approved by

USFDA. Firm is

operating at

acceptable level

of GMP

compliance as per

inspection dated

10-04-2019

-




Manufacturer of API Jiangsu Yongan Pharmaceutical

API Lot No. 3804-201803001

Description of Pack



Real Time: 30°C ± 2°C / 65% ± 5%RH

Time Period Accelerated: 06 months Real Time: 12 months



Batch No. 18SB-121-01 18SB-122-02 18SB-123-03




No. of Batches 03

Date of Submission 08-11-2019



COA of API Yes





Yes






Yes


Copy of Form 6 (License to Import drug for

clinical trial examination, test or analysis) issued

by Assistant Director (I & E) DRAP (Karachi)

dated 16-05-2018, for the import of Vortioxetine











documents.

Yes




1978. Yes

REMARKS OF EVALUATOR (AD PEC-I)


Batches.






1.




years.




on 11-13th April, 2018.















2.






has been submitted.

3.



impurity standards.

The firm has submitted copy of letters from M/s Neon chemicals in the

name of M/s Genix Pharma (Pvt.) Ltd, Karachi,


Vortioxetine

hydrobromide

3804-201802001

(W/S)

3 gm

4.




country of origin.




5.


qualification




Version no: 01

Copy of “Vendor’s Audit form” filled for M/s Jiangsu Yongan


6.



impurity standards

Copy of COAs of Vortioxetine hydrobromide, working standards and

impurity standards issued by M/s Jiangsu Yongan Pharmaceutical Co.

Ltd .is submitted. Detail is as under


Vortioxetine

hydrobromide

3804-201803001 300gm

Vortioxetine

hydrobromide

3804-201802001

(W/S)

3 gm

7.



development?



8.






Production Data

9.







for both Vortex Tablets 5mg, 10mg, 15mg and 20mg. Copies of stability

protocols have also been submitted for Vortex Tablets 10mg.

10.






18SB-121-01 1500 Tablets 07-2018

18SB-122-02 1500 Tablets 07-2018

18SB-123-03 1500 Tablets 07-2018


11.



The firm has attached Record of remaining quantities of stability batches

QA / QC DATA

12.




chambers (real time &

accelerated)

The firm has submitted photocopies of digital printouts of graphical chart

for Real Time and Accelerated Conditions starting from 01-06-2018 to

31-08-2019.

13.


along with COA.


testing procedures and report for Vortioxetine Hydrobromide

(batch#3804-201803001) along-with COAs for Vortioxetine

hydrobromide from M/s Jiangsu Yongan Pharmaceutical Co. Ltd., China

14.





data sheets etc.)




15.






16.


used.



17.


studies.



similar to that of innovator’s product i.e. Trintellix tablet and also

stability studies have not shown any incompatibility or significant

degradation.

18.


dissolution data.

Firm has submitted F2 factor protocol (QC/PRO/CD/29) & dated 18-09-

2019. The detail is as follows: feature Reference product Product of M/s Genix

Pharma



mediums:




19.





formulation






Sr.

No.

Name & Address

of Manufacturer /

Applicant

Brand Name





Type of Form,

Initial Diary &

Date, Fee

(including

differential fee),

Demanded Price

/ Pack size

International


Availability

GMP Inspection

Report Date &

Remarks

Previous

DRB

Decision /

Remarks

(if any)

87. Genix Pharma

(Pvt.) Ltd.

Karachi

Vortex Tablets 15mg


contains:

Vortioxetine



Form 5D

18-04-2017,

Fee: 50,000/-

As per SRO

Approved by

USFDA

Firm is operating

at acceptable

level of GMP

compliance as

per inspection

dated 10-4-2019

-





API Lot No. 3804-201803001

Description of Pack



Real Time: 30°C ± 2°C / 65% ± 5%RH




Batch No. 18SB-124-01 18SB-125-02 18SB-126-03




No. of Batches 03




COA of API Yes




Yes






Yes

















documents.

Yes




1978.

Yes


(AD PEC-I)


Batches.






1.




years.




on 11-13th April, 2018.














2.






has been submitted.

3.



impurity standards.

The firm has submitted copy of letters from M/s Neon chemicals

indenters of Pharmaceuticals Raw materials and chemicals., China, in

the name of M/s Genix Pharma (Pvt.) Ltd, Karachi,



Vortioxetine

hydrobromide

3804-201802001

(W/S)

3 gm

4.




country of origin.

Approved source as per decision of 275th meeting of Registration Board

5.


qualification




Version no: 01

Copy of “Vendor’s Audit form” filled for M/sJiangsu Yongan


6.



impurity standards





Vortioxetine

hydrobromide

3804-201803001 300gm

Vortioxetine

hydrobromide

3804-201802001

(W/S)

3 gm

7.



development?



8.






Production Data

9.







for Vortex Tablets 10mg, 15mg and 20mg Copies of stability protocols

have also been submitted for Vortex Tablets 15mg.

The master formulation and manufacturing method mentioned in

development protocol is same as that of reference product.

10.


record of three stability

batches.




18SB-124-01 1500 Tablets 07-2018

18SB-125-02 1500 Tablets 07-2018

18SB-126-03 1500 Tablets 07-2018

11.




QA / QC DATA

12.




The firm has submitted copies of digital printouts of graphical chart for

Real Time and Accelerated Conditions starting from 01-06-2018 to 31-

08-2019.



accelerated)

13.


along with COA.

The firm has submitted ocopy of raw material specifications, raw

material testing procedures and report for Vortioxetine Hydrobromide

(batch # 3804-201803001) along with COAs for Vortioxetine

hydrobromide from M/s Jiangsu Yongan PharmaceuticalCo. Ltd., China

14.





data sheets etc.)




15.






16.


used.

The firm has submitted copies of its own Analytical reports for all


17.


studies.



similar to that of innovator’s product i.e. Trintellix

Tabletsand also stability studies have not shown any incompatibility or

significant degradation.

18.


dissolution data.


10-2019.

feature Reference

product

Product of M/S

Genix Pharma

Brand name Trintellix

tablet 15mg

Vortex Tablets

15mg


mediums:




19.





formulation





Sr.

No.

Name & Address

of Manufacturer /

Applicant

Brand Name

(Proprietary Name + Dosage Form

+ Strength), Composition,



Type of Form,

Initial Diary &

Date, Fee

(including

differential fee),

Demanded Price /

Pack size

International


Availability

GMP Inspection

Report Date &

Remarks

Previous DRB

Decision /

Remarks

(if any)

88. Genix Pharma

(Pvt.) Ltd.

Vortex Tablets 20mg

Form 5D

26-12-2014,

Approved by

USFDA

-


Karachi


contains:-

Vortioxetine



Fee: 50,000/-

As per SRO

Firm is operating

at acceptable

level of GMP

compliance as

per inspection

dated 10-4-2019





API Lot No. 3804-201803001

Description of Pack



Real Time: 30°C ± 2°C / 65% ± 5%RH


Frequency Accelerated: 0, 1, 2,3,4 & 6 (Months) Real Time: 3,6, 9 , 12 (Months)

Batch No. 18SB-127-01 18SB-128-02 18SB-129-03




No. of Batches 03




COA of API Yes




Yes






Yes








M/sJiangsu Yongan Pharmaceutical Co. Ltd., China

has been submitted. Copy of Commercial Invoice

(invoice no. ZY18031601G/W) dated attested by


16-03-2018 has been submitted.



documents.

Yes





1978. Yes

REMARKS OF EVALUATOR (AD PEC-I)


Batches.






1.




years.




on 11-13th April, 2018.














2.






has been submitted.

3.



impurity standards.

The firm has submitted copy of letters from M/s Neon Chemicals

indentors of Pharmaceutical Raw material and chemicals, in the name of

M/s Genix Pharma (Pvt.) Ltd, Karachi,


Vortioxetine

hydrobromide

3804-201802001

(W/S)

3gm

4.




country of origin.




5.


qualification




Version no: 01

Copy of “Vendor’s Audit form” filled for M/sJiangsu Yongan



6.



impurity standards





Vortioxetine

hydrobromide

3804-201803001 300 gm

Vortioxetine

hydrobromide

3804-201802001

(W/S)

3gm

7.



development?



8.






Production Data

9.







for both Vortex Tablets 5mg, 10mg, 15mg and 20mg. Copies of stability

protocols have also been submitted for Vortex Tablets 20mg.

10.






18SB-127-01 1500 Tablets 07-2018

18SB-128-02 1500 Tablets 07-2018

18SB-129-03 1500 Tablets 07-2018

As per submitted record all the activities of manufacturing i.e.

dispensing, granulation, drying, compression & coating has been

performed in PD lab.

11.




QA / QC DATA

12.

Record of Digital data logger for



(real time & accelerated)

The firm has submitted photocopies of digital printouts of graphical chart

for Real Time and Accelerated Conditions starting from 01-06-2018 to

03-04-2019.

13.


along with COA.


testing procedures and report for Vortioxetine Hydrobromide (batch #

3804-201803001) along with COAs for Vortioxetine hydrobromide from

M/s Jiangsu Yongan Pharmaceutical Co. Ltd., China

14.





data sheets etc.)




15.







16.


used.



17.


studies.



similar to that of innovator’s product i.e. Trintellix tablet and also

stability studies have not shown any incompatibility or significant

degradation.

18.


dissolution data.


09-2019. The detail is as follows: feature Reference product Product of M/S Genix

Pharma



mediums:




19.





formulation





Item No. 4: Agenda of Evaluator PEC-III

Case No. 01 Registration applications of CTD cases

a. New cases

89. Name, address of Applicant / Marketing

Authorization Holder

M/s Bio-Labs (Pvt) Ltd. Plot No. 145, Industrial Triangle

Kahuta Road Islamabad.

Name, address of Manufacturing site. M/s Bio-Labs (Pvt) Ltd. Plot No. 145, Industrial Triangle

Kahuta Road Islamabad.

Status of the applicant ☒ Manufacturer

☐ Importer

☐ Is involved in none of the above (contract giver)

Status of application ☐ New Drug Product (NDP)

☒ Generic Drug Product (GDP)

Intended use of pharmaceutical product ☒ Domestic sale

☐ Export sale

☐ Domestic and Export sales

Dy. No. and date of submission Dy. No. 8159: 12-06-2019

Details of fee submitted PKR 20,000/-: 11-06-2019

The proposed proprietary name / brand

name BioChlor Gel 7.1%

Strength / concentration of drug of Active

Pharmaceutical ingredient (API) per unit

Each gram gel contains

Chlorhexidine gluconate………7.1%w/w


Pharmaceutical form of applied drug Almost light yellow color viscous gel

Pharmacotherapeutic Group of (API) Antiseptics and disinfectants, biguanides and amidines

Reference to Finished product

specifications

BP

Proposed Pack size 20gm gel

Proposed unit price As per SRO

The status in reference regulatory

authorities

Umbipro 7.1% w/w Gel by GSK EMA No.

EMEA/H/W/003799/001

For generic drugs (me-too status) Cordin gel by Global Pharma (Reg# 096587)

Name and address of API manufacturer. Unilab chemical and pharmaceuticals Pvt Ltd. W-32, MIDC

Phase-II Dombivli East MH 421 204 India.

Module-II (Quality Overall Summary) Firm has submitted QOS as per WHO QOS-PD template.

Module-III Drug Substance: Firm has submitted complete data of drug substance from the

API manufacturer.

Stability Studies of Drug Substance

(Conditions & duration of Stability

studies)

Firm has submitted stability study data sheets of API as per

zone IV-A for 36 months.

Module-III Drug Product: Firm has submitted all the drug product data required for

module 3

Pharmaceutical Equivalence and

Comparative Dissolution Profile

Firm has submitted pharmaceutical equivalence data in

comparison with the innovator product Umbipro 7.1% w/w Gel.

Analytical method validation/verification

of product

Firm has submitted analytical method validation data.


Manufacturer of API Unilab chemical and pharmaceuticals Pvt Ltd. W-32, MIDC Phase-II Dombivli

East MH 421 204 India.

API Lot No. F/151/18

Description of Pack

(Container closure system) 20 gram tube




Frequency Accelerated: 0, 1, 2, 3, 4, 6 (Months) Real Time: 0, 3, 6 (Months)

Batch No. CXG-001 CXG-002 CXG-003

Batch Size 80 tubes 80 tubes 80 tubes



No. of Batches 03



COA of API Yes

Approval of API by regulatory authority of

country of origin or GMP certificate of API


Firm has submitted copy of GMP certificate issued by FDA

Mahrashtra dated 28-12-2017 valid till December 2020.


country of origin.






Yes

Documents confirming import of API etc. Firm has submitted copy of invoice cleared by DRAP

Islamabad office dated 04-09-2018 specifying import of 2kg

chlorhexidine gluconate 20% solution


sign and stamp) for ensuring authenticity of data

/ documents.

Yes



Commitment to follow Drug Specification

Rules, 1978. Yes


Firm has provided evidence of Cream (General) section.

How the homogeneity in the gel texture is ensured without the use of high-pressure homogenizer.

The use of guar gum having pH 5.5 to 7.5 (acidic pH) can potentially cause degradation of chlorhexidine.

How the firm will control this process of degradation.

Report on investigation of authenticity / genuineness of data submitted for registration of BioChlor Gel

7.1% by M/s Bio-labs (Pvt) Ltd. Plot No. 145, Industrial Triangle Kahuta Road, Islamabad.

Reference No: No. F.1-2/2020-PEC dated 18th February, 2020.

Investigation Date & Time: 11th March, 2020

Investigation Site: Factory premises of M/s Bio-labs (Pvt) Ltd. Plot No. 145, Industrial Triangle Kahuta Road,

Islamabad.

Background: Chairman Registration Board has constituted the panel of M/s Bio-labs (Pvt) Ltd. Plot No. 145, Industrial

Triangle Kahuta Road, Islamabad for BioChlor Gel 7.1% for on-site investigation to confirm the authenticity /

genuineness of stability data and associated documents, import of API, quality, specification, test analysis and

facilities etc for further consideration by the Registration Board.


1. Dr. Qurban Ali, Member Registration Board

2. Mst. Tehreem Sara, Deputy Director (RRR) PE&R Division DRAP, Islamabad

3. Mr. Muhammad Haseeb Tariq, Assistant Director PEC, PE&R Division DRAP, Islamabad.

Scope of Investigation:

Investigation of the authenticity / genuineness of the data, manufacturing of stability batches and stability studies

on these batches.

Tool for investigation:

The investigation was conducted by using a structured questionnaire of DRAP. For objective evidence physical

inspection of the facilities for manufacturing and quality control, material used and retained, personnel involved,

ongoing studies, printed data and integrity and security of data in respective databases were also audited. The

details of investigation may be summarized as under:


Detail of investigation for BioChlor Gel 7.1%

Sr.

No.

Description Observation by panel


import of API including approval from

DRAP?

Firm has all necessary documents including invoice /AD

clearance dated 04-09-2018 confirming import of 2 kg

Chlorhexidine gluconate 20% solution from M/s Unilab

Chemicals & Pharma Pvt. Ltd. India.

2. Do you have any rationale behind selecting

the particular manufacturer

Firm has a developed SOP for vendor qualification

including Vendor Evaluation Form and they have

selected this vendor based on its GMP certificate, DMF

as well as stability study data.


Import of Reference standard and Impurities

standards?

Working standard of Chlorhexidine gluconate was

provided by the supplier and the firm has imported

reference standard and impurity standard from USP.

4. Do you have certificate of analysis of API

reference standard & impurities standards?

Firm has certificate of analysis of API, working standard

as well as impurity standards.

5. Do you have any approval of API or GMP

certificate of manufacturer issued by

regulatory authority of country of origin?

Firm has copy of GMP certificate of M/s Unilab

Chemicals & Pharma Pvt. Ltd. India issued by Food and

Drug Administration Mahrashtra state dated 28-12-2017.


Testing for testing of API?

The firm has used BP method of testing for carrying out

tests of API.

7. Do you have stability Studies Report on

API?

The firm has real time and accelerated stability study data

sheets provided by the API manufacturer. The real time

stability study data as per zone IV-A till 36 months was

provided by the API manufacturer.

8. If Yes, whether the stability testing has been

performed as per SIM method and

degradation products have been quantified?

The stability studies have been performed as per SIM

method and the API manufacturers have quantified the

degradation products.



The firm has used BP method for quantifying the

impurities in the API.


the API, Its reference standard and

impurities standard?

Firm has some remaining quantity of API and working

standards.


excipients?

Firm has used pharmaceutical grade excipients in the

manufacturing of stability batches.



Firm has necessary documents confirming import /

purchase of used excipients.

13. Do you have test reports and other records

on the excipients?

The firm has test reports and certificate of analysis for all

excipients used in the manufacturing of stability batches.


protocols for development drug product?

The firm has written and authorized protocols for the

development of BioChlor Gel 7.1%.

15. Have you performed Drug-Excipient


Firm has demonstrated that their formulation is

qualitatively similar to the innovator product (Umbipro

Gel by GSK), therefore they have not performed drug-

excipient compatibility studies.


dissolution studies?

Not applicable since this product is Gel. However, the

firm has performed pharmaceutical equivalence studies

with the innovator product as per requirement of CTD.


17. Do you have Product Development / R&D

Section?

Firm has seprate area / room for product development

with small scale equipment.

18. Do you have necessary equipment’s


for development drug product?

Firm has necessary equipment available in product

development section for development of trial batches.

19. Are the equipment’s in product

development qualified?

The equipment present in product development area were

qualified.


calibration / re-qualification program for the

equipment used in PD?

The firm has proper maintenance and calibration for the

equipment used in product development section.


development section with proper knowledge

& training in product development?

Firm has trained & qualified staff in product development

section with proper knowledge and training in product

development and testing.


batches for the stability studies of drug

product?

Three stability batches have been manufactured for the

stability studies of BioChlor Gel 7.1% with batch

numbers CXG-001, CXG-002 and CXG-003.

23. Do you have any criteria for fixing the batch

size of stability of batches?

The firm has informed that their criteria for fixing batch

size is based on number of tests required, testing

frequencies and number of units used in each test.

24. Do you have complete record of production


The firm has complete batch manufacturing record of all

the batches of BioChlor Gel 7.1%

25. Do you have protocols for stability testing


Firm has written protocols for stability testing of the

stability batches.



The firm has developed and validated HPLC method for

testing of the stability batches.


when the method of testing being used by

your firm is by any other lab?

NA


qualification of equipment / instruments

being used in the test and analysis of the

product’s API and drug product?

Firm has complete record of qualification of equipment /

instruments used in the test and analysis of API and

BioChlor Gel 7.1%.

29. Do your method of analysis Stability

indicating?

The firm has used BP method for testing of the finished

product; however the firm was advised to quantify the

degradation products for commercial batches.

30. Is your HPLC software 21CFR compliant? The firm has a dedicated HPLC (Schimadzu LC-20

Gradient) for testing of new drug products placed on

stability studies. The HPLC software for that particular

HPLC is 21 CFR compliant with audit trail option

activated. However the firm has only 1 login account in

the software which is used by various analysts on the

same system. The firm was advised to get separate

account for each analyst.

31. Can you show audit trail reports on drug

product testing?

Audit trail reports for testing of BioChlor Gel 7.1% were

available.



The firm has remaining quantities of stability batches

which are kept in stability chamber for ongoing real time

stability study.

33. Do you have batches kept on stability

testing?

The firm has kept the remaining quantities of all batches in

stability chamber for on-going real time stability study.



equipment’s used in drug product’s


The firm has valid calibration status of all equipment used

in production and analysis of BioChlor Gel 7.1%.

35. Do Proper and Continuous monitoring and

control are available for stability chamber?

The firm has stability chambers for carrying out accelerated

and real time stability studies provided with uninterrupted

power supply and USB data loggers, which are set for

recording temperature and humidity after every hour.



compliant?

Firm has dedicated area for product development. Related

manufacturing area, equipment, personnel and utilities

were cGMP compliant to satisfactory level.

However, firm has got approval of only Cream (General)

section from Licensing Division, DRAP. The firm has

steam jacketed mixer (400kg) which can operate from 20

to 3000 rpm. The firm is using the same manufacturing /

filling line for cream, ointment as well as gel.

37. How the homogeneity in the gel texture is

ensured without the use of high-pressure

homogenizer

The firm has steam jacketed mixer (400kg) installed in

Cream (General) Section area which can operate from 20

to 3000 rpm. The firm intends to use the same production /

filling line for cream, ointment as well as gel products. The

firm has following documents / studies to justify the

manufacturing and filling of gel in the same section.

Performance qualification protocols and reports for steam

jacketed mixer (400kg) installed in cream (general) section.

The report specifies less than 3% deviation in rpm when

used as high speed homogenizer (3000rpm).

Prospective/concurrent validation report of 3 batches of

their already registered product “Proxicam Gel 25 gm”

wherein the reports suggest acceptable results for assay,

physical appearance and weight variation.

38. The use of guar gum having pH 5.5 to 7.5

(acidic pH) can potentially cause

degradation of chlorhexidine. How the firm

will control this process of degradation.

The firm has used guar gum as a gelling agent in their

formulation. The same ingredient is also used by the

innovator product “Umbipro Gel”. Sodium acetate

trihydrate is used to maintain the pH of gel within the

range of 5.0 to 7.0. The innovator product has also used

the same ingredient to control the pH. The control of pH

has been demonstrated through the results till 12 months

stability studies. The firm also demonstrated the pH of the

gel in front of panel. The results of the pH tested in front

of the panel was 6.6 which is within the acceptable range

of BP monograph.

Conclusion:

On the basis of risk-based approach the genuineness / authenticity of stability data submitted by the firm

for registration of BioChlor Gel 7.1% is verifiable to satisfactory level.

Related manufacturing area, equipment, personnel & Utilities are rated as GMP Compliant to

satisfactory level. However, the firm do not have approval of Gel section from Licensing Division, DRAP. The

firm has demonstrated that the manufacturing / filling line available in Cream (General) section is capable of

working as high speed homogenizer for the manufacturing and filling of applied product.

Decision: Registration Board decided to approve registration of BioChlor Gel 7.1% by M/s Bio-

labs (Pvt) Ltd. Plot No. 145, Industrial Triangle Kahuta Road, Islamabad. Manufacturer will

place first three production batches on long term stability studies throughout proposed shelf life

and on accelerated studies for six months. Manufacturer will also perform process validation

studies on first three commercial batches as per the commitment submitted along with

registration application.




M/s Highnoon Laboratories Ltd., 17.5KM.,Multan Road,

Lahore

Name, address of Manufacturing site. M/s Highnoon Laboratories Ltd, 17.5KM, Multan Road,

Lahore

Status of the applicant ☒ Manufacturer

☐ Importer

☐ Is involved in none of the above (contract giver)

GMP status of the firm Firm has submitted copy of GMP certificate issued on the basis

of inspection conducted dated 08-11-2018.

Evidence of approval of manufacturing

facility

Firm has submitted copy of GMP certificate dated 15-11-2018

specifying Tablet General non antibiotic section

Status of application ☐ New Drug Product (NDP)

☒ Generic Drug Product (GDP)

Intended use of pharmaceutical product ☐ Domestic sale

☐ Export sale

☒ Domestic and Export sales

Dy. No. and date of submission Dy. No. 21124: 18-10-2019


The proposed proprietary name / brand

name

Biforge 5mg/80mg Tablet




Amlodipine………….5mg

Valsartan……………80mg

Pharmaceutical form of applied drug Blue round biconvex film coated tablet with bisect line on one

side

Pharmacotherapeutic Group of (API) Anti hypertensive

Reference to Finished product

specifications

USP

Proposed Pack size 14’s, 28’s

Proposed unit price As per SRO

The status in reference regulatory

authorities

Exforge 5mg/80mg film coated tablets (USFDA Approved)

For generic drugs (me-too status) Exforge tablets by Novartis

Name and address of API manufacturer. Amlodpine: Cadila Pharmaceuticals Limited. 294, GIDC,

Industrial Estate Ankleshwar 393 002, Gujrat India.

Valsartan: Zheijiang Tianyu Pharmaceuticals

No.15 Donghai 5th Avenue, Zhejiang.

Module-II (Quality Overall Summary) Firm has submitted QOS as per WHO QOS-PD template.

Module-III Drug Substance: Firm has submitted drug substance data for both API separately

as per the CTD module 3.2.S.

Stability Studies of Drug Substance

(Conditions & duration of Stability

studies)

Amlodipine: Firm has submitted stability study data of 3

batches of API at accelerated and real time conditions. The real

time stability data is conducted as per zone IV-A conditions.

Valsartan: Firm has submitted stability study data of 3 batches

of API at accelerated and real time conditions. The real time

stability data is conducted as per zone IV-A conditions.


Module-III Drug Product: Firm has submitted data of drug product as per the requirements

of Module 3.2.P

Pharmaceutical Equivalence and

Comparative Dissolution Profile

Firm has submitted detailed process and results for formulation

development, the firm has developed 4 trials of the applied

formulation and based on the results trial 4 was finally selected.

Firm has performed pharmaceutical equivalence studies and

comparative dissolution studies with the reference product and

the selection of final trial batch was based on the results of these

trials. The results of pharmaceutical equivalence and CDP were

satisfactory justifying the formulation development.

Analytical method validation/verification

of product

Firm has submitted reports of verification studies of analytical

method, since this finished product specifications are available

in USP.


Manufacturer of API Amlodpine: Cadila Pharmaceuticals Limited. 294, GIDC, Industrial Estate

Ankleshwar 393 002, Gujrat India.

Valsartan: Zheijiang Tianyu Pharmaceuticals No.15 Donghai 5th Avenue,

Zhejiang.

API Lot No. Amlodpine: 17ADM1060

Valsartan: 10230-161205

Description of Pack

(Container closure system) Alu-Alu Blister




Frequency Accelerated: 0, 3, 6 (Months) Real Time: 0, 3, 6, 9, 12, 18 (Months)

Batch No. RD-18056 RD-18057 RD-18058

Batch Size 10,000 tablet 10,000 tablet 10,000 tablet



No. of Batches 03


# Documents To Be Provided Status

1. COA of API Yes

2. Approval of API by regulatory authority of


manufacturer issued by regulatory authority

of country of origin.

Amlodipine: Firm has submitted copy of European CEP

certificate for the same manufacturing site.

Valsartan: The firm has submitted copy of GMP Certificate

(Certificate#ZJ20160065) for M/s Zhejiang Tianyu

pharmaceutical Co. Ltd., China issued by China Food and

Drug Administration, China. It is valid till 05-12-2021.

3. Protocols followed for conduction of stability


4. Data of 03 batches will be supported by

attested respective documents like

chromatograms, laboratory reports, data

sheets etc.

Yes

5. Documents confirming import of API etc. Amlodipine: Firm has submitted copy of invoice specifying


import of 100Kg amlodipine. The invoice is signed by AD

DRAP Lahore, dated 23-05-2017

Valsartan: Firm has submitted copy of invoice specifying

import of 500Kg Valsartan. The invoice is signed by AD

DRAP Lahore, dated 21-06-2017

6. All provided documents will be attested

(name, sign and stamp) for ensuring

authenticity of data / documents.

Yes

7. Commitment to continue real time stability

study till assigned shelf life of the product. Yes

8. Commitment to follow Drug Specification

Rules, 1978. Yes


Decision: Registration Board decided to approve registration of Biforge 5mg/80mg Tablet by

M/s Highnoon Laboratories Limited 17.5 KM. Multan Road, Lahore. Manufacturer will place


on accelerated studies for six months. Manufacturer will also perform process validation studies

on first three commercial batches as per the commitment submitted along with registration

application.



a. New cases

Sr.

No.

Name & Address of

Manufacturer /

Applicant

Brand Name





Type of Form,

Initial Diary & Date,

Fee (including

differential fee),

Demanded Price /

Pack size

International Availability / Local

Availability

GMP Inspection Report Date &

Remarks

91. M/s Genix Pharma

(Pvt) Ltd., 44, 45-B,

Korangi Creek

Road, Karachi

Movcol Paediatric Sachet

Each sachet contains:

Macrogol 3350……6.563g

Sodium chloride….0.1754g

Sodium bicarbonate

…………0.0893g

Potassium chloride..0.0233g

Form 5-D

Dy No. 26683

29-12-2017

PKR 50,000/-

(28-12-2017)

MOVICOL-Half 6.9g sachet,

powder for oral solution (MHRA

Approved)

Last GMP inspection conducted

on 16-02-2018

Specifies satisfactory level of

cGMP compliance.


The firm has initially applied for the formulation, which have different strength of potassium chloride, later

dated 30-8-2019 the firm has submitted revised form 5D along with 50,000/- fee and correct composition as

per reference product.

Now the firm has submitted stability study data along with required documents as per checklist approved in

251st meeting of Registration Board. Detailsof submitted data are as under:

(Dy.# 16898 dated 05-9-2019)


Drug Movcol Paediatric Sachet

Name of Manufacturer M/s Genix Pharma (Pvt) Ltd., 44,45-B, Korangi Creek Road, Karachi

Manufacturer of API Polyethylene glycol 3350: Avesta Pharma (Pvt) Ltd. Mahrashtra State India

Sodium chloride: Dominion Salt Limited, New Zealand

Sodium bicarbonate: Hangzhou Zhongbao Corp Ltd Hanghzou China.

Potassium chloride: K+S KALI GmbH, Germany

API Lot No. Polyethylene glycol 3350: AP0918048

Sodium chloride: 24042018

Sodium bicarbonate: 20180822

Potassium chloride: 2015056

Description of Pack

(Container closure system) Printed aluminium foil




Frequency Accelerated: 0, 1, 2, 3, 4, 6 (Months) Real Time: 0, 3, 6 (Months)

Batch No. 18SB-185-01 18SB-186-02 18SB-187-03

Batch Size 1500 Sachet 1500 Sachet 1500 Sachet



No. of Batches 03

Date of Submission Dy.# 16898 dated 05-9-2019




a) COA of API Yes

b) Approval of API by regulatory authority

of country of origin or GMP certificate of

API manufacturer issued by regulatory

authority of country of origin.

Polyethylene Glycol: Firm has submitted copy of GMP certificate

of Avesta Pharma (Pvt) Ltd issued by FDA Mahrashtra dated 09-

05-2019.

Sodium chloride: Firm has submitted copy of GMP certificate of

Dominion Salt Limited, New Zealand issued by Medsafe,

NewZealand Medicine and Medical Device Safety Authority

which is valid till 09-02-2020.

Sodium bicarbonate:

Potassium chloride: Firm has submitted copy of GMP certificate

of K+S KALI GmbH, Germany issued by Regierungsprasidium

Darmstadt Pharmazie Luisenplatz 2 Darmstadt Deutschland dated

12 April 2018.

c) Protocols followed for conduction of

stability study and details of tests. Yes

d) Data of 03 batches will be supported by



sheets etc.

Yes

e) Documents confirming import of API etc. Polyethylene Glycol: Firm has submitted copy of commercial

invoice specifying import of 9275 Kg Polyethylene Glycol 3350

USP from Avesta Pharma Pvt. Ltd. India. The invoice was cleared

by DRAP Karachi office on 24-9-2018.

Sodium chloride: Firm has submitted copy of invoice of Mak

Kemikal dated 06-09-2018 specifying purchase of 400Kg sodium

chloride. The invoice does not specify the details regarding

manufacturer, batch number and expiry / re test date of API.

Sodium bicarbonate: Firm has submitted copy of invoice of U.T

corporation dated 08-10-2018 specifying purchase of 500Kg

potassium chloride. The invoice does not specify the details

regarding manufacturer, batch number and expiry / re test date of

API.

Potassium chloride: Firm has submitted copy of invoice of U.T

corporation dated 05-09-2018 specifying purchase of 49.4Kg

potassium chloride. The invoice does not specify the details

regarding manufacturer, batch number and expiry / re test date of

API.

f) All provided documents will be attested



Yes

g) Commitment to continue real time

stability study till assigned shelf life of the

product.

Yes

h) Commitment to follow Drug Specification

Rules, 1978. Yes


Shortcomings communicated Response by the firm


Submit clear copy of Assistant Director (I & E) DRAP

attested commercial invoice for import of polyethylene

glycol 3350, since the submitted invoice is not properly

readable.

Firm has submitted clear invoice.

Submit evidence of procurement of all drug substances

from licensed pharmaceutical manufacturer’s having

valid GMP certificates, since the submitted evidence of

proof do not specify the manufacturer as well as details

pertaining to the specific batch like batch number and

expiry / re-test date.

Firm has submitted that the material was locally

purchased and was analysed according to

pharmacopoeia. CoA are attached.

Submit valid and clear copies of GMP certificate of drug

substance manufacturer’s from which the drug

substance was procured.

Firm has submitted GMP certificate of

manufacturers of all APIs.

Justify the identification test of Macrogol 3350 through

assay by UV in the finished product specification, since

the drug substance manufacturer specifies IR testing for

identification of macrogol 3350.

The standard absorbance corresponds to sample

preparation at 440nm as performed in assay.

In Raw material testing PEG is identified by FTIR,

while in finished product there is mixture of multiple

APIs and excipients so we selected UV method by

absorbance at wavelength of standard and sample

preparation.

Justify the identification of sodium bicarbonate and

sodium chloride through assay which are being tested

using titration method.

Both titration points are different. In sodium

bicarbonate faint pink colour is the end point which

is titrated by 0.1N HCl.

Sodium chloride is titrated by 0.1N silver nitrate and

develop pink color precipitate in the form of silver

chloride at end point.

Justify the development of raw material testing methods

in January 2019 while the stability studies were initiated

in October 2018.

The submitted testing method is version 3. This

testing method is revised due to format change in Jan

2019 as mentioned in revision history but the method

is same.

Justify why the moisture content is not determined in the

drug product.

Our manufacturing process is dry mixing. No wet

granulation procedure is adapted and no material is

hygroscopic that’s why it is not applicable for

moisture content.

Justify why the dissolution test is not performed on the

drug product.

The electrolytes and PEG 3350 is highly water

soluble that’s why dissolution test is skipped.

ICH guidelines Stability testing of new drug substances

and products Q1A(R2), recommends “Stability testing

of the drug product after constitution or dilution, if

applicable, should be conducted to provide information

for the labeling on the preparation, storage condition,

and in-use period of the constituted or diluted product.

This testing should be performed on the constituted or

diluted product through the proposed in-use period on

primary batches as part of the formal stability studies at

initial and final time points.” Justify why the in-use

stability testing is not performed and what are the

recommendations for reconstitution of the sachet and

what are the recommended storage conditions and

maximum time till which the reconstituted solution can

be used.

As it is directed in the label it should be freshly

prepared and used that’s why it is not applicable.

Report on Investigation of Authenticity / Genuineness of data submitted for registration of Movcol

Paediatric Sachet (Macrogol 3350, Sodium Chloride, Sodium Bicarbonate, Potassium Chloride) by M/s

Genix Pharma Pvt. Limited, Karachi.


Reference No: F.1-2/2020-PEC dated 1st January, 2020.

Investigation Date and Time: 7th February, 2020. (Forenoon)

Investigation Site: Factory premises of Genix Pharma Pvt. Ltd. Karachi.

Background:

Chairman Registration Board considered the applications of M/s. Genix Pharma (Pvt.) Ltd., Karachi for

registration of Movcol Paediatric Sachet (Macrogol 3350, Sodium Chloride, Sodium Bicarbonate, and Potassium

Chloride) and constituted a three member panel to investigate the authenticity / genuineness of data (import of raw

material and stability data). Panel was advised to conduct inspection of the firm and to submit report for further

consideration. The panel was also advised to verify:

“Procurement of APIs before manufacturing of stability batches”


1. Dr. Rafeeq Alam Khan, Meritorious Professor and Dean Faculty of Pharmacy, Ziauddin University,

Karachi.

2. Dr. Kirshan, Assistant Director, DRAP, Karachi.

3. Dr. Affan Ali Qureshi, Assistant Director, CDL, DRAP, Karachi.


Investigation of the authenticity / genuineness of data (import of raw material and stability data),

manufacturing of stability batches and stability studies on these batches.


The investigation was conducted by using a structured questionnaire of DRAP. For objective evidence

physical inspection of the facilities for manufacturing and quality control, material used and retained, personnel

involved, ongoing studies, printed data and integrity and security of data in respective databases were also audited.

The details of investigation may be summarized as under:

Details of Investigation:

S.No Description Observation by panel

1

Do you have documents confirming

the import of API including

approval from DRAP?

The firm has imported Macrogol 3350 from M/s Avesta Pharma

and obtained proper approval from DRAP, Karachi, whereas

other ingredients like Sodium Chloride, Sodium Bicarbonate,

and Potassium Chloride are procured through local vendors.

2

Do you have any rationale behind

selecting the particular

manufacturer

There is proper vendor evaluation process being implemented by

the firm and the rationale behind vendor selection is controlled

through:

Postal Audit checklist

GMP approval by competent authority

3


the Import of Reference standard

and Impurities standards?

The firm has all the documents confirming the procurement of

APIs, reference standard and impurity standards.

4

Do you have certificate of analysis

of the API reference standard and


The firm has Certificate of Analysis for APIs and working

standards.

5

Do you have any approval of API or

GMP certificate of manufacturer


country of origin?

The firm has provided copy of GMP certificates for all the active

ingredients.

6

Do you use API manufacturer

method of Testing for testing of

API?

The firm has used USP method of testing for Macrogol 3350,

where European Pharmacopoeia method of testing for Sodium

Chloride, Sodium Bicarbonate and Potassium Chloride.

7

Do you have stability Studies

Report on API?

The firm has stability studies report of API Macrogol 3350,

Sodium Chloride, Sodium Bicarbonate, Potassium Chloride

conducted by API manufacturer.


8

If Yes, whether the stability testing

has been performed as per SIM

method and degradation products

have been quantified?

The manufacturer of API has performed the stability studies of

API as per Pharmacopoeial methods.

9 Do you have method for quantifying

the impurities in the API?

The firm has methods for quantifying the impurities in Macrogol

3350.

10

Do you have some remaining

quantities of the API, Its reference

standard and impurities standard?

The firm has remaining quantity API Macrogol 3350, Sodium

Chloride, Sodium Bicarbonate, Potassium Chloride their

reference standards and impurity standards.

11 Have you used pharmaceutical

grade excipients?

The firm has used pharmaceutical grade excipient i.e. Lime

flavour.

12 Do you have documents confirming

the import of the used excipients

The firm has documents confirming the procurement of the used

excipient.

13 Do you have test reports and other

records on the excipients?

The firm has test reports and other records on the excipient.

14

Do you have written and authorized

protocols for the development of

Movcol Paediatric Sachet?


development of Movcol Paediatric Sachet.

15 Have you performed Drug-

Excipient compatibility studies?

Since firm has used same excipients as used by the innovator.

Therefore, compatibility studies were not performed.

16 Have you performed comparative

studies?

Firm has performed comparative studies with innovator Movicol

Junior.

17 Do you have Product Development /

R&D Section?

The firm has product development (R&D) Section with the

facility of manufacturing only whereas analysis part was

performed in routine Analytical Laboratory.

18

Do you have necessary equipment’s

available in product development

section for development of Movcol

Paediatric Sachet?

The firm has necessary equipment available in product

development section for development of tablets and inhalers

whereas the product in question is developed in routine

production area.

19 Are the equipment’s in product

development qualified?

The available equipment in Product Development are qualified.

20

Do you have proper maintenance

/calibration/re-qualification program

for the equipment used in PD?

There is proper maintenance / calibration program for the

equipment used in PD.

21

Do you have qualified staff in

product development section with

proper knowledge and training in

product development?

The firm has a team of 13 scientists including one PhD, one

MPhil, Chemists and Pharmacists for product development and

analytical method development and analysis of stability batches.

22

Have you manufactured three

stability batches for the stability

studies of Movcol Paediatric Sachet

as required?

The firm has manufactured three stability batches of each 1500

sachets.

Movcol Paediatric Sachet

Batch No Date of Mfg. Expiry Date

18SB-185-01 22-10-2018 22-10-2020

18SB-186-02 22-10-2018 22-10-2020

18SB-187-03 24-10-2018 24-10-2020

23

Do you have any criteria for fixing

the batch size of stability of batches?

The firm has SOP for fixing the batch size of stability batches

which include capacity of the R&D equipment and number of

sachets required per testing frequency and total testing

frequencies.


24 Do you have complete record of


The firm has complete record for the stability batches of Movcol

Paediatric Sachet.

25 Do you have protocols for stability

testing of stability batches.

The firm has protocols for testing of stability batches.

26

Do you have developed and

validated the method for testing of

stability batches

The firm has developed and validated method of testing of finish

product Movcol Paediatric Sachet, based on pharmacopoeial

method of testing of API.

27

Do you have method transfer studies

in case when the method of testing

being used by your firm is by any

other lab.

Method transfer studies is not applicable as the firm developed

and validated their own method.

28


the qualification of equipment /

instruments being used in the test

and analysis of the product’s API

and product Movcol Paediatric

Sachet?

The firm has proper documents confirming the qualification of

equipment / instruments being used in the test and analysis of the

Movcol Paediatric Sachet.

29 Do your method of analysis Stability

indicating?

The firm’s Method of analysis is Stability indicating.

30 Do your HPLC software 21CFR

compliant?

The HPLC software is 21CFR compliant.

31 Can you show audit trail reports on

Movcol Paediatric Sachet testing?

The firm has audit trail Reports on testing of macrogol 3350,

whereas other ingredients are analysed by titration method which

was confirmed by log books and analyst register.

32

Do you have some remaining

quantities of degradation products

and stability batches?

The firm has some remaining quantities of stability batches only.

33 Do you have batches kept on

stability testing?

The firm has three stability batches kept on stability for Real

time stability testing. Accelerated stability studies have been

completed.

34

Do you have valid calibration status

for the equipment’s used in Movcol

Paediatric Sachet production and

analysis?

The firm has valid calibration status for the equipment used in

Movcol Paediatric Sachet production and analysis.

35

Do Proper and Continuous

monitoring and control are available

for stability chamber?

Adequate monitoring and control are available for stability

chamber. Chambers are controlled and monitored through

software 21CFR compliance.

36

Do related manufacturing area,

equipment, personnel and utilities

be rated as GMP compliant?

Related manufacturing area, equipment, personnel and utilities

can be rated as GMP compliant.

37.

Any other query raised by PE&R

Division:

Procurement of API before

manufacturing of stability batches

The firm has procured all the APIs before manufacturing of

stability batches.

Conclusions:


for registration of Movcol Paediatric Sachet (Macrogol 3350, Sodium Chloride, Sodium Bicarbonate,

and Potassium Chloride) is verifiable to satisfactory level.

2. The related manufacturing area, equipments, personnel and utilities are GMP compliant and are suited

for the manufacturing of Movcol Paediatric Sachet.

Decision: Registration Board decided to approve registration of Movcol Paediatric Sachet with

innovator’s specification by M/s Genix Pharma (Pvt) Ltd., 44, 45-B, Korangi Creek Road, Karachi.


Manufacturer will place first three production batches on long term stability studies throughout

proposed shelf life and on accelerated studies for six months.

Sr.

No.

Name & Address of

Manufacturer /

Applicant

Brand Name


Form + Strength),

Composition,



Type of Form,


Fee (including

differential fee),

Demanded Price /

Pack size


Availability


Remarks

92. Ameer & Adnan

Pharmaceuticals

(Pvt) Ltd. Plot No.

47, Sundar

Industrial Estate,

Raiwind Road

Lahore.

Omdexo 30mg Capsule

Each capsule contains:

Dexlansoprazole (as dual

delayed release

pellets)….30mg

PPI

Form 5

Dy No. 8689

27-02-2019

PKR 20,000/-

(26-02-2019)

Dexilant Capsule (USFDA

Approved)


conducted on 29-11-2018 and the

report concludes satisfactory

level of GMP compliance.

Evaluation by PEC:

Firm has submitted accelerated and real time stability data of 6 months as per the requirement of

Registration Board.


Drug Omdexo 30mg Capsule

Name of Manufacturer Ameer & Adnan Pharmaceuticals (Pvt) Ltd. Plot No. 47, Sundar Industrial

Estate, Raiwind Road Lahore.

Manufacturer of API Vision Pharmaceuticals, Islamabad

API Lot No. DLP420

Description of Pack

(Container closure system)

Alu-Alu foil blister sealed with aluminium foil. The blister are introduced into

unit carton.




Frequency Accelerated: 0, 1, 3, 6 (Months) Real Time: 0, 3, 6 (Months)

Batch No. CZ-001 CZ-002 CZ-003

Batch Size 1900 capsule 1900 capsule 1900 capsule



No. of Batches 03




1. COA of API Yes

2. Approval of API by regulatory authority of country



The firm was inspected on 11.02.2019, wherein the

panel recommended the grant of GMP certificate.

3. Protocols followed for conduction of stability study





Yes


5. Documents confirming import of API etc. Firm has submitted copy of commercial invoice dated

11-02-2019 specifying purchase of 2 Kg of pellets.

6. All provided documents will be attested (name, sign


documents.

Yes



8. Commitment to follow Drug Specification Rules,

1978. Yes


Panel may be requested to verify the following

Testing of pellets at pH 1.2, 5.5 and 6.75/7 to confirm dual delayed release profile as per the decision of 276th

meeting of Registration Board.

Dissolution testing at buffer stage at pH 7.0 with 5mM SLS as per the FDA dissolution database.

Sr.

No.

Name & Address of

Manufacturer /

Applicant

Brand Name


Form + Strength),

Composition,



Type of Form,


Fee (including

differential fee),

Demanded Price /

Pack size


Availability


Remarks

93. Ameer & Adnan

Pharmaceuticals

(Pvt) Ltd. Plot No.

47, Sundar

Industrial Estate,

Raiwind Road

Lahore.

Omdexo 60mg Capsule


Dexlansoprazole (as dual

delayed release

pellets)….60mg

PPI

Form 5

Dy No. 8688

27-02-2019

PKR 20,000/-

(26-02-2019)

Dexilant Capsule (USFDA

Approved)


conducted on 29-11-2018 and the

report concludes satisfactory

level of GMP compliance.

Evaluation by PEC:


Registration Board.


Drug Omdexo 60mg Capsule

Name of Manufacturer Ameer & Adnan Pharmaceuticals (Pvt) Ltd. Plot No. 47, Sundar Industrial

Estate, Raiwind Road Lahore.

Manufacturer of API Vision Pharmaceuticals, Islamabad

API Lot No. DLP420

Description of Pack


Alu-Alu foil blister sealed with aluminium foil. The blister are introduced into

unit carton.



Time Period Real time: 6 months

Accelerated: 6 months

Frequency Accelerated: 0, 1, 3, 6 (Months)

Real Time: 0, 3, 6 (Months)

Batch No. CZ-001 CZ-002 CZ-003

Batch Size 961 capsule 961 capsule 1900 capsule




No. of Batches 03




1. COA of API Yes




The firm was inspected on 11.02.2019, wherein the

panel recommended the grant of GMP certificate.






Yes


11-02-2019 specifying purchase of 2 Kg of pellets.



documents.

Yes




1978. Yes


Panel may be requested to verify the following

Testing of pellets at pH 1.2, 5.5 and 6.75/7 to confirm dual delayed release profile as per the decision of 276th

meeting of Registration Board.

Dissolution testing at buffer stage at pH 7.0 with 5mM SLS as per the FDA dissolution database.

Report on Investigation of Authenticity / Genuineness of data submitted for registration of Omdexo 30mg

and 60mg capsules by M/s Ameer & Adnan, 47-Sunder industrial Estate, Lahore. The panel inspection of Ameer & Adnan, 47-Sunder industrial Estate, Lahore for verification of authenticity of

stability data of Omdexo 30mg and 60mg capsules was conducted on 07-11-2019 and 23-01-2020.

The panel comprised of

a) Shaheen Iqbal, Director, Drug Testing Laboratory, Lahore

b) Ufaq Tanveer Federal Inspector of Drugs, DRAP, Lahore

c) Anam Saeed Assistant Director, DRAP, Lahore.

S.

No.

Question Observation by Panel

1 Do you have documents confirming the import of

API including approval from DRAP?

The firm purchased API from M/s. Vision

Pharmaceuticals (Pvt) Ltd,

2 What was the rationale behind selecting the


The rationale behind selecting the particular

manufacturer was its GMP compliant status and good

well in the market.

3 Do you have documents confirming the import

of reference standard and impurity standards?

Working standards and impurities standards were given

to the firm by M/s. Vision Pharmaceuticals (Pvt) Ltd,

4 No you have certificate of Analysis of the API,

reference standards and impurity standards

Yes

5 Do you have GMP certificate of API


country of origin?

Yes


6 Do you use API manufacturer method of testing

for testing API?

No. The firm developed its own method for testing of

API.

7 Do you have stability studies report of API? Yes. M/s. Vision Pharmaceuticals (Pvt) Ltd, Provided

stability studies on two batches of API.

8 If yes, whether the stability testing has been



No.

9 Do you have method for quantifying the


Yes-HPLC was used for this purpose. In house method

was used.

10 Do you have some remaining quantities of the

API, its reference standard and impurities

standards?

No API was left Some quantity of working standard and

impurities standards were left.

11 Have you used pharmaceutical grade

excipients?

N/A

12 Do you have documents confirming the import

of the used excipients?

N/A

13 Do you have test reports and other records on

the excipients used?

N/A

14 Do you have written and authorized protocols

for the development of applied product?

SOP for product development was provided but product

development protocol was not developed.

15 Have you performed Drug-excipients


N/A

16 Have you performed comparative dissolution

studies?

Yes. However, the firm purchased reference product

from M/s. Sami Pharmaceuticals (Delanzo) not from the

innovator. The innovator comparative dissolution profile

was incomplete. Testing at buffer PH 5.5 was missing

for accelerated study stability batches. It was advised to

do dissolution at PH 5.5 for the remaining quantities of

stability hatches.

17 Do you have product development (R&D)

section

Yes.

18 Do you have necessary equipments available in

product development section for development

of applied product?

No. Firm utilized production area of capsules section for

manufacturing their product.

19 Are the equipments in product development

section qualified?

Yes

20 Do you have proper maintenance / calibration /


in PD section?

Yes

21 Do you have qualified staff in product


and training in product development?

Yes.

List attached.

22 Have you manufactured three stability batches

for the stability studies of applied product as

required.

Yes.

Omdexo 30mg Omdexo 60mg

CZ-001 1900 CZ-001 961

CZ-002 1900 CZ-002 961

CZ-003 1900 CZ-003 961

23 Do you have any criteria for fixing the batch size


As per stability protocol.

24 Do you have complete record of production of

stability batches?

Yes

25 Do you have protocols for stability testing of

stability batches?

Yes


26 Do you have developed and validated the

method for testing of stability batches.

Firm had developed its own method but the method was

not stability indicating.

27 Do you have method transfer studies in case



N/A

28 Do you have documents confirming the

qualification of equipments / instruments being

used in the test and analysis of API and the

finished drugs?

Yes.

29 Is your method of analysis stability indicating? No.

Is your HPLC software is 21CFR compliant? No.

30 (Details of Model, software, description/version

(i.e. software validation report for 21 CFR Part

11 compliance including audit trail, password

protection, date & time lock and user

authorizations shall also be reported).

No.

31 Can you show Audit Trail reports on stability

studies testing?

No.

32 Do you have some remaining quantities of


Yes.

Stability batches are still in stability chamber.

33 Do you have stability batches kept on stability

testing?

Yes.

For long term stability.

34 Do you have valid calibration status for the

equipments used in production and analysis?

Yes.

35 Do proper and continuous monitoring and


(Number and utilized/available capacity of

stability chambers shall also be reported).

Yes.

36 Do related manufacturing area, equipment,

personnel and utilities berated as GMP

compliant?

Yes.

Conclusion:

The panel inspection of Ameer & Adnan, 47-Sunder industrial Estate, Lahore for verification of

authenticity of stability data of Omdexo 30mg and 60mg capsules was conducted on 07-11-2019 and 23-01-2020

and the details are as given above. The panel also verified the following.

i) Testing of pellets at pH 1.2,5.5 and 6.75/7 to confirm dual delayed release profile as per the decision

of 276th meeting of Registration Board.

ii) Dissolution testing at buffer stage at pH 7.0 with 5mM SLS as per the FDA dissolution database.

However it seems from the data that the firm did not perform accelerated salability studies testing at PH 5.5. Also

the firm developed its own method for testing of raw material and stability batches. The detailed report is being

submitted to the competent authority for further consideration.

Discussion: Registration Board deliberated on the analytical method adopted by the firm and reiterated that the

firm can either adopt the API manufacturer’s method of testing (since it is a validated method) or develop and

validate analytical method based on ICH guidelines. The Board further deliberated that in any case the analytical

method should be properly validated.

Decision: Registration Board decided to defer the case of Omdexo 30mg and 60mg capsules for

submission of data of validation of analytical method since the firm has not used API

manufacturer’s method of testing.


b. Exemption from onsite verification of stability data

New Cases

Sr.

No.

Name & Address of

Manufacturer /

Applicant

Brand Name

(Proprietary Name +

Dosage Form + Strength),

Composition,


Finished Product

Specification

Type of Form,


Fee (including

differential fee),

Demanded Price /

Pack size


Local Availability

GMP Inspection Report Date

94. Getz Pharma (Pvt) Ltd.

29-30/27, Korangi

Industrial Area,

Karachi.

Vonoget 10mg Tablet


contains:

Vonoprazan as

fumarate…..10mg

Potassium-Competitive

Acid Blocker

Form 5D

03-08-2018

PKR 50,000/-

03-08-2018

Takecab Tablets

(PMDA Japan Approved)

01-07-2019: acceptable level of

compliance of GMP

requirements.


Drug Vonoget 10mg Tablet

Name of Manufacturer M/s Getz Pharma (Pvt) Ltd. 29-30/27, Korangi Industrial Area, Karachi.

Manufacturer of API Jiangsu Yongan Pharmaceutical Co. Ltd. No. 18, 237 Provincial Highway, Jiangsu

Hua’ian Economic Development Zone, China.

API Lot No. 20180812

Description of Pack


Red coloured, oblong shaped, biconvex film coated tablet plain on both sides packed

in Alu-PVC blister, further packed in secondary carton.

Stability Storage Condition Accelerated: 40°C ± 2°C/75%±5% RH

Real Time: 30°C ± 2°C/65%±5% RH

Time Period Accelerated: 6 (months) Real Time: 6 (months)

Frequency Accelerated: 0, 1, 2, 3, 4, 6 (Months) Real Time : 0, 3, 6 (Months)

Batch No. 454DS01 454DS02 454DS03


Manufacturing Date 12 – 2018 12 – 2018 12 – 2018


No. of Batches 03

Date of Submission 21125 (18-10-2019)



1. COA of API. Yes




country of origin.

Firm has submitted copy of GMP certificate No.

JS20160548 issued by China Food and Drug

Administration which is valid till 03-03-2021.


study and details of tests.

Yes




Yes


5. Documents confirming import of API etc. Firm has submitted copy of commercial invoice dated 05-

09-2018 specifying import of 2.5Kg Vonoprazan

Fumarate attested by AD DRAP, Karachi.

6. All provided documents will be attested (name,


/ documents.

Yes

7. Commitment to continue real time stability study

till assigned shelf life of the product.

Yes


1978.

Yes


The firm has requested for Exemption from On-site Investigation of their submitted stability data and provided the

following documents in conjunction with the checklist approved by the Registration Board in its 278th Meeting:





Firm has referred to their last onsite inspection conducted for

product Arcox Tablet 90mg and 120mg on 17th September, 2018.

The said inspection report was discussed in 286th meeting of

Registration Board held on 14-16th November 2018 and the case was

approved. The inspection report confirms following points:

The HPLC software is 21CFR Compliant as per record available

with the firm.

Audit trail on the testing reports is available.

Adequate monitoring and control are available for stability chamber.

Chambers are controlled and monitored through software having

alarm system for alerts as well.

Related manufacturing area, equipment, personnel and utilities are

GMP compliant.



case of import).

Firm has submitted copy of commercial invoice dated 05-09-2018

specifying import of 2.5Kg Vonoprazan Fumarate attested by AD

DRAP, Karachi.



standards.

The firm has submitted an undertaking specifying that we have

procured reference standard of vonoprazan Fumarate Batch No.

20171128 and impurity standards as free of cost sample from the API

manufacturer. We have used Relative Retention Time for location and

calculation of related substance as provided by API manufacturer.

Firm has also submitted copy of invoice for reference standard (0.5g)

and Impurities i.e. Z-1-5mg, Z-3-5mg, Z-7-15mg and Z-8-5mg.


certificate of API manufacturer issued

by regulatory authority of country of

origin.

Firm has submitted copy of GMP certificate No. JS20160548 issued

by China Food and Drug Administration which is valid till 03-03-

2021.


qualification

Firm has submitted copy of vendor certification checklist filled and

signed by technical persons of the firm in April 2018, before the

import of API.



standards.

Firm has submitted analytical report and copy of COA of API and

reference and impurity standard.



development?

The firm has submitted documents for procurement of excipients used

in the formulation of applied product.




experience.

The firm has submitted List of qualified staff involved in R&D

department.

Production Data



trial batches.

The firm has submitted copy of protocols for stability study of primary

batches of vonoprazan tablets.

10. Complete batch manufacturing record

of three stability batches.

The firm has submitted copy of Batch Manufacturing Records of all

the three Batches.


stability batches.

Firm has provided following remaining quantities for each batch:

454DS01: 14 Packs

454DS02: 14 Packs

454DS03: 14 Packs

QA / QC DATA


temperature and humidity monitoring

of stability chambers (real time and

accelerated)

Firm has submitted copies of data logger record for stability chambers

with real time and accelerated stability testing


along with COA.

The firm has submitted copy of Raw Material Specifications, Raw

Material Testing Procedures along with COA.


complete record of testing of stability

batches (i.e. chromatograms, lab

reports, raw data sheets etc.)

The firm has submitted copy of Finished Product Testing Procedure

and specification.


from manufacturer.

The firm have submitted stability study data of 3 batches as per

conditions of zone IV-A.

15. Analysis reports for excipients used. Firm has submitted analysis reports for all excipients used in applied

product development


studies.

Firm has submitted that they have used same excipients in their

formulation as used by the innovator “Takecab” Tablets. The only

difference is in film coating material. Therefore drug-excipient

compatibility studies are not required.


data.

Firm has submitted comparative dissolution profile data at 1.2 pH

HCl, 4.5 pH acetate buffer and 6.8 pH phosphate buffer. The

dissolution is reported to be more than 85% in 15 minutes in all

dissolution medium.


software 21CFR & audit trail reports

on product testing.

Audit trail on testing reports for the applied product has been

submitted by the firm.

Remarks of the evaluator:

Shortcoming communicated

Justify the adaptation of dissolution parameters including type of apparatus, speed (rpm), dissolution medium,

volume and time keeping in view the solubility and pKa of the drug substance, pH – pKa solubility profile and

recommendations from general chapters of official pharmacopoeia.

Response by the firm:

Vonoprazan is a highly soluble drug substance based on ICH Q6A, which states that the drug substance should

be considered highly soluble if it meets following two conditions:

1. The dissolution profile of all strengths of the dosage form should be rapid i.e. Dissolution >80 % in 15

minutes at pH 1.2, 4.0 & 6.8.


2. The highest drug product’s strength is soluble in 250mL or less of aqueous media over the pH range of 1.2

to 6.8 at 37°C ± 1°C. In other words, the highest strength divided by 250 should be less than or equal to the

lowest solubility observed over the entire pH range of 1.2 - 6.8 i.e. dose/solubility volume < 250 mL from

pH 1.2 to 6.8.

As per ICH Q6A, for dosage forms having drug substances falls in above conditions will be considered as highly

soluble drugs and do not require development of discriminatory dissolution method / parameters. Generally, a

single time point with one medium is acceptable.

Getz Pharma Product ‘Vonoget Tablets’ as well as the Innovator Product ‘Takecab Tablets’ releases more than

85% in all three mediums within 15minutes at 50 RPM. Also, the dose solubility of Vonoprazan is very high

throughout the physiological pH range (1.2 to 6.8). The lowest solubility of Vonoprazan is found to be in pH

6.8 i.e. is about 4.7 mg/ml which is greater than the highest strength divided by 250 (20mg/250=0.08mg/ml).

Based on above literature and studies, we selected dissolution medium having pH 6.8 as a worst-case scenario,

since the solubility of Vonoprazan in pH 6.8 is less as compared to solubility in pH 1.2 (about 16.5mg/ml) & pH

4.5 (8.1mg/ml).

In light of above discussion and high solubility of drug substance, discriminatory dissolution parameters is not

required for Vonoprazan Tablets 10mg and 20mg. Therefore, generalized lowest 50 RMP with 900ml medium

(most common volume as per USP <1092>) was selected for release and stability studies of the drug product.

As per USP general chapter <1092>, “Dissolution Procedure: Development and Validation”, Immediate release

dosage form should release within 30 to 60 minutes. Therefore, we selected the lowest time point i.e. 30 minutes

for dissolution.

Decision: Registration Board decided to approve registration of Vonoget 10mg Tablet with

innovator’s specification by M/s Getz Pharma (Pvt) Ltd. 29-30/27, Korangi Industrial Area,

Karachi. Manufacturer will place first three production batches on long term stability studies

throughout proposed shelf life and on accelerated studies for six months.

Sr.

No.

Name & Address of

Manufacturer /

Applicant

Brand Name

(Proprietary Name +


Composition,


Finished Product

Specification

Type of Form,


Fee (including

differential fee),

Demanded Price /

Pack size


Local Availability


95. Getz Pharma (Pvt) Ltd.

29-30/27, Korangi

Industrial Area,

Karachi.

Vonoget 20mg Tablet


contains:

Vonoprazan as

fumarate…..20mg

Potassium-Competitive

Acid Blocker

Form 5D

03-08-2018

PKR 50,000/-

03-08-2018

Takecab Tablets

(PMDA Japan Approved)

01-07-2019: acceptable level of

compliance of GMP

requirements.


Drug Vonoget 20mg Tablet

Name of Manufacturer M/s Getz Pharma (Pvt) Ltd. 29-30/27, Korangi Industrial Area, Karachi.

Manufacturer of API Jiangsu Yongan Pharmaceutical Co. Ltd. No. 18, 237 Provincial Highway, Jiangsu

Hua’ian Economic Development Zone, China.


Description of Pack


Red coloured, oblong shaped, biconvex film coated tablet plain on both sides packed

in Alu-PVC blister, further packed in secondary carton.


Real Time: 30°C ± 2°C/65%±5% RH

Time Period Accelerated: 6 (months) Real Time: 6 (months)

Frequency Accelerated: 0, 1, 2, 3, 4, 6 (Months) Real Time : 0, 3, 6 (Months)


Batch No. 455DS01 455DS02 455DS03




No. of Batches 03




1. COA of API. Yes




country of origin.






Yes




Yes


09-2018 specifying import of 2.5Kg Vonoprazan

Fumarate attested by AD DRAP, Karachi.



/ documents.

Yes



Yes


1978.

Yes








Firm has referred to their last onsite inspection conducted for product

Arcox Tablet 90mg and 120mg on 17th September, 2018. The said

inspection report was discussed in 286th meeting of Registration

Board held on 14-16th November 2018 and the case was approved.

The inspection report confirms following points:

The HPLC software is 21CFR Compliant as per record available

with the firm.


Adequate monitoring and control are available for stability chamber.

Chambers are controlled and monitored through software having

alarm system for alerts as well.

Related manufacturing area, equipment, personnel and utilities are

GMP compliant.




case of import).

Firm has submitted copy of commercial invoice dated 05-09-2018

specifying import of 2.5Kg Vonoprazan Fumarate attested by AD

DRAP, Karachi.



standards.

The firm has submitted an undertaking specifying that we have

procured reference standard of vonoprazan Fumarate Batch No.

20171128 and impurity standards as free of cost sample from the API

manufacturer. We have used Relative Retention Time for location and

calculation of related substance as provided by API manufacturer.

Firm has also submitted copy of invoice for reference standard (0.5g)

and Impurities i.e. Z-1-5mg, Z-3-5mg, Z-7-15mg and Z-8-5mg.




country of origin.

Firm has submitted copy of GMP certificate No. JS20160548 issued

by China Food and Drug Administration which is valid till 03-03-2021.


qualification

Firm has submitted copy of vendor certification checklist filled and

signed by technical persons of the firm in April 2018, before the import

of API.



standards

Firm has submitted analytical report and copy of COA of API and

reference and impurity standard.



development?

The firm has submitted documents for procurement of excipients used

in the formulation of applied product.



experience.


department.

Production Data



trial batches.

The firm has submitted copy of protocols for stability study of primary

batches of vonoprazan tablets.



The firm has submitted copy of Batch Manufacturing Records of all

the three Batches.


stability batches.


455DS01: 10 Packs

455DS02: 11 Packs

455DS03: 10 Packs

QA / QC DATA





Firm has submitted copies of data logger record for stability chambers

with real time and accelerated stability testing


along with COA.


Material Testing Procedures along with COA.






and specification.


from manufacturer.

The firm have submitted stability study data of 3 batches as per

conditions of zone IV-A.

15. Analysis reports for excipients used. Firm has submitted analysis reports for all excipients used in applied

product development



studies.

Firm has submitted that they have used same excipients in their

formulation as used by the innovator “Takecab” Tablets. The only

difference is in film coating material. Therefore drug-excipient

compatibility studies are not required.


data.

Firm has submitted comparative dissolution profile data at 1.2 pH HCl,

4.5 pH acetate buffer and 6.8 pH phosphate buffer. The dissolution is

reported to be more than 85% in 15 minutes in all dissolution medium.


software 21CFR & audit trail reports

on product testing.

Audit trail on testing reports for the applied product has been submitted

by the firm.


Shortcoming communicated

Justify the adaptation of dissolution parameters including type of apparatus, speed (rpm), dissolution medium,

volume and time keeping in view the solubility and pKa of the drug substance, pH – pKa solubility profile and

recommendations from general chapters of official pharmacopoeia.

Response by the firm:

Vonoprazan is a highly soluble drug substance based on ICH Q6A, which states that the drug substance should

be considered highly soluble if it meets following two conditions:

1. The dissolution profile of all strengths of the dosage form should be rapid i.e. Dissolution >80 % in 15

minutes at pH 1.2, 4.0 & 6.8.

2. The highest drug product’s strength is soluble in 250mL or less of aqueous media over the pH range of

1.2 to 6.8 at 37°C ± 1°C. In other words, the highest strength divided by 250 should be less than or

equal to the lowest solubility observed over the entire pH range of 1.2 - 6.8 i.e. dose/solubility volume

< 250 mL from pH 1.2 to 6.8.

As per ICH Q6A, for dosage forms having drug substances falls in above conditions will be considered as highly

soluble drugs and do not require development of discriminatory dissolution method / parameters. Generally, a

single time point with one medium is acceptable.

Getz Pharma Product ‘Vonoget Tablets’ as well as the Innovator Product ‘Takecab Tablets’ releases more than

85% in all three mediums within 15minutes at 50 RPM. Also, the dose solubility of Vonoprazan is very high

throughout the physiological pH range (1.2 to 6.8). The lowest solubility of Vonoprazan is found to be in pH

6.8 i.e. is about 4.7 mg/ml which is greater than the highest strength divided by 250 (20mg/250=0.08mg/ml).

Based on above literature and studies, we selected dissolution medium having pH 6.8 as a worst-case scenario,

since the solubility of Vonoprazan in pH 6.8 is less as compared to solubility in pH 1.2 (about 16.5mg/ml) &

pH 4.5 (8.1mg/ml).

In light of above discussion and high solubility of drug substance, discriminatory dissolution parameters is not

required for Vonoprazan Tablets 10mg and 20mg. Therefore, generalized lowest 50 RMP with 900ml medium

(most common volume as per USP <1092>) was selected for release and stability studies of the drug product.

As per USP general chapter <1092>, “Dissolution Procedure: Development and Validation”, Immediate release

dosage form should release within 30 to 60 minutes. Therefore, we selected the lowest time point i.e. 30 minutes

for dissolution.

Decision: Registration Board decided to approve registration of Vonoget 20mg Tablet with

innovator’s specification by M/s Getz Pharma (Pvt) Ltd. 29-30/27, Korangi Industrial Area,




Sr.

No.

Name & Address of

Manufacturer /

Applicant

Brand Name





Type of Form,


Fee (including

differential fee),

Demanded Price /

Pack size

International Availability


Date & Remarks

96. M/s Hilton Pharma

(Pvt) Ltd., Plot 13 &

14, Sector 15, Korangi

Industrial Area,

Karachi

Dapa-Met XR 2.5/1000mg

tablets

Each film coated bilayer tablet

contains:

Dapagliflozin (as propanediol

monohydrate) …… 2.5 mg

Metformin hydrochloride

(Extended release)…. 1000mg

(Antidiabetic)

Form 5-D

Diary No. 103

27-01-2016.

Rs.50,000/- dated

27-01-2016

Approved by USFDA



& report concludes

satisfactory level of GMP

compliance




Industrial Area,

Karachi

Dapa-Met XR 5/500mg tablets


contains:


monohydrate) …… 5 mg



(Antidiabetic)

Form 5-D

Dy. No. 102

27-01-2016.

Rs.50,000/-

27-01-2016




Industrial Area,

Karachi

Dapa-Met XR 10/500mg tablets


contains:


monohydrate) …… 10 mg



(Antidiabetic)

Form 5-D

Dy. No. 104

27-01-2016.

Rs.50,000/-

27-01-2016


The firm has submitted stability study data along with required documents as per checklist approved in 251st

meeting of Registration Board. Detailsof submitted data are as under:

(Dy.# 24048 dated 15-11-2019)


Manufacturer of API Dapagliflozin: Jiangsu Yongan Pharmaceutical Co. Ltd., China.

Metformin hydrochloride: Abhilash Chemicals & Pharmaceuticals (Pvt.)

Ltd., India.

API Lot No. Dapagliflozin: 201806001

Metformin: MET/01/18061066

Description of Pack


Alu-Alu blister foil with unit carton


Real Time: 30°C ± 2°C / 65% ± 5%RH

Time Period Accelerated: 6 Months

Real Time: 6 Months

Frequency Real Time: 0,3 & 6 (months)

Accelerated: 0,3 & 6 (months)

DAPA-MET XR 2.5/1000MG TABLET


Batch No. DMX-309106-19 DMX-309206-20 DMX-309306-21




DAPA-MET XR 5/500MG TABLET










No. of Batches 03



COA of API Yes

Approval of API by regulatory authority of country of

origin or GMP certificate of API manufacturer issued

by regulatory authority of country of origin.

Dapagliflozin: Firm has submitted copy of GMP

certificate (No. JS20160548) of M/s Jiangsu Yongan

Pharmaceutical Co. Ltd, issued by CFDA China. The

certificate is valid till 3-3-2021.

Metformin: Firm has submitted copy of GMP certificate

(No. WC-0345) of M/s Abhilash Chemicals issued by

Central Drugs Standard Control Organization,

Government of India. The certificate is valid till 27-09-

2021.

Protocols followed for conduction of stability study and





Yes

Documents confirming import of API etc. Dapagliflozin: Firm has submitted copy of commercial

invoice dated 16-7-2018 specifying import of 75 Kg

dapagliflozin propanediol monohydrate. The invoice has

been signed by AD DRAP Karachi.

Metformin: Firm has submitted copy of commercial


metformin HCl. The invoice is signed by AD DRAP

Karachi.



documents.

Yes




Commitment to follow Drug Specification Rules, 1978. Yes

DATA FOR EXEMPTION FROM ONSITE INVESTIGATION OF SUBMITTED STABILITY DATA

ADMINISTRATIVE PORTION




years.

Firm has referred to last onsite inspection of their product HILVEL Tablets

(Sofosbuvir / Velpatasvir) which was considered and approved by

Registration Board in its 277th Meeting with following details:

Date of Inspection: 14-12-2017.

The HPLC is 21CFR Compliant.

Audit trail on the testing reports were available.

2. Documents for the procurement



Dapagliflozin: Firm has submitted copy of commercial invoice dated 16-7-

2018 specifying import of 75 Kg dapagliflozin propanediol monohydrate.

The invoice has been signed by AD DRAP Karachi.

Metformin: Firm has submitted copy of commercial invoice dated 27-6-

2018 specifying import of 5000 Kg metformin HCl. The invoice is signed

by AD DRAP Karachi.



impurity standards.

Firm has submitted copy of invoice of purchase of working reference

standard and impurity.



issued by regulatory authority


Dapagliflozin: Firm has submitted copy of GMP certificate (No.

JS20160548) of M/s Jiangsu Yongan Pharmaceutical Co. Ltd, issued by

CFDA China. The certificate is valid till 3-3-2021.

Metformin: Firm has submitted copy of GMP certificate (No. WC-0345)

of M/s Abhilash Chemicals issued by Central Drugs Standard Control

Organization, Government of India. The certificate is valid till 27-09-2021.


qualification

Firm has submitted copy of vendor’s audit form and SOPs for selection of

vendor.

6. Certificate of analysis of the


impurity standards

Firm has submitted COA of API, and reference standard.



development?

Firm has submitted documents for procurement of excipients.

8. List of qualified staff involved



Firm has provided list of technical staff of product development section.

PRODUCTION DATA

9. Authorized Protocols/SOP for



Firm has submitted authorized general protocols/SOPs for the development

& testing of trial batches.



Firm has provided Batch Manufacturing Record for all the three batches

11. Record of remaining quantities



DAPA-MET XR 2.5/1000MG TABLET

DMX-309106-19: 140 Tablets

DMX-309206-20: 140 Tablets

DMX-309306-21: 140 Tablets


DMX-285909-4: 84 Tablets





DMX-289811-16: 112 Tablets

DMX-289911-17: 112 Tablets

DMX-290011-18: 112 Tablets

QA/QC DATA

12. Record of Digital data logger




accelerated)

Firm has submitted record of Digital data logger for temperature and

humidity monitoring of stability chambers.


along with COA.

Firm has submitted COA and method of analysis of API.

14. Method used for analysis of

FPP & complete record of

testing of stability batches (i.e.

chromatograms, lab reports,

raw data sheets etc.)

Firm has submitted method of analysis of FPP and complete record of

testing of stability batches along with chromatograms

15. Reports of stability studies of


Firm has submitted both accelerated (40°C ± 2°C & 75±5%RH) stability

studies & long term (30°C ± 2°C & 65±5%RH) stability studies reports of

three batches of both API’s.


used.

Firm has submitted analysis reports for all excipients used.


studies.

Firm has submitted that their formulation is as per reference product so they

do not require drug excipient compatibility studies.

18. Record of comparative

dissolution data. Firm has submitted data of comparative dissolution profile at pH 1.2

buffer, 4.5 buffer, 6.8.phosphate buffer and calculated difference of %

release with innovator product and also calculated f2 factor. The value of

f2 factor in all dissolution medium for all the strengths fall in acceptable

range.




Firm has submitted audit trail reports for HPLC analysis for all the three

batches.

Evaluation by PEC:

Decision: Registration Board decided to approve registration of Dapa-Met XR 2.5/1000mg tablets,

Dapa-Met XR 5/500mg tablets and Dapa-Met XR 10/500mg tablets with innovator’s specification

by M/s Hilton Pharma (Pvt) Ltd., Plot 13 & 14, Sector 15, Korangi Industrial Area, Karachi.



Sr.

No.

Name & Address of

Manufacturer /

Applicant

Brand Name





Type of Form,


Fee (including

differential fee),

Demanded Price /

Pack size



Date & Remarks




Industrial Area,

Karachi

Empa-Met XR 5/1000mg tablet


Empagliflozin …….. 5 mg


(Extended release)…..1000mg

(Antidiabetic)

Form 5-D

Diary No. 2740

24-02-2017

PKR.50,000/-

23-02-2017

Approved by USFDA



and the report concludes

satisfactory level of GMP

compliance





Industrial Area,

Karachi





(Extended release)….1000 mg

(Antidiabetic)

Form 5-D

Diary No. 2741

24-02-2017

PKR.50,000/-

23-02-2017




Industrial Area,

Karachi

Empa-Met XR 12.5/1000mg

tablet


Empagliflozin …….. 12.5 mg



(Antidiabetic)

Form 5-D

Diary No. 2738

24-02-2017

PKR.50,000/-

23-02-2017




Industrial Area,

Karachi






(Antidiabetic)

Form 5-D

Diary No. 2739

24-02-2017

PKR.50,000/-

23-02-2017


Firm has initially submitted application with brand name Empa-Met XR, later on the firm has

submitted stability studies with brand name Xenglu-Met XR Tablets.

The firm has submitted stability study data along with required documents as per checklist approved in

251st meeting of Registration Board. Detailsof submitted data are as under:

(Dy.# 26176 dated 05-12-2019)


Manufacturer of API Empagliflozin: Jiangsu Yongan Pharmaceutical Co., Ltd. No. 18, Provincial

Highway 237, Huaian Economic Development Zone, Jiangsu

Metformin hydrochloride: Abhilash Chemicals & Pharmaceuticals (Pvt.)

Ltd., India.

API Lot No. Empagliflozin: 4500-201902001

Metformin: MET/01/18122315

Description of Pack


Alu-Alu blister foil with unit carton


Real Time: 30°C ± 2°C / 65% ± 5%RH

Time Period Accelerated: 6 Months Real Time: 6 Months

Frequency Real Time: 0,3 & 6 (months)

Accelerated: 0,3 & 6 (months)

XENGLUMET XR 5/1000MG TABLET

Batch No. EMP-404109-6 EMP-404209-7 EMP-404309-8










XENGLUMET XR 12.5/1000MG TABLET










No. of Batches 03



COA of API Yes

Approval of API by regulatory authority of country of



Empagliflozin: Firm has submitted copy of GMP

certificate (No. JS20160548) of M/s Jiangsu Yongan

Pharmaceutical Co. Ltd, issued by CFDA China. The

certificate is valid till 3-3-2021.

Metformin: Firm has submitted copy of GMP certificate

(No. WC-0345) of M/s Abhilash Chemicals issued by

Central Drugs Standard Control Organization,

Government of India. The certificate is valid till 27-09-

2021.






Yes

Documents confirming import of API etc. Empagliflozin: Firm has submitted copy of commercial


Empagliflozin. The invoice has been signed by AD DRAP

Karachi.

Metformin: Firm has submitted copy of commercial

invoice dated 28-12-2018 specifying import of 200 x 50kg

metformin HCl. The invoice is signed by AD DRAP

Karachi.



documents.

Yes



Commitment to follow Drug Specification Rules, 1978. Yes



ADMINISTRATIVE PORTION




years.

Firm has referred to last onsite inspection of their product HILVEL Tablets

(Sofosbuvir / Velpatasvir) which was considered and approved by

Registration Board in its 277th Meeting with following details:

Date of Inspection: 14-12-2017.

The HPLC is 21CFR Compliant.

Audit trail on the testing reports were available.




Empagliflozin: Firm has submitted copy of commercial invoice dated 01-

03-2019 specifying import of 60 Kg Empagliflozin. The invoice has been

signed by AD DRAP Karachi.

Metformin: Firm has submitted copy of commercial invoice dated 28-12-

2018 specifying import of 200x50kg metformin HCl. The invoice is signed

by AD DRAP Karachi.



impurity standards.

Firm has submitted copy of invoice of purchase of working reference

standard and impurity.



issued by regulatory authority


Empagliflozin: Firm has submitted copy of GMP certificate (No.

JS20160548) of M/s Jiangsu Yongan Pharmaceutical Co. Ltd, issued by

CFDA China. The certificate is valid till 3-3-2021.

Metformin: Firm has submitted copy of GMP certificate (No. WC-0345)

of M/s Abhilash Chemicals issued by Central Drugs Standard Control

Organization, Government of India. The certificate is valid till 27-9-2021.


qualification

Firm has submitted copy of vendor’s audit form and SOPs for selection of

vendor.

6. Certificate of analysis of the


impurity standards

Firm has submitted COA of API, and reference standard.



development?

Firm has submitted documents for procurement of excipients.

8. List of qualified staff involved



Firm has provided list of technical staff of product development section.

PRODUCTION DATA

9. Authorized Protocols/SOP for



Firm has submitted authorized general protocols/SOPs for the development

& testing of trial batches.



Firm has provided Batch Manufacturing Record for all the batches

11. Record of remaining quantities




EMP-404109-6: 133 Tablets







XENGLUMET XR 12.5/1000MG TABLET









QA/QC DATA

12. Record of Digital data logger




accelerated)

Firm has submitted record of Digital data logger for temperature and

humidity monitoring of stability chambers.


along with COA.

Firm has submitted COA and method of analysis of API.

14. Method used for analysis of

FPP & complete record of

testing of stability batches (i.e.

chromatograms, lab reports,

raw data sheets etc.)

Firm has submitted method of analysis of FPP and complete record of

testing of stability batches along with chromatograms

15. Reports of stability studies of


Firm has submitted both accelerated (40°C ± 2°C & 75±5%RH) stability

studies & long term (30°C ± 2°C & 65±5%RH) stability studies reports of

three batches of both API’s.


used.

Firm has submitted analysis reports for all excipients used.


studies.

Firm has submitted that their formulation is as per reference product so they

do not require drug excipient compatibility studies.

18. Record of comparative

dissolution data.

Firm has submitted data of comparative dissolution profile at pH 1.2 buffer,

4.5 buffer, 6.8.phosphate buffer and calculated difference of % release with

innovator product and also calculated f2 factor. The value of f2 factor in all

dissolution medium for all the strengths fall in acceptable range.




Firm has submitted audit trail reports for HPLC analysis for all the three

batches.

Evaluation by PEC:

Firm has developed the formulation as per the innovator product having extended release inner core of

metformin hydrochloride and outer coating containing immediate release empagliflozin.

Decision: Registration Board decided to approve registration of Empa-Met XR 5/1000mg tablet,

Empa-Met XR 10/1000mg tablet, Empa-Met XR 12.5/1000mg tablet and Empa-Met XR 25/1000mg

tablet with innovator’s specification by M/s Hilton Pharma (Pvt) Ltd., Plot 13 & 14, Sector 15,

Korangi Industrial Area, Karachi. Manufacturer will place first three production batches on long


Sr.

No.

Name & Address of

Manufacturer /

Applicant

Brand Name

(Proprietary Name +


Composition,


Finished Product

Specification

Type of Form,


Fee (including

differential fee),

Demanded Price / Pack

size


Local Availability


Remarks

103. The Searle company

Limited F-319 S.I.T.E

Karachi.

Trelaglip 50mg Tablet


contains:

Form 5D

01-02-2017

PKR 50,000/-

Zafatek Tablets (PMDA Japan

Approved)

Last inspection report dated 30-


Trelagliptin (as

succinate)….50mg

Antidiabetic

(01-02-2017)

DUPLICATE

01-2019 confirms that firm is

operating at a Good level of

GMP compliance.

104. The Searle company

Limited F-319 S.I.T.E

Karachi.



contains:

Trelagliptin (as

succinate)….100mg

Antidiabetic

Form 5D

01-02-2017

PKR 50,000/-

(01-02-2017)

DUPLICATE

Zafatek Tablets (PMDA Japan

Approved)

Last inspection report dated 30-

01-2019 confirms that firm is

operating at a Good level of

GMP compliance.

Evaluation by PEC:


Registration Board.


Manufacturer of API Ruyuan HEC Pharm Co. Ltd. Xiaba Development zone, Ruyuan County,

Shaoguan city, Guandong province China.

API Lot No. TGLT-201712001

Description of Pack


Pale yellowish red color, oval shaped biconvex film coated tablets packed in

Alu-Alu blister (2x10’s) in a carton





Frequency Accelerated: 0, 3, 6 (Months)

Real Time: 0, 3, 6 (Months)


Batch No. 18PD-116 18PD-128 18PD-130



Date of Initiation 06-2018 03-12-2018 03-12-2018


Batch No. 18PD-174 18PD-180 18PD-181



Date of Initiation 06-2018 03-12-2018 03-12-2018

No. of Batches 03




1. COA of API Yes




Copy of GMP Certificate for M/s Ruyuan HEC Pharm

Co., Ltd, China issued by Shaoguan Food and Drug

Administration, China is submitted. It is valid till 18-12-

2019.


and details of tests. No





No

5. Documents confirming import of API etc. Firm has submitted copy of Assistant Director (I & E)

DRAP attested invoice confirming import of 1Kg

trelagliptin succinate dated 30-01-2018.



documents.

Yes




1978. Yes


Shortcoming Response by the firm

GMP certificate of the API manufacturer issued by

provincial or federal regulatory authority since the

submitted GMP certificate is issued by Shaoguan

Food and Drug Administration which is a district

regulatory authority.

Copy of GMP Certificate for M/s Ruyuan HEC Pharm Co.,

Ltd, China issued by Shaoguan Food and Drug


2021.

Scientific justification for selection of dissolution

specifications i.e. type of apparatus, volume, speed

(rpm), dissolution medium and dissolution time.

Due to un availability of monograph for trelagliptin and

there is no reference for dissolution available at US FDA.

We, selected the dissolution specification of Sitagliptin

from FDA dissolution data base for trelagliptin because

both molecules are of same therapeutic class having same

BCS classification and have similar mechanism of action.

Justify the variation in dissolution results of

individual tablets i.e. 90.11% to 116.71% at first

time point for batch 18PD-116

We have checked dissolution results of the said batch and

the average values are within specified limits.


Firm has submitted data for exemption from onsite investigation of submitted stability data as per the guidelines of

293rd meeting of Registration Board.

1. Reference of previous approval of applications

with stability study data of the firm

Firm has referred to last onsite inspection of their product

Tapendol Tablets 50mg, 75mg and 100mg (Tapentadol)

which was considered and approved by Registration

Board in its 289th Meeting with following details:

Date of Inspection: 11-03-2019

2. Certificate of Analysis of API from both API

Manufacturer and Finished Product manufacturer.

Firm has submitted CoA of API from API manufacturer.

Firm has also submitted copy of CoA of the API

generated by FPP manufacturer.

3. Method used for analysis of API from both API

Manufacturer and Finished Product

manufacturer

Firm has submitted method of analysis of API from both

API manufacturer as well as FPP manufacturer.

4. Stability study data of API from API manufacturer Firm has submitted stability study data of 3 batches of

API as per the conditions of zone IV-A.

5. Approval of API/ DML/GMP certificate of API

manufacturer issued by concerned regulatory


Copy of GMP Certificate for M/s Ruyuan HEC Pharm

Co., Ltd, China issued by Shaoguan Food and Drug


2021.


6. Documents for the procurement of API with

approval from DRAP (in case of import).

Firm has submitted copy of Assistant Director (I & E)

DRAP attested invoice confirming import of 1Kg

trelagliptin succinate dated 30-01-2018.


study

Firm has submitted protocols for conduction of stability

studies.

8. Method used for analysis of FPP Firm has submitted drug product testing method.

9. Drug-excipients compatibility studies (where

applicable)

Firm has submitted that their formulation is as per

reference product so they do not require drug excipient

compatibility studies.

10. Complete batch manufacturing record of three

stability batches.

Firm has submitted batch manufacturing record of three

batches of both strengths.

11. Record of comparative dissolution data (where

applicable)

Firm has submitted results of CDP of both strengths with

the innovator product. The results of CDP were within

acceptable limits.



Raw data sheets, COA, summary data sheets etc.

Yes submitted by the firm

13. Compliance Record of HPLC software 21CFR &

audit trail reports on product testing.

Firm has submitted record of HPLC including audit trail

reports for testing on the applied product

14. Record of Digital data logger for temperature and

humidity monitoring of stability chambers


Firm has submitted record of Digital data logger for

temperature and humidity monitoring of stability

chambers.


Scientific justification for selection of dissolution specifications i.e. type of apparatus, volume, speed (rpm),

dissolution medium and dissolution time was provided by the firm in which they have responded that “Due to un

availability of monograph for trelagliptin and there is no reference for dissolution available at US FDA. We, selected

the dissolution specification of Sitagliptin from FDA dissolution data base for trelagliptin because both molecules

are of same therapeutic class having same BCS classification and have similar mechanism of action”

Decision: Deferred for scientific justification of using dissolution specifications of Sitagliptin tablets

for performing dissolution test of trelagliptin tablets.

Deferred cases

Sr.

No.

Name & Address of

Manufacturer /

Applicant

Brand Name

(Proprietary Name +


Composition,


Finished Product

Specification

Type of Form,


Fee (including

differential fee),

Demanded Price /

Pack size


Availability


105. Werrick

Pharmaceuticals,

Plot # 216-217, I-

10/3, Industrial Area

Islamabad.

Xetine 10mg Tablet


contains:

Vortioxetine as

hydrobromide…..10mg

Antidepressant

Form 5

Dy No. 41745

07-12-2018

PKR 20,000/-

07-12-2018

TRINTELLIX Tablets

(USFDA Approved)

GMP compliant dated

07/12/17―Good compliance to

GMP


Drug Xetine 10mg Tablet

Name of Manufacturer M/s Werrick Pharmaceuticals, Plot # 216-217, I-10/3, Industrial Area Islamabad.

Manufacturer of API Lianyungang Jari Pharmaceutical Co. Ltd. # 18, Zhenhua Road, Lianyunguang,

Jiangsu Province China.



Description of Pack


Blistered in Alu-PVC packed in card box unit carton of 14’s tablets


Real Time: 30°C ± 2°C/65%±5% RH

Time Period Accelerated: 6 (months)

Real Time: 6 (months)

Frequency Accelerated: 0, 3 ,6 (Months)

Real Time : 0, 3 ,6 ,9, 12, 18 (Months)

Batch No. T#01 T#02 T#03




No. of Batches 03




COA of API. Yes




country of origin.


JS20140353 issued by China Food and Drug Administration

which is valid till 19-11-2019.



Yes




Yes

4. Documents confirming import of API etc. Firm has submitted copy of commercial invoice dated 15-5-

2018 specifying import of 0.5Kg vortioxetine hydrobromide

attested by AD DRAP, Islamabad.


sign and stamp) for ensuring authenticity of

data / documents.

Yes


study till assigned shelf life of the product.

Yes


Rules, 1978.

Yes





1. Reference of last onsite panel inspection for

instant dosage form conducted during last

two years.

Registration Board approved Cell-Tab (Sofosbuvir 400mg)

Tablets in its 276th Meeting.

Dates of Inspection:

o Initial (M-256):

10th December 2015 (Afternoon).


o Subsequent (M-269):

19th April, 2017 (Forenoon).

o Last Inspection (M-276):

20th November, 2017.

Following points related to HPLC Software and Audit Trail

were reported

Software of HPLC present in the firm is 21CFR compliant

and audit trail on the testing reports was available and

confirmed. Panel reviewed chromatograms for testing of API

and trial batches at 0, 3 and 6 months for real time and

accelerated stability testing.



Firm has submitted copy of commercial invoice dated 15-5-



3. Documents for the procurement of reference

standard and impurity standards.

The firm has submitted letter that the reference standard were

provided along with API and therefore separate invoice is not

available.

4. Approval of API/ DML/GMP certificate of



Firm has submitted copy of GMP certificate No. JS20140353

issued by China Food and Drug Administration which is valid

till 19-11-2019.

5. Mechanism for Vendor pre-qualification Firm has submitted work instructions for evaluation of

suppliers and vendors

6. Certificate of analysis of the API, reference

standards and impurity standards

Firm has submitted copy of COA of API and reference and

impurity standard.

7. Documents for the procurement of excipients

used in product development?

The firm has submitted documents for procurement of

excipients used in the formulation of applied product.

8. List of qualified staff involved in product

development with relevant experience.


department.

Production Data


development & stability testing of trial

batches.

The firm has submitted copy of product development protocols.

10. Complete batch manufacturing record of

three stability batches.

The firm has submitted copy of Batch Manufacturing Records

of all the three Batches.

11. Record of remaining quantities of stability

batches.

Firm has provided following remaining quantities for each

batch:

T#01: 69 Packs

T#02: 71 Packs

T#03: 72 Packs

QA / QC DATA

12. Record of Digital data logger for temperature

and humidity monitoring of stability

chambers (real time and accelerated)

Firm has submitted copies of data logger record for stability

chambers with real time and accelerated stability testing

13. Method used for analysis of API along with

COA.

The firm has submitted copy of Raw Material Specifications,

Raw Material Testing Procedures along with COA.

14. Method used for analysis of FPP & complete

record of testing of stability batches (i.e.

chromatograms, lab reports, raw data sheets

etc.)

The firm has submitted copy of Finished Product Testing

Procedure and specification.

15. Reports of stability studies of API from

manufacturer.

The firm has submitted stability study data of 3 batches of API

as per the conditions of Zone IV-A.


16. Analysis reports for excipients used. Firm has submitted analysis reports for all excipients used in

applied product development

17. Drug-excipients compatibility studies. Firm has submitted that stability studies are indicative of

chemical and physical compatibility with the drug product.

These studies clearly demonstrate that the excipients used for

manufacture of the dosage form are compatible with the API.

18. Record of comparative dissolution data. Firm has submitted data sheets of comparative dissolution

profile with the innovator brand in which both the reference and

test product show more than 85% release in 15 minutes at pH

1.2 and 4.5pH buffer.

19. Compliance Record of HPLC software

21CFR & audit trail reports on product

testing.





Justify the acceptance criteria of dissolution test

NLT 85% after 45 minutes since USFDA

chemistry review for the innovator product

“Trintellix Tablet” specifies that the acceptance

criteria for dissolution test is NLT (Q+5) in 30

minutes.

USFDA reference (updated on 28-5-2015) for the

acceptance criteria of dissolution test NLT Q+5 after 45

minutes is attached.

Firm has referred to the recommended sampling times

mentioned in FDA dissolution methods database in which

time point 10, 15, 20, 30 and 45 minutes is mentioned. As

per the stance of the firm since the last time point is 45

minutes that’s why they have adopted the same as

dissolution acceptance criteria.

As per the Dissolution Methods Database Frequently

Asked Questions, The "Recommended Sampling Times"

field specifies the times recommended for taking

dissolution samples for a particular drug product to

generate a dissolution profile.

Justify why similarity factor f2 is not calculated at

phosphate buffer pH 6.8 since more than 85% drug

is not released at 15 minutes time point.

Firm has now submitted f2 values which are more than 50.

Justify the difference in release behaviour of

proportionately equal strengths of the innovator

product in acetate buffer pH 4.5 and phosphate

buffer pH 6.8. The average release of 10mg

strength at acetate buffer pH 4.5 at 15 minutes time

interval is 91.9%, while the same for 20mg strength

is 76%. Similarly the release of 20mg tablet is

significantly lower at phosphate buffer pH 6.8 as

compared to 10mg strength as per the details

provided in the table below.

The difference in release behaviour of proportionately

equal strengths depends on the solubility of vortioxetine

(API) in different pH. The solubility decreases with

increase in pH of medium. Due to decrease in solubility

and saturation of drug in the medium, the %age release of

10mg tablet is higher than the 20mg tablets i.e. increasing

the drug concentration in low soluble medium will

decrease the %age of dissolved drug.

Further justify how the drug release at a later time

point i.e. 30 min or the 45 min can be less than the

drug release at earlier time point i.e. 15 min. For

example the drug release of 10mg tablet in acetate

buffer pH 4.5 at 15 min time point is 92.97% and

the drug release at 30min time point in the same

medium is 85.01%.

The drug release in question of innovator product and is on

as is basis, hence we cannot comment on the release

behaviour of innovator product. However the release

behaviour of our applied product “Xetine Tablets” does not

show such behaviour.

The exact results of comparative dissolution profile are

attached in Table 3 below. As per the results both Brintellix

as well as Xetine Tablets have the same issue as

highlighted in bold or italic in Table 3. The dissolution

testing as well as CDP is performed through UV method.

Any document for validation of the UV method is not

submitted, documents for validation of HPLC method for


assay has been submitted along with testing method of

finished product.

Table 1

Sr. No Acetate buffer pH 4.5

10mg Tablet 20mg Tablet

15 min 30 min 45 min 15 min 30 min 45 min

1 94.34 92.46 91.69 76.38 73.51 82.14

2 86.81 92.46 91.43 75.42 77.66 85.33

3 92.97 85.01 86.81 74.47 82.14 85.97

4 94.26 87.84 93.49 75.10 86.29 85.65

5 91.69 88.86 90.66 76.70 75.42 83.73

6 88.35 91.43 92.46 77.98 76.06 82.46

Avg 91.90 89.68 91.09 76.00 78.51 84.21

Table 2

Sr. No Phosphate buffer pH 6.8



1 68.06 68.87 77.79 27.42 27.07 45.92

2 64.28 73.73 83.46 25.70 32.21 45.24

3 67.25 72.92 76.98 33.24 34.61 50.72

4 66.98 72.65 82.11 32.21 30.16 40.44

5 63.74 79.41 78.06 27.42 38.38 41.13

6 69.95 82.92 74.00 31.53 29.82 45.58

Avg 66.71 75.08 78.73 29.58 32.04 44.58

Table 3

Sr. No 0.1N HCl

15 min (%) 30 min (%) 45 min(%)

Brintellix Xetine Brintellix Xetine Brintellix Xetine

1 98.67 96.73 99.15 96.73 99.40 96.98

2 98.91 96.25 98.67 96.01 99.15 97.46

3 98.19 95.77 99.64 96.49 98.43 96.01

4 98.91 95.53 98.67 97.46 99.64 98.19

5 97.94 96.25 99.40 96.73 98.67 96.73

6 99.64 97.22 98.43 96.25 99.15 97.46

Avg 98.71 96.29 98.99 96.61 99.07 97.14


15 min (%) 30 min (%) 45 min(%)


1 97.34 89.63 92.46 88.86 91.69 88.35

2 86.81 87.07 92.46 87.84 91.43 89.38

3 92.97 85.01 85.01 89.38 86.81 88.09

4 94.26 87.07 87.84 87.58 93.49 89.12

5 91.69 89.38 88.86 88.61 90.66 88.86

6 88.35 88.61 91.43 89.38 92.46 88.61

Avg 91.90 87.80 89.68 88.61 91.09 88.74


15 min (%) 30 min (%) 45 min(%)


1 68.06 65.09 68.87 74.27 77.79 75.63

2 64.28 64.28 73.73 73.46 83.46 76.71

3 67.25 65.36 72.92 72.65 76.98 77.25

4 66.98 63.20 72.65 73.73 82.11 76.44


5 63.74 64.28 79.41 73.19 78.06 75.36

6 69.95 64.55 82.92 74.0 74.0 76.98

Avg 66.71 64.46 75.08 73.55 78.73 76.40

Decision of 293rd meeting of Registration Board:

Registration Board decided to consider the case after onsite inspection for verification of authenticity of submitted

data for comparative dissolution profile due to reason recorded above.

Sr.

No.

Name & Address of

Manufacturer /

Applicant

Brand Name

(Proprietary Name +


Composition,


Finished Product

Specification

Type of Form,


Fee (including

differential fee),


size


Local Availability


106. Werrick

Pharmaceuticals,

Plot # 216-217, I-

10/3, Industrial Area

Islamabad.

Xetine 20mg Tablet


contains:

Vortioxetine as

hydrobromide…..20mg

Antidepressant

Form 5

Dy No. 41746

07-12-2018

PKR 20,000/-

07-12-2018

TRINTELLIX Tablets

(USFDA Approved)

GMP compliant dated

07/12/17―Good compliance

to GMP


Drug Xetine 20mg Tablet

Name of Manufacturer M/s Werrick Pharmaceuticals, Plot # 216-217, I-10/3, Industrial Area Islamabad.

Manufacturer of API Lianyungang Jari Pharmaceutical Co. Ltd. # 18, Zhenhua Road, Lianyunguang,

Jiangsu Province China.


Description of Pack


Blistered in Alu-PVC packed in card box unit carton of 14’s tablets


Real Time: 30°C ± 2°C/65%±5% RH

Time Period Accelerated: 6 (months)

Real Time: 6 (months)

Frequency Accelerated: 0, 3 ,6 (Months)

Real Time : 0, 3 ,6 ,9, 12, 18 (Months)

Batch No. T#01 T#02 T#03




No. of Batches 03




COA of API. Yes




country of origin.







Yes



chromatograms, laboratory reports, data sheets

etc.

Yes


5-2018 specifying import of 0.5Kg vortioxetine

hydrobromide attested by AD DRAP, Islamabad.



data / documents.

Yes



Yes


Rules, 1978.

Yes


The firm has requested for Exemption from On-site Investigation of their submitted stability data and provided

the following documents in conjunction with the checklist approved by the Registration Board in its 278th

Meeting:


1. Reference of last onsite panel inspection for

instant dosage form conducted during last

two years.

Registration Board approved Cell-Tab (Sofosbuvir

400mg) Tablets in its 276th Meeting.

Dates of Inspection:

o Initial (M-256):

10th December 2015 (Afternoon).

o Subsequent (M-269):

19th April, 2017 (Forenoon).

o Last Inspection (M-276):

20th November, 2017.

Following points related to HPLC Software and Audit Trail

were reported

Software of HPLC present in the firm is 21CFR compliant

and audit trail on the testing reports was available and

confirmed. Panel reviewed chromatograms for testing of

API and trial batches at 0, 3 and 6 months for real time and

accelerated stability testing.



Firm has submitted copy of commercial invoice dated 15-5-



3. Documents for the procurement of reference

standard and impurity standards.

The firm has submitted letter that the reference standard were

provided along with API and therefore separate invoice is not

available.




Firm has submitted copy of GMP certificate No. JS20140353

issued by China Food and Drug Administration which is valid

till 19-11-2019.

5. Mechanism for Vendor pre-qualification Firm has submitted work instructions for evaluation of

suppliers and vendors

6. Certificate of analysis of the API, reference

standards and impurity standards

Firm has submitted copy of COA of API and reference and

impurity standard.


7. Documents for the procurement of excipients

used in product development?

The firm has submitted documents for procurement of

excipients used in the formulation of applied product.

8. List of qualified staff involved in product

development with relevant experience.

The firm has submitted List of qualified staff involved in

R&D department.

Production Data



batches.

The firm has submitted copy of product development

protocols.



The firm has submitted copy of Batch Manufacturing

Records of all the three Batches.

11. Record of remaining quantities of stability

batches.

Firm has provided following remaining quantities for each

batch:

T#01: 69 Packs

T#02: 71 Packs

T#03: 72 Packs

QA / QC DATA

12. Record of Digital data logger for temperature

and humidity monitoring of stability

chambers (real time and accelerated)

Firm has submitted copies of data logger record for stability

chambers with real time and accelerated stability testing

Method used for analysis of API along with

COA.

The firm has submitted copy of Raw Material Specifications,

Raw Material Testing Procedures along with COA.

13. Method used for analysis of FPP & complete

record of testing of stability batches (i.e.

chromatograms, lab reports, raw data sheets

etc.)

The firm has submitted copy of Finished Product Testing

Procedure and specification.


manufacturer.

The firm has submitted stability study data of 3 batches of

API as per the conditions of Zone IV-A.

15. Analysis reports for excipients used. Firm has submitted analysis reports for all excipients used in

applied product development

16. Drug-excipients compatibility studies. Firm has submitted that stability studies are indicative of

chemical and physical compatibility with the drug product.

These studies clearly demonstrate that the excipients used for

the manufacture of the dosage form are compatible with the

API.

17. Record of comparative dissolution data. Firm has submitted data sheets of comparative dissolution

profile with the innovator brand



testing.





Justify the acceptance criteria of dissolution test

NLT 85% after 45 minutes since USFDA

chemistry review for the innovator product

“Trintellix Tablet” specifies that the acceptance

criteria for dissolution test is NLT (Q+5) in 30

minutes.

USFDA reference (updated on 28-5-2015) for the

acceptance criteria of dissolution test NLT Q+5 after 45

minutes is attached.

Firm has referred to the recommended sampling times

mentioned in FDA dissolution methods database in which

time point 10, 15, 20, 30 and 45 minutes is mentioned. As

per the stance of the firm since the last time point is 45

minutes that’s why they have adopted the same as

dissolution acceptance criteria.


As per the Dissolution Methods Database Frequently

Asked Questions, The "Recommended Sampling Times"

field specifies the times recommended for taking

dissolution samples for a particular drug product to

generate a dissolution profile.

Justify why similarity factor f2 is not calculated at

phosphate buffer pH 6.8 since more than 85% drug

is not released at 15 minutes time point.

Firm has now submitted f2 values which are more than 50.

Justify the difference in release behaviour of

proportionately equal strengths of the innovator

product in acetate buffer pH 4.5 and phosphate

buffer pH 6.8. The average release of 10mg

strength at acetate buffer pH 4.5 at 15 minutes time

interval is 91.9%, while the same for 20mg

strength is 76%. Similarly the release of 20mg

tablet is significantly lower at phosphate buffer pH

6.8 as compared to 10mg strength as per the details

provided in the table below.

The difference in release behaviour of proportionately

equal strengths depends on the solubility of vortioxetine

(API) in different pH. The solubility decreases with

increase in pH of medium. Due to decrease in solubility

and saturation of drug in the medium, the %age release of

10mg tablet is higher than the 20mg tablets i.e. increasing

the drug concentration in low soluble medium will

decrease the %age of dissolved drug.

Further justify how the drug release at a later time

point i.e. 30 min or the 45 min can be less than the

drug release at earlier time point i.e. 15 min. For

example the drug release of 10mg tablet at acetate

buffer pH 4.5 at 15 min time point is 92.97% and

the drug release at 30min time point at the same

medium is 85.01%.

The drug release in question of innovator product and is

on as is basis, hence we cannot comment on the release

behaviour of innovator product. However the release

behaviour of our applied product “Xetine Tablets” does

not show such behaviour.

The exact results of comparative dissolution profile are

attached in Table 3 below. As per the results both

Brintellix as well as Xetine Tablets have the same issue as

highlighted in bold or italic in Table 3. The dissolution

testing as well as CDP is performed through UV method.

Any document for validation of the UV method is not

submitted, documents for validation of HPLC method for

assay has been submitted along with testing method of

finished product.

Table 1




1 94.34 92.46 91.69 76.38 73.51 82.14

2 86.81 92.46 91.43 75.42 77.66 85.33

3 92.97 85.01 86.81 74.47 82.14 85.97

4 94.26 87.84 93.49 75.10 86.29 85.65

5 91.69 88.86 90.66 76.70 75.42 83.73

6 88.35 91.43 92.46 77.98 76.06 82.46

Avg 91.90 89.68 91.09 76.00 78.51 84.21

Table 2




1 68.06 68.87 77.79 27.42 27.07 45.92

2 64.28 73.73 83.46 25.70 32.21 45.24

3 67.25 72.92 76.98 33.24 34.61 50.72

4 66.98 72.65 82.11 32.21 30.16 40.44

5 63.74 79.41 78.06 27.42 38.38 41.13

6 69.95 82.92 74.00 31.53 29.82 45.58

Avg 66.71 75.08 78.73 29.58 32.04 44.58


Table 3

Sr. No 0.1N HCl

15 min (%) 30 min (%) 45 min(%)


1 97.24 96.01 96.32 96.32 101.24 98.16

2 105.55 95.09 99.40 97.24 100.32 96.63

3 103.70 95.70 102.16 96.63 100.63 95.70

4 94.47 96.32 102.47 99.09 103.40 97.86

5 96.32 97.86 104.01 99.40 102.78 100.01

6 95.39 98.16 97.86 95.09 103.40 99.70

Avg 98.77 96.52 100.38 97.29 101.96 98.01


15 min (%) 30 min (%) 45 min(%)


1 76.38 75.74 73.51 74.47 82.14 79.90

2 75.42 72.55 77.66 76.38 85.33 81.18

3 74.47 70.63 82.14 77.02 85.97 82.78

4 75.10 74.47 86.29 77.34 85.65 84.37

5 76.70 73.83 75.42 80.86 83.73 83.73

6 77.98 77.66 76.06 76.06 82.46 82.14

Avg 76.00 74.14 78.51 77.02 84.21 82.35


15 min (%) 30 min (%) 45 min(%)


1 27.42 33.24 27.07 31.82 45.92 43.53

2 25.70 25.70 32.21 28.79 45.24 42.15

3 33.24 24.67 34.61 26.73 50.72 45.92

4 32.21 27.07 30.16 29.13 40.44 38.04

5 27.42 26.04 38.38 30.50 41.13 39.09

6 31.53 26.73 29.82 25.36 45.58 36.67

Avg 29.58 27.24 32.04 28.63 44.58 40.89


Registration Board decided to consider the case after onsite inspection for verification of authenticity of submitted

data for comparative dissolution profile due to reason recorded above

Report on investigation of authenticity / genuineness of CDP data submitted for registration of Xetine

Tablets 10 & 20mg by M/s Werrick Pharmaceuticals, Plot # 216-217, I-10/3, Industrial Area Islamabad.


Investigation Date & Time: 3rd March, 2020

Investigation Site: Factory premises of Werrick Pharmaceuticals, Plot # 216-217, I-10/3, Industrial

Area Islamabad.

Background: Registration Board in its 293rd meeting considered the case of Xetine (Vortioxetine) Tablet 10mg & 20mg

of M/s Werrick Pharmaceuticals, Plot # 216-217, I-10/3, Industrial Area Islamabad. Registration Board decided

to consider the case after onsite inspection for verification of authenticity of submitted data for comparative

dissolution profile due to the reasons mentioned in the minutes. Chairman Registration Board has constituted the

following panel for the purpose.



2. Mr. Hanif Ullah, Assistant Director PEC, PE&R Division DRAP, Islamabad.



Investigation of the authenticity / genuineness of submitted data for comparative dissolution profile due to the

reasons mentioned in the minutes.

The observations made by Registration Board for Xetine 10mg & 20mg Tablet were

Justify the difference in release behaviour of proportionately equal strengths of the innovator product in

acetate buffer pH 4.5 and phosphate buffer pH 6.8. The average release of 10mg strength at acetate buffer

pH 4.5 at 15 minutes time interval is 91.9%, while the same for 20mg strength is 76%. Similarly the

release of 20mg tablet is significantly lower at phosphate buffer pH 6.8 as compared to 10mg strength as

per the details provided in the table-1 &2 below.

Table 1




1 94.34 92.46 91.69 76.38 73.51 82.14

2 86.81 92.46 91.43 75.42 77.66 85.33

3 92.97 85.01 86.81 74.47 82.14 85.97

4 94.26 87.84 93.49 75.10 86.29 85.65

5 91.69 88.86 90.66 76.70 75.42 83.73

6 88.35 91.43 92.46 77.98 76.06 82.46

Avg 91.90 89.68 91.09 76.00 78.51 84.21

Table 2




1 68.06 68.87 77.79 27.42 27.07 45.92

2 64.28 73.73 83.46 25.70 32.21 45.24

3 67.25 72.92 76.98 33.24 34.61 50.72

4 66.98 72.65 82.11 32.21 30.16 40.44

5 63.74 79.41 78.06 27.42 38.38 41.13

6 69.95 82.92 74.00 31.53 29.82 45.58

Avg 66.71 75.08 78.73 29.58 32.04 44.58

Further justify how the drug release at a later time point i.e. 30 min or the 45 min can be less than the

drug release at earlier time point i.e. 15 min. For example the drug release of 10mg tablet at acetate buffer

pH 4.5 at 15 min time point is 92.97% and the drug release at 30min time point at the same medium is

85.01%. (Table 3)

Table 3

Sr. No 0.1N HCl

15 min (%) 30 min (%) 45 min(%)


1 98.67 96.73 99.15 96.73 99.40 96.98

2 98.91 96.25 98.67 96.01 99.15 97.46

3 98.19 95.77 99.64 96.49 98.43 96.01

4 98.91 95.53 98.67 97.46 99.64 98.19

5 97.94 96.25 99.40 96.73 98.67 96.73

6 99.64 97.22 98.43 96.25 99.15 97.46

Avg 98.71 96.29 98.99 96.61 99.07 97.14


15 min (%) 30 min (%) 45 min(%)


1 97.34 89.63 92.46 88.86 91.69 88.35

2 86.81 87.07 92.46 87.84 91.43 89.38

3 92.97 85.01 85.01 89.38 86.81 88.09

4 94.26 87.07 87.84 87.58 93.49 89.12


5 91.69 89.38 88.86 88.61 90.66 88.86

6 88.35 88.61 91.43 89.38 92.46 88.61

Avg 91.90 87.80 89.68 88.61 91.09 88.74


15 min (%) 30 min (%) 45 min(%)


1 68.06 65.09 68.87 74.27 77.79 75.63

2 64.28 64.28 73.73 73.46 83.46 76.71

3 67.25 65.36 72.92 72.65 76.98 77.25

4 66.98 63.20 72.65 73.73 82.11 76.44

5 63.74 64.28 79.41 73.19 78.06 75.36

6 69.95 64.55 82.92 74.0 74.0 76.98

Avg 66.71 64.46 75.08 73.55 78.73 76.40

Detail of investigation for Xetine Tablets 10mg & 20mg:

Based on the records available with the firm and after detailed discussion with the qualified person and the analyst

who performed comparative dissolution profile testing, the panel observed the following important points:

1. Authenticity of the performance of comparative dissolution profile was confirmed through log book of

the dissolution apparatus, availability of the innovator pack against which the testing was performed.

However, relevant entries in UV spectrophotometer log book were not found. The firm informed that

during product development and stability studies, they usually maintain a single log book for dissolution

apparatus. However the panel advised the firm to maintain separate log book for UV along with

dissolution apparatus. The firm agreed to the advice of panel and shown firm commitment to maintain

separate log book for UV apparatus.

2. The deviation observed in trends of comparative dissolution profile was also noted by the firm during

stability studies and reported the exact results.

3. Previously, the firm performed comparative dissolution profile using UV analytical method. After the

observations raised by the Registration Board, the firm validated their UV analytical method on 19

February, 2020. In addition, the firm also developed HPLC method and performed comparative

dissolution profile using HPLC method, which did not show those deviations as observed with UV

spectrophotometric method.

The above observations of the panel are forwarded for consideration by the Registration Board.

Decision: Registration Board decided to approve registration of Xetine Tablets 10mg and Xetine

Tablets 20mg with innovator’s specification. Manufacturer shall place first three production

batches on long term stability studies throughout proposed shelf life and on accelerated studies

for six months. The Board further decided that the firm shall use HPLC method for dissolution

testing of their production batches.


Item No. 5: Agenda of Evaluator PEC-IV.

Case no. 01 Registration applications of drugs for which stability study data is submitted

Sr.

No.

Name & Address

of Manufacturer

/ Applicant

Brand Name

(Proprietary Name + Dosage Form +

Strength), Composition,



Type of Form,

Initial Diary & Date, Fee

(including differential

fee),


size

International


Availability


Date & Remarks

107. Neutro pharma

(Pvt.) Ltd. 9.5

km Sheikhupura

Road

Lahore

Nupreced Injection

Each 2ml contains:-

Dexmedetomidine

Hydrochloride…………….200mcg

(Sedative)

e alpha2-adrenergic agonist

Manufacturer specifications

Form 5-D

Dy.No.17-05-13

Fee Rs.60,000/-+

Rs.90,000 (28-05-13)

2ml

Rs.5500/-per

ampoule

Precedex of USFDA

approved


Previous Decision (M-239):

Deferred for confirmation of availability of formulation in FDA, EMA,Australia and Japan (M-239)

Previous Decision (M-241): The request of firm was deferred for opinion of following experts.

Head. Department of ICU, MH, Rawalpindi.

Head. Department of Anesthesia, PIMS, Islamabad.

Brig. Dr.Muhammad Aslam khan

Previous Decision (M-249): The firm has the submitted that the third expert nominated by the Board is Head of

Department of ICU,Rawalpindi , is also Brig. Dr. Muhammad Aslam Khan who has already provided expert

opinion and both the experts has commented as under:-

Name of expert. Comments

Prof. M. Iqbal Memon

1. Said drug is already in practice worldwide and few centers in

Pakistan.

2. On page 14 there is typographical mistake showing that said

firm not checked before submission on serial No. 1. It is not

Lidocaine but Dexmedatomidine HCl as active ingredient.

Calculation from gram to microgram may be revisited

according to their statement of manufacturing step (25L to 206

litres).

3. Said firm has not mentioned about the country of import for

raw material and how quality of that material will be

maintained during transport to Pakistan.

4. Are they going to check the efficacy drug in animal lab?

Brig. Dr.Muhammad

Aslam khan

Dexmedetomidine is a highly selective, centrally acting alpha-

2-agonist with anxiolytic, sedative, and some analgesic effects. It has

no deleterious effects on respiratory drive. According to the approved

product information from the United States Food and Drug

Administration (FDA), dexmedetomidine is indicated for initial

sedation of mechanically ventilated patients for up to 24 hours.

Its indications include sedation of initially-intubated and

medicinally-ventilated patients during treatment in an intensive care

setting. Procedural sedation prior to and/ or during awake fiber optic

intubation; sedation prior to and/ or during surgical or other

procedures of nonintubated patients.

Dexmedetomidine may be less likely to cause delirium, than

sedative agents in the ICU. It will be a useful addition in the


armamentarium of the intensivist unit and anesthetists.

In view of the above I recommend this drug for registration at

an affordable price

Registration Board discussed and agreed to above expert opinions.

However, the Board advised firm to submit laboratory scale scientifically rational stability

data for above registration application. (M-249)


Drug Nupreced Injection

Name of Manufacturer Neutro pharma (Pvt.) Ltd. 9.5 km Sheikhupura Road

Lahore

Manufacturer of API Cisen pharmaceuticals Co Ltd, China

API Lot No. 170802

Description of Pack


USP Type I glass Ampoule

Stability Storage Condition Real time : 30°C ± 2°C / 75% ± 5% RH

Accelerated: 40°C ± 2°C / 75% ± 5% RH


Frequency Accelerated: 0, 1, 2 , 3, 4 ,6 (month) Real Time: 0,3 ,6, 9 (month)

Batch No. 001 002 003

Batch Size 2 Liter 2 Liter 2 Liter


Date of Initiation 23-02- 2018 02-03- 2018 02-03- 2018

No. of Batches 3



Sr. Documents To Be Provided Status

1. COA of API Copy of COA by Cisen pharmaceuticals Co Ltd,

China is submitted.




Copy of GMP Certificate No. SD20130130 by

China Food and Drug Adminstration valid till 04-

11-2018


details of tests.

Yes




Yes

5. Documents confirming import of API etc.


stamp) for ensuring authenticity of data / documents.

Yes


assigned shelf life of the product.

Yes




S.NO Shortcomings Reply Evaluation

1) Valid GMP of API source is still not

submitted.

We have already submitted GMP

certificate. This certificate is valid

when we have submitted

application, now the said company

is merge in another company so we

are unable to submit new GMP

certificate because they refused to

give us also refused to give any

merging letter

Issue date 05-11-2013

Valid date 04-11-2018

Cisen pharmaceuticals

Co Ltd, China

2) You have claimed that you have

imported API via FedEx and did not

get Assistant Director (I & E) DRAP

attestation of imported API, while

Reference standard has been imported

& Assistant Director (I & E) DRAP

attested invoice has been submitted.

Justify and clarify.

We have import API through

FedEx in Nov. 2017 while

reference standard received in

December 2018 and get its

approval which unfortunately

attached, we have used working

standard prepared by analysis

through non aqua titration method

given by API manufacturer, which

is attached for as a reference.

On Website that tracking

No, can not be found.

3) As per submitted Assistant Director (I

& E) DRAP attested Commercial

invoices, the reference standard have

been imported in December 2018,

while the submitted record shows the

manufacturing of trial batches in

February & march , 2018. Justification

shall be submitted in this regard.

4) In previous stability sheets Batch No#

004 , Batch No# 005, Batch No# 006

mentioned and in reply in stability

sheets Batch No# 001, Batch No# 002

and Batch No# 003 mentioned. Please

clarify.

The Actual batches were 001, 002,

and 003 but by mistake batch no

04, 05 and o6 were written in the

previous data so, we have rectified

that in the submitted data.

In raw data sheets

batches were 001, 002,

and 003 while previously

certificate of analysis

mentioned batch no 004,

005 and 006.

Decision: Deferred for submission of submission of valid GMP certificate of API manufacturer issued by


Sr.

No.

Name & Address of

Manufacturer /

Applicant

Brand Name

(Proprietary Name +


Composition,


Finished Product

Specification

Type of Form,

Initial Diary &

Date, Fee

(including

differential fee),

Demanded Price

/ Pack size


/ Local Availability


Date & Remarks

108. M/s. Vision

Pharmaceuticals , Plot #

22-23, Industrial

Triangle, Kahuta road,

Islamabad

K-Fast 50mg Sachet

Each Sachet contains:-

Diclofenac Potassium

………..50mg

NSAID

Manufacturer’s specification

Dy.No.2695;

21-01-2019;

Rs.50,000/-

21-01-2019

30’s

As per SRO

CAMBIA

(USFDA) approved

Last inspection conducted

on 26-01-2018 and report

concludes that firm was

operating at Good level of

GMP compliance.


Drug K-Fast 50mg Sachet

Name of Manufacturer M/s. Vision Pharmaceuticals , Plot # 22-23, Industrial Triangle, Kahuta

road, Islamabad


Manufacturer of API Huixian Dongpu Chemicals co Ltd , China


Description of Pack


Paper coated aluminium sachet





Frequency Accelerated: 0, 3,6 (month)

Real Time: 0,1,2 3,4,5,6 (month)

Batch No. NPD801(T-01) NPD801(T-02) NPD801(T-03)




No. of Batches 3




1. COA of API Copy of COA Shanghai Pharma group Changzhou kony

Pharmaceuticals co., Ltd is submitted




country of origin.

Copy of GMP Certificate No.HN20160178 issued by

Cfda is attached but could not verified from CFDA

database



Yes




sheets etc.

Yes

5. Documents confirming import of API etc. Copy of Assistant Director (I & E) DRAP (Karachi)

attested dated: 21-06-2018 Commercial Invoice No

WIS180048 Dated:05-06-2018 is submitted.




Yes



Yes


Rules, 1978.

Yes


Certificate No on GMP certificate in China FDA database is for another manufacturer

GMP certificate of API manufacturer issued by regulatory authority of country of origin could not be

confirmed from China FDA database.


Initially firm submitted stability data containing API Diclofenac Potassium from Huixian Dongpu Chemicals co

Ltd , China. GMP of Huixian Dongpu Chemicals co Ltd, China can not be verified from CFDA database.

Thereafter, the firm submitted new stability data with API source i.e Henan Dongtai Pharma co Ltd , China.

NEW STABILITY DATA SUBMITTED BY THE FIRM

Drug K-Fast 50mg Sachet

Name of Manufacturer M/s. Vision Pharmaceuticals , Plot # 22-23, Industrial Triangle, Kahuta road,

Islamabad

Manufacturer of API Henan Dongtai Pharma co Ltd , China

API Lot No. 303161222-6

Description of Pack

(Container closure system) Paper coated aluminium sachet




Frequency Accelerated: 0, 3,6 (month) Real Time: 0,1,2 3,4,5,6 (month)

Batch No. NPD801 A (T-01) NPD801 A (T-02) NPD801 A (T-03)




No. of Batches 3




1. COA of API Copy of COA Henan Dongtai Pharma co Ltd ,

China is submitted




Copy of GMP Certificate No.HA20170001 issued

by CFDA is attached. Valid till 22-01-2022


and details of tests.

Yes




Yes

5. Documents confirming import of API etc. Copy of Assistant Director (I & E) DRAP

(islamabad) attested dated: 09-01-2017 Commercial

Invoice No DT1612132Y Dated: 11-01-2017 is

submitted.



documents.

Yes



Yes


1978.

Yes



The panel may be requested to verify and report about following point in addition to authenticity of

stability data and associated documents,

Whether stability studies from both API sources performed. Initially firm submitted stability data containing

API Diclofenac Potassium from Huixian Dongpu Chemicals co Ltd , China. GMP of Huixian Dongpu Chemicals

co Ltd , China can not be verified from CFDA database. Thereafter, the firm submitted new stability data with

API source i.e Henan Dongtai Pharma co Ltd , China .

Report on Inspection for verification of Authenticity/Genuineness of data submitted by M/s. Vision

Pharmaceuticals (Pvt.) Ltd., Plot No. 22-23, Industrial Estate Triangle, Kahuta Road, Model Town,

Islamabad for registration of K-fast 50mg (Diclofenac potassium) sachet

Inspection Date and Time: 17, 18 and 19 December, 2019

Inspection Site: M/s. Vision Pharmaceuticals (Pvt.) Ltd., Plot No. 22-23 Industrial Estate Triangle, Kahuta

Road, Model Town, Islamabad.

Background:

M/s. Vision Pharmaceuticals (Pvt.) Ltd., Plot No. 22-23, Industrial Estate Triangle, Kahuta Road, Model Town,

Islamabad applied for registration of K-fast 50mg (Diclofenac potassium) sachet with following composition:

K-fast sachet 50mg

Each sachet contains:-

Diclofenac potassium…………50mg

Chairman Registration Board constituted a three member panel for on-site investigation to confirm the

genuineness/authenticity of submitted stability data and associated documents, import of API, quality,

specification, test analysis, facilities etc. Panel was requested to conduct inspection of the firm to verify the data

submitted by the firm and to submit a report on approved format for further consideration of case by the

Registration Board. The Chairman Registration Board further advised the panel to verify and report about

following point:

Initially, the firm has submitted stability studies data containing API Diclofenac potassium imported from Huixian

Dongpu Chemicals Co. Ltd, China. GMP of Huixian Dongpu Chemicals Co. Ltd, China cannot be verified from

the official database of SFDA. Thereafter, the firm submitted new stability data with new API source Henan

Dongtai Pharma Co. Ltd., China.

The Panel was requested to confirm whether the firm has conducted stability studies with each API from

two different sources. It was clarified during audit that the firm conducted stability studies with API

imported from M/s Henan Dongtai Pharm Co. Ltd., East Changhong Tangyin Henan, China only. The

firm did not continue the studies with API imported from source M/s Huixian Dongpu Chemicals Co. Ltd,

China and submitted the destruction record (Report no. 1725/NCR dated 22 March, 2019) of stability

batches manufactured from this earlier source.


1. Dr. Qurban Ali, (Member Registration Board).

2. Mr. Babar Khan, Area FID, DRAP, Islamabad.

3. Mr. Hanifullah, Assistant Director (PEC) DRAP, Islambad.

Scope of Inspection:

On-site investigation to confirm the genuineness/authenticity of submitted stability data and associated documents

like import of API, quality specification and test analysis facilities etc.

Tools for Inspection:

The Inspection was conducted by using a structured questionnaire approved by DRAP. For objective evidence

physical inspection of the facilities for manufacturing and quality control, material used and retained, personnel

involved, ongoing studies, printed data integrity and security of data in respective databases were also audited.

The detail of inspection is summarized as under:

(Some of the observations have been highlighted as bold with bullet point against the respective question).


Q.

No.

Question Observation by panel

1. Do you have documents

confirming the import of

API including approval

from DRAP?

DICLOFENAC POTASSIUM

Invoice Number: DT1612132Y

Assistant Director (I & E) DRAP attestation date: 09.02.17

Exporter: M/s Henan Dongtai Pharm CO LTD, EAST CHANGHONG

TANGYIN HENAN, CHINA

Manufacturer: as above

Batch No. 303161222-6

Mfg. Date: 22-12-2016

Exp. Date: 21-12-2020

Quantity: 300Kg

2. What was the rationale

behind selecting the

particular manufacturer of

API?

The firms provide the rational that

1. Since Diclofenac Potassium is already being used at VISION

PHARMACEUTICALS PVT. LTD. in the product Diclofenac Potassium

32% pellets since quite long, therefore, based on the track record of HENAN

DONGTAI PHARM CO. LTD. the API source is validated and use of same

source is preferred rather than going for an unknown source.

2. The documents of source, HENAN DONGTAI PHARM CO. LTD.,

are more authentic.

The firm has submitted a document comparing the parameters

between two sources namely M/s Henan Dongtai Pharm Co. Ltd. China and

M/s Huxian Doungpu Chemicals Co. Ltd. China. The document shows the

concluding remarks that M/s Henan Dongtai Pharm Co. Ltd. China will be

the preferred source with date of 28th August, 2018. While the firm mentioned

the manufacturing date of 10th August 2018, 11th August 2018 and 14th August

2018 in the stability studies for the batch # NPD801 (T-01), NPD801 (T-02)

and NPD801 (T-03) respectively. This means that the source was qualified

after the API has been used in the manufacturing of Finished product batches.



Diclofenac potassium

reference standard and

impurity standards?

The firm imported following reference standard and impurity standard:

Diclofenac potassium primary reference standard from the USP (Lot

No. R034L0)

o Order placing date: 08 June, 2018

o Shipment date:11.06.2018

o Commercial Invoice no. 31068571(Dated 11 June, 2018)

o AD attestation date 11.07.2018

Firm has also imported impurity (Diclofenac related compound A

USP RS) for identification/quantification of specified impurities from

Pharmaffiliates:

o Invoice no. EXP/2019-20/121 dated 21.06.2019

o Lot no. PA/ACE/01109

o AD attestation date 11.07.2018

4. Do you have certificate of

Analysis of the API,

reference standards and

impurity standards?

The firm has submitted COAs of API, reference standards and impurity

standards as per details below:

Diclofenac potassium API from Henan Dongtai Pharm CO.LTD

(for Batch No.303161222-6)

Diclofenac potassium primary reference standard USP (Lot No.

R034L0)

Diclofenac potassium Impurity A RS USP from Pharmaffiliates (Lot

no. PA/ACE/01109).

5. Do you have GMP

certificate of API

manufacturer issued by

The firm has submitted copy of GMP certificate No:HA20170001 in the name

of Manufacturer that is “M/s Henan Dongtai Pharm Co. Ltd, East Changhong

Road, Tangyin County, Anyang City, China” for API Diclofenac Potassium

USP issued by HeNan Province Food and Drug Administration.


regulatory authority of

country of origin?

Issuing date: 23-01-2017

Valid till: 22-01-2022

The name of city “Anyang” is mentioned on GMP while it is not

mentioned on COA.

6. Do you use API

manufacturer method of

testing for testing API?

The firm stated that they have used pharmacopoeial (USP) method for testing

of API as per statement of API source.

7. Do you have stability

studies reports on API?

Firm has submitted data of long term stability studies of three batches 131118-

5 (Mfg: 18th Nov, 2013), 131118-6 (Mfg: 18th Nov, 2013) & 131119-5 (Mfg:

18th Nov, 2013) conducted by the API manufacturer M/s Henan Dongtai

Pharm Co Ltd, East Changhong Tangyin Henan, China, under conditions of

Zone-IV A that is 30 Co + 2 Co & 65 % RH + 5 % (for real time studies) up

to 48 months and 40 Co + 2 Co & 75 % RH + 5 % (for accelerated studies) up

to 6 months for API namely Diclofenac potassium. The data submitted by the

API manufacturer lies within the limits for the Assay & related impurities.

Parameter like pH, viscosity etc. have not been tested by API

manufacture in its studies for stability.

Typo-mistake in limit of impurity A has been noticed that is “NMT

0.15 %” has been mentioned instead of “NMT 0.1 %” in stability studies of

batch no. 131119-6 in real time studies.

8. If yes, whether the stability

testing has been performed

as per SIM method and

degradation products have

been quantified?

Since the manufacturer has conducted the stability studies using USP

compendia in which they have quantified the impurities as per

pharmacopoeia, which gives sense that the studies have been conducted as per

SIM method.

9. Do you have method for

quantifying the impurities

in the API?

Yes, they have used USP method for quantifying the impurities in the API.

10. Do you have some

remaining quantities of the

API, its reference standard

and impurities standards?

Yes, they have remaining quantities of the API, reference standard and

impurities standards as per details given in the following table which have

been verified by the panel during the visit:

Raw Material Lot No. Place of

Consumption

Quantity

Diclofenac

Potassium

303161222-6 NPD801(T-01) 50 gram

NPD801(T-02) 50 gram

NPD801(T-03) 50 gram

Total Quantity 300kg

Quantity

Consumed

150grams

Remaining

Quantity

299.85kg (Rest used in commercial

manufacturing)

Item Type Lot No. Total Quantity Remaining

Quantity

Diclofenac

Potassium

Reference

Standard

R034LO 200mg 125mg

Item Type Lot No. Total Quantity Remaining

Quantity

Diclofenac

Potassium

Related

Compound A

PA/ACE/01109 25mg 10mg


11. Have you used

pharmaceutical grade

excipients?

The firm has used following excipients of pharmaceutical grade except flavors

Anise and Mint:

S. No. Excipients Pharma grade

1 Sucralose BP

2 Mannitol BP/USP/EP

3 Aspartame BP

4 Potassium Hydrogen

Carbonate

BP

5 Anise Flavour Manufacturer’s Specification

6 Mint Flavour Manufacturer’s Specification

The firm has used flavors Anise and Mint which were of

manufacturer’s specifications.




The firm has imported only one excipient MANNITOL for the applied

formulation through exporter M/s HANGZHOU STARSHINE

PHARMACEUTICAL CO LTD (Room B2, 10F, Tianyuan Building, No.508

Wensan Road, Hangzhou, China) from the manufacturer M/s SHANDONG

TIANLI PHARMACEUTICAL CO LTD (South of Anshun Street and West

of Xingyuanxi Road, Gucheng subdistrict office, Shouguang, Shandong,

China) with Batch No. 301802314, manufacturing date:15th Feb, 2018 Expiry

Date: 14th Feb, 2020.

The firm acquired following other raw material excipients from local suppliers

as per details below:

The firm procured the excipient from local supplies. The firm has

developed an SOP for vendor qualification but above listed suppliers are not

included in the approved list of vendor suppliers.

S.No. Excipient Supplier Batch No.

1. Sucralose Global

Laboratories

A17071614

2. Aspartame National

Trading

W 16121510

3. Potassium

Hydrogen

Carbonate

Carbonate

Musaji

Adam &

Sons

PO201PD1

4. Anise Hamza

Traders

24151

5.. Mint Hamza

Traders

24152

13. Do you have test reports

and other records on the

excipients used?

The firm has performed tests on the excipients as per details below:

S. No. Excipients Report No. Release Date

1 Sucralose 0916/RM/17 15.12.2017

2 Mannitol 0414/RM/18 30.05.2018

3 Aspartame 0264/RM/17 10.04.2017

4 Potassium Hydrogen

Carbonate

0417/RM/18 31.05.2018

5 Anise Flavour 0409/RM/18 29.05.2018

6 Mint Flavour 0410/RM/18 29.05.2018

The firm did not acquire COAs of above excipient before purchase or

during vendor qualifications. However, the firm provided COA of all

excipients during audit.

The QC report for Sucralose have no signature of QA Manager for

release of excipient.

Some tests done by source like tests for microorganism for Sucralose

(artificial sweetner) but not performed by firm.


14. Do you have written and

authorized protocols for the

development of K-FAST

50mg Sachet (Diclofenac

Potassium)?

The firm has written and authorized protocols No.RD/PD/001 for the

development of K-FAST 50mg Sachet (Diclofenac Potassium) in accordance

with ICH Q-8 Pharmaceutical Development guidelines.

15. Have you performed Drug-

excipients compatibility

studies?

The firm has not performed Drug-Excipients compatibility studies. They have

submitted the reason/logic for this that as their formulation (API &

Excipients) is similar/comparable to that of Voltfast sachet of Novartis

Pharma, Switzerland approved by Swissmedics. The quantities of sweetening

agents that is Sucralose and Aspartame were within safe limits as per USFDA

inactive ingredient database.

The firm referred the product approved by the Swiss Medic which

contains Aspartame and saccharine sodium. Hence, the firm should perform

compatibility studies.

16. Have you performed

comparative dissolution

studies?

The comparative dissolution studies have not been performed by the firm.

However, the firm has performed comparative assay, LOD and pH studies in

comparison with Voltfast to which firm is referring as reference product. This

so-called reference product seemed approved by UAE drug agency as it

contains UAE: NDC 4924-6116-01-03 & NAFDAC Reg. No. 04-9014.

Though it is mentioned on box that it is manufactured by M/s Miphar S.p.A.,

Milan, Italy for M/s Novartis Pharma AG, Basle, Switzerland.

It was advised to the firm to perform comparative dissolution profile

according to WHO guidelines in at least 3 different media of pH 1.2, 4.5 &

6.8 (to simulate the in vivo absorption site) in comparison with the reference

product approved by reference drug agency.

The firm has been using sucralose and aspartame in the formulation

while the product to which they are referring as reference product namely

Voltfast contains aspartame and saccharine sodium.

17. Do you have product

development (R&D)

section

The firm possesses a Research & Development (R&D) section for product

development studies.

18. Do you have necessary

equipment available in

product development

section for development of

K-fast?

Yes, the firm has following necessary equipment in R & D section though for

the development of K-fast sachet. Following is the list of equipments. Sr.

No.

Equipment Name Equipment

ID

Qualification

Date

1 Multi Functional

Pharmaceutical R&D

Machinery

VP/RD/001 20 July 2016

2 Bag Forming Filling

Sealing Machine

DXDK80CH 04 Feb 2016

19. Are the equipments in

product development

section qualified?

The following equipments used in production and analysis of trial batches are

qualified. S.

No.

Equipment Name Equipment

ID

Qualification

Date

1 Multi Functional

Pharmaceutical R&D

Machinery

VP/RD/001 20 July 2016


Sealing Machine

DXDK80CH 04 Feb 2016

20. Do you have proper

maintenance/calibration/re-

qualification program for

The firm has maintenance/calibration program for the equipment used in R &

D as per following details.


the equipment used in PD

section?

S. No. Equipment Name Equipment ID Last Maintenance

Date

1 Multi Functional

Pharmaceutical R&D

Machinery

VP/RD/001 October 2019


Sealing Machine

DXDK80CH October 2019

21. Do you have qualified staff

in product development

section with proper

knowledge and training in

product development?

The firm has provided the details of their technical personnel involved in the

development of K-fast Sachet.

The above technical persons were involved in the development of

product and however persons at S.No.1, 2, 4, 6 & 7 have now left the firm.

Dr. Zia ud Din, Chief Operating Officer/TD (Technical Director) also

meet the panel on last day of inspection to detail about the formulation

development.

S.No. Name Designation Qualification Experience

1 Dr. Zia Ud

Din

Chief

Operating

Officer/ TD

(Technical

Director)

B Pham

(Pak), PGD

(UK), MS

(UK)

27 Years

2 Aatikah

Younis

Manager

R&D

Pharm-D 9 Years

3 Humera

Iqbal

Manager QC M.Sc

Chemistry

21 Years

4 Saima

Yasmeen

Assistant

Manager QC

Pharm-D 9 Years

5 Altaf

Usmani

Deputy

Manager QA

M.Sc

Chemistry

13 Years

6 Muhammad

Mudassar

Ali

Assistant

Manager

R&D

Pharm-D 5 Years

7 Laila Tul

Qadar

R&D Officer Pharm-D 3 Years

22. Have you manufactured

three stability batches for

the stability studies of K-

FAST Sachet as required?

The firm has manufactured following three stability batches for the stability

studies of K-fast Sachet:

S. No. Stability Batches Batch Sizes

1. NPD801(T-01) 3kg

2. NPD801(T-02) 3kg

3. NPD801(T-03) 3kg

23. Do you have any criteria for

fixing the batch size of

stability batches?

The firm has set the criteria for fixing the batch size of stability batches based

on the quantity sufficient for testing during the studies both for accelerated

and real time studies to cover all testing time points.

Trial

No.

Batch

Size

Theoretical

Quantity

Actual

Packs

Yield

Packs

for

Real

Time

Packs for

Accelerated

Total

Packs

Required

Trial

No 1

3 Kg 1000

Sachets

30

Packs

8

Packs

7 Packs 15 Packs

Trial

No 2

3 Kg 1000

Sachets

30

Packs

8

Packs

7 Packs 15 Packs

Trial

No 3

3 Kg 1000

Sachets

30

Packs

8

Packs

7 Packs 15 Packs

24. Do you have complete

record of production of

stability batches?

The firm has complete record of production of stability batches. The firm has

shown the BMR of all three batches showing the complete history of

manufacturing and testing of batches step by step:

NPD801 (T-01) 3 Kg

NPD801 (T-02) 3 Kg

NPD801 (T-03) 3 Kg


25. Do you have protocols for

stability testing of stability

batches?

The firm has controlled protocol no. SOR 03544 for testing the stability

batches of applied formulation at 30 Co + 2 Co & 65 % RH + 5 % for real time

studies and at 40 Co + 2 Co & 75 % RH + 5 % for accelerated studies with

them.

26. Do you have developed and

validated the method for


The firm has used pharmacopoeia (USP) method of Diclofenc potassium

tablets for testing of Diclofenac potassium sachet and validate this method

through their method validation protocol No: MVP/032/2018 for batch No:

NPD801. The firm has also submitted a report No: MVR/032/2018 for batch

No: NPD801 T01 verifying the validation studies of the analytical method

covering following parameters of validation as defined in compendia:

i.Specificity

ii.Precision

iii.Repeatability

iv.Accuracy and recovery

v.Ruggedness

vi.Robustness

vii.Linearity and range

27. Do you have method

transfer studies in case

when the method of testing

being used by your firm is

given by any other lab?

The firm has not conducted method transfer studies. The firm submitted that

since they have developed the method from pharmacopoeia (Pharmacopoeial

method of tablets) in their own laboratory and they have validated it so there

is no need to do such studies.


confirming qualification of

equipment/ instruments

being used in the test and

analysis of APIs and

finished drugs.

The firm showed documents like Report No.2477 dated 16.05.2019 by

Kamstec International authorized by Waters (the firm showed the evidence

from the website for this authorization), confirming the qualification of HPLC

(Waters e 2695) being used in the test and analysis of APIs and the finished

drug.

29. Do your method of analysis

stability indicating?

The firm has performed SIM studies on the product and covering aspects like

Photolytic degradation, peroxide degradation, thermal degradation, acid

degradation, and base degradation studies for 72 hours.

The number of theoretical plates and tailing factor are missing in the

chromatograms.

30. Do your HPLC software is

21CFR compliant?

Complete product development as well as stability studies have been

performed on 21CFR complaint HPLC (Waters e 2695) with software version

Empower 3 Software database version 7.40.00.00 Waters 2002-2017.

31. Can you show Audit Trail

reports on K-fast sachet?

Yes, the firm has showed the audit trail record. Moreover, record and

chromatograms are attached with stability record. It has a limited/controlled

access as well.

32. Do you have some

remaining quantities of

degradation products and

stability batches?

The firm has remaining quantities of stability batches as per following details:

NPD801 (T-01) 6 packs

NPD801 (T-02) 6 Packs

NPD801 (T-03) 6 Packs

33. Do you have stability

batches kept on stability

testing?

The firm has completed the accelerated stability testing on the three stability

batches of K-fast Sachet. Also the firm has completed the real time stability

testing up to 12 months on all three batches with satisfactory results.

34. Do you have valid

calibration status for the

equipments used in

production in analysis?

The firm has valid calibration status for the equipment used in K-fast Sachet

production and analysis as detailed in following table. S.

No.

Equipment Name Equipment ID Last

calibration

date

Last calibration

date


1 Multi Functional

Pharmaceutical R&D

Machinery

VP/RD/001 October 2019 October 2019


Sealing Machine

DXDK80CH October 2019 October 2019

35. Do proper and continuous

monitoring and control are

available for stability

chamber?

Continuous power supply and monitoring with back up of 1 kv generator is

available for stability chamber to address the problem of load shedding and

for continuous/uninterrupted power supply. Portable digital data loggers are

available for continuous monitoring of temperature and humidity conditions

of stability chamber. The firm submitted date-wise data of temperature and

humidity conditions of stability chambers used for accelerated and real time

studies for every next hour.

36. Do related manufacturing

area, equipment, personnel

and utilities be rated as

GMP compliant?

The related manufacturing area, equipment, personnel and utilities are rated

as GMP compliant.

The firm was advised to increase the capacity of the R&D in terms of facilities,

technical staff and training thereof.

Conclusions & Recommendations:

1. It was clarified during audit that the firm conducted stability studies with API imported from M/s Henan

Dongtai Pharm Co. Ltd., East Changhong Tangyin Henan, China only. The firm did not continue the studies with

API imported from source M/s Huixian Dongpu Chemicals Co. Ltd, China and submitted the destruction record

(Report no. 1725/NCR dated 22 March, 2019) of stability batches manufactured from this earlier source.

2. On the basis of risk based approach, the genuineness/authenticity of stability data submitted by the firm

for registration of K-Fast Sachet is verifiable to an acceptable/satisfactory level. However, during audit it was

revealed that the firm is not clear regarding reference product compare to which they would have to establish the

formulation and perform pharmaceutical development studies. Earlier, they referred the brand “Cambia” of

Assertio as their reference product whose formulation was found as different (e.g., mannitol has been used with

specific particle size) from the applied one by the panel. It is hence, recommended that the assessment related to

formulation and manufacturing technology may be carried out again by PEC so as to ascertain/ensure the

similarity/comparability of same in the light of approval by reference agency(ies) before grant of registration by

the Registration Board.

3. The related manufacturing area, equipment, personnel and utilities are GMP compliant and suitable for

the manufacturing of K-fast 50mg (Diclofenac potassium) sachet therefore, the panel recommends the registration

of K-fast 50mg (Diclofenac potassium) sachet in the name of the manufacturer.

Evaluation by PEC:

Firm submitted an undertaking that their reference product was Voltfast Sachet 50mg of Swissmedic.

The assessment related to formulation and manufacturing technology may be carried out again by PEC

and it is revealed that firm follow manufacturing process of Voltfast of Swissmedic

Firm submitted dissolution and compare it with Voltfast Sachet 50mg of Swissmedic. Valaue of Q is

greater than 90% in 5 minutes.

Excipients are different from Voltfast Sachet 50mg but they did not perform compatibility studies.

Decision: Registration Board after thorough deliberation decided to defer the case for re

evaluation of the firm’s applied formulation and the USFDA as well as Swissmedic approved

reference product by Pharmaceutical Evaluation Cell.

Item No. 6: Agenda of Evaluator PEC-V CLB in its 273rd meeting held on 15th Jan, 2020 considered the case of M/s D-Haans Pharmaceuticals.Plot No.

9/A, Industrial Estate, Bhimber Pakistan and approved the grant of DML by way of formulation with following

sections.

New Approved Sections

S. No Section No. of products No. of molecules

1. Oral Powder Section-I (Vet) 32 10

2. Oral Powder Section-II (Vet) 20 10


Oral Powder Section-I (Vet)

10 Molecules 10 Products

109. Name and address of

Manufacturer / Applicant

"M/s D-Haans Pharmaceuticals.

Plot No. 9/A, Industrial Estate, Bhimber"

Brand Name +Dosage Form + Strength Hascoli-50% W/S Powder

Composition "Each 100g Contains:

Colistin Sulphate…50g"

Diary No. Date of R&I &fee Dy.No 1879 dated 19-02-2020 Rs.20,000/- (17-02-2020)


Type of Form Form 5

Finished product Specification Inhouse

Pack size & Demanded Price 100g, 250g, 500g,1Kg,5Kg,10kg

Me-too status 053941; CN-Mont Oral Powder

M/s Westmont Pharmaceuticals Industry Rawalpindi"

GMP status CLB in its 273rd meeting held on 15th Jan, 2020 considered the

case of M/s D-Haans Pharmaceuticals.Plot No. 9/A, Industrial

Estate, Bhimber Pakistan and approved the grant of DML by

way of formulation with following four sections.


Decision: Referred to expert working group for rationalization of colistin formulations.





Brand Name +Dosage Form + Strength Hascoli-400 W/S Powder


Colistin Sulphate…400 MIU"



Type of Form Form 5



Me-too status 049783

Coliser Water Soluble Powder M/s Attabak Pharma
















Type of Form Form 5



Me-too status 049784; Colibak Forte WSP Water Soluble Powder

M/s Attabak Pharma Islamabad













Composition "Each g Contains:

Colistin Sulphate…600,000IU"



Type of Form Form 5

Finished product Specification Imhouse


Me-too status 089855; Neflorex 60 Water Soluble Powder

M/s. Breeze Pharma (Pvt) Ltd., Kahuta Road, Islamabad.











Brand Name +Dosage Form + Strength Hansredin 1% Powder


Amantadine HCl…10g"

Diary No. Date of R&I &fee Form-5 Dy.No 1882 (19-02-2020) Rs.20,000/- (17-02-2020)

Pharmacological Group Antiviral

Type of Form Form 5



Me-too status 075697; Amantabak Powder

"M/s Attabak Pharmaceuticals, Industrial Area, Islamabad."
















Type of Form Form 5



Me-too status 088040 ; "Metadine powder

"M/S. Farm Aid Group, Hattar Industrial Estate, Haripur"

















Type of Form Form 5



Me-too status 093841; Amadine-98 Oral Powder

"M/S. Aptly Pharmaceuticals, Faisalabad."











Brand Name +Dosage Form + Strength Hansydox-80% Powder


Doxycycline HCl…800mg"

Diary No. Date of R&I &fee Dy.No 1884 (19-02-2020) Rs.20,000/- (17-02-2020)


Type of Form Form 5



Me-too status 082504; "Doxyral 80% Water Soluble Powder For Oral Route

"M/s. Orient Animal Health (Pvt.) Limited, Karachi-75100"





Remarks of the Evaluator The drug already approved by DRAP (generic / me-too status)

provided by you mention “Doxycycline hyclate…...923.32mg

(eq. To 800mg doxycycline)” whereas, you have applied for

“Doxycycline HCl…800mg".

Decision: Deferred for revision of formulation as per the DRAP approved generic product along

with submission of requisite fee.





Brand Name +Dosage Form + Strength Hansydox-50% Powder


Doxycycline HCl…500mg"



Type of Form Form 5



Me-too status 096840; Doxson Oral W/S Powder "M/s. D-Maarson

Pharmaceuticals, National Industrial Zone,Rawat, Islamabad."












Brand Name +Dosage Form + Strength Neo-Hans 60% W/S Powder


Neomycin Sulphate…60g"



Type of Form Form 5



Me-too status 069625; Neocin-S Water Soluble Powder M/s Alina Combine

Pharmaceuticals (Pvt) Ltd., Karachi.
















Type of Form Form 5



Me-too status 075694; Neomycin 70% Powder

"M/s Attabak Pharmaceuticals, Industrial Area, Islamabad."
















Type of Form Form 5



Me-too status 078297; N-72 Water Soluble Powder "M/s. Nawal

Pharmaceuticals, Rawalpindi"







Decision: Deferred for scientific rational for neomycin 72% water soluble powder, since neomycin

70% water soluble powder is already approved.





Brand Name +Dosage Form + Strength Linc-Hans 1.1% Powder


Lincomycin HCl…1.1g"



Type of Form Form 5



Me-too status 031403; Lincofeed Oral Powder

M/s Mediexcel Pharmaceuticals, Islamabad.






provided by you mentions “Lincomycin HCl monohydrate

1.1g.whereas, you have applied for Lincomycin HCl …1.1g.

Decision: Approved with innovator’s specification and with following label claim.

Each 100g Contains:

Lincomycin HCl monohydrate……1.1g





Brand Name +Dosage Form + Strength Linc-Hans 11% Powder


Lincomycin HCl…11g"



Type of Form Form 5



Me-too status 078267; Dm-Premix

"M/S. D-Maarson Pharmaceuticals, Rawat, Islamabad."











Brand Name +Dosage Form + Strength Linc-Hans 4.4% Powder


Lincomycin HCl…4.4g"




Type of Form Form 5




Lincos-P Powder M/s A & K Pharmaceutical, Faisalabad.











Brand Name +Dosage Form + Strength Linc-Hans 44% Powder


Lincomycin HCl…44g"



Type of Form Form 5



Me-too status 080157; Licogrow-44 Oral Powder

"M/s. Ras Pharmaceuticals (Pvt) Ltd., Multan."











Brand Name +Dosage Form + Strength Hanster-30% W/S Powder


Amprolium HCl…30g"


Pharmacological Group Anticoccidial

Type of Form Form 5

Finished product Specification USP


Me-too status 063816; Amprobak-30 Water Soluble Powder.

M/s Attabak Pharmaceuticals Islamabad






Decision: Approved.











Type of Form Form 5



Me-too status 072631; Ampro Powder

"M/s Nawal Pharmaceuticals, Rawalpindi."






provided by you mentions “Amprolium as HCl”, whereas, you

have applied for “Amprolium HCl”.

Decision: Approved.










Type of Form Form 5



Me-too status 046673; Amprox 60% Water Soluble Powder

M/s Alina Combine Pharmaceuticals (Pvt) Ltd. Karachi.






Decision: Approved.










Type of Form Form 5



Me-too status 053917; Amcox Powder

M/s Attabak Pharmaceuticals Islamabad.






Decision: Approved.











Type of Form Form 5



Me-too status 088630; "Ampro-Forte Oral Powder

"M/s. Breeze Pharma (Pvt) Ltd., Kahuta Road, Islamabad."






Decision: Approved.





Brand Name +Dosage Form + Strength Respi-Hans 10% Powder

Composition "Each Kg Contains:

Oxytetracycline HCl…100g"



Type of Form Form 5

Finished product Specification BP


Me-too status 049713; Polyqueen Gold Water Soluble Powder.

M/s Attabak Pharmaceuticals, Islamabad.






Decision: Approved.










Type of Form Form 5



Me-too status 029637; FA-TM-200 Powder

M/s Farm Aid Group Pakistan, Hattar, Haripur, N.W.F.P.






Decision: Approved.











Type of Form Form 5



Me-too status 063643; Nobitet 50% Powder

M/s Noble Pharma, Industrial Area, Mirpur Azad Kashmir.






Decision: Approved.










Type of Form Form 5



Me-too status 034526; Oxy-950 Powder

M/s Attabak Pharmaceutical Industries, Islamabad.






Decision: Approved.





Brand Name +Dosage Form + Strength Neo-Cin W/S Powder


Florfenicol…15g




Type of Form Form 5



Me-too status 087961; "Neo Flor Water Soluble Powder

M/s. Farm Aid Group, Hattar Industrial Estate, Haripur."











Brand Name +Dosage Form + Strength FLO-OTC W/S Powder



Oxytetracycline HCl…15g

Florfenicol…15g"



Type of Form Form 5



Me-too status 080726; Oxy-Floro Water Soluble Powder

"M/s. Intervac (Pvt) Ltd., Sheikhupura."











Brand Name +Dosage Form + Strength FLO-OTC 30 W/S Powder


Oxytetracycline Hcl…30%

Florfenicol…30%"



Type of Form Form 5



Me-too status 063747; Ampronil-50 Oral Powder

M/s Westmont Pharmaceutical Industry, Rawalpindi











Brand Name +Dosage Form + Strength Tylohans-D20 Powder


Doxycycline HCl…20g

Tylosin Tartrate…10g"



Type of Form Form 5



Me-too status 072630; Doxytyl Oral Powder.

"Each 100gm Contains:-

Tylosin ……………..10gm.

Doxycycline ………. 20gm.

M/s Nawal Pharmaceuticals, Rawalpindi."







provided by you mentions “Each 100g contains:-

Tylosin……..10g, Doxycycline. 20g whereas, you have

applied for Doxycycline HCl…20g, Tylosin Tartrate…10g".













Type of Form Form 5



Me-too status 031434; Tylo-Cycline 450 Powder

M/s Farm Aid Group Pakistan, Hattar.













Doxycycline HCl…40mg




Type of Form Form 5



Me-too status





Remarks of the Evaluator Me to couold not be confirmed.














Type of Form Form 5



Me-too status 069628, Dot Powder

M/s Attabak Pharmaceutical, Islamabad."







Oral Powder Section-II (Vet)

10 Molecules 10 Products





Brand Name +Dosage Form + Strength CRD HAANS-42 W/S Powder


Doxycyline Hcl…40g

Tylosin Tartrate…20g

Colistin Sulphate…6g

Bromhexine Hcl…2g"



Type of Form Form 5



Me-too status 062127; NOBI TDC 680 Oral Powder.

"Each 1000gm Contains: -

Tylosin Tartarte…..200gm.

Doxycycline Hcl….400gm.

Colistine Sulphate…60gm.

Bromhexine……….20gm.

"M/S Noble Pharma, Mirpur Azad Kashmir."




















Type of Form Form 5



Me-too status 044951; Biosin Td Powder.



Tylosin Tartrate……… 10gm.

Doxycycline…………. 20gm.

Bromhexine………….. 10gm.

Colistin Sulphate ……. 3gm.

M/s Leads Pharma (Pvt) Ltd., Islamabad.






provided by you mentions: “Doxycycline……20g

,Bromhexine…10g” whereas, you have applied for

“Doxycyline HCl…20g,Bromhexine HCl…10g"















Type of Form Form 5



Me-too status 058962; Brocotyd Powder


Doxycycline Hyclate…Bp…40gm

Tylosin Tartrate…Bp….20gm

Colistin Sulphate….Bp…10gm

Bromhexine Hcl….Bp…2gm

M/s Univet Pharmaceutical Rawalpindi






provided by you mentions “Doxycycline Hyclate…40g”

whereas, you have applied for “Doxycyline Hcl…40g”.











Colistin Sulphate…500 MIU




Type of Form Form 5




Me-too status 074096; Dox-40 Water Soluble Powder

"M/s. Nawal Pharmaceuticals, Rawalpindi."



















Type of Form Form 5



Me-too status 049712; CRD-RAZE Water Soluble Powder.


Tylosine Tartrate (Bp) 100gm.

Doxycycline Hydrochloride (Bp) 200gm.

Colistin Sulphate (Bp) 500 Miu.

Bromohexine Hcl (Bp) 5gm.

M/S Attabak Pharmaceuticals, Islamabad











Brand Name +Dosage Form + Strength CRD Haans-450 W/S Powder








Type of Form Form 5



Me-too status 071036; Tylodox+BC Powder of M/s Intervac (Pvt) Ltd.

"Each Kg Water Soluble Powder Contains:-

Tylosin Tartrate……..170gm

Doxycycline HCl……130gm

Bromhexine…………..5gm

Colistin Sulphate…….30gm







provided by you mentions “Bromhexine” whereas, you have

applied for “Bromhexine Hcl”.







Brand Name +Dosage Form + Strength Sulpamed-30 W/S Powder


Oxytetracycline Hcl…25g





Type of Form Form 5



Me-too status 071068; Oxycol Forte Powder.


Oxytetracycline Hcl 250gm.

Neomycin Sulphate 250gm.

Colistin Sulphate 300miu.

"M/s Attabak Pharmaceutical, Islamabad."


















Type of Form Form 5



Me-too status 074074; Clorytin Water Soluble Powder

"Each 100g Contains:-


Neomycin Sulphate ….20g

Colistin Sulphate….24MIU

"M/s. D-Maarson Pharmaceuticals, Rawat, Islamabad."



















Type of Form Form 5



Me-too status 075659; NCO-60

"Each Gm Contains:-

Oxytetracycline Hcl……………...20% W/V

Colistin Sulphate………………...20% W/V

Neomycin……………………….20% W/V

"M/S. Breeze Pharma (Pvt.) Ltd., Kahuta Road, Islamabad."






provided by you mentions “Neomycin” whereas, you have

applied for “Neomycin Sulphate".










Colistin Sulphate…50MIU




Type of Form Form 5



Me-too status 073952; Oxyneoriq-C Water Soluble Powder

"Each 1000gm contains:-

Oxytetracycline HCL…300gm

Neomycin Sulphate…..250gm

Colistin Sulphate……500 MIU

"M/s Baariq Pharmaceuticals, Lahore."












Brand Name +Dosage Form + Strength Hansflor-F W/S Powder


Oxytetracycline Hcl…300mg

Florfenicol…100mg

Neomycin Sulphate…150mg"



Type of Form Form 5








Remarks of the Evaluator Ne too coulod not be confirmed.







Brand Name +Dosage Form + Strength Hansflor W/S Powder


Oxytetracycline Hcl…300mg

Florfenicol…100mg

Neomycin Sulphate…150mg"



Type of Form Form 5








Remarks of the Evaluator Ne too coulod not be confirmed.







Brand Name +Dosage Form + Strength Beracin-H W/S Powder


Fosfomycin Calcium…….20g

Tylosin Tartrate………….10g

Fructose………………….18g

Sodium Phosphate……….15g

Magnesium Phosphate…...10g

Sodium Chloride qty sufficient to make…100g"


Pharmacological Group Antibacterial, Electrolyte Replenisher

Type of Form Form 5




Me-too status 075626; Fofact Powder


Calcium Fosfomycin.20gm

Tylosin Tartrate……..5gm

Fructose 1,6 Diphosphate………...18gm

Sodium Phosphate…15gm

Magnesium Phosphate…………..10gm

Sodium Chloride Gs-To………………….100gm

"M/s. Univet Pharmaceuticals, Rawalpindi."





Remarks of the Evaluator The cover letter and composition mentions Tylosin

Tartrate……..5g whereas, Form 5 mentions Tylosin

Tartrate……..10g. Clarification is required with respect to

applied strength.

Decision: Deferred for clarification of applied composition, since different composition is

mentioned on covering letter and form 5.





Brand Name +Dosage Form + Strength Beracin W/S Powder


Fosfomycin Calcium…….20g

Tylosin Tartrate………….10g

Fructose…………………18g

Sodium Phosphate……….15g

Magnesium Phosphate…..10g"


Pharmacological Group Antibacterial, Electrolyte Replenisher

Type of Form Form 5



Me-too status 078240; Fosfotyl Powder


Fosfomycin Calcium ……20gm

Tylosin Tartrate…………10gm

Fructose………………….18gm

Sodium Phosphate ……...15gm

Magnesium Sulphate ..…10 Gm

"M/s. Leads Pharma (Pvt) Ltd., Islamabad."






provided by you mentions “Magnesium Sulphate” whereas

applied formulation is Magnesium Phosphate".







Brand Name +Dosage Form + Strength Bem-Cool W/S Powder



Vitamin C……………20g

Aspirin……………….6.7g"


Pharmacological Group Anti-oxidant, Analgesic, Antipyretic

Type of Form Form 5



Me-too status 049778; Bursa Gold Water Soluble Powder


Acetyl Salicyclic Acid….6.7gm

Vitamin C…………..….20gm

M/s Attabak Pharma, Islamabad












Brand Name +Dosage Form + Strength Bimbo-H W/S Powder

Composition "Each 100g Powder Contains:

Potassium Citrate…18g

Sodium Citrate…12g

Vitamin B1…0.03g

Vitamin B2…0.015g

Nicotinamide…0.32g

Menadione Bisulfate…0.115g

Vitamin C…1.10g"


Pharmacological Group Vitamin,Mineral

Type of Form Form 5



Me-too status 046581; Anti Gumbo Powder


Potassium Citrate ….. 18gm.

Sodium Citrate …….. 12gm.

Vitamin B1…………. 0.03gm.

Vitamin B2…………. 0.015gm.

Nictinamide ……….. 0.32gm.

Menadione Bisulfite…0.115gm.

Vitamin C………….. 1.10gm.

(Vitamin Preparation).

M/s Leads Pharma (Pvt) Ltd., Islamabad












Brand Name +Dosage Form + Strength Bimrol-C W/S Powder


Vitamin C…20g

Paracetamol…2g

Potassium Chloride…4g

Calcium Carbonate…4.5g

Magnesium Sulphate…3.5g"


Pharmacological Group Antioxidant, Analgesic, Antipyretic

Type of Form Form 5



Me-too status 078239; Spin-C Powder


Paracetamol………….2gm

Vitamin C (Ascorbic Acid)…………….20gm

Calcium Carbonate……..4.5gm

Magnesium Sulphate…...3.5gm

Potassium Chloride……….4gm

"M/s. Leads Pharma (Pvt) Ltd., Islamabad."











Brand Name +Dosage Form + Strength Broncho-EZ W/S Powder


Doxycycline Hcl…200mg

Tylosin tartrate…100mg

Colistin Sulphate…0.5MIU

Bromhexine Hcl…5mg

Streptomycin Sulphate…20mg"



Type of Form Form 5



Me-too status 078296; Riz Wan-S Water Soluble Powder

"Each g Contains:-

Doxycycline Hcl………200mg

Tylosin Tartrate………..100mg

Colistin Sulphate……...0.5MIU

Bromhexine Hcl …………5mg

Steptomycin Sulphate……20mg

"M/s. Nawal Pharmaceuticals, Rawalpindi"













Brand Name +Dosage Form + Strength Broc-Haans W/S Powder


Doxycycline Hcl…………200g

Tylosin tartrate……………100g

Colistin Sulphate…………450MIU

Bromhexine Hcl………….5g

Streptomycin Sulphate……36g"



Type of Form Form 5



Me-too status 071069; Pulmodox-S Powder.


Tylosine Tartarate 100gm.

Doxycycline Hydrochloride 200gm.

Colistin Sulphate…450MIU.

Bromohexine Hvdrocloride…5gm.

Streptomycin Sulphate…….36gm.

"M/s Attabak Pharmaceutical, Islamabad."












Brand Name +Dosage Form + Strength Fura-Hans W/S Powder


Furosemide…20g

Manganese Sulphate…1g

Potassium Chloride…4g

Calcium Carbonate…45g

Magnesium Sulphate…35g

Sodium Chloride…35g"


Pharmacological Group Diuretic, Electrolyte Supplement.

Type of Form Form 5



Me-too status 078265; F-Maars Water Soluble Powder


Furosemide………………...20g

Potassium Chloride…………4g

Calcium Carbonate………...45g

Manganese Sulphate ………..1g

Sodium Chloride………..…35g

Magnesium Sulphate………35g

"M/S. D-Maarson Pharmaceuticals, Rawat, Islamabad."








Item No. 7: Agenda of Evaluator PEC-VI

Case no. 02 Registration applications of newly granted DML or New section (Human)

a. New DML

CLB in its 270th meeting held on 23rd may, 2019 has considered & approved the grant of DML of M/s

Healthcare Pharnaceuticals by the way of formulation with following 8 sections:

1. Tablet section (general)

2. Capsule section (general)

3. Sachet section (general)

4. Dry suspension section (general)

5. Cream and ointment (general) section

6. Oral liquid syrup/suspension(general) section

7. External application

8. Liquid repacking section.

Now the applicant has applied for following molecules/products against each section:

Extension in implementation timelines of SRO 713(I)/2018

The Authority in its 72nd meeting discussed regarding the “Extension in implementation timelines of SRO

713(I)/2018 and decided as follows:-

1. Allowed those companies, for which panel for inspection has been constituted before 07-03-2019, to

submit registration applications on Form 5 instead of Form 5F for initial 10 molecules per section only.

2. The exemption will remain valid till 31-12-2019.

3. No further exemption will be granted in any case.

4. Inspectors / panel members are advised to formally report every visit. Concerned Division was advised to

specify a timelines for conducting/ concluding panel inspection.

a) Details of issuance of DML are as follow: Name of Firm Date of issuance of

panel inspection letter

Date of issuance

of DML

Date of Submission

of applications

M/s Healthcare Pharmaceuticals

Multan

31st January 2019 28th June 2019 November &

December 2019

M/s KBR Pharmaceuticals, Hattar 8th March 2018 28th June 2019 November 2019

The submission of following applications on foirm-5 are in line with the decision of Authority

Capsule (general): 10Molecules; 20Products;


Applicant

M/S Health Care Pharmaceuticals 40-Km,Lahore Road Multan

Brand Name +Dosage Form + Strength Dolin 100mg Capsule

Composition Each Capsule contains:

Doxycycline Hyclate eq.to

Doxycycline……..100mg

Diary No. Date of R& I & fee Dy.No. 24696 ;(22-11-2019);Rs.20,000/-( 19-11-2019)

Pharmacological Group Antibiotic (Tetracyclines)

Type of Form Form-5


Pack size & Demanded Price 10x10’s; As fixed by MoH



MHRA Approved

Me-too status Dok-C-M Capsule 100mg of M/s Mediate Pharmaceuticals

GMP status New DML 000905 28/06/2019

Evaluation by PEC

Decision: Approved.



Applicant

M/S Health Care Pharmaceuticals 40-Km, Lahore Road Multan

Brand Name +Dosage Form + Strength DENSO 60 mg Capsule


Dual Delayed Release dexlansoprazole pellets eq to

Dexlansoprazole ….………..60mg

Diary No. Date of R& I & fee Dy.No. 24694 ;(22-11-2019);Rs.20,000/-(19-11-2019)

Pharmacological Group Proton Pump inhibitor

Type of Form Form -5

Finished product Specification (Manufacturers specifications)

Pack size & Demanded Price As per SRO



Dexilant Delayed Release Capsule 30mg of USFDA approved

Me-too status Lansodex Capsule 30mg of M/S Getz Pharma


Evaluation by PEC Stability studies and other relevant documents are not provided.

Decision: Registration Board deferred the case for submission of stability study data as per the

guidelines provided in 278th and 293rd meeting of Registration Board.


Applicant

DENSO 30mg Capsule

Brand Name +Dosage Form + Strength Each Capsule contains:

Dual Delayed Release dexlansoprazole pellets eq to

Dexlansoprazole ….………..30mg

Composition Dy.No. 24693; (22-11-2019); Rs.20,000/

Diary No. Date of R& I & fee Proton Pump inhibitor

Pharmacological Group Form -5

Type of Form (Manufacturers specifications)

Finished product Specification As per SRO

Pack size & Demanded Price Dexilant Delayed Release Capsule 30mg of USFDA approved



Lansodex Capsule 30mg of M/S Getz Pharma

Me-too status New DML 000905 28/06/2019

GMP status DENSO 30mg Capsule

Evaluation by PEC Stability studies and other relevant documents are not provided.

Decision: Registration Board deferred the case for submission of stability study data as per the

guidelines provided in 278th and 293rd meeting of Registration Board.


Applicant


Brand Name +Dosage Form + Strength LOXETIN 20mg Capsule

Composition Each capsule contains: - Enteric coated pellets of Duloxetine HCl

eq. to Duloxetine…………..20mg

Diary No. Date of R& I & fee Dy.No.26390 ;( 09-12-2019);Rs.20,000

Pharmacological Group Antipsychotic






Duloxetine 30 mg gastro-resistant capsules By Tillomed

Laboratories Ltd. (PL: 11311/0554) MHRA Approved.

Me-too status SYMPTA Capsules Polyfine Chempharma (Pvt,) Ltd. Peshawar

GMP status New License (DML 000905) (Inspection Date: 28/06/2019)

Evaluation by PEC Pellets details are not provided.

Decision: Deferred for source of pellets, along with stability studies data, GMP certificate of

supplier and differential fee in case of import of pellets.



Applicant



Composition Each capsule contains: - Enteric coated pellets of Duloxetine HCl

eq. to Duloxetine…….….…………..30mg

Diary No. Date of R& I & fee Dy.No. 26391 ;( 09-12-2019);Rs.20,000/-










(Reg.# 078462)






Applicant


Brand Name +Dosage Form + Strength LEXO 60mg Capsule


Fexofenadine HCl……....60mg


Pharmacological Group Antihistamine



Pack size & Demanded Price 10‘s and 20‘s; As per PRC




Me-too status Exo Capsule English Pharmaceuticals


Evaluation by PEC Reference product could not be confirmed

Decision: Deferred for evidence of approval of applied formulation in reference regulatory

authorities / agencies which were adopted by the Registration Board in its 275th meeting.


Applicant





Diary No. Date of R& I & fee Dy.No.26400 ;( 09-12-2019);Rs.20,000/-















Applicant



















Applicant


Brand Name +Dosage Form + Strength CLOFEN 50mg CAPSULES


SR pellets of diclofenac sodium ……….50mg

Source of Pellets: Vision pharmaceuticals

Diary No. Date of R& I & fee Dy.No. 23167 ;07 -11-2019; Rs.20,000

Pharmacological Group Antiinflammatory and antirheumatic products, non-steroids

(Acetic acid derivatives and related substances)

Type of Form Form 5

Finished product Specification Mfg

Pack size & Demanded Price 2 x 10‘s: As per SRO



DIFENE Ireland Approved.

Me-too status 071688; Hegen-50 Capsules, Healers Pharma, Peshawar.


Evaluation by PEC

Decision: Approved with BP specification.


Applicant


Brand Name +Dosage Form + Strength CLOFEN SR 100mg CAPSULES


SR pellets of diclofenac sodium ……….100mg

Source of Pellets: Vision pharmaceuticals

Diary No. Date of R& I & fee Dy.No.23168 ;07 -11-2019; Rs.20,000

Pharmacological Group Antiinflammatory and antirheumatic products, non-steroids

(Acetic acid derivatives and related substances)

Type of Form Form 5

Finished product Specification Mfg

Pack size & Demanded Price 2 x 10‘s: As per SRO



Rhumalgan XL100 mg Modified-Release Capsules MHRA

Approved

Me-too status Phlogen capsule 100mg by Brookes


Evaluation by PEC

Decision: Approved with BP specification.



Applicant


Brand Name +Dosage Form + Strength Amadole 100mg Capsule


Tramadol HCl…100mg


Pharmacological Group Opioid Analgesi

Type of Form Form 5





Tramadol 50mg capsule by Milpharm Ltd, approved by MHRA

of UK.

Me-too status Tramal capsule 100mg by Impex Plus Karachi


Evaluation by PEC

Decision: Approved.


Applicant


Brand Name +Dosage Form + Strength Opezole 20mg Capsule

Composition Each capsule contains:

Enteric coated pallets of Omeprazole eq. to Omeprazole ….20mg

Diary No. Date of R& I & fee Dy.No23150 ;07 -11-2019; Rs.20,000

Pharmacological Group Proton Pump Inhibitor

Type of Form Form 5


Pack size & Demanded Price 10‘s, 14‘s & 100‘s/As per DPC



OMEPRAZOLE 20 mg GASTRO-RESISTANT CAPSULES of

M/s DEXCEL-PHARMA LIMITED UK

Me-too status Alomep 20mg Capsule of M/s Alson


Evaluation by PEC Pellets detail are not provided




Applicant


Brand Name +Dosage Form + Strength Opezole 40mg Capsule

Composition Each capsule contains: Enteric coated pallets of Omeprazole eq.

to Omeprazole ….40mg

Diary No. Date of R& I & fee Dy.No. 23151;07-11-2019; Rs.20,000


Type of Form Form 5


Pack size & Demanded Price 10‘s, 14‘s & 100‘s/As per DPC



OMEPRAZOLE 40 mg GASTRO-RESISTANT CAPSULES of

M/s DEXCEL-PHARMA LIMITED UK

Me-too status Alomep 40mg Capsule of M/s Alson


Evaluation by PEC Pellets detail are not provided




Applicant


Brand Name +Dosage Form + Strength Amadole 50mg Capsule



Tramadol HCl…50mg


Pharmacological Group Opioid Analgesi

Type of Form Form 5





Adolonta 50 mg hard capsules by Grünenthal Pharma, SA

(Spain Approved)

Me-too status Tramal capsule 50mg by Impex Plus Karachi (Reg#010170)


Evaluation by PEC

Decision: Approved.


Applicant


Brand Name +Dosage Form + Strength Flunaz 150mg Capsule


Fluconazole…150mg


Pharmacological Group Antimycotics for systemic use

Type of Form Form 5


Pack size & Demanded Price 1‘s / As per SRO



Fluconazole 150mg capsule by Bristol Laboratories MHRA

Approved

Me-too status Fungon Capsules 150mg by Dyson Research Lab.(R.#055353)


Evaluation by PEC

Decision: Approved.


Applicant


Brand Name +Dosage Form + Strength Esopra 40mg Capsule

Composition Each capsule enteric-coated pellets contains:

Esomeprazole as Magnesium Dihydrate…….40m



Type of Form Form 5


Pack size & Demanded Price 14‘s & Rs. 323/- per 14 capsules



MHRA Approved

Me-too status Ulcicare 40mg capsules of M/s Jawa Pharma (Reg. # 050300)


Evaluation by PEC Pellets details are not provided




Applicant


Brand Name +Dosage Form + Strength Esopra 20mg Capsule

Composition Each capsule enteric- coated pellets contains: Esomeprazole as

Magnesium Dihydrate…….20mg

Diary No. Date of R& I & fee Dy.No. 23143 ;07 -11-2019; Rs.20,000


Type of Form Form 5



Pack size & Demanded Price 14‘s & Rs. 170/- per 14 capsules



MHRA Approved

Me-too status Esante 20mg capsules of M/s Macter International (Reg. #

050576)


Evaluation by PEC Pellets details are not provided




Applicant


Brand Name +Dosage Form + Strength Azithrocare 250mg Capsule


Azithromycin As Dihydrate………………..250mg


Pharmacological Group Macrolide

Type of Form Form 5


Pack size & Demanded Price 10‘S, 20‘S & 30‘S; As Per Prc



TGA Approved

Me-too status Arcin 250 Mg Capsule Linear Pharma


Evaluation by PEC

Decision: Approved.


Applicant


Brand Name +Dosage Form + Strength Dolin 50mg Capsule

Composition Doxycycline Hyclate eq. to Doxycycline……..50mg

Diary No. Date of R& I & fee Dy.No. 24695 ;(22-11-2019);Rs.20,000/

Pharmacological Group Antibiotic (Tetracyclines)

Type of Form Form-5


Pack size & Demanded Price 10x10’s; As fixed by MoH



USFDA Approved

Me-too status Dok-C-M Capsule 50mg of M/s Mediate Pharmaceuticals


Evaluation by PEC

Decision: Approved.


Applicant



Composition Each capsule contains: -

Enteric coated pellets of Duloxetine HCl eq. to

Duloxetine…….….…………..60mg

Diary No. Date of R& I & fee Dy.No.26392 ;( 09-12-2019);Rs.20,000/-















M/s. KBR Pharmaceuticals, Plot # 123 - B, Phase V, Industrial Estate, Hattar.

Following registration dossiers have been received vide letter No. dated 07/03/ 2019 stating that the firm

has been granted approval of new DML by way of formulation by Central Licensing Board in its 269th

meeting for following eight (8)sections

1. Capsule Section (General)

2. Dry powder Suspension Section (General)

3. Cream/Ointment/Gel Section

4. Sachet Section (General)

5. Liquid Injection Section (General)

6. Capsule Section (Cephalosporin)

7. Dry Powder Suspension Section (Cephalosporin)

8. Dry powder injection (Cephalosporin)

Capsule Section (General) 24 products/ 10 molecules


Applicant

M/s KBR Pharmaceuticals, 123 - B, Phase V, Industrial Estate,

Hattar

Brand Name +Dosage Form + Strength Ribek Capsule 20 mg

Diary No. Date of R& I & fee Diary No: 23181 , 08-11-2019 , Rs: 20,000/- , 06-11-2019


Omeprazole (as enteric coated pellets)…..20mg

Source: Vision Pharmaceuticals

Pharmacological Group Proton pump Inhibitor

Type of Form Form-5

Finished Product Specification USP Specs

Pack size & Demanded Price 7, 10,14 & 100’s / As per SRO



Prilosec 20 mg Capsule by M/s Dr. Reddy’s Laboratories UK

Me-too status Ompiget 20 mg Capsule by M/s Novae Pharmaceuticals

Anzo 20 mg Capsule by Searle Pakistan

GMP status New License ( DML # 000906 Dated 28-06-2019)


Decision: Approved.


Applicant


Hattar

Brand Name +Dosage Form + Strength Ribek Capsule 40 mg

Diary No. Date of R& I & fee Diary No:23182 , 08-11-2019 , Rs: 20,000/- , 06-11-2019


Omeprazole (as enteric coated pellets)…..40mg



Type of Form Form-5





Prilosec 40 mg Capsule by M/s Dr. Reddy’s Laboratories UK


Me-too status Ompiget 40 mg Capsule by M/s Novae Pharmaceuticals

Anzo 40 mg Capsule by Searle Pakistan



Decision: Approved.


Applicant


Hattar

Brand Name +Dosage Form + Strength Ribek S Capsule 20 mg /1100 mg


Composition "Each capsule contains:

Omeprazole…20 mg

Sodium bicarbonate…1100 mg"

Pharmacological Group Proton pump Inhibitor / Ant Acid

Type of Form Form-5


Pack size & Demanded Price 7, 10,14, 20 & 30’s / As per SRO



ZEGERID Capsule /Approved in US-FDA

Me-too status MEP – B CAPSULE by Genix Pharma

Omega Capsule by Ferozsons laboratories limited.



Decision: Approved.


Applicant


Hattar

Brand Name +Dosage Form + Strength Ribek Plus Capsule 40 mg/ 1100 mg


Composition "Each capsule contains:

Omeprazole…40 mg

Sodium bicarbonate…1100 mg"

Pharmacological Group Proton pump Inhibitor / Ant Acid

Type of Form Form-5


Pack size & Demanded Price 7, 10,14, 20 & 30’s / As per SRO



ZEGERID Capsule /Approved in US-FDA

Me-too status MEP – B CAPSULE by Genix Pharma

Omega Capsule by Ferozsons laboratories limited.



Decision: Approved.


Applicant


Hattar

Brand Name +Dosage Form + Strength Rexim Capsule 20 mg



Esomeprazole (as enteric coated pellets)…..20mg



Type of Form Form-5





Nexium 20mg Capsule by AstraZeneca Pharmaceuticals

US


Me-too status Essonave 20 mg Capsule by M/s Novae Pharmaceuticals

Esso 20 mg Capsule by Shaigan Pharmaceuticals



Decision: Approved.


Applicant


Hattar

Brand Name +Dosage Form + Strength Rexim Capsule 40 mg



Esomeprazole (as enteric coated pellets)…..40mg



Type of Form Form-5





Nexium 40mg Capsule by AstraZeneca Pharmaceuticals

US

Me-too status Essonave 40 mg Capsule by M/s Novae Pharmaceuticals

Esso 40 mg Capsule by Shaigan Pharmaceuticals



Decision: Approved.


Applicant


Hattar

Brand Name +Dosage Form + Strength Racobac Capsule 250 mg



Azithromycin as Dihydrate……250mg

Pharmacological Group Macrolide Antibiotic

Type of Form Form-5


Pack size & Demanded Price 6‘s,10‘s; As per SRO



MHRA Approved

Me-too status Navozith 250 mg Capsule by M/s Novae Pharmaceuticals

Azomax 250 mg Capsule by Sandoz Pakistan



Decision: Approved.


Applicant


Hattar

Brand Name +Dosage Form + Strength Riflucan Capsule 50 mg



Fluconazole…..50mg

Pharmacological Group Anti Fungal

Type of Form Form-5

Finished Product Specification BP

Pack size & Demanded Price 1, 4, 5, 7 & 10’s / As per SRO



MHRA Approved

Me-too status Fluderm 50 mg Capsule by M/s Nabi Qasim Industries

Fugix 50 mg Capsule by Helix Pharma




Decision: Approved.


Applicant


Hattar






Type of Form Form-5

Finished Product Specification BP Specs




MHRA Approved

Me-too status Axicon 150 mg Capsule by M/s Axis Pharma

Candia 150 mg Capsule by Fynk Pharma



Decision: Approved.


Applicant


Hattar






Type of Form Form-5





MHRA Approved

Me-too status Mycol 200 mg Capsule by M/s Nex Pharma

Fcozole 200 mg Capsule by MediCraft Pharma



Decision: Approved.


Applicant


Hattar

Brand Name +Dosage Form + Strength Reldene Capsule 20 mg



Piroxicam…..20 mg

Pharmacological Group NSAID

Type of Form Form-5

Finished Product Specification Mfg Specs

Pack size & Demanded Price 10,20 & 30’s / As per SRO



Feldene 20 mg Capsules by Pfizer (USFDA approved)

Me-too status Axicam 20 mg Capsule by M/s Mas Pharmaceuticals

Biocam 20 mg Capsule by Biorax Pharma


Remarks of the Evaluator. Complete salt name is not written


Decision: Deferred for revision of formulation including salt form as per reference product along



Applicant


Hattar

Brand Name +Dosage Form + Strength Rhlogin Capsule 50 mg



Diclofenac Sodium (as SR pellets)…..50mg



Type of Form Form-5

Finished Product Specification Mfg

Pack size & Demanded Price 10, 20 & 30’s / As per SRO



DIFENE Ireland Approved.

Me-too status Amfac 50mg Capsules by M/S Ambrosia Pharma



Decision: Approved with BP specifications.


Applicant


Hattar




Diclofenac Sodium (as SR pellets)…..75mg



Type of Form Form-5





MHRA Approved

Me-too status Fenal 75mg Capsules by M/S Alson Pharma

Zwitter 75 mg Capsules by Willshire Labs





Applicant


Hattar




Diclofenac Sodium (as SR pellets)…..100 mg



Type of Form Form-5





Rhumalgan XL100 mg Modified-Release Capsules MHRA

Approved

Me-too status Anifen 100 mg Capsules by M/S Medera Pharma

Dycnom 100 mg Capsules by M/S Genome Pharma






Applicant


Hattar

Brand Name +Dosage Form + Strength Ransamin Capsule 250 mg



Tranexamic Acid…..250 mg

Pharmacological Group Antifibrinolytics

Type of Form Form-5


Pack size & Demanded Price 10, 20, 30 & 100’s / As per SRO



TOWA 250 mg Capsules by M/S Towa Pharmaceuticals Japan

Me-too status BRINO 250 mg Capsules by M/S Sami Pharma

BTROL 250 mg Capsule by M/S Bosch Pharma



Decision: Approved.


Applicant


Hattar

Brand Name +Dosage Form + Strength Ransamin Capsule 500 mg



Tranexamic Acid…..500 mg

Pharmacological Group Antifibrinolytics

Type of Form Form-5


Pack size & Demanded Price 10, 20, 30 & 100’s / As per SRO



Tranex 500mg Capsule (AIFA Italy Approved)

Me-too status BRINO 500 mg Capsules by M/S Sami Pharma

BTROL 500 mg Capsule by M/S Bosch Pharma

GMP status

Remarks of the Evaluator. Reference product could not be confirmed

Decision: Approved.


Applicant


Hattar

Brand Name +Dosage Form + Strength Rylica Capsule 50 mg



Pregabalin…….50mg

Pharmacological Group Anticonvulsants

Type of Form Form-5

Finished Product Specification MfgSpecs




Alzain 50 mg Capsules, Hard. MHRA approved

Me-too status Hilin 50 mg Capsule by Highnoon Pharma

Zeegap 50 mg Capsule by Hilton Pharma






Applicant


Hattar






Type of Form Form-5

Finished Product Specification MfgSpecs











Applicant


Hattar


Diary No. Date of R& I & fee Diary No: 23191, 08-11-2019 , Rs: 20,000/- , 06-11-2019




Type of Form Form-5












Applicant


Hattar






Type of Form Form-5













Applicant


Hattar






Type of Form Form-5





Lyrica 200 mg Capsules by Pfizer

Me-too status XAAR 200 mg Capsule by Wilshire Labs

Sigab 200 mg Capsule by Atco Labs





Applicant


Hattar






Type of Form Form-5





Lyrica 300 mg Capsules by Pfizer







Applicant


Hattar

Brand Name +Dosage Form + Strength Relbax Capsule 100 mg



Celecoxib .............….100mg


Type of Form Form-5





Celebrex 100mg capsule of M/s Pfizer Limited (MHRA

Approved)

Me-too status Celexx 100mg Capsules by M/S GETZ Pharma.

Celetab 100mg Capsules by M/S INDUS Pharma





Applicant


Hattar

Brand Name +Dosage Form + Strength Relbax Capsule 200 mg




Celecoxib .............….200mg


Type of Form Form-5





Celebrex 100mg capsule of M/s Pfizer Ltd (MHRA Approved)

Me-too status Celexx 200mg Capsules by M/S GETZ Pharma.

Celetab 200mg Capsules by M/S INDUS Pharma




Liquid Injection Section (General) 11 products/ 10 molecules


Applicant


Hattar

Brand Name +Dosage Form + Strength Roltval N Injection (IM/IV) 75mg + 20mg/2 mL


Composition Each 2 mL Ampoule Contains:

Diclofenac sodium…….…75mg

Lidocaine HCl…….20mg

Pharmacological Group NSAID & Local Anesthesia

Type of Form Form-5

Finished Product Specification Manufacturer’s specs

Pack size & Demanded Price 2 mL x 5’s & 10’s / As per SRO




Me-too status Diclotal 2 mL Injection by M/s Berlex labs, Multan






Applicant


Hattar

Brand Name +Dosage Form + Strength Roltval Injection (IM/IV) 75mg/3 mL


Composition Each 3 mL Ampoule Contains:

Diclofenac sodium…….…75mg


Type of Form Form-5


Pack size & Demanded Price 3 mL x 5’s, 10’s & 100’s / As per SRO




Me-too status Defnac 3 mL Injection by M/s Searle






Applicant


Hattar

Brand Name +Dosage Form + Strength Rindrop Injection (IM/IV) 5mg / mL



Composition Each mL Ampoule Contains:

Vitamin D3 ………. 5 mg

Pharmacological Group Vitamin D Analogue

Type of Form Form-5





Vitamin D3 Bon Injection (ANSM France Approved)

Me-too status D . Drop 5 mg/mL Injection by M/s Ipram Pharma





Applicant


Hattar

Brand Name +Dosage Form + Strength Rethycobal Injection (IM/IV) 500 mcg / mL



Mecobalamin ………. 500 mcg

Pharmacological Group Vitamin B 12 Analogue

Type of Form Form-5





Mecobalamin Injection 500 mcg (PMDA Japan Approved)

Me-too status Cobolmin 500 mcg/mL Injection by M/s Macter Pharma





Applicant


Hattar

Brand Name +Dosage Form + Strength Revofer Injection (IV) 100 mg / 5mL


Composition Each 5mL Ampoule Contains:

Iron Sucrose ………. 100 mg

Pharmacological Group Haematenic

Type of Form Form-5

Finished Product Specification USP specs




Venofer 100 mg / 5ml Injection By Vifor Pharma

Me-too status Irofit 100 mg/5 mL Injection by M/s Zafa Pharma


Remarks of the Evaluator. Equivalency factor is not written

Decision: Deferred for revision of label claim as per reference product along with submission of

requisite fee.


Applicant


Hattar

Brand Name +Dosage Form + Strength Re - Spa Injection (IM/IV) 40 mg / 2mL



Drotaverine hydrochloride ………. 40 mg

Pharmacological Group Antispasmodic


Type of Form Form-5





reference for drotaverine 40mg/2ml injection in three

European countries

Me-too status Spink In 40 mg/2 mL Injection by M/s GT Pharma





Applicant


Hattar

Brand Name +Dosage Form + Strength Ramal Injection (IM/IV) 100 mg / 2mL



Tramadol hydrochloride ………. 100 mg

Pharmacological Group Opioid Analgesic

Type of Form Form-5


Pack size & Demanded Price 2 mL x 1’s, 5’s, 10’s, 20’s & 50’s / As per SRO



Zydol 100 mg / 2 ml Injection (MHRA Approved)

Me-too status Tramed 100 mg/2 mL Injection by M/s Cirin Pharma





Applicant


Hattar

Brand Name +Dosage Form + Strength Rvil Injection (IM/IV) 25 mg / 2mL



Pheniramine Maleate ………. 25 mg


Type of Form Form-5






Me-too status Zafvil 25 mg/2 mL Injection by M/s Zafa Pharma






Applicant


Hattar

Brand Name +Dosage Form + Strength Water For Injection (WFI) (IM/IV)



Water for Injection ………. 100 %

Pharmacological Group Diluent

Type of Form Form-5


Pack size & Demanded Price 2 mL & 5mL x 1’s, 5’s, 10’s, 50’s & 100’s / As per SRO




Water for Injection (MHRA Approved)

Me-too status Water for Injection by M/s Pulse Pharma



Decision: Approved. Firm will select one volume either 2ml or 5ml and Chairman Registration

Board is authorized to issue Registration letter accordingly.


Applicant


Hattar

Brand Name +Dosage Form + Strength Ryloxaine Injection (IM) 20 mg / 2mL



Lignocaine hydrochloride ………. 10 mg

Pharmacological Group Local Anaesthetic

Type of Form Form-5


Pack size & Demanded Price 2 mL x 5’s, 10’s, 50’s & 100’s / As per SRO



Lidocaine 1 % Injection (MHRA approved)

Me-too status MHRA Approved



Decision: Approved.


Applicant


Hattar

Brand Name +Dosage Form + Strength Ryloxaine Injection (IM) 40 mg / 2mL



Lignocaine hydrochloride ………. 20 mg

Pharmacological Group Local Anaesthetic

Type of Form Form-5


Pack size & Demanded Price 2 mL x 5’s, 10’s, 50’s & 100’s / As per SRO



Lidocaine 2 % Injection (MHRA approved)

Me-too status Locaine 40 mg/2 mL Injection by M/s Saydon Pharma



Decision: Approved.

Dry Powder Injection Section (Cephalosporin)

29 products/ 07 molecules


Applicant


Hattar

Brand Name +Dosage Form + Strength Korephin Injection (I.M.) 250 mg


Composition Each vial Contains:

Ceftriaxone sodium eq. to Ceftriaxone……250mg

Pharmacological Group Cephalosporin Antibiotic

Type of Form Form-5


Pack size & Demanded Price 1’s, 5’s & 10’s / As per SRO



USFDA Approved


Me-too status Oxidil 250 mg Injection by M/s Sami Pharma



Decision: Approved.


Applicant


Hattar

Brand Name +Dosage Form + Strength Korephin Injection (I.M.) 500 mg



Ceftriaxone sodium eq. to Ceftriaxone……500mg


Type of Form Form-5





USFDA Approved




Decision: Approved.


Applicant


Hattar

Brand Name +Dosage Form + Strength Korephin Injection (I.M.) 1 g



Ceftriaxone sodium eq. to Ceftriaxone……1g


Type of Form Form-5





MHRA Approved

Me-too status Oxidil 1 g Injection by M/s Sami Pharma



Decision: Approved.


Applicant


Hattar

Brand Name +Dosage Form + Strength Korephin Injection (I.M.) 2 g



Ceftriaxone sodium eq. to Ceftriaxone……2 g


Type of Form Form-5





Could not be confiremd








Applicant


Hattar

Brand Name +Dosage Form + Strength Korephin Injection (I.V.) 250 mg



Ceftriaxone sodium eq. to Ceftriaxone……250 mg


Type of Form Form-5





USFDA Approved




Decision: Approved.


Applicant


Hattar

Brand Name +Dosage Form + Strength Korephin Injection (I.V.) 500 mg



Ceftriaxone sodium eq. to Ceftriaxone……500 mg


Type of Form Form-5





USFDA Approved




Decision: Approved.


Applicant


Hattar

Brand Name +Dosage Form + Strength Korephin Injection (I.V.) 1 g





Type of Form Form-5





USFDA Approved




Decision: Approved.


Applicant


Hattar

Brand Name +Dosage Form + Strength Korephin Injection (I.V.) 2 g






Type of Form Form-5





MHRA Approved




Decision: Approved.


Applicant


Hattar

Brand Name +Dosage Form + Strength Spaforan Injection (IM/IV) 250 mg



Cefotaxime Sodium eq to Cefotaxime………250mg


Type of Form Form-5





MHRA Approved

Me-too status Rifodime 250 mg Injection by M/s Medimarkers Labs



Decision: Approved.


Applicant


Hattar

Brand Name +Dosage Form + Strength Spaforan Injection (IM/IV) 500 mg



Cefotaxime Sodium eq to Cefotaxime………500mg


Type of Form Form-5





MHRA Approved

Me-too status Rifodime 500 mg Injection by M/s Medimarkers Labs



Decision: Approved.


Applicant


Hattar

Brand Name +Dosage Form + Strength Spaforan Injection (IM/IV) 1 g



Cefotaxime Sodium eq to Cefotaxime………1 g


Type of Form Form-5






MHRA Approved

Me-too status Rifodime 1g Injection by M/s Medimarkers Labs



Decision: Approved.


Applicant


Hattar

Brand Name +Dosage Form + Strength Spaforan Injection (IM/IV) 2 g



Cefotaxime Sodium eq to Cefotaxime………2 g


Type of Form Form-5





MHRA Approved

Me-too status Rifodime 2g Injection by M/s Medimarkers Labs



Decision: Approved.


Applicant


Hattar

Brand Name +Dosage Form + Strength Roftum Injection (IM/IV) 250 mg



Ceftazidime pentahydrate eq to Ceftazidime buffered with

Sodium Carbonate………250mg


Type of Form Form-5





Fortum 250 mg Dry Powder Injection M/s GlaxoSmithKline UK

(MHRA Approved)

Me-too status Biomed 250 mg Injection by M/s MediCraft Pharma



Decision: Approved.


Applicant


Hattar

Brand Name +Dosage Form + Strength Roftum Injection (IM/IV) 500 mg




Sodium Carbonate ………500mg


Type of Form Form-5





Zorvolex 500 mg Injection by Iroko Pharmaceuticals

(MHRA Approved)


Me-too status Biomed 500 mg Injection by M/s MediCraft Pharma

GMP status New License (DML # 000906 Dated 28-06-2019)


Decision: Approved.


Applicant


Hattar

Brand Name +Dosage Form + Strength Roftum Injection (IM/IV) 1 g




Sodium Carbonate ………1 g


Type of Form Form-5





Zorvolex 1g Injection by Iroko Pharmaceuticals

(MHRA Approved)

Me-too status Biomed 1 g Injection by M/s MediCraft Pharma



Decision: Approved.


Applicant


Hattar

Brand Name +Dosage Form + Strength Raxifime Injection (IM/IV) 500 mg



Cefipime as HCl (with L-Arginine)………..500mg


Type of Form Form-5





USFDA Approved

Me-too status Cepime 500 mg Injection by M/s Shaigan Pharma



Decision: Approved.


Applicant


Hattar

Brand Name +Dosage Form + Strength Raxifime Injection (IM/IV) 1 g



Cefipime as HCl (with L-Arginine)………..1 g


Type of Form Form-5





USFDA Approved

Me-too status Cepime 1 g Injection by M/s Shaigan Pharma




Decision: Approved.


Applicant


Hattar

Brand Name +Dosage Form + Strength Ramnex Forte Injection (IM/IV) 1 g



Cefoperazone Sodium eq. to Cefoperazone …… 500mg

Sulbactum Sodium eq. to Sulbactum ………...…500mg


Type of Form Form-5

Finished Product Specification JP Specs




SULPERAZONE INJECTION by Pfizer Inc.

(PMDA Approved)

Me-too status Cebac 1 g Injection by M/s Bosch Pharma



Decision: Approved.


Applicant


Hattar

Brand Name +Dosage Form + Strength Ramnex Forte Injection (IM/IV) 2 g



Cefoperazone Sodium eq. to Cefoperazone …… 1000mg

Sulbactum Sodium eq. to Sulbactum ………...…1000mg


Type of Form Form-5

Finished Product Specification JP Specs




Approved in 03 European countries, i.e., Czech Republic,

Poland and Slovakia

Me-too status Cebac 2 g Injection by M/s Bosch Pharma



Decision: Approved.


Applicant


Hattar

Brand Name +Dosage Form + Strength SepStar Injection (IM/IV) 500 mg



Cefepime Hydrochloride eq to Cefepime………500mg


Type of Form Form-5





Cefipime hydrochloride 500mg Injection

M/s Hospira, Inc. (USFDA approved)

Me-too status USPIME 500 mg Injection by M/S USAWAPharma



Decision: Approved.



Applicant


Hattar

Brand Name +Dosage Form + Strength SepStar Injection (IM/IV) 1000 mg



Cefepime Hydrochloride eq to Cefepime………1000mg


Type of Form Form-5





Cefipime hydrochloride 500mg Injection

M/s Hospira, Inc. (USFDA approved)

Me-too status USPIME 1000 mg Injection by M/S USAWAPharma



Decision: Approved.


Applicant


Hattar

Brand Name +Dosage Form + Strength Refron Injection (IV) 500 mg



Cefpirome Sulphate eq. to Cefpirome ………500mg


Type of Form Form-5

Finished Product Specification Manufacturer’s Specs




Cefrom Injection, ANSM (France) Approved

Me-too status Cefrom 500mg Injection by Sanofi Aventis





Applicant


Hattar

Brand Name +Dosage Form + Strength Refron Injection (IV) 1000 mg



Cefpirome Sulphate eq. to Cefpirome ………1000mg


Type of Form Form-5

Finished Product Specification Manufacturer’s Specs




Cefrom Injection, ANSM (France) Approved

Me-too status Cefrom 1000mg Injection by Sanofi Aventis





Applicant


Hattar

Brand Name +Dosage Form + Strength Rizacef Injection (IM/IV) 125 mg




Cefuroxime sodium eq. to Cefuroxime……. 125 mg


Type of Form Form-5





Cefuroxime by M/s Flynn Pharma Ltd, (MHRA Approved)

Me-too status CEFUSAVE 125mg Injection by M/S MEDISAVE Pharma



Decision: Approved.


Applicant


Hattar






Type of Form Form-5





ZINNAT 250 mg INJECTION by GSK UK, (MHRA

Approved)

Me-too status CEFUR 250 mg Injection by M/S Maxitech Pharma



Decision: Approved.


Applicant


Hattar






Type of Form Form-5






Approved)

Me-too status CEFUR 500 mg Injection by M/S Maxitech Pharma



Decision: Approved.


Applicant


Hattar






Type of Form Form-5







Approved)

Me-too status EVOROX750mg Injection by M/S Pharm EVO



Decision: Approved.


Applicant


Hattar






Type of Form Form-5





ZINNAT 1000mg INJECTION by GSK UK,(MHRA

Approved)

Me-too status EVOROX 1000 mg Injection by M/S Pharm EVO



Decision: Approved.


Applicant


Hattar

Brand Name +Dosage Form + Strength Rizacef Injection (IM/IV) 1.5 g



Cefuroxime sodium eq. to Cefuroxime……. 1.5 g


Type of Form Form-5





ZINNAT 1.5 g INJECTION by GSK UK,(MHRA Approved)

Me-too status KEFROX1.5g Injection by M/S CCL Pharma



Decision: Approved.


c. Verification of stability study data 245. Name and address of manufacturer /

Applicant

M/s Sami Pharmaceuticals (Pvt.) Ltd. F-95, Off. Hub River

Road, S.I.T.E., Karachi

Brand Name +Dosage Form + Strength Lagita Double Action Suspension

500mg+213mg+325mg

Diary No. Date of R& I & fee Dyn:15674, 07-03-2019, Rs.50,000/- (04-03-2019)

Composition Each 10ml suspension contains:

Sodium Alginate…. 500mg

Sodium Bicarbonate…213 mg

Calcium Carbonate…325mg

Pharmacological Group Antacid

Type of Form Form-5 D



Pack size & Demanded Price As per Drug Pricing policy, amber glass bottle 120ml, USP type

III

Approval status of product in Reference

Regulatory Authorities.

Gaviscon Double Action aniseed

MHRA Approved

Me-too status N/A

GMP status


STABILITY STUDY DATA SUBMITTED INITIALLY

Drug Lagita Chewable Tablet

250mg+133.5mg+80mg

Name of Manufacturer M/s Sami Pharmaceuticals (Pvt.) Ltd. F-95, Off. Hub River Road, S.I.T.E., Karachi

Manufacturer of API Sodium Alginate

Qingdao Bright Moon

Seaweed Group Co. Ltd

Add:67, Haibin 1st Road,

Jiaonan , Qingdao, China

Sodium Bicarbonate

TATA Chemicals Europe

Limited Winnington

Lane, Northwich,

Cheshire, UK

Calcium Carbonate

Sudeep Pharma Pvt. Ltd.

Gujarat

API Lot No. H051707037 3195SB00950 18C/CP/080

Description of Pack


Alu PVC blister

Stability Storage Condition Real Time: 30°C ± 2°C / 65% ± 5%RH


Time Period Real Time: 6 months Accelerated: 6 months

Frequency Real Time: 0,3,6,9,12,18,24,36 (months) Accelerated:0,1,2,3,4,6 (months)

Batch No. Lab-01 Lab-02 Lab-03


Manufacturing Date July-2018

Date of Initiation July-2018

No. of Batches 3

Date of Submission Dyn:15674, 07-03-2019,


Sr.

No.


1. COA of API Yes



manufacturer issued by regulatory


Yes Yes

3. Protocols followed for conduction of

stability study and details of tests. Yes




sheets etc.

Yes


5. Documents confirming import of API etc. Sodium Alginate

Copy of Commercial Invoice (invoice no. BMM17132)

attested by Assistant Director (I & E) DRAP (Karachi)

dated 19-09-2017.

Quantity: 5000 Kg.

Sodium Bicarbonate

Copy of Commercial Invoice (invoice no. 8100088448)

attested by Assistant Director (I & E) DRAP (Karachi)

dated 1-06-2018.

Quantity: 5.250Kg.

Calcium Carbonate

Copy of Commercial Invoice (invoice no. SPP/EX021/18-

19) attested by Assistant Director (I & E) DRAP (Karachi)

dated 2-05-2018.

Quantity: 12Kg.




Yes


study till assigned shelf life of the product. Yes


Rules, 1978.

Yes

REMARKS OF EVALUATOR2

Report on Investigation of Authenticity / Genuineness of data submitted for registration of Lagita Double

Action Suspension 500mg + 213mg + 325mg (Sodium Alginate + Sodium bicarbonate + Calcium Carbonate)

Suspension by M/s. Sami Pharmaceutical (Pvt.) Ltd., F-95, S.I.T.E, Karachi.

Reference No: F.13-11/2017-PEC (pt) dated 26th December, 2019.

Investigation Date and Time: 30th January, 2020 (Morning).

Investigation Site: Factory premises of M/S. Sami Pharmaceutical (Pvt.) Ltd., F-95, S.I.T.E, Karachi.

Background:

Registration Board meeting considered the applications of M/s. Sami Pharmaceutical (Pvt.) Ltd., F-95, S.I.T.E,

Karachi for registration of Lagita Double Action Suspension 500mg + 213mg + 325mg (Sodium Alginate +

Sodium bicarbonate + Calcium Carbonate) Suspension. Registration Board considered scientifically rational

laboratory scale data submitted by the firm as pre-requisite of registration being new formulation and constituted

a three member panel to investigate the authenticity / genuineness of data (import of raw material and stability

data). Panel was advised to conduct inspection of the firm as per decision of Registration Board and to submit

report for further consideration.


1. Dr. Rafeeq Alam Khan, Meritorious Professor, Department of Pharmacology, University of Karachi,

Karachi, Member Registration Board, Islamabad.

2. Dr. Saif-ur-Rehman Khattak, Director / FGA, CDL, DRAP, Karachi.

3. Mr. Kirshan Das, Assistant Director, DRAP Office, Karachi.


Investigation of the authenticity / genuineness of data (import of raw material and stability data), manufacturing

of stability batches and stability studies on these batches.







Detail of Investigation:

Sr.# Questions Remarks


import API including approval from DRAP?

The firm has imported Sodium Alginate from M/s. Qingdao

bright moon seaweed – China (B.no. HO51707037) Qty.

received 5000 Kg as per invoice no. BMM17152, Sodium

Bicarbonate M/s TATA Chemicals – UK

(B.no.0000042802) Qty. received 25 Kg, Calcium

carbonate M/s Sudeep Pharma – India (B.No.18C/CP/080)

Qty. received 12kg as per invoice no. SPPL/EX021/18-19

and all material are cleared by ADC.

All these APIs are used in our already registered product,

hence the trial batches of Lagita double action suspension

manufactured from commercial import.



Sodium Alginate is already approved source using in other

registered products, having GMP, Vendor Evaluation form

and DMF.

Sodium Bicarbonate: Source is GMP qualified and having

DMF & Vendor Evaluation form.

Calcium Carbonate: Source is GMP qualified and having

DMF & Vendor Evaluation form.


import of API reference standard and

impurity standards?

The firm has necessary documents related to import of the

sodium alginate and sodium bicarbonate reference

standards. No known impurity related to both APIs has been

reported in any pharmacopeia and relevant DMF.

4. Do you have certificate of Analysis of the

API, reference standards and impurity

standards?

The firm has CoAs of APIs and reference standards of the

APIs.

5. Do you have GMP certificate of APIs


of country of origin?

The firm has the GMP certificate of Sodium Alginate from

M/s. Qingdao bright moon seaweed – China, Sodium

Bicarbonate from M/s TATA Chemicals – UK & Calcium

carbonate from M/s Sudeep Pharma – India.

6. Do you use APIs manufacturer method of

testing for testing APIs?

All APIs have been tested as per pharmacopeia (BP).

7. Do you have stability studies reports on API? The firm has the Stability study reports of APIs.




Since there is no apparent degradation of the API’s, hence

no quantification of the degradation products can be made.

The stability indicating method in this case is not valid.



Since there is no apparent degradation of the API’s, hence

no quantification of the degradation products can be made.

The stability indicating method in this case is not valid.


the API, its reference standard and impurities

standards?

The firm has some quantities in hand for working standards

of sodium alginate and sodium bicarbonate. Impurity

standards are invalid.


excipients?

The firm has used pharmaceutical grade excipients

including methyl paraben, propyl paraben, carbomer 974P,

sodium saccharine, peppermint flavor and sodium

hydroxide.



The firm has documents confirming the import of

excipients used.

13. Do you have test reports and other records on


The firm has complete test reports and other records of the

excipients.


protocols for the development of Lagita

double action Suspension?


development of product based on QbD approach.




The firm has performed drug-excipients compatibility

studies as part of the QbD approach.

16. Have you performed comparative studies? The firm has performed comparative studies with Gaviscon

Double Action Suspension of M/s Reckitt Benkiser, UK for

this this dosage form.


section

The firm has dedicated section for the product development

(R&D).

18. Do you have necessary equipment available

in product development section for

development of Lagita double action

Suspension?

The firm has necessary equipment and instruments for the

development of products in our development section.

19. Are the equipments in product development

section qualified?

All equipments in product development section are

qualified.


calibration / re-qualification program for the

equipment used in PD section?

The firm has proper maintenance / calibration / re-

qualification program for the equipment used in Product

Development section.




The firm has trained & qualified staff in product

development section with proper knowledge and training in

product development.


batches for the stability studies of Lagita

double action Suspension as required?

The firm have manufactured three stability batches for

stability studies of Lagita double action Suspension with

batch numbers Lab-01, Lab-02 and Lab-03.

The batch sizes of all three batches are 26 liters each.


size of stability batches?

Batch size of stability batches are fixed according to the

sample requirements as per testing and frequencies during

stabilities studies.

24. Do you have complete record of production


The firm has complete record of production of stability

batches.


stability batches?

The firm has protocols for stability testing of stability

batches.



The firm has developed and performed analytical method

validation studies for the testing of Lagita double action

Suspension.



your firm is given by any other lab?

The firm has used the in-house developed and validated

method.



being used in the test and analysis of API and

the finished drug?

The firm has proper documents confirming the qualification

of equipment / instruments being used in the test and

analysis of API and the finished drug.


indicating?

Not applicable

30. Do your HPLC software 21CFR Compliant? The HPLC software is 21CFR Compliant.

31. Can you show Audit trail reports? Audit trail report are available and reviewed.



The firm has remaining quantities of stability batches.


stability testing?

The firm has kept all the 3 batches on real time stability

program. 18 months studies are complete and results are

satisfactory.


equipments used in Lagita double action

Suspension production and analysis?

The firm has valid calibration status for the equipment used

in Lagita double action Suspension.


35. Do proper and continuous monitoring and



chambers.

Data Loggers are attached with stability chambers.



compliant?

All manufacturing area, equipment, personnel and utilities

are GMP compliant.

Conclusions:


for registration of Lagita Double Action Suspension 500mg + 213mg + 325mg (Sodium Alginate + Sodium

bicarbonate + Calcium Carbonate) Suspension is verifiable to satisfactory level.

2. The related manufacturing area, equipment, personnel and utilities are GMP compliant and well suited

for the manufacturing of Lagita Double Action Suspension 500mg + 213mg + 325mg (Sodium Alginate + Sodium

bicarbonate + Calcium Carbonate) Suspension.

Recommendations:

The firm may kindly be granted necessary registration of Lagita Double Action Suspension 500mg + 213mg +

325mg (Sodium Alginate + Sodium bicarbonate + Calcium Carbonate) Suspension.

Decision: Registration Board decided to approve registration of Lagita Double Action Suspension

by M/s Sami Pharmaceutical (Pvt.) Ltd., F-95, S.I.T.E, Karachi. Manufacturer will place first

three production batches on long term stability studies throughout proposed shelf life and on

accelerated studies for six months.



M/s CCL Pharmaceuticals Pvt Ltd. 65-Industrial Estate,

Kot Lakhpat, Lahore-54770, Pakistan.

Name, address of Manufacturing site. M/s CCL Pharmaceuticals Pvt Ltd. 62-Industrial Estate,

Kot Lakhpat, Lahore-54770, Pakistan.

Status of the applicant Manufacturer Importer

Is involved in none of the above (contract giver)

Dy No. and date of submission Dy No. 13406, : 5-12-2018


The proposed proprietary name/brand name Dexlan DR Capsule 60mg




Dexlansoprazole (as Delayed release pellets)…….60mg

Dosage form of applied drug Capsule

Route of administration Oral

Pharmacotherapeutic Group of (API) Antacids/ Antiflatulents/Antipeptic ulcerant

Pharmacopoeial reference Firm has submitted:- “Innovators Specifications”

Proposed Pack size 10’s, 14’s, 20’s, 28’s and 30’s

Proposed unit price As per Innovator’s Price

The status in reference regulatory authorities USFDA Approved

For generic drugs (me-too status)

Valid drug manufacturing license/Drug Sale

License

Copy of Drug manufacturing License by way of

formulation issued on 21-7-2015 is submitted.

Evidence of approval of manufacturing

facility / approved section from licensing

authority

Copy of grant of Additional section (Capsule General

section Revised) from CLB is submitted

Type of Application New Drug Product (NDP)

Generic Drug Product (GDP)


Intended use of pharmaceutical product Domestic sale

Export sale

Domestic and Export sales

For imported products, please specify one of

following:

Finished Pharmaceutical Product Import

Bulk Import and local repacking (Specify status of

bulk)

Bulk Import local repacking for Export purpose only

Contract Manufacturing as per Rule 20-A of

Drugs (Licensing, Registering and

Advertising) Rules, 1976

Domestic Manufacturing

List of registered products NA

Manufacturer’s site master file and

credentials (for importers)

Yes

Identification of signature of authorized persons, Incharge

Production, Quality Control & Quality Assurance of manufacturer.

Yes

Proposed label (outer (secondary) & inner (primary)) & colour

scheme in accordance with Drug (Labelling & Packing) Rules,

1986 along with specimens

Yes

Description of Batch numbering system Yes

Training evidence of technical staff with respect of manufacturing

of applied drug (mandatory in case of specially designed

pharmaceutical product / Novel Dosage Form).

Not Applicable

Summary of Product Characteristics (SmPC) including

Prescribing Information (PI) along with Patient information

Leaflet (PIL) of the Finished Pharmaceuticals Product (FPP).

Yes

Commitments Firm has submitted

undertaking/commitments on it’s

letter head

Protocols along with the commitment to follow Good Laboratory

Practices (GLP) by the Manufacturer.

Yes

Protocols to implement Good Pharmacovigilance Practice by the

Pharmacovigilance department/section of the Manufacturer /

Company.

Yes

Information on Prior-related Applications N/A

Electronic Review Package N/A

QIS (Quality Information Summary) Yes

Drug Substance related Document including following:

a. Name and address of API manufacturer. M/s Vision Pharmaceuticals Pvt Ltd.

Plot No. 22, Industrial Triangle Kahuta road,

Islamabad

b. Approval of manufacturing facility of API by

regulatory body of country and validity.

Copy of Drug manufacturing License by way

of Semi-basic issued on 2-12-2014 is

submitted.

c. Vendor qualification / audit is Document based

Site inspection based

d. Reason for above point (c) Already approved vendor for other API’s

MODULE 2: OVERVIEWS & SUMMARIES


Drug Substance Firm has submitted overall summary of drug substance including general

information, specification, and characterization, control of the API,

reference standard, container closure system and stability.

Drug Product Firm has submitted summary of drug product including description and

composition of drug product, pharmaceutical development, manufacture,

control of excipients, manufacturing process development, container

closure system, microbiological attributes and compatibility, controls of

drug product, reference standards or materials and stability studies.

MODULE 3: QULITY / CMC

3.2.S: Drug substance

Firm has submitted details of drug substance and pellets including the stability studies data.

3.2.P: Drug Product

Description and composition of

drug product

Firm has submitted description and composition of drug product

Pharmaceutical development Firm has provided details of drug substance, excipients, formulation

development, overages, physicochemical and biological properties,

manufacturing process development, container closure system,

microbiological attributes and compatibility.

Manufacture Firm has submitted detail of manufacturer, batch formula,

description of manufacturing process and process controls, controls

of critical steps and intermediates, process validation and or

evaluation.

Control of excipients N/A

Control of drug product Firm has submitted details of specification, analytical procedures,

validation of analytical procedures, batch analysis, and

characterization of impurities and justification of specification.

Reference standard or materials Firm has submitted certificate of analysis of reference standards and

impurity standards

Container closure system HDPE bottle with dessicant

Stability Firm has provided complete stability study data of 3 batches as per

Zone IV-A

Comparative dissolution profile

MODULE 4: NON-CLINICAL / SAFETY

Pharmacology Firm has submitted that being a generic product non-clinical data is

not Applicable

Pharmacokinetics Firm has submitted that being a generic product non-clinical data is

not Applicable

Toxicology Firm has submitted that being a generic product non-clinical data is

not Applicable

MODULE 5: CLINICAL / EFFICACY

Firm has submitted that being a generic product clinical data is not Applicable while in-vitro dissolution

tests complementary to bioequivalence studies.


Manufacturer of API M/s Vision Pharmaceuticals Pvt Ltd.

Plot No. 22, Industrial Triangle Kahuta road, Islamabad

Firm is obtaining API pellets from the above Manufacturer.

API Lot No. Batch NO. DLP287


Description of Pack


Alu-Alu blister pack





Frequency Accelerated: 0, 3,6 (Months)

Real Time: 0, 3,6(Months)

Batch No. DXB T1/18 DXB T2/18 DXB T3/18

Batch Size 1500 capsules 1500 capsules 1500 capsules

Manufacturing Date July-2018 July-2018 July-2018

Date of Initiation July-2018 July-2018 July-2018

No. of Batches 03



COA of API Yes

Approval of API by regulatory authority of country of origin

or GMP certificate of API manufacturer issued by regulatory


cGMP certificate is valid until 25-1-

2019.


details of tests.

Yes

Data of 03 batches will be supported by attested respective

documents like chromatograms, laboratory reports, data

sheets etc.

Yes

Documents confirming import of API etc. Yes

All provided documents will be attested (name, sign and


Yes


Dexlan DR Capsule 60mg

S.# Shortcoming/Letter communicated to firm Firm Reply/Evaluation of firm’s reply

1. 1. Ref to your response (Annexure-IV). Process

validation data is not provided. Summary of validation

studies including the proposed protocol that will be

used for the validation of three commercial batches is

not provided.

2. Ref to your response (Annexure-X). The submitted

justification for specification is not considered

satisfactory. All specifications are developed as per In-

house standards and the same is mentioned in

justification. Kindly justify the specification with the

scientific rationale.

3. Ref to your response (Annexure-XV). Your response

is considered not satisfactory. You have to perform

comparative dissolution profile of your drug product

against the innovators product in three dissolution

mediums i.e. pH1.2, 4.5 and 6.8 as per dissolution

parameters defined in FDA dissolution database.

Firm has submitted, “Process validation

will be performed of 3 stability batches and

it shall be submitted to drap. However,

Process validation protocol is submitted.”

Firm has only provided the use of the test

parameter and not the justification.

Firm has performed CDP only on pH 7.0


Results of dissolution should be presented after

calculation of similarity factor f2.



M/s CCL Pharmaceuticals Pvt Ltd. 65-Industrial

Estate, Kot Lakhpat, Lahore-54770, Pakistan.

Name, address of Manufacturing site. M/s CCL Pharmaceuticals Pvt Ltd. 62-Industrial

Estate, Kot Lakhpat, Lahore-54770, Pakistan.

Status of the applicant Manufacturer Importer

Is involved in none of the above (contract giver)

Dy No. and date of submission Dy No. 13405, : 5-12-2018


The proposed proprietary name / brand name Dexlan DR Capsule 30mg




Dexlansoprazole (as Delayed release

pellets)…….30mg

Dosage form of applied drug Capsule

Route of administration Oral

Pharmacotherapeutic Group of (API) Antacids/ Antiflatulents/Antipeptic ulcerant

Pharmacopoeial reference Firm has submitted:- “Innovators Specifications”

Proposed Pack size 10’s, 14’s, 20’s, 28’s and 30’s

Proposed unit price As per Innovator’s Price

The status in reference regulatory authorities USFDA Approved

For generic drugs (me-too status)

Valid drug manufacturing license/Drug Sale

License


formulation issued on 21-7-2015 is submitted.

Evidence of approval of manufacturing facility

/ approved section from licensing authority

Copy of grant of Additional section (Capsule General

section Revised) from CLB is submitted

Type of Application New Drug Product (NDP)


Intended use of pharmaceutical product Domestic sale

Export sale


For imported products, please specify one of

following:


Bulk Import and local repacking (Specify status of

bulk)

Bulk Import local repacking for Export purpose only

Contract Manufacturing as per Rule 20-A of

Drugs (Licensing, Registering and

Advertising) Rules, 1976


List of registered products NA

Manufacturer’s site master file and credentials

(for importers)

Yes

Identification of signature of authorized persons, Incharge

Production, Quality Control & Quality Assurance of manufacturer.

Yes


Proposed label (outer (secondary) & inner (primary)) & colour

scheme in accordance with Drug (Labelling & Packing) Rules, 1986

along with specimens

Yes

Description of Batch numbering system Yes

Training evidence of technical staff with respect of manufacturing of

applied drug (mandatory in case of specially designed pharmaceutical

product / Novel Dosage Form).

Not Applicable

Summary of Product Characteristics (SmPC) including Prescribing

Information (PI) along with Patient information Leaflet (PIL) of the

Finished Pharmaceuticals Product (FPP).

Yes

Commitments Firm has submitted

undertaking/commitments on

it’s letter head

Protocols along with the commitment to follow Good Laboratory

Practices (GLP) by the Manufacturer.

Yes

Protocols to implement Good Pharmacovigilance Practice by the

Pharmacovigilance department/section of Manufacturer / Company.

Yes

Information on Prior-related Applications N/A

Electronic Review Package N/A

QIS (Quality Information Summary) Yes

Drug Substance related Document including following:

a. Name and address of API manufacturer. M/s Vision Pharmaceuticals Pvt Ltd. Plot No.

22, Industrial Triangle Kahuta road, Islamabad

b. Approval of manufacturing facility of API by

regulatory body of country and validity.


Semi-basic issued on 2-12-2014 is submitted.

c. Vendor qualification / audit is Document based


d. Reason for above point (c) Already approved vendor for other API’s

MODULE 2: OVERVIEWS & SUMMARIES

Drug Substance Firm has submitted overall summary of drug substance including

general information, specification, and characterization, control of

the API, reference standard, container closure system and stability.

Drug Product Firm has submitted summary of drug product including description

and composition of drug product, pharmaceutical development,

manufacture, control of excipients, manufacturing process

development, container closure system, microbiological attributes

and compatibility, controls of drug product, reference standards or

materials and stability studies.

MODULE 3: QULITY / CMC

3.2.S: Drug substance

Firm has submitted details of drug substance and pellets including the stability studies data.

3.2.P: Drug Product

Description and composition of

drug product

Firm has submitted description and composition of drug product

Pharmaceutical development Firm has provided details of drug substance, excipients,

formulation development, overages, physicochemical and

biological properties, manufacturing process development,


container closure system, microbiological attributes and

compatibility.

Manufacture Firm has submitted detail of manufacturer, batch formula,

description of manufacturing process and process controls,

controls of critical steps and intermediates, process validation and

or evaluation.

Control of excipients N/A

Control of drug product Firm has submitted details of specification, analytical procedures,

validation of analytical procedures, batch analysis, and

characterization of impurities and justification of specification.

Reference standard or materials Firm has submitted certificate of analysis of reference standards

and impurity standards

Container closure system HDPE bottle with dessicant

Stability Firm has provided completed stability study data of 3 batches as

per Zone IV-A

Comparative dissolution profile

MODULE 4: NON-CLINICAL / SAFETY

Pharmacology Firm has submitted that being a generic product non-clinical data

is not Applicable

Pharmacokinetics Firm has submitted that being a generic product non-clinical data

is not Applicable

Toxicology Firm has submitted that being a generic product non-clinical data

is not Applicable

MODULE 5: CLINICAL / EFFICACY

Firm has submitted that being a generic product clinical data is not Applicable while in-vitro dissolution

tests complementary to bioequivalence studies.


Manufacturer of API M/s Vision Pharmaceuticals Pvt Ltd.

Plot No. 22, Industrial Triangle Kahuta road, Islamabad

Firm is obtaining API pellets from the above Manufacturer.

API Lot No. Batch NO. DLP287

Description of Pack


Alu-Alu blister pack





Frequency Accelerated: 0, 3,6 (Months)

Real Time: 0, 3,6(Months)

Batch No. DXB T1/18 DXB T2/18 DXB T3/18

Batch Size 1500 capsules 1500

capsules

1500 capsules

Manufacturing Date July-2018 July-2018 July-2018

Date of Initiation July-2018 July-2018 July-2018

No. of Batches 03




COA of API Yes

Approval of API by regulatory authority of country of origin

or GMP certificate of API manufacturer issued by regulatory


cGMP certificate is valid until 25-1-

2019.

Protocols followed for conduction of stability study and details

of tests.

Yes


documents like chromatograms, laboratory reports, data sheets

etc.

Yes


All provided documents will be attested (name, sign and


Yes


Dexlan DR Capsule 30mg

S.No Shortcoming/Letter communicated to firm Firm Reply / Evaluation of the firm’s

reply

2. 4. Ref to your response (Annexure-IV). Process validation

data is not provided. Summary of validation studies

including the proposed protocol that will be used for the

validation of three commercial batches is not provided.

5. Ref to your response (Annexure-X). The submitted

justification for specification is not considered satisfactory.

All specifications are developed as per In-house standards

and the same is mentioned in justification. Kindly justify

the specification with the scientific rationale.

6. Ref to your response (Annexure-XV). Your response is

considered not satisfactory. You have to perform

comparative dissolution profile of your drug product

against the innovators product in three dissolution

mediums i.e. pH1.2, 4.5 and 6.8 as per dissolution

parameters defined in FDA dissolution database. Results

of dissolution should be presented after calculation of

similarity factor f2.

Firm has submitted, “Process validation

will be performed of 3 stability batches

and it shall be submitted to drap.

However, Process validation protocol is

submitted.”

Firm has only provided the use of the test

parameter and not the justification.

Firm has performed CDP only on pH 7.0

Inspection Report

PART-I:

1.1 General Information.

Name of Manufacturer M/s CCL Pharmaceuticals (Pvt.) Ltd.

Physical Address 62 Industrial Estate, Kot Lakhpat, Lahore.

Drug Manufacturing License

No. and validity

000052 by way of formulation

Valid till 20-07-2020.

Contact Address Mr. Irfan Sohail

Senior Manager Regulatory Affairs 0308-8884984

Date of Inspection. 26-08-2019

Purpose of Inspection Verification of authenticity of stability data for purpose of registration of

drugs with reference to DRAP’s letter No. F.13-11/2017-PEC (Pt) dated

30-07-2019.

Name of Inspector 01. Mr. Shaheen Iqbal, Director, DTL, Lahore.

02. Ms. Aisha Irfan, Area FID, DRAP, Lahore.


03. Mr. Hafiz Ahsan, Assistant Director, PEC (DRAP) Islamabad.

Name of firm Representatives Dr. Rizwan Mahmood, Director Quality Operations

Mr. Kamran Atif, Director Regulatory Affairs

Mr. Irfan Sohail, Senior Manager Regulatory Affairs

Mr. Shahid Anwar, General Manager R&D

Mr. Muhammad Fiaz, Quality Control Manager

Mr. Farhan Qureshi, Quality Assurance Manager

General Information about unit:

The firm is located in the industrial area at 62 Industrial Estate, Kot Lakhpat, Lahore, Pakistan. The firm was

established in 1965 initially and shifted to the existing site in 1984. The firm has production facility, supply chain,

engineering, quality control, quality assurance, research & development, regulatory and administrative

departments. The production operations at firm involve manufacturing, packaging and distribution of finished

pharmaceutical products. The firm is manufacturing generic products.

1.2 Focus of Inspection:

The inspection was focused on a thorough evaluation of data for stability studies of following products namely:


01 Dexlan DR Capsule 30mg


Dexlansoprazole (as Delayed release pellets)………….30mg

02 Dexlan DR Capsule 60mg


Dexlansoprazole (as Delayed release pellets)………….60mg

Panel also visited the R&D Laboratory and Quality Control Laboratory of the firm. The data was evaluated

according to the checklist provided as given below:

Details of investigation:

i) Dexlan DR Capsule 30mg and Dexlan DR Capsule 60mg

Q.# Questions Observation by panel


import of Dexlansoprazole delayed

release pellets APIs including approval

from DRAP?

The firm has procured 2kg Dexlansoprazole DDR 22.5%

pellets from M/s. Vision Pharmaceuticals, Islamabad (Batch

No. DLP287 and Invoice No. is 501646). API

Dexlansoprazole was procured from M/s Integrin Life

Sciences, Telangana, India by Vision Pharma.

2. What was the rationale behind selecting

the particular manufacturer of API?

Firm informed that they selected M/s Vision

Pharmaceuticals, Islamabad based on their Vendor

Qualification SOP.


import of reference standard and impurity

standards?

Firm purchased Dexlansoprazole working standard from

M/s Vision Pharmaceuticals, Islamabad, invoice no. 501646

dated 03.05.2018, and Dexlansoprazole sulphone and

sulphide impurities from M/s Vision Pharmaceuticals,

Islamabad, through Ref no. PO#IMP-0419 dated

01.04.2019 manufactured by M/s Integrin Life Sciences,

Telangana, India

4. Do you have certificate of Analysis of the


standards?

The firm had certificate of analysis for Dexlansoprazole

DDR Pellets, working standards and impurities standards

manufactured by M/s Integrin Life Sciences, Telangana,

India.



authority of country of origin?

Firm had provided valid GMP Certificate of M/s Vision

Pharmaceuticals, Islamabad issued by Additional Director

(QA & LT-I), DRAP, Islamabad dated 25th Feb, 2019.




The firm used pellets manufacturer’s method of testing

which was validated.


API?

The firm had stability studies reports on DDR pellets from

Vision Pharma conducted at Zone IV-A conditions.

8. If yes, whether the stability testing has

been performed as per SIM method and


quantified?

The stability testing had been performed as per SIM

method.



Firm had testing method to quantify the impurities as per

raw material manufacturers.


the API, its reference standard and


The firm had some remaining quantities of the DDR pellets

(Quantity = 187.25g) whereas working standard and

impurities are NIL.


excipients?

Since the product is filling of already prepared pellets in

Hard gelatin capsule and capsule shells used (size # 2 for

60mg & size # 4 for 30mg) were of pharmaceutical grade as

per the COA and related documents.



The firm has purchased Hard gelatin capsule shell from

local source i.e., M/s Gelcap, Karachi.

13. Do you have test reports and other records

on the excipients used?

The firm has test reports and other records on the excipient

used.



Dexlansoprazole Capsule?

The firm had written and authorized protocols for the

development of Dexlansoprazole Capsules. However, firm

was advised to improve the product development protocol.



Not applicable.



The firm has performed comparative dissolution studies

with reference product DEXILANT 30mg and 60mg

capsules manufactured by M/s. Takeda, USA. The

dissolution profiles of the firm capsules are comparable to

that of the reference product.


section

The firm had product development (R&D) section.

18. Do you have necessary equipment


for development of Dexlansoprazole

Capsule?

The firm had used commercial production area for filling of

pellets in capsules using automatic capsule filling machine.

19. Are the equipment in product


The equipments used in product development were

qualified.


calibration / re-qualification program for

the equipment used in PD section?

The firm had proper maintenance / calibration / re-

qualification program for the equipment used in product

development section.




development?

The firm had 06 Pharmacists and 02 Chemists in product

development section with suitable knowledge and training

in product development.


batches for the stability studies of

Dexlansoprazole Capsule as required?

The firm had manufactured three stability batches for the

stability studies of Dexlansoprazole Capsules (30mg and

60mg) with batch numbers i.e. DXA-T1-18, DXA-T2-18

and DXA-T3-18 for 30mg strength and DXB-T1-18, DXB-

T2-18 and DXB-T3-18 for 60mg strength. The batch size

for these batches are 1,500 capsules each.




The firm had criteria for fixing the batch size of stability

batches as per their internal document CQP-004-H in the

light of DRAP letter No. F.3-2/2014-I&E dated 08-12-2015.



The firm had record of production of stability batches for

which firm has provided Trial Forms.

25. Do you have protocols for stability testing


The firm had detailed protocols for stability testing of

stability batches.



The firm had developed and validated method of testing for

finished product based on method of testing of API

manufacturer. Validation of assay method was completed in

September, 2018 while first analysis of trial batches was

performed in July, 2018. Dissolution method validation was

not performed.




lab?

NA



being used in the test and analysis of

Dexlansoprazole Capsule API and the

finished drug?

The firm had proper documents confirming the qualification


analysis of API and the finished drug.


indicating?

The firm had used spike method to demonstrate that their

method is stability indicating.

30. Do your HPLC software 21CFR

Compliant?

HPLC used in the stability studies of current products was

gradient and not 21CFR 11 compliant. However, now the

firm has procured HPLC software 21CFR Compliant.

31. Can you show Audit trail reports on

Dexlansoprazole Capsule testing?

The audit trail was not active on the testing reports and log

of data was available in the HPLCs. The data was also

confirmed through record, chromatograms and logbooks.


degradation products and stability

batches?

The firm had remaining quantities (108 capsules of each

batch) of stability batches.


stability testing?

The firm had stability batches kept on stability testing.


the equipment used in Dexlansoprazole

Capsule production and analysis?

The firm had valid calibration status for the equipment used

in Dexlansoprazole Capsule production and analysis.

35. Do proper and continuous monitoring &

control are available for stability

chamber?

Adequate monitoring and control was available for stability

chamber. The firm has provided uninterrupted power supply

by UPS and generator.

36. Do related manufacturing area,

equipment, personnel and utilities be rated

as GMP compliant?

Requisite facilities were satisfactory and GMP compliant.

CLARIFICATION:

(i) The firm has developed Process Validation Protocols and has committed to perform Process Validation

on commercial batch.

(ii) The firm has performed comparative dissolution profile at three mediums i.e. 0.1N HCl pH 1.2, Acetate

buffer pH 4.5 & Phosphate buffer pH 6.8.

RECOMMENDATIONS:

Based on the area inspected, the technical personnel met and the documents reviewed, and considering the

findings of inspection, the panel is of the opinion that the data provided by the firm M/s. CCL Pharmaceuticals


(Pvt.) Ltd., 62 Industrial Estate, Kot Lakhpat, Lahore, Pakistan regarding stability studies of following products

was satisfactory and the stability studies were conducted by the firm.

Decision of 291st : Deferred for following:

Clarification/justification for not submitting details of drug substance as mentioned in 3.2.S of Module 3 of

CTD.

Justification is required for not performing process validation as mentioned in 3.2.P.3.5 of Module 3 of CTD.

Evaluation by PEC:

The firm has submitted DMF of dexlansoprazole API from the supplier i.e. M/s Everest Organics Ltd, India

The firm has stated that Process Validation of dexlansoprazole pellets has been performed by our source i.e

M/s Vision Pharmaceuticals, Islamabad which is duly DRAP approved. CCL only filled said pellets leading to

blistering and packaging of trial baches. In addition, CCL commit to perform process validation at commercial

batches.

Decision: Registration Board decided to approve registration of Dexlan DR Capsule 30mg &

Dexlan DR Capsule 60mg with Innovator’s specifications by M/s CCL Pharmaceuticals (Pvt.)

Ltd., 62 Industrial Estate, Kot Lakhpat, Lahore. Manufacturer will place first three production

batches on long term stability studies throughout proposed shelf life and on accelerated studies

for six months. Manufacturer will also perform process validation studies on first three

commercial batches as per the commitment submitted along with registration application.

Sr.

No.

Name & Address of

Manufacturer /

Applicant

Brand Name

(Proprietary Name +

Dosage Form +



Finished Product

Specification

Type of Form,

Initial Diary &

Date, Fee

(including

differential fee),

Demanded Price

/ Pack size

International


Availability

GMP Inspection

Report Date &

Remarks

Previous DRB

Decision /

Remarks

(if any)

248. M/s Hiranis

Pharmaceuticals

Pvt Ltd. Plot No.E-

145 to E-149, Port

Qasim, Karachi

Etoxib 120mg tablets


contains:

Etoricoxib……120mg

COX-2 Inhibitor

Dy. 42315

Form-5-D

7’s- Rs.585

10’s-Rs.835

20’s-Rs.1670

11-12-2018

Rs.50,000

11-12-2018

MHRA Approved

7-9-2017 Overall

GMP compliance is

found at

satisfactory level.

Manufacturer’s

Specifications.


Drug Etoxib 120mg tablets

Name of Manufacturer M/s Hiranis Pharmaceuticals Pvt Ltd. Plot No.E-145 to E-149, Port Qasim,

Karachi

Manufacturer of API M/s Glenmark, Maharashtra, India

API Lot No. Batch No. 84170430

Description of Pack


Alu/Alu packing

Stability Storage Condition Accelerated: 40°C ± 2°C & 75±5%RH

Real Time: 30°C ± 2°C & 65±5%RH

Time Period Accelerated: 6Months Real Time: 6Months

Frequency Accelerated: Initial,1,3,6(Months) Real Time: Initial, 1,3,6 (Month)

Batch No. TF-020418 TF-030418 TF-040418





No. of Batches 03

Date of Submission Dairy 42315, 11-12-2018



1. COA of API COA from M/s Glenmark, Maharashtra, India is

attached.




GMP certificate issued from Food and Drug

Administration Bandra-Kurla Complex, Mumbai,

Maharashtara, India that is valid upto 24-5-2021



Yes




Yes

5. Documents confirming import of API etc. Yes



documents.

Yes



Yes


1978.

Yes

REMARKS OF EVALUATOR(VI)

The panel is requested to evaluate the addition of 5% overage in the finish product stability batches.

Sr. No.

Name & Address of

Manufacturer /

Applicant

Brand Name

(Proprietary Name +


Composition,


Finished Product

Specification

Type of Form,

Initial Diary &

Date, Fee

(including

differential fee),

Demanded

Price / Pack size

International


Availability

GMP Inspection

Report Date &

Remarks

Previous DRB

Decision /

Remarks

(if any)

249. M/s Hiranis

Pharmaceuticals

Pvt Ltd. Plot

No.E-145 to E-

149, Port Qasim,

Karachi

Etoxib 90mg tablets


contains:

Etoricoxib……90mg

COX-2 Inhibitor

Dy. 42314

Form-5-D

10’s- Rs.630

14’s-Rs.870

20’s-Rs.1260

11-12-2018

Rs.50,000

11-12-2018

MHRA Approved

7-9-2017 Overall

GMP compliance

is found at

satisfactory level.

Manufacturer’s

Specifications.


Drug Etoxib 90mg tablets

Name of Manufacturer M/s Hiranis Pharmaceuticals Pvt Ltd. Plot No.E-145 to E-149, Port Qasim,

Karachi

Manufacturer of API M/s Glenmark, Maharashtra, India

API Lot No. Batch No. 84170430

Description of Pack Alu/Alu packing




Real Time: 30°C ± 2°C & 65±5%RH

Time Period Accelerated: 6Months

Real Time: 6Months

Frequency Accelerated: Initial,1,3,6(Months)

Real Time: Initial, 1,3,6 (Month)

Batch No. TF-050418 TF-060418 TF-070418




No. of Batches 03

Date of Submission Dairy 42314, 11-12-2018



1. COA of API COA from M/s Glenmark, Maharashtra, India is

attached.




GMP certificate issued from Food and Drug

Administration Bandra-Kurla Complex, Mumbai,

Maharashtara, India that is valid upto 24-5-2021



Yes




Yes

5. Documents confirming import of API etc. Yes



documents.

Yes



Yes


1978.

Yes

REMARKS OF EVALUATOR(VI)

The panel is requested to evaluate the addition of 5% overage in the finish product stability batches.

Report on Investigation of Authenticity / Genuineness of data submitted for registration of Etoxib 90mg

and 120mg (Etoricoxib) Tablets by M/s Hiranis Pharmaceuticals Pvt. Ltd., Plot # E-145 to E-149, Port

Qasim, Karachi.

Reference No: F.13-11/2017-PEC (Vol.I) dated 25th April, 2019.

Investigation Date and Time: 29th October, 2019 (Morning).

Investigation Site: Factory premises of M/s. Hiranis Pharmaceuticals Pvt. Ltd., Plot # E-145 to E-149, Port

Qasim, Karachi.

Background:

Chairman Registration Board considered the applications of M/s. Hiranis Pharmaceuticals Pvt. Ltd., Plot # E-145

to E-149, Port Qasim, Karachi for registration of Etoxib 90mg and 120mg (Etoricoxib) Tablets and constituted a


three member panel to investigate the authenticity/genuineness of data (import of raw material and stability data).

Panel was advised to conduct inspection of the firm and to submit report for further consideration.


1. Dr. Ghulam Sarwar, Dean, Faculty of Pharmacy, Jinnah University for Women, Karachi. (Member

Registration Board) Islamabad.

2. Dr. Saif ur Rehman Khattak, Director, CDL, DRAP, Karachi.

3. Mr. Kirshan Das, Assistant Director, DRAP Office, Karachi.


Investigation of the authenticity / genuineness of data (import of raw material and stability data), manufacturing

of stability batches and stability studies on these batches.






ETOXIB 90mg & 120mg TABLETS

Q.# Question Observation by panel


import of Etoricoxib API including

approval from DRAP?

The firm has used Etoricoxib API for manufacturing of

stability batches of Etoxib 90mg & 120mg tablets from

50kg commercial consignment imported form M/s

Glenmark Pharmaceuticals Ltd, India and has approval

from DRAP for import vide License No.0111/17-DRAP

(K) dated 11.01.2017.

2. What was the rationale behind

selecting the particular manufacturer of

API?

There is proper vendor evaluation process being

implemented by the firm including Postal Audit checklist,

API stability reports and availability of valid GMP approval

by competent authority.

Etoricoxib is the approved API of the firm and regularly

procuring it for the manufacture of their registered and

marketed product ‘Etoxib Tablets 60mg’.


import of Etoricoxib reference standard

and impurity standards?

Firm has imported Etoricoxib reference standard from M/s

Glenmark Pharmaceuticals Ltd, India vide invoice No.

F200E002064 dated 28.09.2017 and invoice No.

F20000002385 dated 23.02-2018 from M/s Glenmark

Pharmaceuticals Ltd, India. The firm has also imported

reference standard of the API from M/s. Sigma Aldrich,

USA. As per API manufacturer DMF there is no non

impurity.

4. Do you have certificate of Analysis of

the API, reference standards and

impurity standards?

The firm has certificates of analysis for API and reference

standard of the API.



authority of country of origin?

Firm has provided copy of valid GMP certificate of M/s

Glenmark Pharmaceuticals Ltd, India valid till 10-02-2020.

6. Do you use API manufacturer method

of testing for testing API?

The firm has used API manufacturer’s method of testing.


API?

The firm has stability studies reports on API.


8. If yes, whether the stability testing has

been performed as per SIM method and


quantified?

The stability testing has been performed as per SIM method

however; no specific degradation product has been

mentioned / monitor in the stability reports.

9. Do you have method for quantifying

the impurities in the API?

The firm has performed area normalization method for

quantifying the impurities (any unknown impurities).


of the API, its reference standard and


The firm has some remaining quantities of the API and

Working standard of the API.


excipients?

The firm have used pharmaceutical grade excipients which

include Microcrystalline Cellulose (Avicel PH-102),

Dibasic Calcium Hydrogen Phosphate Anhydrous,

Croscarmellose Sodium, Colloidansilicon dioxide (Aerosil

200), Purified Talk and Magnesium Stearate. Film coating

materials include Sheff Coat PVA + White 5Y00089 for

Etoxib 120mg tablets and Sheff Coat PVA + White

5Y00089 + Lake Brilliant Blue FCF (C.1.No.42090-1) for

Etoxib 90mg Tablets.



The firm has necessary documents confirming the import of

the used excipients.

13. Do you have test reports and other

records on the excipients used?

The firm has test reports and other records on the excipients

used.



Etoricoxib tablets?


development of Etoricoxib Tablets 90mg & 120mg.



Since firm has used same excipients as used by the

innovator. Therefore, compatibility studies have not been

performed.



The firm has performed Comparative Studies with

Arcoxia Tablets 90mg Batch no. M022039

Arcoxia Tablets 120mg Batch no. M045935

Manufactured by M/s Merck Sharp & Dohme Limited,

Hertford Road, Hoddesdon, Hertfordshire EN 11 98U, UK.

The firm’s products (Etoricoxib Tablets 90mg & 120mg)

show comparable dissolution profile with innovator product

Arcoxia Tablets 90mg & 120mg.

17. Do you have product development

(R&D) section?

The firm has dedicated product development (R&D) section

with requisite manufacturing equipments whereas testing

facilities are performed in the QC laboratory for routine

testing.

18. Do you have necessary equipment

available in product development

section for development of Etoricoxib

tablets?

The firm has necessary equipment available in product

development section for development of Etoricoxib Tablets

90mg & 120mg.

19. Are the equipment in product


The available equipment in product development section

are qualified.


calibration / re-qualification program

for the equipment used in PD section?

The firm has proper maintenance / calibration with re-

qualification program for the equipment used in PD section.



The firm has qualified staff in product development section

with proper knowledge and training in product

development. 02 Pharmacists working in R&D Section.



development?


batches for the stability studies of

Etoricoxib tablets as required?

The firm has manufactured three stability batches of

Etoricoxib Tablets 90mg & 120mg. Packed in Alu-Alu

blisters:

Etoricoxib Tablets 90mg


TF050418 April 2018 2500 Tablets










The criteria for fixing the batch size of stability batches is

the capacity of their R&D equipment where probable

simulation of manufacturing procedure of production

batches is expected as well as quantity of tablets required

per testing frequencies.




batches. All the Log Books are properly maintained.

25. Do you have protocols for stability


The firm has detailed protocols for stability testing of

stability batches having protocol number:


Batch No. Protocol No.

TF050418 QCS-0504-18

TF060418 QCS-0604-18

TF070418 QCS-0704-18


Batch No. Protocol No.

TF020418 QCS-0204-18

TF030418 QCS-0304-18

TF040418 QCS-0404-18

26. Do you have developed and validated

the method for testing of stability

batches?

The firm has developed and validated the method for testing

of stability batches based on the API manufacturer method

for testing the API supported by forced degradation study.




lab?

The firm has developed and validated method of testing for

finished product and complete Method Validation Report is

available.


qualification of equipments /

instruments being used in the test and

analysis of Etoricoxib API and the

finished drug?

The firm has proper documents confirming the qualification


analysis of Etoricoxib API and the finished drug.


indicating?

The firm has performed forced degradation (FD) study on

their product Etoricoxib Tablets 90mg & 120mg for the

conformance of its stability indicating nature.

30. Do your HPLC software 21CFR

Compliant?

The HPLC software is 21CFR Compliant as per record

available with the firm.


31. Can you show Audit trail reports on

Etoricoxib testing?



of degradation products and stability

batches?

The firm has remaining quantities of stability batches only.


stability testing?

The firm has three stability batches kept on real time

stability testing.


the equipments used in Etoricoxib

tablets production and analysis?

The firm has valid calibration status for the equipment used

in production and analysis of Etoricoxib Tablets 90mg &

120mg.

35. Do proper and continuous monitoring

and control are available for stability

chamber?


chamber. Chambers are controlled and monitored through

software having alarm system for alerts as well.

36. Do related manufacturing area,

equipment, personnel and utilities be

rated as GMP compliant?

Related manufacturing area, equipment, personnel and

utilities are GMP compliant.

37. Any Comments?

Evaluation of the addition of 5%

overage in the finish product stability

batches.

The firm presented the following justification before the

inspection panel which has already been submitted to

Islamabad vide letter No. Nil dated 07-02-2019.

The same statement has been refreshed in letter No. Nil

dated 30-10-2019 (copy enclosed) which states as under:

In master formulation of above product 5% overage had

been added. This addition was not due to any specific reason

and we commit that in commercial batch formulation 5%

overage will not be included. Furthermore, it is stated that

Etoxib tablet (Etoricoxib) 60mg is our registered product

having Reg. No. 073741 and we are not using any overage

in this product. The same was also verified by the panel

member at the time of inspection.

Conclusions:


for registration of Etoxib (Etoricoxib) 90mg & 120mg Tablets is verifiable to satisfactory level.

2. The related manufacturing area, equipment, personnel and utilities are GMP compliant and well suited

for the manufacturing of Etoxib 90mg & 120mg Tablets.

Recommendations:

1. The firm may kindly be granted necessary registration of Etoxib 90mg & 120mg tablets.


Registration Board decided to defer the case of Etoxib 90mg & Etoxib 120mg tablets and directed the firm to

submit dissolution testing data with specifications of “NLT Q within 15 minutes” at initial and one month time

point at both accelerated and real time stability conditions for 2 batches.

Response by the firm and Evaluation of PEC:

In accordance to directives of Registration Board meeting minutes, the firm has conducted dissolution test in 15

minutes of stability batches after 22 months at real time storage condition and 01 month at accelerated stability

condition. The dissolution results at both real time as well as accelerated conditions fall within acceptable range

as per the revised dissolution specifications of the firm i.e. NLT 75%(Q) in 15 minutes.

Decision: Registration Board decided to approve registration of Etoxib 90mg tablets & Etoxib

120mg tablets with Innovator’s specifications by M/s Hiranis Pharmaceuticals Pvt. Ltd., Plot # E-

145 to E-149, Port Qasim, Karachi. Manufacturer will place first three production batches on long



Sr.

No.

Name & Address of

Manufacturer /

Applicant

Brand Name





Type of Form,

Initial Diary &

Date, Fee (including

differential fee),

Demanded Price /

Pack size


Local Availability


Remarks

250. M/s The Searle

Company Limited,

F-319, S.I.T.E.,

Karachi

Sacusar Tablets 97/103mg


Contains:

Sacubitril ….…97mg

Valsartan …… 103mg

Anti-hypertensive

In-house specifications

Form 5D

Dy. No 14655

dated

7-03-2019

Rs. 50,000/- dated

06-03-2019,

As per SRO

Approved by USFDA

The firm was inspected on

27.06.2018, wherein the GMP

of the firm was rated good.


Drug Sacusar 97/103mg Tablets

Name of Manufacturer M/s The Searle Company Limited, F-319, S.I.T.E., Karachi

Manufacturer of API M/s Zhuhai Rundu Pharmaceuticals Co. Ltd, Guangdong,519041,

China

API Lot No. 57318060103

Description of Pack


Alu Alu Blisters 2x 10’s in unit carton


Real Time: 30°C ± 2°C & 75±5%RH


Frequency Accelerated: 0,3,6 (Months) Real Time: 0,3,6 (Month)

Batch No. 19PD-066 19PD-071 19PD-072


Manufacturing Date Mar-2019 Mar-2019 Mar-2019

Date of Initiation Mar-2019 Mar-2019 Mar-2019

No. of Batches 03

Date of Submission



1. COA of API COA of both API’s manufacturer (Lot NO:

57318060103) and Finished product manufacturer has

been provided.




country of origin.

GMP certificate for API manufacturing issued from

Zhuhai Food and Drug Administration and is valid till

21/12/2021



Yes




Yes


5. Documents confirming import of API etc. The firm has submitted copy of commercial invoice for

the purchase of API’s (4.5Kg) attested by ADC, DRAP

Karachi dated 07-08-2018.



/ documents.

Yes



Yes


Rules, 1978.

Yes

EXEMPTION DATA SUBMITTED AS PER 293RD MEETING OF REGISTRATION BOARD

Check List Firm’ Response

1. Reference of previous approval of

applications with stability study data of

the firm

Firm has referred to last onsite inspection report of their product

“Ticor 60mg & 90mg Tablets”, which was presented in 293rd

meeting of Registration board. Registration Board decided to

approve registration of above stated drug product of M/s The

Searle company Ltd., Karachi.

Date of inspection: 11th March-2019

According to inspection report, following points were

confirmed.

The HPLC software of the firm is 21 CRF compliant.

The firm has installed software for adequate monitoring and

control of temperature / humidity of the chamber.

2. Certificate of Analysis of API from both

API Manufacturer and Finished Product

manufacturer.

COA of both API’s manufacturer (Lot NO:- 57318060103 ) and

Finished product manufacturer has been provided.

3. Method used for analysis of API from

both API Manufacturer and Finished

Product

manufacturer

The firm has submitted Raw Material Specifications, Raw

Material Testing Procedures along with COAs

4. Stability study data of API from API

manufacturer

M/s Zhuhai Rundu Pharmaceuticals has performed accelerated

stability studies for 6 months at 40’C and 75% for 3 batches and

real time stability studies for 12 months at 30’C/75% for 3

batches.

5. Approval of API/ DML/GMP certificate

of API manufacturer issued by

concerned regulatory authority of

country of origin.

GMP certificate for API manufacturing issued from Zhuhai

Food and Drug Administration and is valid till 21/12/2021

6. Documents for the procurement of API

with approval from DRAP (in case of

import).

The firm has submitted copy of commercial invoice for the

purchase of API’s (4.5Kg) attested by ADC, DRAP Karachi

dated 07-08-2018.


stability study

The firm has submitted protocol for the conduction of stability

studies.

8. Method used for analysis of FPP The firm has submitted copy of Finished Product Testing

Procedure along with Stability Study Reports.

9. Drug-excipients compatibility studies

(where applicable)

Firm has stated that our excipients are in-line with the

innovator’s, therefore we did not perform the studies



The firm has submitted complete batch manufacturing record of

the three batches.


11. Record of comparative dissolution data

(where applicable)

The firm has performed comparative dissolution studies in three

media including pH 1.2, pH 4.5 and pH 6.8 buffers with

Entresto Tablets. The firm‘s product results are comparable to

that of the comparator product.



chromatograms, Raw data sheets, COA,

summary data sheets etc.


documents like chromatograms, Raw data sheets, COA,

summary data sheets was submitted



testing.

Audit trail on testing reports of Sacubitril/Valsartan from has

been submitted by the firm.


temperature and humidity monitoring of

stability chambers(real time and

accelerated)

Record of Digital data logger for temperature and humidity

monitoring of stability chambers (real time and accelerated) has

been submitted


The firm has performed dissolution as per the USFDA dissolution acceptance criteria i.e.

Apparatus Speed Volume Medium Detection Acceptance

Criteria

USP-II 50 rpm 900ml Phosphate

Buffer, pH 6.8

HPLC/UV

Wavelength=255nm

Q= __% at

25minutes

Decision: Registration Board decided to approve registration of Sacusar Tablets 97/103mg with

Innovator’s specifications by M/s The Searle Company Limited, F-319, S.I.T.E., Karachi.



Sr. No.

Name & Address

of Manufacturer /

Applicant

Brand Name





Type of Form,


Fee (including

differential fee),


size

International


Availability

GMP Inspection

Report Date &

Remarks

251. M/s The Searle

Company Limited,

F-319, S.I.T.E.,

Karachi



Contains:



Anti-hypertensive


Form 5D

Dy. No 14656 dated

7-03-2019

Rs. 50,000/- dated

06-03-2019,

As per SRO

Approved by USFDA

The firm was

inspected on

27.06.2018, wherein

the GMP of firm was

rated good.




Manufacturer of API M/s Zhuhai Rundu Pharmaceuticals Co. Ltd, Guangdong,519041, China

API Lot No. 57318060103

Description of Pack




Real Time: 30°C ± 2°C & 75±5%RH


Frequency Accelerated: 0,3,6 (Months) Real Time: 0,3,6 (Month)


Batch No. 18PD-281 18PD-287 18PD-288


Manufacturing Date Nov-2018 Dec-2018 Dec-2018

Date of Initiation Dec-2018 Jan-2019 Jan-2019

No. of Batches 03

Date of Submission



1. COA of API COA of both API’s manufacturer (Lot NO:-

57318060103 ) and Finished product manufacturer has

been provided.




country of origin.



21/12/2021



Yes




Yes






data / documents.

Yes



Yes


Rules, 1978.

Yes




applications with stability study data of the

firm

Firm has referred to last onsite inspection report of their

product “Ticor 60mg & 90mg Tablets”, which was presented

in 293rd meeting of Registration board. Registration Board

decided to approve registration of above stated drug product

of M/s The Searle company Ltd., Karachi.



confirmed.





API Manufacturer and Finished Product

manufacturer.

COA of both API’s manufacturer (Lot NO:- 57318060103 )

and Finished product manufacturer has been provided.


3. Method used for analysis of API from both

API Manufacturer & Finished Product

manufacturer




manufacturer

M/s Zhuhai Rundu Pharmaceuticals has performed

accelerated stability studies for 6 months at 40’C and 75%

for 3 batches and real time stability studies for 12 months at

30’C/75% for 3 batches.


API manufacturer issued by concerned








dated 07-08-2018.


stability study

The firm has submitted protocol for the conduction of

stability studies.




(where applicable)





The firm has submitted complete batch manufacturing record

of the three batches.


(where applicable)

The firm has performed comparative dissolution studies in

three media including pH 1.2, pH 4.5 and pH 6.8 buffers with

Entresto Tablets. The firm‘s product results are comparable

to that of the comparator product.






documents like chromatograms,

Raw data sheets, COA, summary data sheets was submitted



testing.





stability chambers (real time/accelerated)


monitoring of stability chambers (real time and accelerated)

has been submitted




Criteria


Buffer, pH 6.8

HPLC/UV

Wavelength=255nm

Q= __% at

25minutes

Decision: Registration Board decided to approve registration of Sacusar Tablets 24/26mg with





Sr. No.

Name & Address of

Manufacturer /

Applicant

Brand Name


Form + Strength),

Composition,



Type of Form,


Fee (including

differential fee),

Demanded Price /

Pack size




Date & Remarks

252. M/s The Searle

Company Limited,

F-319, S.I.T.E.,

Karachi



Contains:



Anti-hypertensive


Form 5D

Dy. No 14657 dated

7-03-2019

Rs. 50,000/- dated

06-03-2019,

As per SRO

Approved by USFDA

The firm was inspected

on 27.06.2018, wherein

the GMP of the firm was

rated good.




Manufacturer of API M/s Zhuhai Rundu Pharmaceuticals Co. Ltd, Guangdong,519041, China

API Lot No. 57318060103

Description of Pack




Real Time: 30°C ± 2°C & 75±5%RH


Real Time: 06 Months

Frequency Accelerated: 0,3,6 (Months)

Real Time: 0,3,6 (Month)

Batch No. 19PD-011 19PD-056 19PD-246


Manufacturing Date Jan-2019 Feb-2019 Feb2019

Date of Initiation Feb-2019 Mar-2019 Mar-2019

No. of Batches 03

Date of Submission



1. COA of API COA of both API’s manufacturer (Lot NO:-

57318060103 ) and Finished product manufacturer has

been provided.




country of origin.



21/12/2021



Yes




Yes







/ documents.

Yes



Yes


1978.

Yes




applications with stability study data of

the firm


“Ticor 60mg & 90mg Tablets”, which was presented in 293rd


approve registration of above stated drug product of M/s The

Searle company Ltd., Karachi.



confirmed.





API Manufacturer & Finished Product

manufacturer.

COA of both API’s manufacturer (Lot NO: 57318060103) and

Finished product manufacturer has been provided.

3. Method used for analysis of API from

both API Manufacturer and Finished

Product

manufacturer




manufacturer

M/s Zhuhai Rundu Pharmaceuticals has performed accelerated

stability studies for 6 months at 40’C and 75% for 3 batches and

real time stability studies for 12 months at 30’C/75% for 3

batches.



concerned regulatory authority of

country of origin.





import).



dated 07-08-2018.


stability study

The firm has submitted protocol for the conduction of stability

studies.




(where applicable)





The firm has submitted complete batch manufacturing record of

the three batches.



(where applicable)

The firm has performed comparative dissolution studies in three

media including pH 1.2, pH 4.5 and pH 6.8 buffers with

Entresto Tablets. The firm‘s product results are comparable to

that of the comparator product.






documents like chromatograms,

Raw data sheets, COA, summary data sheets was submitted



testing.





stability chambers (real time and

accelerated)


monitoring of stability chambers (real time and accelerated) has

been submitted




Criteria


Buffer, pH 6.8

HPLC/UV

Wavelength=255nm

Q= __% at

25minutes

Decision: Decision: Registration Board decided to approve registration of Sacusar Tablets

49/51mg with Innovator’s specifications by M/s The Searle Company Limited, F-319, S.I.T.E.,




Item No. 8: Agenda of Evaluator PEC-VIII

Case No. 01 Registration applications of newly granted DML or New section (Veterinary)

a. New DML /section On recommendation of panel of experts CLB in its 271st meeting held on 12th September, 2019 has considered

& approved following six additional section of M/s. Grand Pharma:

1. Bolus section (general)(veterinary)

2. Oral Powder section (general)(veterinary)

3. Oral Liquid section (general)(veterinary)

4. Oral Powder section (penicillin)(veterinary)

5. Dry Powder Injection section Vials (penicillin)(veterinary)

6. Liquid Injection section Vials (penicillin)(veterinary)

Now the firm has applied for the following:

Sr.# Section No. Of Molecules No. Of Products

1 Oral Liquid section

(general)(veterinary)

10 10

2 Oral Powder section

(general)(veterinary)

7 7

Oral Liquid section (general)(veterinary): Molecules/Products considered: 07M/07P.


Applicant

M/s. Grand Pharma Pvt Ltd Plot No. 5-A, Street No. N5,

National Industrial Zone, Rawat, Rawalpindi

Brand Name+Dosage Form+Strength G-Flor Plus Oral Liquid

Composition "Each 100ml Contains:

Florfenicol…23gm


Diary No. Date of R&I & Fee Dy.No 21148 dated 18-10-2019 Rs. 20,000


Type of Form Form-5

Finished product Specification Manufacturer's Specification

Pack size & Demanded Price 500ml, 1liter, 2.5liter, 5liter; Decontrolled

Me-too status Maxiflor Plus Oral Liquid of BIOGEN Pharma (Reg# 075617).

Each 1000ml Contains:-

Florfenicol…………23gm

Colistin Sulphate...50 MIU

GMP status Oral Liquid section (general)(veterinary)Letter Issuance Date:

26th September, 2019. On recommendation of panel of experts

CLB in its 271st meeting held on 12th September, 2019 has

considered & approved following six additional section of M/s.

Grand Pharma:

1. Bolus section (general)(veterinary)

2. Oral Powder section (general)(veterinary)

3. Oral Liquid section (general)(veterinary)

4. Oral Powder section (penicillin)(veterinary)

5. Dry Powder Injection section Vials (penicillin)(veterinary)

6. Liquid Injection section Vials (penicillin)(veterinary)

Remarks of the Evaluator Evidence of applied formulation/drug already approved by

DRAP (generic / me-too status) alongwith registration number,

brand name & name of firm as provided evidence is of another

strength.





Applicant



Brand Name + Dosage Form + Strength Nor-Ct Oral Liquid


Tylosin Tartrate…5gm

Norfloxacin…10gm




Type of Form Form-5



Me-too status Norcotyl Oral Solution of BIOGEN Pharma (Reg# 071021)

Each 100ml contain:-

Norfloxacin…………10%

Colistin sulphate…250 MIU

Tylosin tartrate……..5%

GMP status Same as recorded for above application.




Applicant



Brand Name + Dosage Form + Strength Brom Aid Oral Liquid


BromhexineHcl…50gm"

Diary No. Date of R&I & Fee Dy.No. 21151 dated 18-10-2019 Rs. 20,000

Pharmacological Group Expectorant / Mucolytic Agent

Type of Form Form-5



Me-too status Brombar-5 Oral Solution of BAARIQ Pharma (R# 073947)

Each ml contains:-

Bromhexine HCL….50mg





Applicant



Brand Name + Dosage Form + Strength Grand Tylcobrox Oral Liquid

Composition "Each ml Contains:

Tylosin Tartrate…200mg

Doxycycline Hcl…250mg

Colistin Sulphate…0.5 MIU

BromhexineHcl…12mg"


Pharmacological Group Antibiotic / Expectorant

Type of Form Form-5



Me-too status Tylotar Fort Liquid of Evergreen Pharma (Reg# 078288).

EACH 1000ML CONTAINS:-

TYLOSIN TARTRATE BP…….200GM

DOXYCYCLINE HCL……….250GM

COLISTIN SULPHATE BP…500MIU


BROMHEXINE HCL BP…….12GM





Applicant



Brand Name + Dosage Form + Strength Grand Ivermec Drench Oral Liquid

Composition "Each ml Contains:

Ivermectin…1%"



Type of Form Form-5



Me-too status Ivosol Drench of BIOGEN PHARMA (Reg# 069608)





Applicant



Brand Name + Dosage Form + Strength Grand Td-400 Oral Liquid


Tylosin Tartrate…20gm

Doxycycline Hcl…20gm"

Diary No. Date of R&I & Fee Dy.No. 21155 dated 18-10-2019 Rs. 20,000


Type of Form Form-5



Me-too status Maxcin-400 Liquid of BIOGEN PHARMA (Reg# 058967)





Applicant



Brand Name + Dosage Form + Strength Enro-Hexin Oral Liquid Suspension


Enrofloxacin…10gm

BromhexineHcl…1gm



Pharmacological Group Antibiotic / Expectorant

Type of Form Form-5


Pack size & Demanded Price 100ml, 500ml, 1liter; Decontrolled

Me-too status En-C-Raft Oral Liquid Of NAWAL PHARMA (Reg#

078251) (not verifiable)



DRAP (generic / me-too status) alongwith registration

number, brand name and name of firm as provided evidence

is of another strength, as provided Me Too is not verifiable.




Oral Powder section (general)(veterinary): Molecules/Products considered: 05M/05P.


Applicant

Grand Pharma Pvt Ltd Plot No. 5-A, Street No. N5, National

Industrial Zone, Rawat, Rawalpindi

Brand Name + Dosage Form + Strength Tylvotart Soluble Granules/Oral Dry Powder

Composition Each gm contains:

Acetyl IsovalerylTylosin Tartrate………...850 mg

Diary No. Date of R&I & Fee Dy. No. 21146 dated 18-10-2019 Rs. 20,000


Type of Form Form-5

Finished product Specification Manufacturer's specification

Pack size & Demanded Price 25gm, 50gm, 100gm 500gm, 1kg, 2.5kg, 5kg; Decontrolled

Me-too status Aivlosin Soluble Granules1gm of Hilton Pharma

GMP status Oral Powder section (general)(veterinary) Letter Issuance

Date: 26th September, 2019.

Remarks of the Evaluator Submitted me-too status is of 1 gm strength.




Applicant



Brand Name + Dosage Form + Strength Floron Oral Powder

Composition Each gram contains:

Neomycin Sulphate ….….....150 mg

Florfenicol……………………100 mg

Oxytetracycline hydrochloride….…300 mg


Pharmacological Group Aminoglycoside/Antibiotic

Type of Form Form-5


Pack size & Demanded Price 0.5kg, 1kg, 2.5kg, 5kg; Decontrolled


Regulatory Authority

N/A

Me-too status E.Col Oral Powder of Evergreen Pharma Registrtion No.

081733 (not verifiable)



DRAP (generic / me-too status) alongwith registration

number, brand name and name of firm, as the provided

evidence is not verifiable.




Applicant



Brand Name + Dosage Form + Strength Grand TD Plus Oral Powder

Composition Each 100 gram contains:

Tylosin Tartrate……………….20 gm

Doxycycline Hyclate……………40 gm

Colistin Sulphate……………….10 gm

Bromhexin HCl………..………....2 gm


Pharmacological Group Antibiotic/ Expectorant

Type of Form Form-5


Pack size & Demanded Price 0.5kg, 1kg, 2.5kg, 5kg; Decontrolled



Regulatory Authority

N/A

Me-too status Tydoxin-60 Powder of Aptly Reg. 093862 (not veriofiable)



DRAP (generic/me-too status) alongwith registration

number, brand name and name of firm, as the provided

evidence is not verifiable.

Decision: Deferred for evidence of applied formulation/drug already approved by DRAP (generic / me-too status) alongwith registration number, brand name and name of firm.

263. Name and address of manufacturer / Applicant

Grand Pharma Pvt Ltd Plot No. 5-A, Street No. N5, National Industrial Zone, Rawat, Rawalpindi

Brand Name + Dosage Form + Strength Doxy-Hy 50 Oral Powder Composition Each kg contains:

Doxycycline Hyclate (BP)……..………500 gm

Diary No. Date of R&I & Fee Dy. No. 21140 dated 18-10-2019 Rs. 20,000 Pharmacological Group Antibiotic Type of Form Form-5

Finished product Specification Manufacturer's specification Pack size & Demanded Price 0.5kg, 1kg, 2.5kg, 5kg; Decontrolled Approval status of product in Reference Regulatory Authority

N/A

Me-too status Doxyvetz Oral Powder of M/s Vetz Pharma Reg. No.088059 (not verifiable)

GMP status Same as recorded for above application. Remarks of the Evaluator Evidence of applied formulation/drug already approved by

DRAP (generic / me-too status) alongwith registration number, brand name and name of firm, as the provided evidence is not verifiable.

Decision: Deferred for evidence of applied formulation/drug already approved by DRAP (generic / me-too status) alongwith registration number, brand name and name of firm.

264. Name and address of manufacturer / Applicant

Grand Pharma Pvt Ltd Plot No. 5-A, Street No. N5, National Industrial Zone, Rawat, Rawalpindi

Brand Name + Dosage Form + Strength Neocin 72% Oral Powder

Composition Each gram contains: Neomycin (as Sulphate) (BP)……….720 mg

Diary No. Date of R&I & Fee Dy. No. 21144 dated 18-10-2019 Rs. 20,000 Pharmacological Group Antibiotic

Type of Form Form-5 Finished product Specification Manufacturer's specification Pack size & Demanded Price 0.5kg, 1kg, 2.5kg, 5kg; Decontrolled

Approval status of product in Reference Regulatory Authority

N/A

Me-too status Neovetz 72% Of Vetz Pharma Reg. 079295 GMP status Same as recorded for above application.


Decision: Deferred for scientific rational for neomycin 72% water soluble powder, since neomycin 70% water soluble powder is already approved.


a. Verification of stability study data 265. Name and address of manufacturer /

Applicant

M/s Zafa Pharmaceutical Laboratories, L-1/B, Block 22,

Federal “B” Industrial Area, Karachi.

Brand Name +Dosage Form + Strength Sofosbuvir Tablet 400mg


Sofosbuvir…. 400mg


Diary No. Date of R& I & fee R&I date: 27-08-2018

Fee 20,000/- (20-08-2018) Duplicate dossier

Pharmacological Group Anti-viral

Type of Form Form-5


Pack size & Demanded Price 28’s(HDPE bottle): As per PRC



Approved in US-FDA


dosage form)

N/A


Drug Sofosbuvir Tablet 400mg

Name of Manufacturer M/s Zafa Pharmaceutical Laboratories, L-1/B, Block 22, Federal “B”

Industrial Area, Karachi.

Manufacturer of API Optimus Drugs PVT Limited,

Factory, Sy No. 239 & 240 Dothigudam(V) Pochampally(M), Nalgonda

Dist., Telangana, India

API Lot No. Batch No.OP-GLD/10/15/037

Description of Pack

(Container closure system) 28’s; HDPE Bottle

Stability Storage Condition Real Time: 30oC ± 2oC / 65% ± 5%RH

Accelerated:40oC ±2oC / 75% ± 5%RH


Frequency Real Time: 0,4,8,12,24 Months Accelerated: 0,4,8,12,24 Months

Batch No. Tr-01 Tr-02 Tr-03


Manufacturing Date August, 2017 August, 2017 August, 2017

Date of Initiation 22th August, 2017 22th August, 2017 22th August, 2017

No. of Batches 03




1. COA of API Firm has submitted copy of COA stating following

information on it:

Product:Sofosbuvir

Batch No.OP-GLD/10/15/037

Manufacturer:Optimus Drugs PVT Limited,




country of origin.

Applicant has submitted GMP certificate having

following information on it:

Certificate No.L.Dis.No.20121/A3/2018

Issued to:Optimus Drugs PVT Limited,

Issued on: 21-05-2018

Validity: One Year From The Date Of Issue



Yes



Yes



5. Documents confirming import of API etc. Firm has submitted copy of commercial invoice stating

following information on it:

Invoice No. 412/EXP

Batch No of API. OP-GLD/10/15/037

Attested by Assistant Director (I & E) DRAP

Karachi On : 03-02-2016



documents.

Yes



Yes


1978.

Yes

Evaluation by PEC:

SOFOSBUVIR TABLET 400MG, M/S ZAFA PHARMACEUTICALS LABORATORIES.

Following panel of inspectors visited M/s Zafa Pharmaceuticals Laboratories for verification of

authenticity of submitted stability study data for registration of Sofosbuvir 400mg Tablet.

1. Syed Adnan Rizvi Director, DTL, Karachi.

2. Dr. Najam-us-Saquib Additional Director DRAP, Karachi.

3. Kirshan, Assistant Director, DRAP, Karachi.

Q.No. Question Observation by panel

1.

Do you have documents confirming the


DRAP?

The firm has imported Sofosbuvir from Optimus Drug

Pvt. Ltd. Hyderabad INDIA, Supplier IRIS Karachi.

Invoice No.412/EXP dated 15-11-2015. Batch # OP-

GLD/10/15/037. The total quantityofAPI purchased

was1.00 kg.The approval from DRAP is available.

(Annex-A)

2.

What was the rationale behind selecting the


Rationale behind selecting the particular manufacturer of

API, as it is GMP compliant and vendor evaluation has

been done. (Annex-B).

3.


import of reference standard and impurity

standards?

The reference standard & impurity standard were

imported through Optimus Drug Pvt. Ltd. Hyderabad

INDIA. In House Reference standard, Batch # OP-

SFS/RS1402, quantity100mg.Impurity standard, Batch #

OP-GLD/St-I/Rp-Isomer/A0453/055, with quantity

10.0mg. (Annex-C)

4.

Do you have certificate of Analysis of the


standards?

The firm has COAs for API, reference standards and

impurity.

5.

Do you have GMP certificate of API


of country of origin?

The firm has GMP Certificate of API manufacturer

issued by Drug Control Administration Govt. of

Telangana INDIA.L.DisNo. 2021/A3/2018 Dated 21-

05-2018.



The Firm has used manufacturer’s method of testing for

the testing of API.

7. Do you have stability studies reports on API? The firm has manufacturers Stability studies report of

API.


8.

If yes, whether the stability testing has been



Stability testing as per SIM method and degradation

products has been quantified by the API manufacturer.



The firm has used HPLC method for chromatographic

impurities that was used for assay purpose.

10.

Do you have some remaining quantities of

the API, its reference standard and impurities

standards?

The firm has some quantities of API (As reference),

reference standard.


excipients?

The firm has used Pharmaceutical grade excipients



The firm has necessary documents confirming the

import of the used excipients.



The firm has test reports and other records of the

excipient used.

14. Do you have written and authorized protocols

for the development of applied product?

The firm has written protocol for the development of

Sofosbuvir Tablets 400 mg.(Annex-D)

15.

Have you performed Drug-excipient


The firm has not performed drug excipient

compatibility studies because the composition of their

tablets/product is similar to that of the innovator’s

product (Sovaldi Tablets)

16.

Have you performed comparative dissolution

studies?

The firm has performed comparative dissolution studies

and their product show comparable dissolution profile

and same were reviewed at time of inspection.


section.

The firm has separate new product development (R&D)

section.

18.

Do you have necessary equipments available


development of applied product?

The firm has used Quality Control Lab instruments for

the development of Sofosbuvir Tablets 400 mg. The

firm has all necessary equipment in QC and Product

development section.

19. Are the equipment in product development

section qualified?

All the equipment used in the development of product

is qualified.

20.

Do you have proper maintenance / calibration

/ requalification program for the equipment

used in PD section?


equipment used in quality Control for the development

of the product.

21.

Do you have qualified staff in product



The firm has qualified staff for the development of the

product with proper knowledge and training in product

development. (Annex-E)

22.

Have you manufactured three stability

batches for the stability studies of applied

products required?

The firm has manufactured three stability batches, of

Sofosbuvir Tablets 400 mg, TR01, TR02, TR03.

23.

Do you have any criteria for fixing the batch


The criteria for fixing the batch size of stability of

batches are the number of tablets as per requirement of

testing.

24.

Do you have complete record of production



batches. All the log books are properly maintained and

reviewed at the time of inspection.


stability batches?

The firm has protocols for testing of the stability

batches.



Yes, the firm has used manufacturer’s method of

testing, the method is validated.

27.

Do you have method transfer studies in case


your firm is given by any other lab?

Not applicable


Conclusion:

M/s Zafa Pharmaceutical Laboratories was inspected as per directions contained in DRAP letter No. 13-11/2017-

PEC (Pt) dated 30th July, 2019. During inspection, the panel inspected/reviewed the relevant record, data and

premises in detail with specific focus on the observations/points made in above referred letter. Following are the

current observations:

1. Criterion/reference for selection of Q Value 70%: - The said molecules was not included in any

official monograph, therefore, the firm previously performed the dissolution test as per general requirement for

dissolution testing and there was no any specific criteria for the selection of Q value 70%. Now, the firm have

performed dissolution test for their product according to US-FDA recommended dissolution method and found

it satisfactory at the time of inspection.

2. Valid GMP Certificate of API Manufacturer is hereby attached for reference.

3. On the basis of risk-based approach the genuineness/ authenticity of stability data submitted by the firm

for registration of Sofosbuvir Tablets 400mg is verifiable to satisfactory level.

4. The related manufacturing area, equipment, personnel and utilities observed in line as per GMP

requirements and well suited for manufacturing of the said product.

Recommendations:

Based on the people met, documents reviewed and observations made during inspection including corrective

action taken by the firm, the panel unanimously recommends that the firm may kindly be granted necessary

registration of Sofosbuvir Tablets 400mg.

28.



being used in the test and analysis of API and

the finished drug?

Yes, the firm has proper documents confirming the

qualification of equipment and instruments being used

in the test and analysis of API and the finished product.


indicating?

Yes the method of analysis is stability indicating.

30. Do your HPLC software is 21CFR

compliant?

HPLC software is 21CFR compliant.

31. Can you show Audit Trail reports on Stability

study testing?

The firm showed the Audit trail report on API and

finished product testing.



The firm has remaining quantities of stability batches.

33. Do you have commitment batches kept on

stability testing?

The firm has three commitment batches kept on stability

testing for real time stability studies.

34.

Do you have valid calibration status for the

equipment used in Production and analysis?

Yes, the firm has valid calibration status for the

equipment used in the production and analysis of

Sofosbuvir Tablets 400 mg.


control are available for stability chambers.

Continuous power supply and monitoring and control

are available for the stability chambers.

36.

Do related manufacturing area, equipment,

personal and utilities be used as GMP

compliance

The relevant manufacturing facilities are GMP

complaint.

Decision: Registration Board decided to defer the case for following submissions:

Submit dissolution testing data with specifications of “NLT Q within 15 minutes” at initial and

one month time point at both accelerated and real time stability conditions for 2 batches.

Valid GMP certificate of the API manufacturer.


Applicant

M/s Biolabs, Kahuta Road, Islamabad.

Brand Name +Dosage Form + Strength Dexerid Capsule 30mg


Dexlansoprazole…30mg

Diary No. Date of R& I & fee Form-5 Dy.No 7194 (26-02-2018) Rs.20,000/- (26-02-2018)

Pharmacological Group PPI







Approved in US-FDA


dosage form)

Razodex Capsule by M/s Getz Pharma


Drug Dexerid Capsule 30mg

Name of Manufacturer M/s Biolabs, Kahuta Road, Islamabad.

Manufacturer of API M/s Murli Krishna Pharma, D-98, MIDC., Rajangaon, ShirurTaluka, Pune Dist.

Maharashtra, India

API Lot No. Dexlansoperazole pellets 23.0% w/w. (Batch. # MKPPLR-DLF-18018)

Description of Pack

(Container closure system) Alu-Alu blister



Time Period Real Time: 06 Months Accelerated:06Months

Frequency Real Time: 0,3,6 Months(on going) Accelerated: 0,1,2,3,4,6 Months

Batch No. DEX-001 DEX-002 DEX-003

Batch Size 1500 Capsule Capsule Capsule


Date of Initiation - - -

No. of Batches 03

Date of Submission Dy No.3395, 12/04/2019



1. COA of API Yes




The applicant has submitted the following

documents:

Copy Of GMP Certificate:

Certificate No: NEW-WHO-

GMP/CERT/PD/80503/2019/11/27529.

Issued to: M/s Murli Krishna Pharma.

D-98, MIDC.Rajangaon, ShirurTaluka, Pune Dist.

Maharashtra, India.

Issued on: 05-09-2018

Issued by: Food &Drug Administration,Bandra-

Kurla Complex, Maharastra, India.

Validity: 03-04-2022



Yes




Yes

5. Documents confirming import of API etc. Applicant has submitted Copy Of Commercial

Invoice having following information on it:

Dexlansoperazole pellets 23.0% w/w


Quantity: 2000gm

Dexlansoperazole Working Standard

Quantity: 200mg

Signed by AD (I&E) Islamabad on 06-08-18.



documents.

Yes



Yes


1978.

Yes

Evaluation by PEC:

267. Name and address of manufacturer

/ Applicant

M/s Biolabs, Kahuta Road, Islamabad.

Brand Name +Dosage Form + Strength Dexerid Capsule 60mg


Dexlansoprazole…60mg

Diary No. Date of R& I & fee Form-5 Dy.No 7195 (26-02-2018) Rs.20,000/- (26-02-2018)

Pharmacological Group PPI






Approved in US-FDA


dosage form)

Razodex Capsule by M/s Getz Pharma


Drug Dexerid Capsule 60mg

Name of Manufacturer M/s Biolabs, Kahuta Road, Islamabad.

Manufacturer of API M/s Murli Krishna Pharma, D-98, MIDC., Rajangaon, ShirurTaluka, Pune Dist.

Maharashtra, India

API Lot No. Dexlansoperazole DDR pellets 17.0% w/w. (Batch. # DLT/SF/0010117)

Description of Pack

(Container closure system) Alu-Alu blister



Time Period Real Time: 09 Months

Accelerated:06Months

Frequency Real Time: 0,3,6 Months(on going)

Accelerated: 0,1,2,3,4,6 Months

Batch No. DEX-004 DEX-005 DEX-006

Batch Size 1500 Capsule 1500 Capsule 1500 Capsule


Date of Initiation - - -

No. of Batches 03

Date of Submission Dy No.3396, 12/04/2019




1. COA of API Yes




The applicant has submitted the following

documents:

Copy Of GMP Certificate:

Certificate No: NEW-WHO-

GMP/CERT/PD/80503/2019/11/27529.

Issued to: M/s Murli Krishna Pharma.

D-98, MIDC. Rajangaon, ShirurTaluka, Pune Dist.

Maharashtra, India.

Issued on: 05-09-2018

Issued by: Food &Drug Administration,Bandra-

Kurla Complex, Maharastra, India.

Validity: 03-04-2022



Yes




Yes

5. Documents confirming import of API etc. Applicant has submitted Copy Of Commercial

Invoice having following information on it:

Dexlansoperazole pellets 23.0% w/w

Quantity: 2000gm

Dexlansoperazole Working Standard

Quantity: 200mg

Signed by AD (I&E) Islamabad on 06-08-18.



documents.

Yes



Yes


1978.

Yes

Evaluation by PEC:

Report on investigation of authenticity / genuineness of data submitted for registration of Dexerid

(Dexlansoprazole) 30mg & 60mg Capsule by M/s Bio-labs (Pvt) Ltd. Plot No. 145, Industrial Triangle

Kahuta Road, Islamabad.


Investigation Date & Time: 11th March, 2020

Investigation Site: Factory premises of Bio-labs (Pvt) Ltd. Plot No. 145, Industrial Triangle Kahuta Road,

Islamabad.

Background: Chairman Registration Board has constituted the panel of M/s Bio-labs (Pvt) Ltd. Plot No. 145, Industrial Triangle

Kahuta Road, Islamabad for Dexerid (Dexlansoprazole) 30mg & 60mg Capsule for on-site investigation to

confirm the authenticity / genuineness of stability data and associated documents, import of API, quality,

specification, test analysis and facilities etc for further consideration by the Registration Board.


1. Dr. Qurban Ali, Member Registration Board

2. Mst. Tehreem Sara, Deputy Director (RRR) PE&R Division DRAP, Islamabad




Investigation of the authenticity / genuineness of the data, manufacturing of stability batches and stability studies

on these batches.

Tool for investigation:




details of investigation is summarized as under:

Detail of investigation for Dexerid (Dexlansoprazole) 30mg & 60mg Capsule

Sr.

No.

Description Observation by panel



DRAP?

Firm presented necessary documents including invoice

/AD clearance dated 06-08-2018 confirming import of

2 kg Dexlansoprazole pellets 23% w/w from M/s Murli

Krishna Pvt. Ltd. India. The date of invoice shown was

26-06-2018 since the firm received the pellets before

ADC clearance. After receiving the pellets, through

FedEx, the firm got AD clearance and then

manufactured three batches in August 2018.

2. Do you have any rationale behind selecting

the particular manufacturer

Firm has developed SOP for vendor qualification

including Vendor Evaluation Form and have selected

the subject vendor based on its GMP certificate, DMF

as well as stability study data.


Import of Reference standard and Impurities

standards?

Working standard of Dexlansoprazole was provided by

the supplier. Working standard was supplied along with

API through the same invoice from M/s Murli Krishna

Pharma Pvt Ltd. India.

4. Do you have certificate of analysis of the API

reference standard and impurities standards?

Firm has certificate of analysis of API and of working

standard.

5. Do you have any approval of API or GMP

certificate of manufacturer issued by

regulatory authority of country of origin?

Firm has copy of GMP certificate from M/s Murli

Krishna Pharma Pvt Ltd. India issued by Food and

Drug Administration Mahrashtra State dated 05-9-

2018.


Testing for testing of API?

The firm used API manufacturer method of testing for

carrying out tests of API.

7. Do you have stability Studies Report on API? The firm has real time and accelerated stability study

data sheets provided by the API manufacturer.

8. If Yes, whether the stability testing has been




method and the API manufacturer has quantified the

degradation products.



The firm has API manufacturer’s method for

quantifying the impurities in the API.

10. Do you have some remaining quantities of the

API, Its reference standard and impurities

standard?

The Firm was found having some remaining quantity

of API and working standards.


excipients?

This formulation only involves filling of pellets in

capsule shells.



Firm has locally purchased the hard gelatine capsule

shells.



the excipients?

The firm has test reports and certificate of analysis for

the hard gelatine capsule shell used in the

manufacturing of stability batches.

14. Do you have written and authorized protocols

for the development drug product?


development of Dexerid (Dexlansoprazole) 30mg &

60mg Capsule.

15. Have you performed Drug-Excipient


Not applicable since this formulation only involves

filling of pellets in hard gelatine capsule shells.


studies?

The Firm performed comparative dissolution studies

with the innovator product i.e. Dexilant capsule

manufactured by Takeda Pharma. The details of

comparative dissolution testing is as follows:

Detail Test product Reference product

Brand Dexerid 30mg

Capsule

Dexilant 30mg capsule

Batch# DEX-001 1538575

Detail Test product Reference product

Brand Dexerid 60mg

Capsule

Dexilant 60mg capsule

Batch# DEX-004 1538589

17. Do you have Product Development / R&D

Section?

Firm has dedicated area for product development.

18. Do you have necessary equipment’s available


development drug product?

Firm has necessary equipment available for product

development manufacture of trial batches.

19. Are the equipment’s in product development

qualified?

The equipment present in product development area

were qualified.

20. Do you have proper maintenance / calibration

/ re-qualification program for the equipment

used in PD?

The firm is preacticing maintenance and calibration for

the equipment used in product development section.




Firm has trained & qualified staff in product

development section with relevant knowledge and

training in product development and testing.


batches for the stability studies of drug

product?

Three stability batches have been manufactured for the

stability studies of Dexerid 30mg Capsule with batch

numbers DEX-001, DEX-002 and DEX-003 and

Dexerid 60mg Capsule with batch numbers DEX-004,

DEX-005 and DEX-006.


size of stability of batches?

The firm has informed that their criteria for fixing batch

size is based on number of tests required, testing

frequencies and number of units used in each test.


stability batches?

The firm has complete batch manufacturing record of

all the batches of Dexerid 30mg Capsule and Dexerid

60mg Capsule.


stability batches?

Firm showed written protocols for stability testing of

the stability batches.



The firm has developed and validated method for

testing of the stability batches.




your firm is by any other lab?

NA



being used in the test and analysis of the

product’s API and drug product?

Firm has complete record of qualification of equipment

/ instruments used in the test and analysis of API and

Dexerid (Dexlansoprazole) 30mg & 60mg Capsule.

29. Do your method of analysis Stability

indicating?

The firm has quantified the degradation products after

12 months of stability testing.

30. Is your HPLC software 21CFR compliant? The firm has a dedicated HPLC (Schimadzu LC-20

Gradient) for testing of new drug products placed on

stability studies. The HPLC software for that particular

HPLC is 21 CFR compliant with audit trail option

activated. However the firm has only 1 login account in

the software which is used by various analysts on the

same system. The firm was advised to get separate

account for each analyst.

31. Can you show audit trail reports on drug

product testing?

Audit trail reports for testing of Dexerid

(Dexlansoprazole) 30mg & 60mg Capsule were

available.




which are kept in stability chamber for ongoing real

time stability study.

33. Do you have batches kept on stability testing? The firm has kept the remaining quantities of all

batches in stability chamber for on-going real time

stability study.


equipment’s used in drug product’s


The firm has valid calibration status of all equipment

used in production and analysis of Dexerid

(Dexlansoprazole) 30mg & 60mg Capsule.

35. Do Proper and Continuous monitoring and


The firm has stability chambers for carrying out

accelerated and real time stability studies provided with

uninterrupted power supply and USB data loggers,

which are set for recording temperature and humidity

after every hour.



compliant?

Firm has dedicated area for product development.


utilities were cGMP compliant to satisfactory level.

37. Dissolution testing of pellets at pH 5.5 and pH

6.75/7 for confirmation of dual delayed

release formulation.

The firm found performed dissolution testing of pellets

at pH 5.5 and pH 6.75/7.0 to confirm the dual delayed

release formulation.

38. Date of initiation of stability studies for all the

three trial batches of applied formulation.

The date of initiation of all the batches of Dexerid

(Dexlansoprazole) 30mg & 60mg Capsule was

provided in the table below:

Product Batch No. Date of

initiation

Dexerid 30mg

Capsule

DEX-001 05-09-2018

DEX-002 05-09-2018

DEX-003 05-09-2018

Dexerid 60mg

Capsule

DEX-004 05-09-2018

DEX-005 05-09-2018

DEX-006 05-09-2018


Conclusion:

On the basis of risk-based approach the genuineness / authenticity of stability data submitted by the firm

for registration of Dexerid (Dexlansoprazole) 30mg & 60mg Capsule is verifiable to satisfactory level.

Related manufacturing area, equipment, personnel & utilities could be rated as GMP Compliant to

satisfactory level.

Decision: Registration Board decided to approve registration of Dexerid 30mg Capsule & Dexerid

60mg Capsule with Innovator’s specifications by M/s Bio-labs (Pvt) Ltd. Plot No. 145, Industrial

Triangle Kahuta Road, Islamabad. Manufacturer will place first three production batches on long


Item No. 9: Agenda of Evaluator PEC-IX Case no. 02 Registration applications of newly granted DML or New section (Human)

b. New/Additional section(s)

M/s Medizan Laboratories (Pvt.) Ltd. CLB in its 273rd meeting has granted the following New Section. The letter was issued on 18th February 2020.

The details of products applied for section is provided below:

It is pertinent to mention that the Licensing Division has issued the letter in the name of M/s Medizan

Pharmaceuticals inbstead of M/s Medizan Laboratories (Pvt.) Ltd. The firm has applied for the necessary

correction.

Section No. of molecules applied No. of products applied

Tablets Section Psychotropic 10 18

Tablet (Psychotropic) section: Molecules-10/ Products-18


/Applicant

M/s Medizan Laboratories (Pvt) Ltd Plot no. 313, Industrial

Triangle Kahuta Road Islamabad, Pakistan.

Brand Name +Dosage Form + Strength ANXOL TABLETS 2mg

Composition Each tablet contains:

Diazepam…….2mg

Diary No. Date of R & I & fee Dy.No. 16013: 07-03-2019 Rs. 20,000/- Dated 07-03-2019

Pharmacological Group Benzodiazepine derivatives

Type of Form Form-5


Pack size & Demanded Price 30’s; as per SRO



Diazepam 2mg Tablets. MHRA approved

Me-too status Diazepam 2 mg Tablets. Reg. No. 79395

GMP Status New section

Remarks of the Evaluator ----

Decision: Approved.


/Applicant





Diazepam…….5mg



Type of Form Form-5






Me-too status VALIUM 5mg. Reg No. 003066




Decision: Approved.


/Applicant





Diazepam…….10mg



Type of Form Form-5






Me-too status VALIUM 10mg. Reg No. 003480



Decision: Approved.


/Applicant



Brand Name +Dosage Form + Strength NIGHTUS TABLETS 0.25mg


Bromazepam…….0.25mg



Type of Form Form-5

Finished Product Specification The firm has innovator’s specifications

Pack size & Demanded Price 30’s, as per SRO




Me-too status Could not be confirmed



Decision: Deferred for the following:

Evidence of approval of applied formulation in reference regulatory authorities/agencies which

were adopted by the Registration Board in its 275th meeting.

Evidence of applied formulation/drug already approved by DRAP (generic / me-too status)

alongwith registration number, brand name and name of firm.


/Applicant



Brand Name +Dosage Form + Strength NIGHTUS TABLETS 1.5mg


Bromazepam…….1.5mg



Type of Form Form-5





BROMAZEPAM ARROW 1.5 mg tablet. ANSM approved

Me-too status Yazd 1.5mg Tablet. Reg No.071219



Decision: Approved.



/Applicant



Brand Name +Dosage Form + Strength NIGHTUS TABLETS 3mg


Bromazepam…….3mg



Type of Form Form-5


Pack size & Demanded Price 30’s, Price as per SRO



Lexotan (3mg, 6mg) Tablets, uncoated. TGA Australia

Approved.

Me-too status Laxomac Tablet 3mg. Reg No. 83866



Decision: Approved.


/Applicant



Brand Name +Dosage Form + Strength ALPAREX 0.25mg TABLETS

Composition Each Tablet Contains:

Alprazolam……..…. 0.25mg


Pharmacological Group Benzodiazepine derivative

Type of Form Form-5





Xanax 250 microgram Tablets, uncoated. MHRA approved

Me-too status Medilap 0.25mg Tablet. Reg. NO. 80861



Decision: Approved.


/Applicant



Brand Name+Dosage Form + Strength ALPAREX 0.5mg TABLETS


Alprazolam……. 0.5mg



Type of Form Form-5





Xanax 500 microgram Tablets, uncoated. MHRA approved

Me-too status Nirlam 0.5 mg Tablets. 79327



Decision: Approved.


/Applicant



Brand Name +Dosage Form + Strength ALPAREX 1mg TABLETS


Alprazolam……. 1mg

Diary No. Date of R & I & fee Dy.No. 16019: 07-03-2019 Rs. 20,000/- dated 07-03-2019



Type of Form Form-5





Xanax (0.25mg, 0.5mg, 1mg, 2mg) uncoated Tablets.

USFDA approved

Me-too status Arnax Tablet 1mg. Reg. No. 78918



Decision: Approved.


/Applicant



Brand Name +Dosage Form + Strength CLEEP 0.5mg TABLETS


Clonazepam…………….0.5mg



Type of Form Form-5





Clonazepam Auden 500mcg Tablets. MHRA approved

Me-too status Clonazerain Tablet 0.5mg. Reg. No. 83865



Decision: Approved.


/Applicant



Brand Name +Dosage Form + Strength CLEEP 2mg TABLETS


Clonazepam…………….2mg



Type of Form Form-5





Clonazepam Auden 500mcg Tablets. MHRA approved

Me-too status Clonazep 2 mg Tablets. Reg. No. 78589



Decision: Approved.


/Applicant



Brand Name +Dosage Form + Strength FENOBARB 30mg TABLETS


Phenobarbital……… 30mg


Pharmacological Group Barbiturates and derivatives

Type of Form Form-5





Phenobarbital Tablets 30mg. MHRA approved


Me-too status Fenotal 30 mg Tablets. Reg. No. 79323



Decision: Approved.


/Applicant



Brand Name +Dosage Form + Strength LOPEZ 1mg TABLETS

Composition Each tablet contains:-

Lorazepam…….…….1mg



Type of Form Form-5





LORAZIUM/Lorazepam Tablets (0.5mg, 1mg, 2.5mg),

uncoated. MHRA approved

Me-too status Lorazepam 1 mg Tablets. Reg. No. 79396



Decision: Approved.


/Applicant



Brand Name +Dosage Form + Strength LOPEZ 2mg TABLETS


Lorazepam…….…….2mg



Type of Form Form-5





Ativan® C-IV (lorazepam) (0.5mg, 1mg, 2mg) Tablets,

uncoated. USFDA approved

Me-too status Lorazepam 2 mg Tablets. Reg. No. 79397



Decision: Approved.


/Applicant



Brand Name +Dosage Form + Strength ZLEEP 10mg TABLETS

Composition Each Film Coated Tablet Contains:

Zolpidem Tartrate…….10mg


Pharmacological Group Benzodiazepine related drugs

Type of Form Form-5





Zolpidem Tartrate (5mg, 10 mg) Tablets, film-coated.

MHRA Approved.

Me-too status Ensomie Tablet 10mg, film-caoted. Reg. No. 85026



Decision: Approved.



/Applicant



Brand Name +Dosage Form + Strength PARACORD TABLETS


Paracetamol…..500mg

Codeine phosphate hemihydrate…..15mg


Pharmacological Group Analgesics

Type of Form Form-5





Co-codamol (8mg/500 mg, 15mg/500 mg, 30mg/500 mg)

Tablets. MHRA Approved

Me-too status CODOGESIC 15mg/500 mg tablet. Reg. No.: 028956


Remarks of the Evaluator The reference product contains Codeine phosphate

hemihydrate ….15mg without equivalency.

Correction is required.

Decision: Deferred for revision of label claim as per reference product along with submission of

requisite fee.


/Applicant



Brand Name +Dosage Form + Strength RITAZAN 10mg TABLETS


Methylphenidate hydrochloride ……...10mg


Pharmacological Group Centrally acting sympathomimetics

Type of Form Form-5





Ritalin Tablet (5mg, 10mg, 20mg). USFDA approved

Me-too status Phenida Tablets 10mg. Reg. No. 34745



Decision: Approved.


/Applicant



Brand Name +Dosage Form + Strength RALIF MAX TABLETS


Ibuprofen ……..………..…200mg

Pseudoephidrine HCl ……..…….30mg


Pharmacological Group Analgesic

Type of Form Form-5





Boots Cold & Flu Relief with Ibuprofen film coated tablet

200mg/30mg. MHRA approved

Me-too status Rovinac Tablets. Reg No. 64206



Decision: Deferred for consideration of the application on its turn, since the applied formulation is

not psychotropic.


Case no. 04 Registration applications of newly granted DML or New section (Veterinary)

a. New DML /section The CLB in its 271st meeting granted new DML to the firm. The letter was issued on 26.09.2019. The firm

has applied for the products mentioned against each section

Section Number of molecules Number of products

Oral Powders 10 11

Oral Liquids 10 10

Oral Powder Section


Applicant

Fizi Pharmaceutical & Chemical Laboratories,

8-Km Sikka Street Bhubatian, Raiwind Road Lahore

Brand Name +Dosage Form + Strength Amandin Water Soluble Powder

Composition Each 1000g Powder Contains

Amantadine HCl …….100g

Diary No. Date of R& I & fee Dy. No. 27676: 19-12-2019 PKR 20,000/-: 19-12-2019

Pharmacological Group Adamantane derivatives

Type of Form Form-5

Finished Product Specification Innovator’s specification

Pack size & Demanded Price 100 g, 250 g, 500 g, 1000 g, 2500 g 5000 g 10000 g and

25000 g ; Decontrolled

Me-too status VIZON WATER SOLUBLE POWDER. Reg. No. 96788

GP status New DML


Decision: Approved with pack size upto 10000g (10kg).


Applicant



Brand Name +Dosage Form + Strength Doxybect-50 Water Soluble Powder

Composition Each 1000g powder Contains

Doxycycline HCl ……………...500g

Diary No. Date of R& I & fee Dy.No. 27674: 19.12.2019 PKR 20,000/-: 19.12.2019

Pharmacological Group Tetracyclines

Type of Form Form-5




Me-too status Doxy-Mix 50 Powder. Reg. No. 059166

GP status New DML




Applicant



Brand Name +Dosage Form + Strength Floxycol Water Soluble Powder

Composition Each g Contains:

Florfenicol…….150 mg



Pharmacological Group Antibiotics

Type of Form Form-5


Pack size & Demanded Price 100 g, 250 g, 500 g, 1000 g, 2500 g 5000 g 10000 g &

25000g ; Decontrolled

Me-too status Floxybar-30 Water Soluble Powder. Reg. No. 072601

GP status New DML





Applicant



Brand Name +Dosage Form + Strength Floxynor Oral Powder

Composition Each g Contain

Neomycin Sulphate…..150 mg.

Florfenicol…….100 mg




Type of Form Form-5




Me-too status Neoxflor Oral Powder. Reg. No. 088638

GP status New DML




Applicant



Brand Name +Dosage Form + Strength Furamin Water Soluble Powder

Composition Each 1000g Contains

Furosemide…….20g

Potassium chloride……..4g

Calcium carbonate…..45g

Magnesium sulphate…….1g


Pharmacological Group Diuretic and electrolytes

Type of Form Form-5




Me-too status Furosebar Water Soluble Powder. Reg. No. 075783

GP status New DML




Applicant



Brand Name +Dosage Form + Strength Colinco Water Soluble Powder

Composition Each g Contains

Lincomycin HCl ……….100 mg.

Colistin Sulphate ….800,000 I.U.


Pharmacological Group ( Antibiotic/Antibacterial )

Type of Form Form-5




Me-too status Nobi-Lincol Powder. Reg. No. 079116

GP status New DML




Applicant



Brand Name +Dosage Form + Strength Multimeth WSP


Composition Each 100 g Powder contains;

Methenamine........... 95g

Vitamin B1............0.80g

Vitamin B2............0.92g

Vitamin K3............0.2g


Pharmacological Group Multivitamins and antibiotics

Type of Form Form-5




Me-too status Diuriq WSP. Reg. No. 080735

GP status New DML




Applicant



Brand Name +Dosage Form + Strength NEOXYCOL POWDER

Composition Each 1000 g Contains:

Neomycin sulphate ...........250g.

Colistin sulphate........... 300 M.I.U.

Oxytetracycline HCl...........250g.



Type of Form Form-5




Me-too status ONC Forte Powder. Reg. No. 078217

GP status New DML




Applicant



Brand Name +Dosage Form + Strength Sulphazine Oral Powder

Composition Each 100g Powder Contains

Sulfachlorpyridazine ….….30g

Diary No. Date of R& I & fee Dy.No : 19.12.2019 PKR 20,000/-: 19.12.2019


Type of Form Form-5




Me-too status Coxiriq Oral Powder. Reg. No. 079814

GP status New DML




Applicant



Brand Name +Dosage Form + Strength Tycobrox Water Soluble Powder

Composition Each 1000 g Contains

Tylosin Tartrate..........100 g

Doxycycline HCl...........200 g

Colistin sulphate...........500M.I.U.


Bromhexine HCl ...........5g


Pharmacological Group Antibiotic and expectorant

Type of Form Form-5




Me-too status Tycobar-D Water Soluble Powder. Reg. No. 071099

GP status New DML




Applicant



Brand Name +Dosage Form + Strength Tycodox Water Soluble Powder

Composition Each 1000 g Contains

Tylosin Tartrate...........100 g

Doxycycline HCl........... 200 g

Colistin sulphate...........450M.I.U.

Bromhexine HCl...........4g


Pharmacological Group Antibiotic and expectorant

Type of Form Form-5




Me-too status Doxyline Water Soluble Powder. Reg. No. 075776

GP status New DML



Oral Liquid Section


Applicant



Brand Name +Dosage Form + Strength Bromfiz Oral Liquid


Bromhexine HCl……50 mg


Pharmacological Group Expectorants

Type of Form Form-5


Pack size & Demanded Price 100 ml, 250 ml, 450 ml, 500, ml, 1000 ml and 5000 ml;

Decontrolled

Me-too status Brombar-5 Oral Liquid. Reg. No. 073947

GP status New DML


Decision: Approved.


Applicant



Brand Name +Dosage Form + Strength Bromfiz Plus Oral Liquid


Menthol …………..40 mg

Bromhexine HCl….20 mg


Pharmacological Group Expectorants

Type of Form Form-5




Decontrolled

Me-too status BROMO PLUS LIQUID. Reg. No. 073917

GP status New DML


Decision: Approved.


Applicant



Brand Name +Dosage Form + Strength Enrobrostin Oral Solution


Enrofloxacin………. 10.0g

Colistin Sulphate …..50MIU

Bromhexine HCl….…5.0g


Pharmacological Group Antibiotics and expectorant

Type of Form Form-5



Decontrolled

Me-too status Inter Flox liquid. Reg. No. 078241

GP status New DML


Decision: Approved.


Applicant



Brand Name +Dosage Form + Strength Enrophen Oral Liquid

Composition Each 100ml contains

Enrofloxacin……… 10.0g

Aminophylline…. …..4.0g

Guaiphenesin………10.0g


Pharmacological Group Antibiotics, bronchodilator and expectorant

Type of Form Form-5



Decontrolled

Me-too status Enrophylin Oral Liquid. Reg. No. 080730

GP status New DML


Decision: Approved.


Applicant



Brand Name +Dosage Form + Strength Floricol Oral Solution

Composition Each 1000 ml contains:

Florfenicol...........200g



Type of Form Form-5



Decontrolled

Me-too status FLUROTIN Liquid. Reg. No. 075751


GP status New DML


Decision: Approved.


Applicant



Brand Name +Dosage Form + Strength Floricol Plus Oral Solution


Florfenicol ...........23g

Colistin sulphate........... 50MIU



Type of Form Form-5



Decontrolled

Me-too status Fenicol-23 oral solution. Reg. No. 080731

GP status New DML


Decision: Approved.


Applicant



Brand Name +Dosage Form + Strength Floxacin Oral Liquid

Composition Each 1000 ml contains:

Enrofloxacin……100g

Diary No. Date of R& I & fee Dy.No.27660: 19.12.2019 PKR 20,000/-: 19.12.2019


Type of Form Form-5



Decontrolled

Me-too status Enroriq-10 Oral Liquid. Reg. No. 079813

GP status New DML


Decision: Approved.


Applicant



Brand Name +Dosage Form + Strength Hepafiz Oral Liquid


L-Carnitine....................50mg

Betaine..........................20mg

Inositol .........................7mg

Choline cholride...........100mg

Sorbitol...............................200mg

Magnesium sulphate...........10mg


Pharmacological Group Liver therapy

Type of Form Form-5



Decontrolled

Me-too status Hepabar Oral Liquid. Reg. No. 080733

GP status New DML


Decision: Approved.



Applicant



Brand Name +Dosage Form + Strength Micosil Oral Liquid


Tilmicosin Phosphate ……..250mg



Type of Form Form-5



Decontrolled

Me-too status Tilmofas oral liquid. Reg. No. 046644

GP status New DML


Decision: Approved.


Applicant



Brand Name +Dosage Form + Strength Sulphatrim-T Oral Solution


Tylosin tartrate….55mg

Sulphadiazine ….175mg

Trimethoprim …..35mg



Type of Form Form-5



Decontrolled

Me-too status Respibar-250 Oral Solution. Reg No. 071095

GP status New DML


Decision: Approved.

CLB in its 271st meeting held on 12th September 2019 has considered and approved the grant of the

following additional section.

Liquid Injection Section Vials (Penicillin Veterinary) (10 molecules/19 products)


Applicant



Brand Name + Dosage Form + Strength Moxillin LA Injection


Amoxicillin as Trihydrate……...150 mg

Diary No. Date of R&I & Fee Dy. No. 21188: 18-10-2019, Rs. 20,000/-: 18-10.2019


Type of Form Form-5


Pack size & Demanded Price 50ml; Decontrolled

Me-too status V-MOX L.A 15% INJECTION (50ml). Reg. 084965

GMP status New Section Veterinary Liquid Injection Penicillin


Decision: Approved.


Applicant



Brand Name + Dosage Form + Strength Moxillin LA Injection


Amoxicillin Trihydrate……...150 mg




Type of Form Form-5



Me-too status Amoxibar LA Injection (100ml). Reg. 087147



Decision: Approved.


Applicant



Brand Name + Dosage Form + Strength Moxillin Plus LA Injection





Type of Form Form-5



Me-too status Zamox LA 20% Injection (10ml, 30ml, 50ml, 100ml).

Ristration No. 048154



Decision: Approved.


Applicant



Brand Name + Dosage Form + Strength Moxillin Plus LA Injection





Type of Form Form-5



Me-too status Zamox LA 20% Injection

(10ml/30ml/50ml/100ml).R.#048154



Decision: Approved.


Applicant



Brand Name + Dosage Form + Strength Mox-C Injection


Amoxicillin as Trihydrate.……..…...100 mg

Colistin Sulphate…………………...250,000 IU

Diary No. Date of R&I & Fee Dy. No. 21190: 18-10-2019, Rs. 20,000/-, 18-10-2019


Type of Form Form-5



Me-too status Colimoxbar Injection (100ml). No. 087151


AMCOCIN INJECTION (50ml). Reg. NO. 82797

(amoxicillin as Trihydrate).



Decision: Approved with innovator’s specifications.


Applicant



Brand Name + Dosage Form + Strength Mox-C Injection


Amoxicillin as Trihydrate..……..…...100 mg

Colistin Sulphate……...…………...250,000 IU



Type of Form Form-5



Me-too status Colimoxbar Injection (100ml). Reg. 087151





Applicant



Brand Name + Dosage Form + Strength Mox-C Plus LA Injection


Amoxicillin as Trihydrate……..…...120 mg

Colistin Sulphate……………….…300,000 IU



Type of Form Form-5



Me-too status COLICILLIN L.A INJECTION (50ml). Reg. No. 87153





Applicant



Brand Name + Dosage Form + Strength Mox-C Plus LA Injection


Amoxicillin as Trihydrate……..…...120 mg

Colistin Sulphate…………….……300,000 IU



Type of Form Form-5



Me-too status Colicillin-LA Injection Baariq Pharma Reg. 087153





Applicant



Brand Name + Dosage Form + Strength Moxigen Injection



Amoxicillin Trihydrate eq. to Amoxicillin……….50mg

Gentamycin Sulphate eq. to Gentamycin…………25mg



Type of Form Form-5



Me-too status G MOX 50ML INJECTION. Reg. 085493





Applicant



Brand Name + Dosage Form + Strength Moxigen Injection


Amoxicillin Trihydrate eq. to Amoxicillin…………….50

mg

Gentamycin Sulphate eq. to Gentamycin……….....25 mg



Type of Form Form-5



Me-too status G Mox Injection (100ml). Reg. 085724





Applicant



Brand Name + Dosage Form + Strength Moxiclav Injection


Amoxicillin as Trihydrate………………………..140mg

Clavulanic Acid as Potassium Clavulanate………35mg



Type of Form Form-5



Me-too status Clavet Injection (50ml, 100ml). Reg. 046519 (does not

depict Potassium Clavulanate salt).


Remarks of the Evaluator Available in BP as amoxicillin and potassium clavulanate

injection.



Applicant



Brand Name + Dosage Form + Strength Moxiclav Injection


Amoxicillin as Trihydrate.………………………..140 mg

Clavulanic Acid as Potassium Clavulanate……….35mg



Type of Form Form-5




Me-too status Clavet Injection (50ml, 100ml). Reg. 046519 (does not

depict Potassium Clavulanate salt).


Remarks of the Evaluator Available in BP as amoxicillin and potassium

clavulanate injection.



Applicant



Brand Name + Dosage Form + Strength Ampicot LA Injection


Ampicillin as Trihydrate.…………….12.5 g

Cloxacillin Base…………..................12.5 g



Type of Form Form-5



Me-too status Ampicox Injection (50ml, 100ml). Reg. 035061





Applicant



Brand Name + Dosage Form + Strength Ampicot LA Injection


Ampicillin as Trihydrate..…………….12.5 gm

Cloxacillin Base…………...........12.5 gm



Type of Form Form-5



Me-too status Ampicox Injection (50ml, 100ml). Reg. 035061





Applicant



Brand Name + Dosage Form + Strength Procapen GP Injection


Penicillin G procaine ………………..300 mg



Type of Form Form-5



Me-too status Nawapen-30 (10ml, 50ml, 100ml). Reg. 053996 (procaine

penicillin)


Remarks of the Evaluator Finished product is available as Procaine penicillin G

injectable suspension in BP. The firm revised procaine

penicillin to Penicillin G procaine without submission of fee.

Decision: Deferred for submission of fee for revision of salt form.



Applicant



Brand Name + Dosage Form + Strength Streptocaine Injection


Penicillin G procaine………………..200 mg

Dihydrostreptomycin Sulphate………...160 mg



Type of Form Form-5



Me-too status Neo Strep-Pen Injection (10ml, 50ml, 100ml). Reg. 053997

(Penicillin procaine, streptomycin Sulphate)


Remarks of the Evaluator Finished product is available as Procaine penicillin G,

dihydrostreptomycin Sulphate injectable suspension in BP.

The firm revised procaine penicillin to Penicillin G procaine

without submission of fee.



Applicant



Brand Name + Dosage Form + Strength Streptocaine Injection


Penicillin G procaine………………..200 mg

dihydrostreptomycin Sulphate………...160 mg



Type of Form Form-5



Me-too status Neo Strep-Pen Injection (10ml, 50ml, 100ml). Reg. 053997

(Penicillin procaine, streptomycin Sulphate)




The firm revised procaine penicillin to Penicillin G procaine

without and streptomycin Sulphate to Dihydrostreptomycin

Sulphate without submission of fee.



Applicant



Brand Name + Dosage Form + Strength Di-Pen Injection


Procaine Penicillin G…………………200,000 IU

Dihydrostreptomycin Sulphate…………..200 mg



Type of Form Form-5



Me-too status Streptomet (50ml). Reg. 080954







Applicant



Brand Name + Dosage Form + Strength Tri-Pen LA Injection


Benzathine Pencillin G.…..………….100,000 IU

Procaine Penicillin G………………..150,000 IU

Dihydrostreptomycin sulphate…………..200 mg



Type of Form Form-5



Me-too status BPS-LA Injection (50ml). Reg. 080951


Remarks of the Evaluator Revise “Dihydrostreptomycin sulphate” to

“Dihydrostreptomycin as sulphate” in the label claim only and

adjust the weight of Dihydrostreptomycin sulphate in Master

formula as per salt factor.

Decision: Deferred for revision of formulation including the salt form as per the DRAP approved

generic product along with submission of revised master formulation and requisite fee.

Item No. 10: Agenda of Evaluator PEC-XI

M/s D.Hanns Pharma (Pvt) Ltd., Plot No. 9/A, Industrial Estate, Bhimber, AJK.

The Central Licensing Board in its 273rd meeting held on 15th January, 2020 has considered and approved the

grant of Drug Manufacturing License to M/s D.Hanns Pharma (Pvt) Ltd., Plot No. 9/A, Industrial Estate, Bhimber,

AJK. by way of Formulation vide approval letter No. F. 1-18/2018-Lic dated 11th February 2020 with following

(04) sections.

S No. Section No. of products No. of Molecules

1. Oral Liquid Section-I (Vet) 28 10

2. Oral Liquid Section-II (Vet) 21 10

3. Oral Powder Section-I (Vet) N/A N/A

4. Oral Powder Section-II (Vet) N/A N/A

Following applications have been submitted for registration by the firm.

Oral Liquid Section-I (10molecules / 28products)

326. Name and address of Manufacturer

/ Applicant

D-Haans Pharma (Pvt) Ltd. Plot No. 9/A, Industrial Estate,

Bhimber, AJK.

Brand Name, Dosage Form, Strength FEN HANS 23 % ORAL LIQUID

Composition Each 100ml contains:-

Florfenicol ………………… 23g


Diary No., Date of R & I & Fee Dy.No 1511 dated 14/02/2020; Rs. 20,000 14/02/2020


Type Of Form Form 5

Finished product Specification Manufacturers Specification

Pack Size and Demanded Price 100ml,150ml, 250ml,500ml,1Litre, 2.5Litre; Decontrolled

Me-Too Status Fentin-23 by M/s Nawal Pharmaceuticals (Reg#078257)

GMP Status New DML (No. 000912) issued on 11-02-2020 on the basis of

inspection conducted on 12-12-2019.


Remarks of Evaluator XI The firm has claimed manufacturer’s specifications and the

product is not present in available pharmacopoeia (USP,BP,IP,JP)



/ Applicant


Bhimber, AJK.







Type Of Form Form 5


Pack Size and Demanded Price 100ml,150ml, 250ml,500ml,1Litre,2.5Litre Decontrolled

Me-Too Status Flocol Liquid by M/s D-Maarson Pharmaceuticals (Reg#074082)



Remarks of Evaluator XI The firm has claimed manufacturer’s specifications & the product

is not present in available pharmacopoeia (USP, BP, IP, JP)

Decision: Deferred for scientific rational for formulation containing 25g/100ml florfenicol, since

formulation containing 23g/100ml florfenicol is already approved.


/ Applicant


Bhimber. AJK.

Brand Name, Dosage Form, Strength FEN HANS 11% ORAL LIQUID






Type Of Form Form 5


Pack Size and Demanded Price 100ml,150ml, 250ml, 500ml, 1Litre, 2.5Litre Decontrolled

Me-Too Status Flo Raft Oral Liquid by M/s Nawal Pharmaceuticals

(Reg#078252)



Remarks of Evaluator XI The firm has claimed manufacturer’s specifications & the product


Decision: Deferred for scientific rational for formulation containing 11g/100ml florfenicol, since

formulation containing 10g/100ml florfenicol is already approved.


/ Applicant


Bhimber. AJK.







Type Of Form Form 5


Pack Size and Demanded Price 100ml,150ml, 250ml, 500ml, 1Litre, 2.5Litre; Decontrolled

Me-Too Status Floro C Oral Liquid by M/s D-Maarson Pharmaceuticals

(Reg#074079)




Remarks of Evaluator XI The firm has claimed manufacturer’s specifications & product is

not present in available pharmacopoeia (USP, BP, IP, JP)



/ Applicant


Bhimber. AJK.

Brand Name, Dosage Form, Strength FLOHANS-23% ORAL LIQUID





Type Of Form Form 5


Pack Size and Demanded Price 100ml,150ml, 250ml,500ml,1Litre, 2.5Litre; Decontrolled

Me-Too Status Floral Plus Oral Liquid by M/s Nawal Pharmaceuticals

(Reg#074090)







/ Applicant


Bhimber. AJK.

Brand Name, Dosage Form, Strength FLOHANS-25 % ORAL LIQUID





Type Of Form Form 5



Me-Too Status Wal-Fen 25% Oral Liquid by M/s Nawal Pharmaceuticals

(Reg#099438)…could not be confirmed



Remarks of Evaluator XI Evidence of applied formulation/drug already approved by DRAP

(generic/me-too status) alongwith registration number, brand

name and name of firm could not be confirmed

The firm has claimed manufacturer’s specifications & product is


Decision: Deferred for following:

Scientific rational for formulation containing 25g/100ml florfenicol, since formulation

containing 23g/100ml florfenicol is already approved.

Evidence of applied formulation/drug already approved by DRAP (generic / me-too status)

alongwith registration number, brand name and name of firm.


/ Applicant


Bhimber. AJK.






Type Of Form Form 5



Pack Size and Demanded Price 100ml, 150ml, 250ml, 500ml, 1Litre, 2.5Litre; Decontrolled

Me-Too Status Florfen-20% Oral Liquid by M/s Nawal Pharma (Reg#074091)







/ Applicant


Bhimber. AJK.






Type Of Form Form 5



Me-Too Status Fencol-10% Oral Liquid by M/s Nawal Pharma (Reg#075741)



Remarks of Evaluator The firm has claimed manufacturer’s specifications & product is




/ Applicant


Bhimber. AJK.

Brand Name, Dosage Form, Strength TIMBER ORAL LIQUID


Tilmicosin Phosphate…………… 250mg



Type Of Form Form 5


Pack Size and Demanded Price 100ml,150ml, 250ml,500ml,1Litre, 2.5Litre Decontrolled

Me-Too Status Tico-Maars Oral Liquid by M/s D-Maarson Pharmaceuticals

(Reg#096841)







/ Applicant


Bhimber. AJK.

Brand Name, Dosage Form, Strength TIMBER-PL ORAL LIQUID


Tilmicosin…………… 250mg



Type Of Form Form 5



Me-Too Status Tilconoor 2.5% Oral Liquid by M/s Kohinoor Industries

(Reg#081312)




Remarks of Evaluator The firm has already applied the same product, in same strength

and same dosage form with salt form.



Decision: Deferred for clarification since the same product in same strength and dosage form (with

salt form) is also applied.


/ Applicant

D-Haans Pharma (Pvt) Ltd. Plot No. 9/A,Industrial Estate,

Bhimber. AJK.

Brand Name, Dosage Form, Strength GUXANIN-AG ORAL LIQUID


Enrofloxacin …… ……… 10g

Guaifenesin………………10g

Aminophylline………….. ..4g


Pharmacological Group Antibiotic, Bronchodilator, Expectorant

Type Of Form Form 5


Pack Size and Demanded Price 100ml,150ml, 250ml,500ml,1Litre, 2.5Litre Decontrolled

Me-Too Status EG Enro Plus Liquid by M/s Elegance Pharma (Reg#074099)







/ Applicant


Bhimber. AJK.

Brand Name, Dosage Form, Strength GUNAXIN-AE ORAL LIQUID



Guaifenesin………………..4g

Aminophylline………….. ..10g


Pharmacological Group Antibiotic, Bronchodilator, Expectorant

Type Of Form Form 5



Me-Too Status Ensol-AG Oral Liquid By M/s Biogen Pharma (Reg#049720)







/ Applicant


Bhimber. AJK.

Brand Name, Dosage Form, Strength SUNRO-E10 ORAL LIQUID






Type Of Form Form 5




Me-Too Status Amtin-C Oral Liquid by M/s D-Maarson Pharma (Reg#074080)







/ Applicant


Bhimber. AJK.







Type Of Form Form 5



Me-Too Status Maxen Liquid by M/s D-Maarson Pharmaceuticals (Reg#075749)







/ Applicant


Bhimber. AJK.







Type Of Form Form 5



Me-Too Status Vetaflox-C 25% Oral Liquid by M/s Vetz Pharmaceuticals

(Reg#079276)







/ Applicant


Bhimber. AJK.

Brand Name, Dosage Form, Strength SUNRO-E ORAL LIQUID



Colistin Sulphate…………3%



Type Of Form Form 5


Pack Size and Demanded Price 100ml, 150ml, 250ml, 450ml, 500ml, 1Litre, 2.5Litre;

Decontrolled


Me-Too Status Enrosir-20 Oral Liquid (Enrofloxacin 20%,

Colistin Sulphate 3%) by M/s Attabak Pharma (Reg#071060)







/ Applicant


Bhimber. AJK.

Brand Name, Dosage Form, Strength HEXBRO-10 ORAL LIQUID


Bromhexine HCl…… ……… 10mg


Pharmacological Group Mucolytics

Type Of Form Form 5



Me-Too Status Wal-Bro-100 Liquid by M/s Nawal Pharmaceuticals

(Reg#097863)







/ Applicant


Bhimber. AJK.

Brand Name, Dosage Form, Strength HEXBRO-50 ORAL LIQUID


Bromhexine HCl…………… 50mg


Pharmacological Group Mucolytics

Type Of Form Form 5



Me-Too Status Wal-Bro-50 Liquid by M/s Nawal Pharmaceuticals

(Reg#097862)







/ Applicant


Bhimber. AJK.

Brand Name, Dosage Form, Strength AMI-HANS ORAL LIQUID


Doxycycline HCl ………………… 20g

Tylosin tartrate ……………….…. 10g

Guaifenesin ….…………………. 20g

Aminophylline ………………… 8g


Pharmacological Group Antibiotic, Expectorant, Bronchodilator

Type Of Form Form 5


Pack Size and Demanded Price 100ml, 150ml, 250ml, 500ml, 1Litre; Decontrolled


Me-Too Status Tyco-G Oral Liquid by M/s Attabak Pharmaceuticals

(Reg#075704)



Remarks of Evaluator The firm has not revised the label claim as per approved Mee-Too

product alongwith submission of applicable fee. The strength of

molecules of the applied product is different as compared to

approved Mee-Too product.



Decision: Deferred for revision of formulation as per DRAP approved me-too / generic product

along with submission of requisite fee.


/ Applicant


Bhimber. AJK.

Brand Name, Dosage Form, Strength BIMRO-10 ORAL LIQUID





Type Of Form Form 5



Decontrolled

Me-Too Status Enrowal-10 Oral Liquid by M/s Nawal Pharma (Reg#072626)



Remarks of Evaluator The firm has claimed for manufacturer’s specifications but the

product is present in USP as oral suspension

Decision: Approved with USP specification.


/ Applicant


Bhimber. AJK.



Enrofloxacin …………… 20g



Type Of Form Form 5



Decontrolled

Me-Too Status Enrowal-20 Oral Liquid by M/s Nawal Pharmaceuticals

(Reg#072627)







/ Applicant


Bhimber. AJK.



Enrofloxacin …………… 25g




Type Of Form Form 5



Decontrolled

Me-Too Status Enro-Gold Liquid by M/s Medicure Laboratories (Reg#058961)







/ Applicant


Bhimber. AJK.

Brand Name, Dosage Form, Strength MENTOVET-54 ORAL LIQUID


Bromhexine HCl…… ……… 50mg

Menthol………………………..40mg


Pharmacological Group Mucolytics, Expectorant

Type Of Form Form 5



Me-Too Status Hexthol Liquid by M/s Nawal Pharmaceuticals (Reg#097984)







/ Applicant


Bhimber. AJK.




Menthol……………………..40mg


Pharmacological Group Mucolytics, Expectorant

Type Of Form Form 5



Me-Too Status Bromo-Plus Liquid by Elegance Pharmaceuticals (Reg#073917)







/ Applicant


Bhimber. AJK.




Menthol……………..……….20mg


Pharmacological Group Mucolytic, Expectorant

Type Of Form Form 5




Me-Too Status Bromotin Liquid by M/s Elegance Pharmaceuticals

(Reg#073999)







/ Applicant


Bhimber. AJK.

Brand Name, Dosage Form, Strength BRO DOX-CT ORAL LIQUID

Composition Each1000 ml contains:-



Colistin Sulphate…………………. 500MIU

Bromhexine HCl….…………………10g


Pharmacological Group Antibiotic, Mucolytic

Type Of Form Form 5



Me-Too Status CRD Liquid by M/s D-Maarson Pharmaceuticals (Reg#072678)







/ Applicant


Bhimber. AJK.

Brand Name, Dosage Form, Strength BRO DOX-C ORAL LIQUID





Bromhexine HCl….……………….. 5g



Type Of Form Form 5



Me-Too Status CRD Mars Liquid by M/s D-Maarson Pharmaceuticals

(Reg#072677)







/ Applicant


Bhimber. AJK.

Brand Name, Dosage Form, Strength BRO DOX-5 ORAL LIQUID






Bromhexine HCl….………………. 5g



Type Of Form Form 5



Me-Too Status CRD-COL Oral Liquid by M/s Attabak Pharma (Reg#058879)






Oral Liquid Section-II (10 molecules/21 products)


/ Applicant


Bhimber. AJK.

Brand Name, Dosage Form, Strength COBAZASOL DS ORAL SUSPENSION


Oxyclozanide ………………… 6%

Levamisole HCl ……………… 3%

Cobalt Chloride………………. 0.15%

Sodium selenite ………………. 0.07%


Pharmacological Group Anthelmintic, Minerals

Type Of Form Form 5



Me-Too Status



Remarks of Evaluator Evidence of applied formulation already approved by DRAP

(generic/me-too status) alongwith registration number, brand name

and name of firm not available

The firm has claimed manufacturer’s specifications & the product





/ Applicant


Bhimber. AJK.

Brand Name, Dosage Form, Strength COBAZASOL-PL ORAL SUSPENSION


Oxyclozanide ………………… 3g

Levamisole HCl ……………… 1.5g

Cobalt Chloride…………… 0.075g

Sodium selenite …………… 0.035g



Type Of Form Form 5



Me-Too Status Nilzole Liquid by M/s Attabak Pharmaceuticals (Reg#034545)




Remarks of Evaluator The firm has claimed manufacturer’s specifications and product is




/ Applicant


Bhimber. AJK.

Brand Name, Dosage Form, Strength LEVA BALT ORAL SUSPENSION


Triclabendazole ………………… 5g

Levamisole HCl ……………… 3.75g

Cobalt sulphate ………………. 0.075g

Sodium selenite ………………. 0.035g



Type Of Form Form 5



Me-Too Status Tenex plus 8.75 Drench by M/s Breeze Pharma (Reg#059107)



Remarks of Evaluator Mee-Too of applied product shows the base form of Levamisole

while the applied formulation contains the hydrochloride salt of

Levamisole. Moreover Mee-Too of applied product shows the

chloride salt of cobalt while the applied formulation contains the

sulphate salt of cobalt. Clarify or revise the salt form of Levamisole

and cobalt in the label claim and master formulation along with

submission of applicable fee.



Decision: Deferred for revision of formulation as per DRAP approved me-too / generic product along



/ Applicant


Bhimber. AJK.

Brand Name, Dosage Form, Strength LEVA BALT-PLUS ORAL SUSPENSION


Triclabendazole …………… 50mg

Levamisole as HCl ……………37.5mg

Cobalt sulphate ……………. 1.67mg

Sodium selenite ……………. 0.35mg



Type Of Form Form 5



Me-Too Status Triclobak plus suspension by M/s Attabak Pharmaceuticals

(Reg#062168)



Remarks of Evaluator The firm has submitted revised form 5 correcting the salt of

Levamisole in label claim as per Mee-Too product along with

submission of Rs. 5000/- on deposit slip No. 1927781 date

06.04.2020.






/ Applicant


Bhimber. AJK.

Brand Name, Dosage Form, Strength LEVA BALT-AD ORAL SUSPENSION


Triclabendazole ………….. 50mg

Levamisole HCl ………..… 37.5mg

Cobalt sulphate …………… 0.075g

Sodium selenite …………… 0.035g



Type Of Form Form 5



Me-Too Status Cobzolewal Oral Suspension by M/s Nawal Pharmaceuticals

(Reg#097904)



Remarks of Evaluator The firm has claimed manufacturer’s specifications & the product




/ Applicant


Bhimber. AJK.

Brand Name, Dosage Form, Strength HANSENID ORAL SUSPENSION


Oxfendazole……….2.265gm


Pharmacological Group Anthelmintic

Type Of Form Form 5



Me-Too Status Oxafen Oral Suspension by M/s Farm Aid Group Pak

(Reg#041250)



Remarks of Evaluator The firm has claimed BP specifications (product not available) but

the product is in available US pharmacopoeia.



/ Applicant


Bhimber. AJK.

Brand Name, Dosage Form, Strength HANSENID–PL ORAL SUSPENSION


Oxfendazole…………...25mg



Type Of Form Form 5



Me-Too Status Arox Drench by M/s Leads Pharma (Reg#046670)




Remarks of Evaluator The firm has submitted revised form 5 correcting the strength in

label claim as per Mee-Too product along with submission of Rs.

5000/- on deposit slip No. 1927782 date 06.04.2020

The firm has claimed BP specifications (product not available) but

the product is in available US pharmacopoeia.

Decision: Deferred for submission of fee Rs 15,000/- for revision of formulation.


/ Applicant


Bhimber. AJK.

Brand Name, Dosage Form, Strength HAN-FAXS ORAL SUSPENSION


Triclabendazole……….. 12g

Albendazole…………… 10g

Ivermectin…………….. 0.2g



Type Of Form Form 5



Me-Too Status Thunder Drench by M/s Star Laboratories (Reg#058941)







/ Applicant


Bhimber. AJK.

Brand Name, Dosage Form, Strength TRILOXAL ORAL SUSPENSION


Triclabendazole……….8.5g

Oxfendazole………...…2.265g



Type Of Form Form 5



Me-Too Status Vorcid Suspension by Breeze Pharma (Reg#063563)



Remarks of Evaluator The firm has submitted revised form 5 correcting the strength of

oxfendazole in label claim as per Mee-Too product along with

submission of Rs. 20,000/- on deposit slip No. 1927783 date

06.04.2020





/ Applicant


Bhimber. AJK.

Brand Name, Dosage Form, Strength AUG-MILK ORAL SUSPENSION


Oxyclozanide………….62.5mg

Oxfendazole……………22.65mg.

Cobalt Sulphate……….1.67mg

Selenium as Sodium Selenate………..0.5mg




Type Of Form Form 5



Me-Too Status O-2 Forte Suspension by M/s D-Maarson Pharma (Reg#078264)







/ Applicant


Bhimber. AJK.

Brand Name, Dosage Form, Strength HANZOLE 2.5% ORAL SUSPENSION


Albendazole……………2.5g.



Type Of Form Form 5



Me-Too Status Albabak-2.5 Oral Suspension by M/s Attabak Pharmaceuticals

(Reg#034538)







/ Applicant


Bhimber. AJK.

Brand Name, Dosage Form, Strength HANZOLE 5% ORAL SUSPENSION


Albendazole……………5g.



Type Of Form Form 5



Me-Too Status Albanil Suspension by M/s Farm Aid Group Pak (Reg#035199)







/ Applicant


Bhimber. AJK.

Brand Name, Dosage Form, Strength HANZOLE 10% ORAL SUSPENSION


Albendazole……………10g.



Type Of Form Form 5




Me-Too Status Bendol 10 Suspension by M/s Breeze Pharma (Reg#059153)







/ Applicant


Bhimber. AJK.

Brand Name, Dosage Form, Strength HANZOLE 12.5% ORAL SUSPENSION


Albendazole……………12.5g



Type Of Form Form 5



Me-Too Status Albadec Super Oral Suspension by M/s Decent Pharma (R#079838)





Decision: Deferred for scientific rational for formulation containing 12.5g/100ml albendazole, since

formulation containing 10g/100ml albendazole is already approved.


/ Applicant


Bhimber. AJK.

Brand Name, Dosage Form, Strength HANZOLE-11.25% ORAL SUSPENSION


Albendazole……………11.25g.



Type Of Form Form 5



Me-Too Status Albensure Drench by M/s Biogen Pharma (Reg#069609)





Decision: Deferred for scientific rational for formulation containing 11.25g/100ml albendazole, since

formulation containing 10g/100ml albendazole is already approved.


/ Applicant


Bhimber. AJK.

Brand Name, Dosage Form, Strength ALBAHANS ORAL SUSPENSION.



Cobalt Sulphate……….0.075g

Sodium Selenite………..0.035g



Type Of Form Form 5




Me-Too Status Nobialba Suspension by M/s Noble Pharma (Reg#62124)







/ Applicant


Bhimber. AJK.

Brand Name, Dosage Form, Strength ALBAHANS-10% ORAL SUSPENSION


Albendazole……………10g





Type Of Form Form 5



Me-Too Status





and name of firm not available






/ Applicant


Bhimber. AJK.

Brand Name, Dosage Form, Strength ALBAHANS-12.5% ORAL SUSPENSION







Type Of Form Form 5



Me-Too Status





and name of firm is not available






/ Applicant


Bhimber. AJK.

Brand Name, Dosage Form, Strength ALBAHANS-7.5% ORAL SUSPENSION



Albendazole……………7.5%

Cobalt Sulphate……….0.075%

Sodium Selenite………..0.035%



Type Of Form Form 5



Me-Too Status Albamont Oral Suspension by Westmont Pharma (Reg#048194)







/ Applicant


Bhimber. AJK.

Brand Name, Dosage Form, Strength HISO-VIT LIQUID


Sulphadiazine………………. 35.50 gm

Sulphadimidine…………... 28.40 gm

Neomycin Sulphate……….. 1.80 gm

Hysocine Methylbromide…. 0.04 gm

Pectin……………………….. 7.10 gm

Kaoline…………………….. 103.30 gm

Vitamin B1………………… 0.15 gm

Vitamin B2…………………. 0.22 gm


Pharmacological Group Antibiotics, Anti-diarrheal, Vitamins

Type Of Form Form 5



Me-Too Status





and name of firm is not available






/ Applicant


Bhimber. AJK.

Brand Name, Dosage Form, Strength PEFROX-BH ORAL LIQUID

Composition Each Litre contains:-

Pefloxacin methanesulfonate equ. to

Pefloxacin…………... 100 gm


Pharmacological Group Fluoroquinolones

Type Of Form Form 5



Me-Too Status


Item No. 11: Agenda of Evaluator PEC-XIV

Case no. 01 Registration applications of drugs for which stability study data is submitted

a. Verification of stability study data

Sr.

No.

Name & Address of

Manufacturer /

Applicant

Brand Name





Type of Form,

Initial Diary &

Date, Fee

(including

differential fee),

Demanded Price /

Pack size


Local Availability


Date & Remarks

375. M/s Ferozsons

Laboratories Ltd., P.O

Ferozsons, Amangarh,

Nowshera-Khyber

Pakhtunkhwa

EMPAGEN Tablet 10mg


Empagliflozin…..10mg

Sodium Glucose Co-Transporter

2 Inhibitor


Form 5

Dy.No.10160

dated

04-03-2019

Rs. 20,000/-

dated

27-02-2019

As per DRAP

Policy

Jardiance 10mg Tablet by

Boehinger Ingelheim,

(USFDA approved)

Emazin 10mg Tablet of

Atco

Panel inspection dated 25-

01-2019 concluded that the

panel recommends the grant

of GMP certificate.


Drug EMPAGEN TABLET 10mg

Name of Manufacturer M/s Ferozsons Laboratories Ltd., P.O Ferozsons, Amangarh, Nowshera-Khyber

Pakhtunkhwa

Manufacturer of API M/s Fuxin Long Rui Pharmaceutical Co., Ltd , China

API Lot No. E-20180425-D01-E06-01

Description of Pack

(Container closure system) Alu-Alu Blister Foil


Accelerated: 40°C ± 2°C/ 75% ± 5% RH


Frequency Accelerated : 0 , 3, 6 (months) Real Time: 0 , 3, 6 (Months)

Batch No. EGTab-001 EGTab-002 EGTab-003




No. of Batches 03

Date of Submission 3802 (17/04/2019)






and name of firm is no available







1. COA of API Copy of COA (Batch # E-20180425-D01-E06-

01) from M/s M/s Fuxin Long Rui

Pharmaceutical Co., Ltd China is submitted.




The firm has submitted copy of GMP certificate

of Fuxin Long Rui Pharmaceutical Co., Ltd

China issued by Fuxin Food and Drug

Administration. The certificate is valid till 19-

09-2019.



4. Data of 03 batches will be supported by attested respective


sheets etc. Yes

5. Documents confirming import of API etc. The firm has submitted copy of Form-6 for the

purchase of Empagliflozin (650 g) attested by

Assistant Director (I & E) DRAP, Peshawar

dated 13-01-2018. The submitted copy of

commercial invoice is not attested.







The firm has submitted 6 months accelerated and 6 months real time stability data of three batches.

Sr.

No.

Name & Address of

Manufacturer /

Applicant

Brand Name





Type of Form,

Initial Diary &

Date, Fee

(including

differential fee),

Demanded Price /

Pack size


Local Availability


Date & Remarks

376. M/s Ferozsons

Laboratories Ltd., P.O

Ferozsons, Amangarh,

Nowshera-Khyber

Pakhtunkhwa

EMPAGEN TABLET 25mg


Empagliflozin……..25mg

Sodium Glucose Co-Transporter

2 Inhibitor


Form 5

Dy.No. 10161

dated

04-03-2019

Rs.20,000/- dated

27-02-2019

As per DRAP

Policy

Jardiance 25mg Tablet by

Boehinger Ingelheim,

(USFDA approved) Emazin 25mg Tablet of

Atco Labs.Ltd.

Panel inspection dated 25-

01-2019 concluded that the

panel recommends the grant

of GMP certificate.


Drug EMPAGEN TABLET 25mg

Name of Manufacturer M/s Ferozsons Laboratories Ltd., P.O Ferozsons, Amangarh, Nowshera-Khyber

Pakhtunkhwa

Manufacturer of API M/s Fuxin Long Rui Pharmaceutical Co., Ltd , China

API Lot No. E-20180425-D01-E06-01

Description of Pack Alu-Alu Blister Foil




Accelerated: 40°C ± 2°C/ 75% ± 5% RH


Frequency Accelerated : 0 , 3, 6 (months) Real Time: 0 , 3, 6 (Months)

Batch No. EGTab-004 EGTab-005 EGTab-006




No. of Batches 03

Date of Submission 3803 (17/04/2019)



1. COA of API Copy of COA (Batch # E-20180425-D01-E06-

01) from M/s M/s Fuxin Long Rui

Pharmaceutical Co., Ltd China is submitted.





of Fuxin Long Rui Pharmaceutical Co., Ltd

China issued by Fuxin Food and Drug

Administration. The certificate is valid till 19-

09-2019.



4. Data of 03 batches will be supported by attested respective


sheets etc. Yes

5. Documents confirming import of API etc. The firm has submitted copy of Form-6 for the

purchase of Empagliflozin (650 g) attested by

Assistant Director (I & E) DRAP, Peshawar

dated 13-01-2018. The submitted copy of

commercial invoice is not attested.







The firm has submitted 6 months accelerated and 6 months real time stability data of three batches.


Verification of Authenticity of Stability Data submitted for Registration of Empagen 10mg and 25mg

Tablet (Empagliflozin) by M/s Ferozesons Laboratories Ltd, Nowshera

Inspection date: 25th October, 2019

Inspection site: Factory Premises of M/s Ferozsons Laboratories Nowshera.

The constituted Panel for the verification of authenticity of stability data was comprised of the following members,

1. Dr. Jamshed Ali Khan, Member Central Licensing Board.

2. Director DTL, Peshawar.

3. Syed Adnan Ali Shah, Assistant Director PE & R, Islamabad.

The constituted panel conducted detailed inspection of M/s Ferozsons Laboratories Ltd, Nowshera, Khyber

Pakhtunkhwa as per following details:

S.# Questions Observation by panel

1. Do you have documents confirming the import

of API including approval from DRAP?

Firm has documents confirming the import of 650gm of

Emagliflozin vide license No. 00335/2018-DRAP

(P)/1390 dated 13-04-2018 from manufacturer M/s.

Fuxin Long Rui Pharmaceutical Co., Ltd China.



The firm has informed that they have selected the said

manufacturer being GMP compliant and has provided

stability data of the said API.

3. Do you have documents confirming the import

of reference standard and impurity standards?

Firm has documents confirming the import of reference

standard (quantity: 0.05gm) and impurity standard

(quantity: 0.05gm) having invoice No.HN180508-C1.

4. Do you have certificate of Analysis of the API,

reference standards and impurity standards?

Firm has certificate of analysis of API (Batch No.E-

20180425-D01-E06-01), working standard

(Batch.No.E6DZ201801) and reference standards

(Batch.No.E5DZ201801).

5.

Do you have GMP certificate of API


country of origin?

Firm has copy of GMP certificate of API manufacturer

issued by regulatory authority of country of origin

(China).

6. Do you use API manufacturer method of testing

for testing API?

The firm has used manufacturer method of testing for

testing of API.

7. Do you have stability studies reports on API? The firm has real time and accelerated stability study

data sheets provided by the API manufacturer.





method.



Firm has used manufacturer’s method for quantifying


10. Do you have some remaining quantities of API,

its reference standard and impurities standards?

The firm has record of remaining quantities of impurity

standard and finished packs.

11. Have you used pharmaceutical grade excipients? All excipients used in the formulation were of

pharmaceutical grade.



The firm has documents confirming the purchase of

excipients used in the formulation from local supplier

and the one imported. COAs were available.

13. Do you have test reports and other records on the

excipients used?

The firm has complete testing records for the excipients

used in the formulation.

14. Do you have written and authorized protocols for

the development of applied product?


development of applied product.




The firm claimed that their formulation is in accordance

with innovator formulation so did not perform Drug-

excipients compatibility studies.


studies? The firm has performed comparative dissolution studies.


section

The firm has dedicated product development (R&D)

section.

18.

Do you have necessary equipments available in

product development section for development

of applied product?

The firm has necessary equipment in product

development section except packaging facility as the

packaging (blistering and packing of the stability batches

have been carried out in commercial production area).

19. Are the equipments in product development

section qualified?

The equipment used in the product development section

was qualified.

20.

Do you have proper maintenance / calibration /


in PD section?


equipment used in product development.




Firm has qualified staff with proper knowledge and

training in product development.

22.

Have you manufactured three stability batches

for the stability studies of applied product as

required?

The firm has manufactured three stability batches for the

stability studies for both strength 10mg and 25mg tablets

as per following batch details:

1) Empari tablets 10mg batch No.

a) EGTab-001

b) EGTab-002

c) EGTab-003

2) Empari tablets 25mg batch No.

a) EGTab-004

b) EGTab-005

c) EGTab-006



Firm has informed that a criterion for fixing batch size

was based on their minimum requirements for stability

samples used in stability studies.


stability batches?

The firm has complete batch manufacturing record of all

the stability batches.


stability batches?

Firm has protocols for stability testing of the stability

batches.



The firm has developed and validated the method for the

testing of stability batches.




Not Applicable


qualification of equipments / instruments being

used in the test and analysis of API and the

finished drug?

Firm has all relevant documents confirming the

qualification of equipments/instruments used in the test

and analysis of API and the finished drug.

29. Is your method of analysis stability indicating? The method of analysis used for analysis of stability

batches was stability indicating.

30. Is your HPLC software is 21CFR compliant? The HPLC software is 21CFR compliant.

31. Can you show Audit Trail reports on stability

studies testing?

Firm has demonstrated audit trail reports of testing.


Furthermore, regarding the additional points identified as per DRAP letter No. F.13-11/2017-PEC(Pt) date 19th

august 2019, the details are as under:

1. Firm has performed and already submitted report of content uniformity testing (as per USP general

chapter <905>. The same is verified by the inspection panel on date of inspection.

2. Firm informed that the gap between date of manufacturing and date of initiation of stability data is due to

Eid holidays. Furthermore, the firm ensured that the batches were kept under control conditions during

that time.

Conclusion:

On risk-based approach the genuineness / authenticity of stability data submitted by the firm for registration of

Empagen 10mg and 25mg Tablet (Empagliflozin) is verifiable to satisfactory level.

Previous Decision: Registration Board decided to defer the cases, (Empagen 10mg and 25mg Tablets) and

directed the firm to submit dissolution testing data with specifications of “NLT Q within 15 minutes” at initial

and one month time point at both accelerated and real time stability conditions for 2 batches

(M-293).

Evaluation by PEC: The firm has submitted following:

01) Stability study data of initial and one month testing, 02) Raw data sheets, 03) Dissolution testing

chromatograms of following 2 batches of each strength.

a) Empagen 10mg Tablet (Empagliflozin) Batch # EGTab-001

b) Empagen 10mg Tablet (Empagliflozin) Batch # EGTab-002

c) Empagen 25mg Tablet (Empagliflozin) Batch # EGTab-004

d) Empagen 25mg Tablet (Empagliflozin) Batch # EGTab-005



The firm has some remaining quantities of stability

batches.

33. Do you have stability batches kept on stability

testing?


kept on stability testing.


equipments used in production and analysis?

The firm has valid calibration status of the equipment

used in production and analysis.



The firm has stability chambers for carrying out

accelerated and real time stability studies provided with

uninterrupted power supply and data loggers.

36.

Do related manufacturing area, equipment,

personnel & utilities be rated as GMP

compliant?


utilities in R&D section are as per GMP compliance.

Decision: Registration Board decided to approve registration of Empagen 10mg Tablet &

Empagen 25mg Tablet with Innovator’s specifications by M/s Ferozsons Laboratories Nowshera.



d. Exemption from onsite verification of stability data

Sr.

No.

Name &

Address of

Manufacturer /

Applicant

Brand Name

(Proprietary Name +


Composition,


Finished Product

Specification

Type of Form,


Fee (including

differential fee),

Demanded Price /

Pack size

International


Availability


Date & Remarks

Previous DRB

Decision /

Remarks

(if any)

377. M/s The Searle

Company

Limited, F-319,

S.I.T.E.,

Karachi

OMARIN 12.5mg Tablet

Each Film coated tablet

contains:

Omarigliptin…12.5mg

Anti-diabetic


Form 5D

Dy. No.Duplicate

dated

27-03-2017

Rs. 50,000/- dated

27-03-2017,

As per SRO

Marizeb Tablet by

MSD

(PMDA Japan

Approved)

The firm was inspected

on 27.06.2018, wherein

the GMP of firm was

rated good.



Drug OMARIN 12.5mg Tablet


Manufacturer of API M/s RUYUAN HEC PHARM Co., LTD, Xiaba Development Zone, Ruyuan County,

Shaoguan City, Guangdong Province, PR, China

API Lot No. OMLT-RD201803002

Description of Pack


Alu Alu Blisters in unit carton


Real Time: 30°C ± 2°C & 65±5%RH





Batch No. 18PD-301 18PD-308 18PD-309


Manufacturing Date Dec-2018 Dec-2018 Dec-2018

Date of Initiation Jan-2019 Jan-2019 Jan-2019

No. of Batches 03

Date of Submission 04-11-2019 (Dy. No.22627)



1. COA of API Copy of COA of API (batch # OMLT-RD201803002)

from M/s RUYUAN HEC PHARM Co., LTD, China

has been submitted.




The firm has submitted copy of GMP certificate issued

by Shaoguan Food and Drug Administration. It is valid

till 04-12-2021.



Yes




Yes


the purchase of Omarigliptin (0.4Kg) attested by

Assistant Director (I & E) DRAP Karachi dated 01-08-

2018.


& stamp) for ensuring authenticity of

data/documents.

Yes



Yes


1978.

Yes

PREVIOUS REMARKS OF EVALUATOR1





Date of submission: 04-11-2019 (Dy. No.22627)






“Ticor 60mg & 90mg Tablets”, which was presented in 293rd meeting

of Registration board. Registration Board decided to approve

registration of above stated drug product of M/s The Searle company

Ltd., Karachi.


According to inspection report, following points were confirmed.






import).

The firm has submitted copy of commercial invoice for the purchase

of Omarigliptin (0.4Kg) attested by ADC, DRAP Karachi dated 01-

08-2018.



standards.

Evidence of procurement of reference standards is required.




origin.

The firm has submitted copy of GMP certificate issued by Shaoguan

Food and Drug Administration. It is valid till 04-12-2021.


qualification

The firm has submitted SOP for Evaluation of Vendors.



standards

Copy of COA of API (batch # OMLT-RD201803002) from M/s

RUYUAN HEC PHARM Co., LTD, China has been submitted.

Copy of COA of working standard (batch # OMLT-

RD0180101A) from API supplier has been submitted.



development?

The firm has submitted documents for the procurement of excipients

used in product development



experience.


department.

Production Data



batches.

The firm has submitted copy of “Protocols/SOP for the Development

of trial batches”.



The firm has submitted copy of Manufacturing protocols of

following 03 Batches:

Batch No. Batch Size Mfg. Date

18PD-301 2500 Tablets Dec-2018




stability batches.


Trial No Batch Size Tablets used for

stability testing

Remaining

Quantities of

tablets

18PD-301 2500 Tabs 795 Tab 30 Blisters



QA / QC DATA




accelerated)

Firm has submitted photocopies of data logger record for chambers

used in Real Time & Accelerated stability studies of applied product.

13. Method used for analysis of API along

with COA.


Material Testing Procedures along with COAs for Omarigliptin.






for “Omarin 25mg Tablet” along with Stability Study Reports.


from manufacturer.

The firm has submitted 6 months accelerated and 24 months real time

stability study data of three batches conducted as per Zone IV-A.

16. Analysis reports for excipients used. The firm has submitted analytical reports of excipients used.

17. Drug-excipients compatibility studies. The firm has submitted that they have used same formulation as that

of innovator.


data.

The firm has not performed comparative dissolution studies of test

formulation with reference formulation. Only dissolution studies of

test formulation in three recommended mediums at pH 1.2, pH 4.5,

pH 6.8 were performed.



testing.

The firm has submitted audit trail reports of applied product.

The firm has submitted 6 months accelerated and 6 months real time stability studies data of 3 batches.

Observations Response of the applicant

Evidence of procurement of reference standards is

required.

The firm has submitted that we received reference

standard from API supplier through DHL.

Comparative dissolution studies do not contain

dissolution studies of reference product in three

mediums.

The firm has submitted that innovator pack was not

available therefore we only performed dissolution

studies of test formulation in three recommended

mediums i.e. 0.1 N HCl pH 1.2, buffer pH 4.5 and

phosphate buffer pH 6.8.

Decision: Registration Board decided to approve registration of OMARIN 12.5mg Tablet with




Sr.

No.

Name &

Address of

Manufacturer /

Applicant

Brand Name

(Proprietary Name +

Dosage Form +



Finished Product

Specification

Type of Form,


Fee (including

differential fee),

Demanded Price /

Pack size

International


Availability


Date & Remarks

Previous DRB

Decision /

Remarks

(if any)

378. M/s The Searle

Company

OMARIN 25mg Tablet

Form 5D Marizeb Tablet by

MSD


Limited, F-319,

S.I.T.E.,

Karachi


contains:

Omarigliptin…25mg

Anti-diabetic


Dy. No.Duplicate

dated

27-03-2017

Rs. 50,000/- dated

27-03-2017,

As per SRO

(PMDA Japan

Approved)

Firm has submitted

copy of GMP

inspection report

conducted on 13-02-18.


Drug OMARIN 25mg Tablet


Manufacturer of API M/s RUYUAN HEC PHARM Co., LTD, Xiaba Development Zone, Ruyuan County,

Shaoguan City, Guangdong Province, PR, China

API Lot No. OMLT-RD201803002

Description of Pack


Alu Alu Blisters in unit carton


Real Time: 30°C ± 2°C & 65±5%RH





Batch No. 19PD-035 19PD-040 19PD-041


Manufacturing Date Jan-2018 Feb-2019 Feb-2019

Date of Initiation Feb-2019 Feb-2019 Feb-2019

No. of Batches 03

Date of Submission 04-11-2019 (Dy. No.22627)



1. COA of API Copy of COA of API (batch # OMLT-RD201803002)

from M/s RUYUAN HEC PHARM Co., LTD, China

has been submitted.




The firm has submitted copy of GMP certificate issued

by Shaoguan Food and Drug Administration. It is valid

till 04-12-2021.



Yes




Yes


the purchase of Omarigliptin (0.4Kg) attested by ADC,

DRAP Karachi dated 01-08-2018.



documents.

Yes




Yes


1978.

Yes





Date of submission: 04-11-2019 (Dy. No.22627)






“Ticor 60mg & 90mg Tablets”, which was presented in 293rd meeting

of Registration board. Registration Board decided to approve

registration of above stated drug product of M/s The Searle company

Ltd., Karachi.








import).


of Omarigliptin (0.4Kg) attested by ADC, DRAP Karachi dated 01-

08-2018.



standards.

Evidence of procurement of reference standards is required.




origin.

The firm has submitted copy of GMP certificate issued by Shaoguan

Food and Drug Administration. It is valid till 04-12-2021.


qualification




standards

Copy of COA of API (batch # OMLT-RD201803002) from M/s

RUYUAN HEC PHARM Co., LTD, China has been submitted.

Copy of COA of working standard (batch # DWS20170801) from

API supplier has been submitted.



development?





experience.


department.

Production Data



batches.









19PD-035 2000 Tablets Jan-2019

19PD-040 2000 Tablets Feb-2019

19PD-041 2000 Tablets Feb-2019


stability batches.

Trial No Batch Size Tablets used

for stability

testing

Remaining

Quantities of

tablets

19PD-035 2000 Tab 795 Tab 30 Blisters



QA / QC DATA




accelerated)




with COA.


Material Testing Procedures along with COAs for Omarigliptin.






for “Omarin 25mg Tablet” along with Stability Study Reports.


from manufacturer.


stability study data of three batches conducted as per Zone IV-A.


17. Drug-excipients compatibility studies. The firm has submitted that they have used same formulation as that

of innovator.


data.

The firm has not performed comparative dissolution studies of test

formulation with reference formulation. Only dissolution studies of

test formulation in three recommended mediums at pH 1.2, pH 4.5,

pH 6.8 were performed.



testing.




Evidence of procurement of reference standards is

required.

The firm has submitted that we received reference

standard from API supplier through DHL.

Comparative dissolution studies do not contain

dissolution studies of reference product in three

mediums.

The firm has submitted that innovator pack was not

available therefore we only performed dissolution

studies of test formulation in three recommended

mediums i.e. 0.1 N HCl pH 1.2, buffer pH 4.5 and

phosphate buffer pH 6.8.

Decision: Registration Board decided to approve registration of OMARIN 25mg Tablet with





Sr.

No.

Name & Address of

Manufacturer /

Applicant

Brand Name

(Proprietary Name +

Dosage Form +



Finished Product

Specification

Type of Form,

Initial Diary &

Date, Fee

(including

differential fee),

Demanded Price /

Pack size

International

Availability /

Local Availability

GMP Inspection

Report Date &

Remarks

Previous DRB

Decision / Remarks

(if any)

379. M/s Pharmatec

Pakistan (Pvt.)

Limited, D-86/A,

S.I.T.E., Karachi

DAPAZIN 10mg Tablet


contains:

Dapagliflozin

propanediol

monohydrate eq. to

dapagliflozin….10mg

Selective sodium

glucose co-transporter

subtype-2 (SGLT2)

Inhibitor


Form 5

Dy. No.37918

dated

16-11-2018

Rs. 20,000/-

dated

26-11-2018,

7’s, 14’s, 28’s,

30’s & 100’s; As

per SRO

Farxiga tablet

10mg (USFDA

approved)

Firm has

submitted copy of

GMP inspection

report

conducted on 30-

04-18 concluding

Good GMP

compliance.


Drug DAPAZIN 10MG TABLET

Name of Manufacturer M/s Pharmatec Pakistan (Pvt.) Limited, D-86/A, S.I.T.E., Karachi

Manufacturer of API M/s Shanghai Pharma Group Changzhou Kony Pharmaceutical Co., Ltd

Address: Daixi Street, Luoyang Town, Wujin District, Changzhou, Jiangsu, China.

API Lot No. DGF20180501

Description of Pack


Alu Alu Blister


Real Time: 30°C ± 2°C & 65±5%RH





Batch No. 18PD084DAPT04 18PD075DAPT02 18PD082DAPT03


Manufacturing Date Aug-2018 July-2018 Aug-2018


No. of Batches 03




1. COA of API Copy of COA of API (batch # DGF20180501) from

M/s Shanghai Pharma Group Changzhou Kony

Pharmaceutical Co., Ltd, China has been submitted.





declaring that M/s Shanghai Pharma Group

Changzhou Kony Pharmaceutical Co., Ltd, China is


following Good Manufacturing Practices. The

certificate is issued by Jiangsu Food and Drug

Administration. It is valid till 01-12-2018.



Yes




Yes


the purchase of Dapagliflozin (1.5Kg) attested by

ADC, DRAP Karachi dated 21-06-2018.



documents.

Yes



Yes


1978.

Yes





Date of submission: 14-10-2019 (Dy. No. 20505)





Firm has referred to onsite inspection report of their product “Apixa

2.5mg & 5mg Tablets”, which was presented in 289th meeting of

Registration board. Registration Board decided to approve

registration of above stated drug product of M/s Pharmatec Pakistan

(pvt) Ltd, Islamabad

Date of inspection: 30th April-2019







import).


of Dapagliflozin propanediol monohydrate (1.5Kg) attested by ADC,

DRAP Karachi dated 21-06-2018.


reference standard & impurity

standards.

Copy of invoice for the purchase of Dapagliflozin propanediol

monohydrate WS from API supplier is submitted.




origin.

The firm has submitted copy of GMP certificate declaring that M/s

Shanghai Pharma Group Changzhou Kony Pharmaceutical Co., Ltd,

China is following Good Manufacturing Practices. The certificate is

issued by Jiangsu Food and Drug Administration. It is valid till 01-

12-2018.


qualification





standards

Copy of COA of API (batch # DGF20180501) from M/s

Shanghai Pharma Group Changzhou Kony Pharmaceutical Co.,

Ltd, China has been submitted.

Copy of COA of working standard (batch # DWS20170801) from

API supplier has been submitted.



development?





experience.


department.

Production Data



batches.






following 03 Batches: Batch No. Batch Size Mfg. Date

18PD075DAPT02 1800 Tablets July-2018

18PD082DAPT03 2500 Tablets Aug-2018

18PD084DAPT04 2500 Tablets Aug-2018


stability batches.

Trial No Batch Size Tablets used for

stability testing

Remaining

Quantities of

tablets

18PD075D

APT02 1800 Tab 795 Tab 46 Blisters

18PD082D


18PD084D


QA / QC DATA




accelerated)




with COA.


Material Testing Procedures along with COAs for Dapagliflozin

Propanediol monohydrate.






for “Dapagliflozin 10mg tablet” along with Stability Study Reports.


from manufacturer.


stability study data of three batches. However, storage conditions for

real time stability studies mentioned are 25oC ± 2 oC/ 65% ± 5%.


17. Drug-excipients compatibility studies. No physical and chemical incompatibilities were found on the basis

of various literatures.


data.

The firm has performed comparative dissolution for “Forxiga 10mg

Tablet (batch#AAS6462) of AstraZeneca” & Dapagliflozin 10mg


Tablet” in three recommended mediums at pH 1.2, pH 4.5, pH 6.8.

Dissolution profiles of both products were considered similar.

If the reference and test products show more than 85% dissolution

within 15 min, the profile is considered similar, no calculation of f2

factor is required.



testing.




Though GMP certificate of API manufacturer was

valid at the time of Assistant Director (I & E) DRAP

clearance, however, it is expired now. Therefore, you

may submit updated copy of GMP certificate of API

manufacturer.

Submitted.

Justify the dissolution acceptance criteria of value of

Q = 80% in 30 min while the innovator product

(Farxiga) has specified the dissolution specifications

of NLT 85% in 15 min.

We have followed FDA dissolution method.

Dissolution time 30 min is mentioned in FDA method.

Complete batch manufacturing record of three

stability batches is required to be submitted.

Submitted.

Drug excipient compatibility studies are required if

formulation is not as per innovator.

The firm has submitted Drug-excipient compatibility

studies assessed by HPLC binary mixtures.

Decision: Registration Board decided to defer the case of DAPAZIN 10mg Tablet and directed the

firm to submit dissolution testing data with specifications of “NLT Q within 15 minutes” at initial

and one month time point at both accelerated and real time stability conditions for 2 batches.

Deferred cases: 380. Name and address of manufacturer /

Applicant

M/s Wilson’s pharmaceuticals, 387-388, Industrial Area,

Islamabad.

Brand Name +Dosage Form + Strength Sofvasc Trio Tablets 40/5/12.5mg


Olmesartan Medoxomil……..40mg

Amlodipine as besylate…..…5mg

Hydrochlorothiazide ..............12.5mg

Diary No. Date of R& I & fee Dy No.338 (11-12-2010/) Rs. 60,000 17-05-2013/

Pharmacological Group Antihypertensive agent, Diuretic


Finished product Specification Manufacturer’s Specifications

Pack size & Demanded Price 10’s, 20’s, 30’s ; Rs. 502 per tablet



Approved in US-FDA

(Tribenzor tablets of Daiichi Sankyo, Germany)

Me-too status

GMP status GMP Inspection conducted on 24-01-2018 with conclusive

remarks that firm is operating at satisfactory level of GMP

compliance.


Drug Sofvasc Trio Tablets 40/5/12.5mg

Name of Manufacturer M/s Wilson’s pharmaceuticals, 387-388, Industrial Area, Islamabad.

Manufacturer of API M/s Glenmark Pharmaceuticals Ltd ,Maharashtra, India(Olmesartan Medoxomil)

M/s Hetero Drugs Ltd (UNIT-IV) , Telangana, India(Amlodipine Besylate)

M/s Suzhou Lixin Pharmaceuticals Co.Ltd ,China(Hydrochlorothiazide)


API Lot No. Lot #:83170554 (Olmesartan Medoxomil)

Lot #:AM0331216 (Amlodipine Besylate)

Lot #:C01-20170102 (Hydrochlorothiazide)

Description of Pack


Alu /Alu Blister Pack in Unit carton

Stability Storage Condition Accelerated:40°C ± 2°C/75%±5% RH

Real Time: 30°C ± 2°C/65%±5% RH

Time Period Accelerated: 6 (Months)

Real Time: 6 (Months)

Frequency Accelerated: 0,1,2,3,4,6 (Months)

Real Time: 0,3,6,9,12,18,24 (Months)

Batch No. Trial #01 Trial #02 Trial #03




No. of Batches 03


Sr.

No.


1. COA of API. Copy of COA (batch #83170554) from M/s

Glenmark Pharmaceuticals Ltd, Maharashtra, India

(Olmesartan Medoxomil)

Copy of COA (batch # AM0331216) from M/s

Hetero Drugs Ltd(UNIT-IV), Telangana, India

(Amlodipine Besylate)

Copy of COA (batch # C01-20170102) from M/s

Suzhou Lixin Pharmaceuticals Co.Ltd, China

(Hydrochlorothiazide)




Copy of GMP certificate (certificate No. 1708289)

issued by Food & Drugs Administration, India. It is

valid until 18-8-2019(Olmesartan Medoxomil)

Copy of GMP certificate (certificate No.1438/E

(G)/TS/2018) issued by Drugs Control

Administration, Telagana, India. It is valid until 04-

04-2019 (Amlodipine Besylate)

Copy of GMP certificate (certificate

No.JS20140325) issued by Food & Drug

Administration, China. It is valid until 25-8-

2019(Hydrochlorothiazide)



Yes




Yes


18-09-2017(Olmesartan Medoxomil) attested by

ADC, DRAP, Islamabad


Firm has submitted copy of commercial invoice dated

19-12-2016(Amlodipine Besylate) attested by ADC,

DRAP, Islamabad

Firm has submitted copy of commercial invoice dated

09-03-2017(Hydrochlorothiazide) attested by ADC,

DRAP, Islamabad



documents.

Yes



Yes


1978.

Yes


● The firm has submitted 6months Accelerated and Real Time Stability Data for 03 Batches.





1. Reference of last onsite panel inspection

for instant dosage form conducted

during last two years.

Firm has referred to onsite inspection reports of their product

“Saferon tablets (Sofosbuvir 400 mg)”, which was presented in 278th

meeting of Registration Board held on 29-31st Jan, 2018

Observations: Software of HPLC present in the firm is 21 CFR

compliant and audit trail on the testing reports was available and

confirmed. Panel reviewed chromatograms for testing of API and

trial batches at 0, 3 and 6 months for real time and accelerated

stability testing.

Decision: Registration Board decided to approve registration of

“Saferon (Sofosbuvir 400mg)” by M/s Wilson Pharmaceuticals,

Islamabad. Manufacturer will place first three production batches on

long term stability studies



import).

Copy of commercial invoice dated 18-09-2017 declaring 10Kgs

quantity of API (Olmesartan Medoxomil has been submitted which

is attested by ADC, DRAP, Islamabad.

Copy of commercial invoice dated 19-12-2016 declaring 300kgs

quantity of API (Amlodipine Besylate) has been submitted which is

attested by ADC, DRAP, Islamabad dated 29-12-2016.

Copy of commercial invoice dated 09-03-2017 declaring 300Kgs

quantity of API (Hydrochlorothiazide) has been submitted which is

attested by ADC, DRAP, Islamabad dated 29-3-2017.



standards.

The firm has submitted copies of invoices for working standard &

impurity Standards regarding Amlodipine besylate, Olmesartan

Medoxomil and Hydrochlorothiazide.



regulatory authority of country of

origin.

The firm has submitted copy of GMP certificate declaring following

information:

Certificate No.1708289

Issued to: M/s Glenmark pharmaceuticals Ltd Plot

No3109,GIDC.Industrial estate, Ankleshwar

Issued by: Food & Drug Administration, Gandhagar Gujarat state

India.

Validity: Valid Till 18-08-2019.



information:

Certificate No.1438/E(G)/TS/2018

Issued to: M/s Hetero Drugs limited Unit IV Sy.No.599,Temple

Road Bonthapally Village ,Gummadidala Mandal,Sangareddy

District,Telangana State,India

Issued by: Food & Drug Administration, Gandhagar Gujarat state

India.



information:

Certificate No.JS20140325

Issued to: M/s Suzhou Lixin Pharmaceuticals Co,Ltd

No.21 Tangxi Road,Suzhou New District,Suzhou

Issued by:Food & Drug Administration,China



qualification




standards

Applicant has submitted following COAs:

Copy of COA olmesartan Medoxomil (batch #83170554)

from M/s Glenmark Pharmaceuticals Ltd ,Maharashtra, India

Copy of COA of Amlodipine besylate (batch # AM0331216)

from M/s Hetero Drugs Ltd(UNIT-IV) ,Telangana, India

Copy of COA of Hydrochlorothiazide (batch # C01-

20170102) from M/s Suzhou Lixin Pharmaceuticals Co.Ltd,

China

Copy of COA of reference standard has been submitted

Copy of COA impurity Standards Olmesartan olefinic,

Olmesartan related compound A, Olmesartan impurity A,

Olmesartan N-Alkyl impurity has been submitted.

Copy of COA impurity Standards Hydrochorothiazide

impurity A&B has been submitted.

Copy of COA impurity Standards of Amlodipine impurity A,

Amlodipine impurity D, Amlodipine impurity E, Amlodipine

impurity F has been submitted.



development?

The firm has submitted copy of purchase order/Commercial

invoices/COAs of all the excipients used in the formulation of

applied product.



experience.


department.

Production Data



batches.


of Sofvasc Trio Tablets 40/10/12.5mg”.



The firm has submitted copy of Batch Manufacturing Records of



Trial # 01 1500 tablets 02-2018

Trial # 02 1500 tablets 02-2018

Trial # 03 1500 tablets 02-2018



stability batches.

The firm has submitted reconciliation sheet mentioning following

details:

Trial No Sofvasc Trio Tablets 40/5/12.5mg

Remaining Quantity

Accelerated Long Term

Trial # 01 110 tablets 216 tablets

Trial # 02 110 tablets 234 tablets

Trial # 03 110tablets 234 tablets

QA / QC DATA



stability chambers (real time and

accelerated).


used in Real Time & Accelerated stability studies of applied product

from 01-02-2018to 31-08-2018.


with COA.

The firm has submitted photocopies of following:

Raw Material Test/Analysis Procedures & Raw Material

Specifications of Amlodipine Besylate , Hydrochlorothiazide and

Olmesartan Medoxomil (In-house+USP) & COAs for Olmesartan

Medoxomil/Amlodipine Besylate/

Hydrochorothiazide (Supplier/Manufacturer).





The firm has submitted photocopies of following:

FPP Test/Analysis Method & FPP Specifications (In-house) for

Sofvasc Trio 40/10/12.5mg tablet along-with analytical record for

complete stability studies.

15 Reports of stability studies of API from

manufacturer.

The firm has submitted copy of 06 Months Accelerated and 60

Months Real Time Stability Study Data of 03 Batches of

Olmesartan Medoxomil M/s Glenmark Pharmaceuticals Ltd

,Maharashtra, India ,

Amlodipine besylate 06 Months Accelerated and 36 Months Real

Time Stability Study Data and

Hydrochorothiazide 06month accelerated and 48 Months Real

Time Stability Study M/s Suzhou Lixin Pharmaceuticals Co. Ltd

,China, as per Zone-IV a conditions.

16 Analysis reports for excipients used. The firm has submitted copy of Analytical reports of excipients used.

17 Drug-excipients compatibility studies. Firm has declared that Drug-excipient compatibility studies are

applicable since they have used similar qualitative formulation as

that of innovator’s product.

18 Record of comparative dissolution data. The firm has performed comparative dissolution studies in three

media including in 0.1NHCl, Acetate Buffer pH 4.5 and phosphate

Buffer pH 6.8 with Tribenzor Tablets 40/10/12.5mg manufactured

by M/s. Daiichi Sankyo, Germany Lot No: 0004213.

The firm‘s product results are comparable to that of the comparator

product.

19 Compliance Record of HPLC software


testing.

Audit trail on testing reports of applied formulation from 22-02-2018

to 22-08-2018 was submitted by the firm.

Remarks:

Valid GMP certificates of all three API manufacturers shall be submitted.

Protocol for stability testing has not been submitted.

As per submitted batch manufacturing record, all the three trial batches have been compressed using single

punch machine.


You have not performed uniformity of dosage unit by content uniformity for in all the strengths, as

recommended by USP General Chapter <905> throughout stability studies. Justification shall be submitted in this

regard.

Firm has performed CDP using 6 tablets each of the reference and applied product. Moreover f2 factor

calculation has not been performed, although submitted results are comparable.

Reference product literature declares the dissolution time as 30 minutes whereas firm has applied limit of

45 minutes for dissolution test.

Previous Decision: Registration Board deferred the case for justification of limits for Dissolution test in terms of

time, since reference product literature declare the dissolution time as 30 minutes whereas firm has applied limit of

45 minutes for dissolution test (M-292).

Evaluation by PEC:

The firm has submitted that it is committed to perform dissolution test of our applied formulation as per innovator’s

specification at next time points of stability data. Similarly we will perform dissolution test as per innovator on our

commercial batches.

Discussion: Registration Board deliberated on the dissolution specifications and acceptance criteria submitted by

the firm and keeping in view its decision of 293rd meeting decided to accept the dissolution specifications since it

falls under the definition of immediate release drug product.

Decision: Registration Board decided as follows:

Accept the stability study data as the dissolution specifications falls within the definition of

immediate release drug product and approved registration of Sofvasc Trio Tablets 40/5/12.5mg with

Innovator’s specifications by M/s Wilson’s Pharmaceuticals, I-9, Industrial Area Islamabad,

wherein manufacturer will adopt the dissolution specifications i.e. NLT Q at 30 minutes for

commercial production batches.

Furthermore, manufacturer will place first three production batches on long term stability


Sr.

No

.

Name & Address

of Manufacturer /

Applicant

Brand Name

(Proprietary Name +

Dosage Form +


Pharmacological

Group,

Finished Product

Specification

Type of Form,

Initial Diary &

Date, Fee

(including

differential fee),

Demanded Price /

Pack size




Date & Remarks

Remarks

381. M/s Wilson’s

Pharmaceuticals,

I-9, Industrial

Area Islamabad.

Sofvasc Trio Tablet

40/10/12.5

Each Tablet contains:

Olmesartan medoxomil

…………….40mg

Amlodipine besylate

…………. 10mg

Hydrochlorothiazide

………… 12.5mg.

Anti-Hypertensive

agent, Diuretic

Form-5-D

10’s, 20’s&30’s

Rs.542/- Tablet

11-12-

2010/3365.

17-05-2013/3125

Rs. 60,000/-

Tribenzor

USFDA Approved

24-01-2018 Conclusion:

“Overall the firm was

found to be operating at a

very good level of CGMP

Compliance at the time of

inspection.”

Drug Sofvasc Trio Tablet 40/10/12.5

Name of Manufacturer M/s Wilson’s Pharmaceuticals,I-9, Industrial Area Islamabad.

Manufacturer of API Olmesartan medoxomil: M/s Glenmark Pharmaceuticals Ltd. India.

Amlodipine besilate: M/s Hetero Drugs Limited (Unit-IV), India.

Hydrochlorothiazide: M/s Suzhou Lixin Pharmaceutical Co.Ltd, China.

API Lot No. Olmesartan medoxomil: 83170554

Amlodipine besilate: AM0321216, AM0331216

Hydrochlorothiazide: C01-20170102


Description of Pack

(Container closure system) Alu-Alu strip



Time Period Real Time: 06 Months Accelerated: 06 Months

Frequency Real Time: 0,3,6 (Months) Accelerated: 0,1,2,3,4,6 (Months)

Batch No. Trial # 01 Trial # 02 Trial # 03




No. of Batches 03




COA of API Yes

Approval of API by regulatory authority of



country of origin.

M/s Glenmark Pharmaceuticals Ltd. India: copy of GMP

Certificate No. 1708289 issued by Food & Drugs Control

Administration (Gujarat) India, valid up to 18-08-2019 is

submitted.

M/s Hetero Drugs Limited (Unit-IV), India:

copy of GMP Certificate No.

1438/E(G)/TS/2018 issued by Drugs Control

Administration (Telangana) India, valid up to 04- 04-

2019 is submitted.

M/s Suzhou Lixin Pharmaceutical Co. Ltd, China: copy

of GMP Certificate No. JS20140325 issued by Jiangsu

Food and Drug Administration China, valid up to 25-08-

2019 is submitted.



No




Yes




documents.

Yes



Yes


1978.

Yes


The firm has provided 6 months Accelerated and 6 months Real Time Stability Study Data for 03 Batches.

Dissolution parameters as submitted with Stability Study Data are as per USFDA recommended dissolution

method.

REQUEST OF EXEMPTION ROM ON SITE INSPECTION



1. Reference of last onsite panel inspection

for instant dosage form conducted

during last two years.

Firm has referred to onsite inspection reports of their product

“Saferon Tablets (Each film coated tablet contains:

Sofosbovir…..400mg) approved in 278th Meeting of Registration

Board.

1. Firm presented test results of trial batches conducted at various

time intervals (0, 3, 6 for both real time and accelerated stability

testing) and real time testing at 9, 12, 18 and 24 months, which

showed that trial batches were of standard quality during

aforementioned test intervals. Moreover, both chambers have

been provided with digital data loggers with record of test period

since January, 2016.

2. Software of HPLC present in the firm is 21CFR compliant and

audit trail on the testing reports was available and confirmed.

Panel reviewed chromatograms for testing of API and trial

batches at 0, 3 and 6 months for real time and accelerated

stability testing.



import).

HYDROCHLORTHIAZIDE

Details of Assistant Director (I & E) DRAP attested

commercial Invoice Invoice No. SZLX2017019A

Quantity imported: 300 Kg

Assistant Director (I & E) DRAP Attestation Date: 29-03-2017

Manufacturer: Suzhou Lixin Pharmaceutical Co. Ltd., No 21, Tangxi

Road, Suzhou, New District, China

Batch No.: C01-20170102

DOM: 19-12-2016

AMLODIPINE BESYLATE


commercial Invoice Invoice No. 1000023678



Manufacturer: Hetero Drugs Limited,7-2-A2, Hetero Corporate,

Industrial Estate, Sanath Nagar, Hyderabad, Telangana, India

Batch No.: AM0321216, AM0331216

DOM: 12-2016,

OLMESARTAN MEDOXOMIL


commercial Invoice Invoice No. 2007601342



Manufacturer: M/s Glenmark Pharmaceuticals Ltd., Plot No. A-80,

MIDC, Kurkumbh, Taluka-Daund, District- Pune, India.

Batch No.: 83170554

DOM: 03-09-2017,



standards.

HYDROCHLORTHIAZIDE

Working Standard

1g from 3J Diagnostic, TRC Canada

Impurities

Impurity A (Suzhou Lixin Pharmaceutical Co. Ltd)

Impurity B (Suzhou Lixin Pharmaceutical Co. Ltd)

Chlorthiazide

Benzothiadiazine Related Compound A


AMLODIPINE BESYLATE WORKING STANDARD

Working Standard

25g from 3J Diagnostic, , TRC Canada

OLMESARTAN MEDOXOMIL WORKING STANDARD

Working Standard

1g from 3J Diagnostic, , TRC Canada

Olmesartan Impurity A (Synpure Labs)

Olmesartan Olefenic Impurity (Synpure Labs)

Olmesartan Related Compound A(Synpure Labs)

Omlesartan Alkyl Impurity(Synpure Labs)




origin.

HYDROCHLORTHIAZIDE:

M/s Suzhou Lixin Pharmaceutical Co. Ltd, China: copy of GMP

Certificate No. JS20140325 issued by Jiangsu Food and Drug

Administration China, valid up to 25-08-2019 is submitted.

AMLODIPINE BESYLATE:

M/s Hetero Drugs Limited (Unit-IV), India: copy of GMP Certificate

No. 6208/E (G)/TS/2017 issued by Drugs Control Administration

(Telangana) India, valid up to 21-04-2018 is submitted.

OLMESARTAN MEDOXOMIL:

M/s Glenmark Pharmaceuticals Ltd. India: copy of GMP Certificate

No. 1708289 issued by Food & Drugs Control Administration

(Gujarat) India, valid up to 18-08-2019 is submitted.


qualification The firm has submitted SOP for Mechanism for Vendor pre-

qualification.



standards

Copy of COAs of all three APIs, have been submitted. Detail is

as under API name Batch No. DOM

Olmesartan medoxomil 83170554

99.6%

09-2017


Standard

TRC Canada

27-SSR-73-1

98%

Olmesartan Olefinic Impurity

Synpure Labs

Olmesartan Related Compund A

Synpure Labs

Olmesartan Impurity A

Olmesartan N-Alkyl Impurity

Amlodipine besilate AM0331216

99.37% Anhy.

12-2016

Amlodipine Working

standard

5-SCC-113-1

98%

Hydrochlorthiazide C01-20170102

101.2%

12-2016

Hydrochlorthiazide

Working Standard

2-SCC-58-1

98%

Impurity A Lixin

Impurity B Lixin0

Amlodipine Working standard Storage Condition Freezer.



development?






experience.

The firm has submitted copy of List of qualified staff involved in

product development comprising of 16 members.

Production Data



batches.

The firm has submitted copy of “Authorized protocols/SOP for

Development.



The firm has submitted copy of Batch Manufacturing Record and

Batch Packaging Record of the following 03 Batches: Batch No. Batch Size Mfg. Date

Trial No.01 1500 Tablets 02-2018




stability batches.

Batch No. Remaining tablets

Accelerated

Remaining tablets

Real time

Trial No.01 110 216

Trial No.02 110 234

Trial No.03 110 234

QA / QC DATA




accelerated)

The firm has submitted photocopies of printouts of data logger charts

for Real Time and Accelerated Conditions starting from 02-2018 to

08-2018.


with COA.

COA of supplier along with COA of manufacturer of finished

product.





The firm has submitted following documents:

copy of Product Specifications & Method of analysis

Stability Protocols.

Analytical method validation report.

Record of testing of stability batches.


manufacturer.


Accelerated: 6 month

Long term : 36 month.

Amlodipine Besilate



Hydrochlorthiazide



16. Analysis reports for excipients used. The firm has submitted photocopies of its own Analytical reports for

all excipients used in product development of Sofvasc Trio Tablets.

Excipient Batch No. Supplier

Red Color 40

Lake

2016118 M.S. Corporation

Avicel pH 200 175012012 Blanver

Magnesium

Stearate

MS-T-17015 S Kank Healthcare, India

Titanium Dioxide 170216 Al-Burque

Manufacturer: Jiangsu

Hongyuan


Pharmacoat 606 7078281 CBC Co. Ltd

Manufacturer

Shin Etsu Chemical

Croscarmellose

Sodium

D205160059 Irfan Traders

Manufacturer

Accent Microcell, India

Starch C7111618 Rafhan Maize

17. Drug-excipients compatibility studies. The firm has not performed Drug-excipients compatibility

studies and has referred to monographs of Hand-book of

Pharmaceutical Excipients in this regard.

Moreover, they have claimed that Ingredients of Sofvasc Trio

and Tribenzor are same. However, the coating material is not similar.

Tribenzor Sofvasc Trio Tablet

Silicified MCC MCC

Pregelatinized Starch Starch

Croscarmellose Sodium Croscarmellose Sodium

Magnesium Stearate Magnesium Stearate

PVA HPMC

PEG 3350 -

Titanium Dioxide Titanium Dioxide

Talc -

Iron Oxide Red Iron Oxide Red

18. Record of comparative dissolution data. Firm has submitted comparative Dissolution studies report. The

details of reference product & Sample product are as follows: Feature Reference

product

Product of M/s

Wilson

Brand

name

Tribenzor

40/10/12.5mg Sofvasc Trio

Tablet

Batch No. 0004213 Trail 01

Comparative dissolution studies have been performed in

following mediums:

i. pH 1.2 HCl buffer

ii. Acetate buffer pH 4.5

iii. Phosphate Buffer pH 6.8



testing.

Firm has submitted audit trail reports of stability studies of

applied formulation

Deficiencies/ Short-comings Firms Response

Submit raw data sheets of all time points. Provide

concentrations of standard and sample solution used in

assay and dissolution, as it is not clear from the

provided method.

Impurities analysis not performed for finished

product. Clarify and justify.

Potency adjustment has not been done for

API’s as evident in BMR. Clarify and justify.

Firm has submitted raw data sheets mentioning

potency of API instead of standard in the calculations

having purity 100%.

Firm has submitted that stability studies of finished

product percentage of all three APIs are found to be

within limits i.e. no degradation in results observed

uptil now nd committed if any variations in result

observed we will perform degradation studies and will

submit data.

Firm has submitted potency adjustment is not required

as assay is 100% as per BMR.


The firms dissolution Specs are NLT 85% is dissolved in 45 minutes whereas, innovators specs mentions 30

minutes.

Previous Decision: Registration Board deferred the case for justification of limits for Dissolution test in terms of

time, since reference product literature declare the dissolution time as 30 minutes whereas firm has applied limit

of 45 minutes for dissolution test (M-292).

Evaluation by PEC:

The firm has submitted that it is committed to perform dissolution test of our applied formulation as per innovator’s

specification at next time points of stability data. Similarly we will perform dissolution test as per innovator on our

commercial batches.

Discussion: Registration Board deliberated on the dissolution specifications and acceptance criteria submitted by

the firm and keeping in view its decision of 293rd meeting decided to accept the dissolution specifications since it

falls under the definition of immediate release drug product.

Decision: Registration Board decided as follows:

Accept the stability study data as the dissolution specifications falls within the definition of

immediate release drug product and approved registration of Sofvasc Trio Tablets 40/10/12.5mg

with Innovator’s specifications by M/s Wilson’s Pharmaceuticals, I-9, Industrial Area Islamabad,

wherein manufacturer will adopt the dissolution specifications i.e. NLT Q at 30 minutes for

commercial production batches.

Furthermore, manufacturer will place first three production batches on long term stability


Sr.

No.

Name & Address

of Manufacturer /

Applicant

Brand Name

(Proprietary Name +


Composition,


Finished Product

Specification

Type of Form,


Fee (including

differential fee),


size


Availability


Remarks

382. M/s Pharmatec

Pakistan (Pvt.)

Limited, D-86/A,

S.I.T.E., Karachi.

Tigrelor 90mg tablet

Each film-coated tablet

contains:

Ticagrelor...90mg

(Platelet Aggregation

Inhibitor)

Innovators’ Specifications

Form- 5

Dy.No.931

Dated: 22-12-2014

Rs.50,000/-

(17-12-2014)

2 x 10’s ; as per SRO

Brilinta 90 mg film-coated tablets

of M/s AstraZeneca UK Limited

(MHRA Approved) / Not

applicable


conducted on 12-12-2017 and

GMP certificate was issued on 15-

12-2017.


Drug Tigrelor 90mg tablet

Name of Manufacturer M/s Pharmatec Pakistan (Pvt.) Limited, D-86/A, S.I.T.E., Karachi.

Manufacturer of API M/s Nantong Chanyoo Pharmatech Co., Ltd. China

API Lot No. RD-TG-201709061

Description of Pack


Alu- Alu Blister





Frequency Accelerated: 0, 3, 6 (month)

Real Time: 0, 3, 6, 9, 12 (months)


Batch No. 17PD064TICT05 17PD081TICT06 17PD089TICT07


Manufacturing Date Nov-2017 Dec-2017 Dec-2017


No. of Batches 04

Date of Submission 16-08-2018 (27937)



1. CoA of API Firm has submitted copy of COA of Ticagrelor (Batch

# RD-TG-201709061) from M/s Nantong Chanyoo

Pharmatech Co., Ltd., China.




Copy of GMP certificate (certificate No.2017006)

issued by Nantong Food & Drug Administration,

China. It is valid until 07/09/2020.



Yes




Yes

5. Documents confirming import of API etc. The firm has submitted commercial invoice for the

import of Ticagrelor (5kg) from M/s. Nantong

Chanyoo Pharmatech Co., Ltd, China attested by

Assistant Director (I & E) DRAP, Karach dated 27-10-

2017.



documents.

Yes



Yes


1978.

Yes


Firm has submitted 6 months accelerated and 12 months real time stability study data of four batches.




Date of submission: 02-07-2019 vide diary no. 10339





Firm has referred to onsite inspection report of their product “Apixa

2.5mg and 5mg (Apixaban) Tablets”, which was presented in 289th


approve registration of above stated drug product of M/s. Pharmatec

Pakistan (Private) Ltd, Karachi.

Date of inspection: 30-04-2019


The firm has 21CFR compliant HPLC software.

The firm has audit trail reports available.




import).

The firm has submitted commercial invoice for the import of

Ticagrelor (5kg) from M/s. Nantong Chanyoo Pharmatech Co., Ltd,

China attested by Assistant Director (I & E) DRAP, Karach dated

27-10-2017.



standards.

The firm has submitted COAs of following working standards &

impurity Standards :

Ticagrelor working standard (B # WS201603001)

Ticagrelor working standard (B # WTG01-170401)

Impurity standards

TG16 WRS (B# WTG05-170401)

De-Ethoxyl of TG WRS (B# WTG06-170401)

4. Approval of API/DML/GMP certificate



origin.

Copy of GMP certificate (certificate No.2017006) issued by

Nantong Food & Drug Administration, China. It is valid until

07/09/2020.


qualification

The firm has submitted SOP for evaluation of vendors.



standards

Firm has submitted copy of COA of Ticagrelor (Batch # RD-TG-

201709061) from M/s Nantong Chanyoo Pharmatech Co., Ltd.,

China.



development?

The firm has submitted copy of Commercial invoices/COAs of the

excipients used in the formulation of applied product



experience.

The firm has submitted List of qualified staff involved in product

development department.

Production Data



batches.


of Ticagrelor 90mg Tablet”.



The firm has submitted copy of Batch Manufacturing Records of



17PD064TICT05 2500 Tablets 29-01-2018

17PD064TICT06 2500 Tablets 29-01-2018

17PD064TICT07 2500 Tablets 30-01-2018


stability batches.

Trial No Total no. of

Tablets

For stability

testing

Tablets

used for

testing

Remaining

Quantities

of tablets

17PD064TICT05 2500 Tablets 1800

Tablets

700 tablets


Tablets

170 tablets


Tablets

170 tablets

QA / QC DATA




accelerated)


used in Real Time & Accelerated stability studies of applied product

from 29-11-2017 to



with COA.


Material Testing Procedures along with COA for Ticagrelor.






for “Ticagrelor 90mg Tablet” along with Stability Study Reports.


manufacturer.

The firm has submitted copy of 06 months Accelerated and 24

months Long term Stability Study Data of 03 Batches from M/s

Nantong Chanyoo Pharmatech Co., Ltd. China. The storage

conditions for real time stability data are 25±2oC/60±5%RH.

16. Analysis reports for excipients used. The firm has submitted copy of Analytical reports of excipients used.

17. Drug-excipients compatibility studies. The compatibility of Ticagrelor 900mg (API) and 40mg Sodium

lauryl sulphate (Excipient) was studied by HPLC analytic techniques

after storage of mixture under accelerated conditions. HPLC analysis

of these mixtures has not shown any significant physical and

chemical instability. Hence the study concludes that Ticagrelor and

sodium lauryl sulphate are compatible.

18. Record of comparative dissolution data. The firm has performed comparative dissolution profile at pH 1.2,

pH 4.5, pH 6.8 between Ticagrelor 90mg tablet and Brilinta 90mg

tablet. The results suggest similarity factor (f2) > 50 and difference

factor (f1) < 15 in all three media.



testing.

The firm has submitted audit trail reports of “Ticagrelor 90mg

Tablet” from.

Sr.# Observations communicated Response by the applicant

1. Digital data logger record does not cover the

duration of stability study data. Clarification is

required.

Digital logger sheets which cover the duration stability

study data.

2. Justification is required for preparation of four

batches for the purpose of carrying out stability

studies.

The first batch exhibiting the batch number

17PD048TICT04, is the pre-formulation batch, the very

initial batch developed at every step of formulation

development, this supports in making decision. These

steps include process feasibility studies, formulation

optimization and manufacturing process.

3. Audit trail reports of only one date are submitted.

It is important to submit the audit trail reports at

all time points of stability studies as well as

comparative dissolution study.

Audit trail on the testing time point is submitted.

4. Polymorphic form of Ticagrelor API is required

to be submitted.

The firm has submitted that polymorphic form-II was

used and further stated that same form of molecule is

discussed in the patent of Astra Zeneca. The form-II of

Ticagrelor is confirmed by the melting points & X-ray

Diffraction.

Storage conditions under which stability studies were conducted are at 25oC±2oC/60%±5% RH.

Previous Decision: Deferred for submission of scientific justification for conducting API stability studies at storage

conditions of 25oC±2oC/60%±5% RH.

Response of the applicant: The firm has submitted that internationally API stability studies are conducted at

25oC±2 oC/60%±5%RH because majority of API manufacturer supplies their product to international market. When

we receive APIs, we keep them in controlled temperature i.e., 25oC. When we manufacture our finished product

with these APIs, we use to conduct stability studies of our products according to our stability Zone i.e., Zone IVA.


Previous Decision: Registration Board deferred the case for submission of valid GMP certificate of M/s Nantong

Chanyoo, Jiangsu province, China, issued by relevant Provincial or state Regulatory authority since the Nantong

Food and Drug Administration is not the relevant provincial regulatory authority (M-293).

Response of the firm: Firm has submitted copy of “License for Drug production” issued by the Jiangsu Food and

Drug Administration in the name of M/s Nantong Chanyoo Pharmatech Co., Ltd., China with License number “S.

20160512” and valid upto 31-12-2020.

The above cited certificate has been verified from the following web link of National Medical Product

Administration of China:

http://app1.sfda.gov.cn/datasearchcnda/face3/base.jsp?tableId=34&tableName=TABLE34&title=%D2%A9%C6

%B7%C9%FA%B2%FA%C6%F3%D2%B5&bcId=152911762991938722993241728138

Decision: Deferred for following submissions:

Submission of real term stability studies data of the product for atleast 1 year along with

degradation studies in the finished pharmaceutical product as per the decision of 290th meeting of

Registration Board since the firm has used API whose stability testing has not been done as per the

conditions of Zone IV-A.

Scientific justification for performance of drug excipient compatibility studies with only 1

excipient (i.e. Sodium lauryl sulphate).

Status whether form-II of Ticagrelor is confirmed by the melting points & X-ray Diffraction

by M/s Pharmatec or API manufacturer

http://app1.sfda.gov.cn/datasearchcnda/face3/base.jsp?tableId=34&tableName=TABLE34&title=%D2%A9%C6%B7%C9%FA%B2%FA%C6%F3%D2%B5&bcId=152911762991938722993241728138

http://app1.sfda.gov.cn/datasearchcnda/face3/base.jsp?tableId=34&tableName=TABLE34&title=%D2%A9%C6%B7%C9%FA%B2%FA%C6%F3%D2%B5&bcId=152911762991938722993241728138


CTD Applications (Deferred cases):

383. MODULE 1: ADMINISTRATIVE

Section Sub-

Section

Heading

1.1 Covering Letter and Fee Deposit Slip Submitted

Dy.No. 1528, dated 22-03-2019,

50,000/- dated 04-02-2019

1.2 Table of Contents (From Module 1 to Module 5) Submitted

1.3 Applicant Information Submitted

1.3.1 Name, address and contact details of Applicant / Marketing Authorization Holder:

M/s Martin Dow Limited., Plot 37, Sector 19, Korangi Industrial Area, Karachi

1.3.2 Name, address and contact details of Manufacturing site.

M/s Nabiqasim Industries Pvt. Ltd., 17/24, Korangi industrial Area, Karachi

1.3.3 Specify whether the Applicant is:

a. Manufacturer

b. Importer

c. Is involved in none of the above (contract giver)

1.3.4 Valid Drug Manufacturing License (DML) of manufacturer / Applicant or Drug Sale

License, whichever is applicable.

Copy of DML of manufacturing site is submitted.

Submitted

1.3.5 Evidence of approval of manufacturing facility / Approved Section from Licensing

Authority

Submitted

1.3.6 List of already approved registered drugs in this section

NA.

1.3.7 Identification of Signature(s) of authorized persons, Incharge Production, Quality Control

and Incharge Quality Assurance

NA

1.3.8 Manufacturer’s Site Master File and Credential (for importer)

Not applicable

1.4 Type of Application Submitted

1.4.1 Application is for the registration of:

New Drug Product (NDP)


1.4.1 Pharmaceutical product is intended for:

Domestic sale

Export sale


1.4.2 For imported products, please specify one of following:


Bulk Import and local repacking (specify status of bulk)

Bulk Import Local Repacking for Export purpose only

1.4.3 Contract Manufacturing as per Rule 20-A of Drugs (Licensing, Registering and

Advertising) Rules, 1976.


Export Purpose Only

1.5 Detailed Information of Drug, Dosage From & Labelling Claims Submitted

1.5.1 Generic name with chemical name & synonyms of the applied drug.

1.5.2 Strength / concentration of drug of Active Pharmaceutical ingredient (API) per unit

Each vial contains:

Esomeprazole as sodium…………40mg

1.5.3 The proposed proprietary name / brand name under which the drug is intended to be sold

with trade mark certification / clearance.

Esomax IV 40mg Injection


1.5.4 Proposed Pack size and Proposed unit price of drug e.g., per tablet / capsule. Maximum

Retail Price (MRP) per pack shall also be mentioned.

1 vial; As per PRC

1.5.5 Pharmacotherapeutic Group of Active Pharmaceutical Ingredient (API)

Proton pump inhibitor (WHO ATC code= A02BC05)

1.5.6 Pharmacopoeial reference / Status of applied formulation

In-house

1.5.7 Route of administration

Intravenous (IV)

1.5.8 For Generic Drug Product, reference of other similar approved medicines with information

pertaining to Manufacturer name, brand name, strength, composition, registration number

& dosage form, Pack size and Price.

Acireg of Barret hodgson Pakistan

1.5.9 The registration status of applied drug in same molecule and salt, strength, dosage form,

container closure system, indications and route of administration etc. in other countries.

The status in reference regulatory authorities is mandatory to mention.

Nexium IV Injection (MHRA Approved)

1.5.10 Dosage form of applied drug

Esomax IV Injection 40mg/ml

Sterile , freeze –dried white colored powder in 5ml vial contains:

Esomeprazole sodium eq. to Esomeprazole……………40mg

1.5.11 Proposed label (outer (secondary) & inner (primary)) & color scheme in accordance with

Drug (Labelling & Packing) Rules, 1986 along with specimens

Attached

1.5.12 Description of Batch numbering system

Not submitted

1.5.13 Training evidence of technical staff with respect of manufacturing of applied drug

(mandatory in case of specially designed pharmaceutical product / Novel Dosage Form).

Not submitted

1.5.14 Summary of Product Characteristics (SmPC) including Prescribing Information (PI) along

with Patient information Leaflet (PIL) of the Finished Pharmaceuticals Product (FPP).

Submitted

1.5.15 Commitment / Undertaking that after registration of applied drug, the Pharmacovigilance

department of the applicant / manufacture is liable to impose similar restrictions, addition

of any clinical information (like in Indications, Contra-indications, Side effects,

Precautions, Dosage & Adverse Drug Reactions etc. in Summary of Product

Characteristics (SmPC), Labelling & Promotional material) or withdraw the drug from

market in Pakistan within fourteen days after knowing that such information (which was

not available or approved by the DRAP at the time of registration) / actions taken (for

safety reasons) by any reference / stringent drug regulatory agency / authority & also

inform the DRAP (Drug Regulatory Authority of Pakistan) for further action in this regard.

Submitted

1.5.16 Commitment / Undertaking that the applicant shall recall the defective Finished

Pharmaceutical Products (FPP) and notify the compliance to the authority along with detail

of actions taken by him as soon as possible but not more than ten days. The level of recall

shall also be defined.

Submitted

1.5.17 Commitment / Undertaking that in case of any false claim / concealing of information, the

DRAP has the right to reject the application at any time, before and even after approval or

registration of the product in case if proved so.

Submitted

1.5.18 Commitment / Undertaking that the firm shall follow the official pharmacopoeia

specifications for product / substance as published in the latest edition & shall update its

specification as per latest editions of the same. In case, the specifications of product /


substance not present in any official pharmacopoeia the firm shall establish the

specifications. In both cases, the validation of specifications shall be done by the applicant.

Submitted

1.5.19 Commitment / Undertaking that in case of any post approval change, the applicant shall

ensure that the product with both approvals shall not be available in the market at the same

time. And the product with new approvals shall be marketed only after consumption /

withdrawal of stock with previous approvals. The company shall be liable to inform the

same regarding marketing status of product to the DRAP after getting such post-

registration approvals.

Not submitted

1.5.20 Other commitment e.g., regarding stability studies etc.

Submitted

1.5.21 Protocols along with the commitment to follow Good Laboratory Practices (GLP) by the

Manufacturer.

Not submitted

1.5.22 Protocols to implement Good Pharmacovigilance Practice by the Pharmacovigilance

department/section of the Manufacturer / Company.

Not submitted

1.6 Miscellaneous Information Not submitted

1.6.1 Information on Prior-related Applications

1.6.2 Appendix

1.6.3 Electronic Review Package

1.6.4 QIS (Quality Information Summary)

1.6.5 Drug Substance related Document including following:

a. Name and address of API manufacturer.

b. Approval of manufacturing facility of API by regulatory body of country and

validity.

c. Vendor qualification / audit is

Document based


d. Reason for point c.

The firm has submitted copy of contract manufacturing agreement dated 12th March, 2019

between M/s Martin Dow Limited, Karachi and Nabiqasim Industries Pvt. Ltd., Karachi.


MODULE 2: CTD SUMMARIES

2.1 Overall CTD Table of Content Submitted

2.2 CTD Introduction Submitted

2.3 Quality Overall Summary (QOS)* Submitted

(Detailed information regarding QOS may be found at the following link) https://extranet.who.int/prequal/sites/default/files/documents/82%20Module%202.3%20QOS_March2017

.docx

1.3 QUALITY OVERALL SUMMARY (QOS)

2.3 2.3.S Drug substance (API)

2.3.S.1 General information Submitted

2.3.S.2 Manufacture Submitted

2.3.S.3 Characterization Submitted

2.3.S.4 Control of drug substance Submitted

2.3.S.5 Reference standards Submitted

2.3.S.6 Container closure system Submitted

2.3.S.7 Stability Submitted

Comments

2.3.P Drug product

2.3.P.1 Description and composition of the drug product Submitted

2.3.P.2 Pharmaceutical development Submitted

2.3.P.2.1 Components of the drug product

2.3.P.2.1.1 Drug substance (API) Submitted

2.3.P.2.1.2 Excipients Submitted

2.3.P.2.2 Finished Pharmaceutical Product Submitted

2.3.P.2.3 Manufacturing process development Submitted

2.3.P.2.4 Container closure system Submitted

2.3.P.3 Manufacture Submitted

2.3.P.4 Control of excipients Submitted

2.3.P.5 Control of drug product Submitted

2.3.P.6 Reference standards and materials Submitted

2.3.P.7 Container closure system Submitted

2.3.P.8 Stability Submittted

Comments

2.4

Non-Clinical Overview Not applicable

2.5 Clinical Overview Not applicable

2.6 Non-Clinical Written and Tabulated Summaries (Normally not required for generics) Not applicable

2.7 Clinical summary Not applicable

https://extranet.who.int/prequal/sites/default/files/documents/82%20Module%202.3%20QOS_March2017.docx



MODULE 3: QUALITY

3.1 Table of Contents of Module 3 Submitted

3.2 Body of Data Submitted

3.2.S DRUG SUBSTANCE (API)

3.2.S.1

GENERAL INFORMATION (May not refer to DMF)

3.2.S.1.1 Nomenclature Submitted

3.2.S.1.2 Structure Submitted

3.2.S.1.3 General properties Submitted

Comments

3.2.S.2 MANUFACTURER

3.2.S.2.1 Manufacturer(s) Submitted

3.2.S.2.2 Description of Manufacturing Process and Process Controls Submitted

3.2.S.2.3 Control of Materials Not submitted

3.2.S.2.5 Process Validation and/or Evaluation Not submitted

The firm has not submitted information of control of materials and Process validation or evaluation

as specified in 3.2.S.2.3 and 3.2.S.2.5. The firm has claimed that this information is confidential hence

it will be covered in closed part of DMF.

3.2.S.3

CHARACTERIZATION

3.2.S.3.1 Elucidation of Structure and other Characteristics Submitted

3.2.S.3.2 Impurities Submitted

Comments

3.2.S.4

CONTROL OF DRUG SUBSTANCE (API)

3.2.S.4.1

Specification Submitted

Comments

3.2.S.4.2

Analytical procedures Submitted

Comments

3.2.S.4.3

Validation of analytical procedures Submitted

(API that meets Pharmacopeia standards MUST provide verification of procedures)

1. Spectra and chromatograms for reference standards and test samples

(ref. std. can be located in 3.2.S.5)

Comments

3.2.S.4.4

Batch analysis

1. Certificate of analysis (COA) specifications and test results from drug

substance (API) manufacturer(s)

2. Drug product manufacturer’s certificate of analysis with API lot numbers

Comments

3.2.S.4.5 Justification of specifications Submitted

Comments

3.2.S.5

REFERENCE STANDARDS OR MATERIALS (Do NOT refer to DMF) Submitted

Comments

3.2.S.6

CONTAINER CLOSURE SYSTEMS Submitted

Storage temperature of the API is between 2°C and 8°C.

3.2.S.7 STABILITY


3.2.S.7.1 Stability Summary and Conclusions Submitted

3.2.S.7.2 Post-approval Stability Protocol and Stability Commitment Submitted

3.2.S.7.3 Stability Data Submitted

Stability study completed up to 6 months at accelerated condition Viz. 25oC±2oC/ 60% ±5% RH and

study completed up to 60 months at long term condition Viz.5oC±3oC.

3.2.P DRUG PRODUCT

3.2.P.1

DESCRIPTION AND COMPOSITION OF THE DRUG PRODUCT Submitted

1. Unit composition with indication of the function of the inactive ingredient(s)

2. Formulation

Comments

3.2.P.2

PHARMACEUTICAL DEVELOPMENT

3.2.P.2.1 Components of the Drug Product

3.2.P.2.1.1 Drug Substance Submitted


3.2.P.2.2 Drug Product

3.2.P.2.2.1 Formulation Development Submitted

Pharmaceutical Equivalence through Comparative Dissolution Profile

Submitted

3.2.P.2.2.2 Overages Not applicable

3.2.P.2.2.3 Physicochemical and Biological Properties Submitted

3.2.P.2.3 Manufacturing Process Development Submitted

3.2.P.2.4 Container Closure System Submitted

3.2.P.2.5 Microbiological Attributes Submitted

3.2.P.2.6 Compatibility Submitted

The firm has submitted following:

Stability of this product under various conditions has been monitored since compatibility study

was not performed. Results from stability studies proved that active ingredients and packaging

material are well suited, and do not exert any adverse impact on finished pharmaceutical product

performance.

3.2.P.3 MANUFACTURE

3.2.P.3.1 Manufacturer(s) Submitted

1. Name and full address(es) of the facility(ies)

2. Contact name, phone and fax numbers, email address

Comments

3.2.P.3.2 Batch formula Submitted

Largest intended commercial batch size

Comments

3.2.P.3.3 Description of manufacturing process and process controls Submitted

1. Description of the manufacturing process and facility

2. Master production batch record(s) for largest intended production runs (no

more than 10x pilot batch) with equipment specified

3. Master packaging records for intended marketing container(s)

Comments

3.2.P.3.4 Controls of critical steps and intermediates Submitted

Comments

3.2.P.3.5 Process validation and/or evaluation Submitted

3.2.P.4 CONTROL OF EXCIPIENTS


3.2.P.4.1 Specifications Submitted

1. Testing specifications (including identification and characterization)

2. Supplier’s COA (specifications and test results)

Comments

3.2.P.4.2 Analytical procedures Submitted

Comments

3.2.P.4.3 Validation of analytical procedures Submitted

Comments

3.2.P.4.4 Justification of specifications (as applicable) Submitted

3.2.P.4.5 Excipients of Human or Animal Origin Not applicable

3.2.P.4.6 Novel Excipients Not applicable

Comments

3.2.P.5 CONTROLS OF DRUG PRODUCT

3.2.P.5.1

Specification(s) Submitted

Comments

3.2.P.5.2


Comments

3.2.P.5.3

Validation of analytical procedures Not submitted

(if using Pharmacopoeial procedure, must provide verification of Pharmacopoeial

procedure)

You have not submitted validation of analytical procedures under control of drug

product. It is very important to submit the data as specified in 3.2.P.5.3 especially where

in-house method is developed.

3.2.P.5.4

Batch analysis Submitted

Certificates of Analysis for finished dosage form

Comments

3.2.P.5.5

Characterization of impurities Submitted

All potential degradation products should be listed in a tabular format

Comments

3.2.P.5.6

Justification of specifications Submitted


Comments

3.2.P.6 Reference Standards or Materials Not submitted

Comments

3.2.P.7 CONTAINER CLOSURE SYSTEM Submitted

1. Summary of container closure system

2. Component specifications and test data

3. Packaging configuration(s) and size(s)

4. Container/Closure Testing (recommended additional testing for all

plastic)

a. Solid orals: water permeation, light transmission

b. Liquids: leachables, extractables, light transmission

i. Injectables with rubber stoppers: extractables

Information in various sections from 3.2.P.5.3 to 3.2.P.5.6 as well as 3.2.P.6 of module

III is not submitted. Relevant information is required to be submitted.


3.2.P.8 STABILITY

3.2.P.8.1 Stability summary and conclusion (Finished Dosage Form) Submitted

Stability protocol submitted

Expiration dating period for marketed packaging

Expiration dating period for bulk packaging (if applicable)

Comments

3.2.P.8.2 Post-approval Stability Protocol and Stability Commitment Submitted

Comments

3.2.P.8.3 Stability Submitted

The firm has submitted stability sheets for 6 months at accelerated conditions and 24

months at real time conditions for three batches of their already marketed product Es-

Loprot 40mg IV Injection. However, the firm has not submitted raw data sheets and

chromatograms.

Sr.

No.

Observations communicated Response of the applicant

1. Identification of Signature(s) of authorized persons,

Incharge Production, Quality Control and Incharge

Quality Assurance is not submitted.

Submitted

2. Quantitative composition of applied formulation

contains Mannitol as mentioned in 2.3.P.1 and

3.3.P.1. However, reference product in MHRA does

not mention such excipient. Justification /

Clarification is required and also the compatibility

studies of API with this excipient is required.

The firm has submitted revised formulation which

does not contain mannitol. Accordingly firm has

submitted BMR and formulation for

Esomeprazole 40mg injection. However, firm has

just submitted template for BMR which does not

contain actual formulation development.

3. You have not submitted validation of analytical

procedures under control of drug product. It is very

important to submit the data as specified in 3.2.P.5.3

especially where in-house method is developed.

Not submitted

4. Information in various sections from 3.2.P.5.3 to

3.2.P.5.6 as well as 3.2.P.6 of module III is not

submitted. Relevant information is required to be

submitted.

The firm has submitted Batch Analyses,

Characterization of impurities and justification of

finished product specifications.

5. You have not submitted supporting documents like

raw data sheets and chromatograms against

submitted stability summary sheets of applied

formulation.

The firm has not submitted chromatograms of

initial time point of applied formulation. The firm

has submitted the data of already marketed

product Es-Loprot 40mg IV Injection of M/s

NabiQasim Industries Pvt. Ltd. karachi.

6. Commitments as specified in sections 1.5.15,

1.5.16, 1.5.17, 1.5.19 and protocols as specified in

sections 1.5.21, 1.5.22 of module I are required to

be submitted.

Submitted

Previous Decision: Registration Board deferred the case for following observations: (M-292)

Scientific justification for the relevance of previously submitted data in section 3.2.P against

recently revised master formulation.

Submission of validation of analytical procedures as specified in 3.2.P.5.3 of module III of CTD.

Submission of chromatograms and raw data sheets of three batches of stability study data of initial

time and details of reference standards and materials as specified in 3.2.P.6.

Evaluation by PEC:

As per information from NabiQasim (contract manufacturer), they have developed the formulation of

Esomeprazole 40mg Injection as per innovator without mannitol and conducted its 06 months stability

studies. Based on satisfactory stability data, BMR of actual product is developed.

01 set of Blank BMR of Esomeprazole 40mg Injection is submitted.


03 sets of filled BMR of developmental batches of Esomeprazole 40mg Injection with their stability

data, raw data sheets and chromatograms are submitted.

For validation of analytical procedures as specified in 3.2.P.5.3, the firm has submitted following

documents:

Method validation protocol

Method validation report

For reference standard, firm has submitted following justification:

“For the analysis of Esomeprazole in lyophilized injection, Reference standard of omeprazole is used as they are

isomer of each other and contain same formula. This practice was adopted from United states Pharmacopoea, as

they are also using Omeprazole as a reference standard for the analysis of Esomeprazole Magnesium delayed

release capsules.”

Verification of Authenticity of formulation of Esomax (Esomeprazole) 40mg IV Injection by M/s. Martin

Dow Limited, K.I.A. Karachi.

Reference No: F.1-2/2020-PEC dated 02nd January, 2020.

Investigation Date and Time: 6th January, 2020. (Afternoon)

Investigation Site: Factory premises of M/s. Nabi Qasim Industries Pvt. Ltd. Karachi.

Background:

The Pharmaceutical Evaluation and Registration Division considered the application of M/s Martin Dow Limited

for registration of Esomax (Esomeprazole) 40mg IV Injection manufactured by M/s Nabi Qasim Industries on

contract manufacturing basis. The Chairman Registration Board constituted a two member panel for investigation

of the query mentioned in the scope of investigation:


1. Ms. Hira Bhutto, Assistant Director, CDL, DRAP, Karachi

2. Dr. Affan Ali Qureshi, Assistant Director, CDL, DRAP, Karachi.


On Site Investigation/verification of the following point:

1. Verification of formulation for use of mannitol as the firm initially submitted the formulation containing

mannitol and upon query for justification they replied that their formulation do not contain mannitol and

their formulation is as per innovator’s product.

Details of Investigation:

1. The panel visited the firm, reviewed the batch records including dispensing, production records, log books,

the available software (ERP), audit trail for the ERP on the system and found that mannitol was never

dispensed for the manufacturing of any batch of the said product:

2. As per record available with the firm the formulation of product is as under:

a. Esomeprazole Sodium (Pyrogen Free) 42.5mg/vial

b. Di Sodium EDETATE (Injectable Grade) 1mg/vial

c. Sodium Hydroxide (Injectable Grade) 0.7mg/vial

d. Water for injection q.s. 2.1ml

Conclusion & Recommendation:

1. On the basis of the site visit, documents reviewed and personnel inquired the panel reached on conclusion

that the firm has not used mannitol in their formulation and their formulation is as per innovator product.

Therefore, in opinion of the panel the firm may kindly be granted registration of the product with current

formulation if there is no more query.

Decision: Registration Board decided to approve registration of Esomax IV 40mg Injection with

Innovator’s specifications by M/s Martin Dow Limited., Plot 37, Sector 19, Korangi Industrial Area,

Karachi.


384. ESVIN INJECTION 40mg

Section Sub-

Section

Heading

1.1 Covering Letter and Fee Deposit Slip Submitted

Dy.No.7859 , dated 31-05-2019, Rs.50,000/- dated 29-05-2019

1.2 Table of Contents (From Module 1 to Module 5) Submitted

1.3 Applicant Information Submitted

1.3.1 Name, address and contact details of Applicant / Marketing Authorization Holder:

M/s. Martin Dow Marker Limited, 7- Jail Road, Quetta.

1.3.2 Name, address and contact details of Manufacturing site.

M/s Nabiqasim Industries Pvt. Ltd., 17/24, Korangi industrial Area, Karachi

1.3.3 Specify whether the Applicant is:

d. Manufacturer

e. Importer

f. Is involved in none of the above (contract giver)

1.3.4 Valid Drug Manufacturing License (DML) of manufacturer / Applicant or Drug Sale

License, whichever is applicable.

Copy of DML of manufacturing site is submitted.

1.3.5 Evidence of approval of manufacturing facility / Approved Section from Licensing Authority

Submitted

1.3.6 List of already approved registered drugs in this section

Not submitted

1.3.7 Identification of Signature(s) of authorized persons, Incharge Production, Quality Control

and Incharge Quality Assurance

Not submitted

1.3.8 Manufacturer’s Site Master File and Credential (for importer)

Not applicable

1.4 Type of Application Submitted

1.4.1 Application is for the registration of:

New Drug Product (NDP)


1.4.1 Pharmaceutical product is intended for:

Domestic sale

Export sale


1.4.2 For imported products, please specify one of following:


Bulk Import and local repacking (specify status of bulk)

Bulk Import Local Repacking for Export purpose only

1.4.3 Contract Manufacturing as per Rule 20-A of Drugs (Licensing, Registering and Advertising)

Rules, 1976.


Export Purpose Only

1.5 Detailed Information of Drug, Dosage From & Labelling Claims Submitted

1.5.1 Generic name with chemical name & synonyms of the applied drug.

1.5.2 Strength / concentration of drug of Active Pharmaceutical ingredient (API) per unit

Each vial contains:

Esomeprazole as sodium…………40mg

1.5.3 The proposed proprietary name / brand name under which the drug is intended to be sold

with trade mark certification / clearance.

ESVIN INJECTION 40mg

1.5.4 Proposed Pack size and Proposed unit price of drug e.g., per tablet / capsule. Maximum Retail

Price (MRP) per pack shall also be mentioned.

1 vial; As per PRC


1.5.5 Pharmacotherapeutic Group of Active Pharmaceutical Ingredient (API)

Proton pump inhibitor (WHO ATC code= A02BC05)

1.5.6 Pharmacopoeial reference / Status of applied formulation

In-house

1.5.7 Route of administration

Intravenous (IV)

1.5.8 For Generic Drug Product, reference of other similar approved medicines with information

pertaining to Manufacturer name, brand name, strength, composition, registration number &

dosage form, Pack size and Price.

Acireg of Barret hodgson Pakistan

1.5.9 The registration status of applied drug in same molecule and salt, strength, dosage form,

container closure system, indications and route of administration etc. in other countries. The

status in reference regulatory authorities is mandatory to mention.

Nexium IV Injection (MHRA Approved)

1.5.10 Dosage form of applied drug

ESVIN Injection 40mg

Sterile , freeze –dried white colored powder in 5ml vial contains:

Esomeprazole sodium eq. to Esomeprazole……………40mg

1.5.11 Proposed label (outer (secondary) & inner (primary)) & color scheme in accordance with

Drug (Labelling & Packing) Rules, 1986 along with specimens

Attached

1.5.12 Description of Batch numbering system

Not provided

1.5.13 Training evidence of technical staff with respect of manufacturing of applied drug

(mandatory in case of specially designed pharmaceutical product / Novel Dosage Form).

Not provided

1.5.14 Summary of Product Characteristics (SmPC) including Prescribing Information (PI) along

with Patient information Leaflet (PIL) of the Finished Pharmaceuticals Product (FPP).

Attached

1.5.15 Commitment / Undertaking that after registration of applied drug, the Pharmacovigilance

department of the applicant / manufacture is liable to impose similar restrictions, addition of

any clinical information (like in Indications, Contra-indications, Side effects, Precautions,

Dosage & Adverse Drug Reactions etc. in Summary of Product Characteristics (SmPC),

Labelling & Promotional material) or withdraw the drug from market in Pakistan within

fourteen days after knowing that such information (which was not available or approved by

the DRAP at the time of registration) / actions taken (for safety reasons) by any reference /

stringent drug regulatory agency / authority & also inform the DRAP (Drug Regulatory

Authority of Pakistan) for further action in this regard.

Submitted

1.5.16 Commitment / Undertaking that the applicant shall recall the defective Finished

Pharmaceutical Products (FPP) and notify the compliance to the authority along with detail

of actions taken by him as soon as possible but not more than ten days. The level of recall

shall also be defined.

Submitted

1.5.17 Commitment / Undertaking that in case of any false claim / concealing of information, the

DRAP has the right to reject the application at any time, before and even after approval or

registration of the product in case if proved so.

Submitted

1.5.18 Commitment / Undertaking that the firm shall follow the official pharmacopoeia

specifications for product / substance as published in the latest edition & shall update its

specification as per latest editions of the same. In case, the specifications of product /

substance not present in any official pharmacopoeia the firm shall establish the

specifications. In both cases, the validation of specifications shall be done by the applicant.

Submitted


1.5.19 Commitment / Undertaking that in case of any post approval change, the applicant shall

ensure that the product with both approvals shall not be available in the market at the same

time. And the product with new approvals shall be marketed only after consumption /

withdrawal of stock with previous approvals. The company shall be liable to inform the same

regarding marketing status of product to the DRAP after getting such post-registration

approvals.

Submitted

1.5.20 Other commitment e.g., regarding stability studies etc.

Submitted

1.5.21 Protocols along with the commitment to follow Good Laboratory Practices (GLP) by the

Manufacturer.

Not applicable

1.5.22 Protocols to implement Good Pharmacovigilance Practice by the Pharmacovigilance

department/section of the Manufacturer / Company.

Not submitted

1.6 Miscellaneous Information Not submitted

1.6.1 Information on Prior-related Applications

1.6.2 Appendix

1.6.3 Electronic Review Package

1.6.4 QIS (Quality Information Summary)

1.6.5 Drug Substance related Document including following:

e. Name and address of API manufacturer.

f. Approval of manufacturing facility of API by regulatory body of country and

validity.

g. Vendor qualification / audit is

Document based


h. Reason for point c.

The firm has submitted copy of contract manufacturing agreement dated 12th March, 2019

between M/s Martin Dow Limited, Karachi and Nabiqasim Industries Pvt. Ltd., Karachi.


MODULE 2: CTD SUMMARIES

2.1 Overall CTD Table of Content Submitted

2.2 CTD Introduction Submitted

2.3 Quality Overall Summary (QOS)* Submitted

(Detailed information regarding QOS may be found at the following link) https://extranet.who.int/prequal/sites/default/files/documents/82%20Module%202.3%20QOS_March2017

.docx

1.4 QUALITY OVERALL SUMMARY (QOS)

2.3 2.3.S Drug substance (API)

2.3.S.1 General information Submitted

2.3.S.2 Manufacture Submitted

2.3.S.3 Characterization Submitted

2.3.S.4 Control of drug substance Submitted

2.3.S.5 Reference standards Submitted

2.3.S.6 Container closure system Submitted

2.3.S.7 Stability Submitted

Comments

2.3.P Drug product

2.3.P.1 Description and composition of the drug product Submitted

2.3.P.2 Pharmaceutical development Submitted

2.3.P.2.1 Components of the drug product

2.3.P.2.1.1 Drug substance (API) Submitted


2.3.P.2.2 Finished Pharmaceutical Product Submitted

2.3.P.2.3 Manufacturing process development Submitted

2.3.P.2.4 Container closure system Submitted

2.3.P.3 Manufacture Submitted

2.3.P.4 Control of excipients Submitted

2.3.P.5 Control of drug product Submitted

2.3.P.6 Reference standards and materials Submitted

2.3.P.7 Container closure system Submitted

2.3.P.8 Stability Submittted

Comments

2.4

Non-Clinical Overview Not applicable

2.5 Clinical Overview Not applicable

2.6 Non-Clinical Written and Tabulated Summaries (Normally not required for generics) Not applicable

2.7 Clinical summary Not applicable




MODULE 3: QUALITY

3.1 Table of Contents of Module 3 Submitted

3.2 Body of Data Submitted

3.2.S DRUG SUBSTANCE (API)

3.2.S.1

GENERAL INFORMATION (May not refer to DMF)

3.2.S.1.1 Nomenclature Submitted

3.2.S.1.2 Structure Submitted

3.2.S.1.3 General properties Submitted

Comments

3.2.S.2 MANUFACTURER

3.2.S.2.1 Manufacturer(s) Submitted

3.2.S.2.2 Description of Manufacturing Process and Process Controls Submitted

3.2.S.2.3 Control of Materials Not submitted

3.2.S.2.5 Process Validation and/or Evaluation Not submitted

The firm has not submitted information of control of materials and Process validation or

evaluation as specified in 3.2.S.2.3 and 3.2.S.2.5. The firm has claimed that this information is

confidential hence it will be covered in closed part of DMF.

3.2.S.3

CHARACTERIZATION

3.2.S.3.1 Elucidation of Structure and other Characteristics Submitted

3.2.S.3.2 Impurities Submitted

Comments

3.2.S.4

CONTROL OF DRUG SUBSTANCE (API)

3.2.S.4.1

Specification Submitted

Comments

3.2.S.4.2


Comments

3.2.S.4.3

Validation of analytical procedures Submitted

(API that meets Pharmacopeia standards MUST provide verification of

procedures)

2. Spectra and chromatograms for reference standards and test samples

(ref. std. can be located in 3.2.S.5)

Comments

3.2.S.4.4

Batch analysis

3. Certificate of analysis (COA) specifications and test results from drug

substance (API) manufacturer(s)

4. Drug product manufacturer’s certificate of analysis with API lot numbers

Comments

3.2.S.4.5 Justification of specifications Submitted

Comments

3.2.S.5

REFERENCE STANDARDS OR MATERIALS (Do NOT refer to DMF) Submitted

Comments

3.2.S.6

CONTAINER CLOSURE SYSTEMS Submitted

Storage temperature of the API is between 2°C and 8°C.

3.2.S.7 STABILITY


3.2.S.7.1 Stability Summary and Conclusions Submitted

3.2.S.7.2 Post-approval Stability Protocol and Stability Commitment Submitted

3.2.S.7.3 Stability Data Submitted

Stability study completed up to 6 months at accelerated condition Viz. 25oC±2oC/ 60% ±5% RH

and study completed up to 60 months at long term condition Viz.5oC±3oC.

3.2.P DRUG PRODUCT

3.2.P.1

DESCRIPTION AND COMPOSITION OF THE DRUG PRODUCT Submitted

3. Unit composition with indication of the function of the inactive ingredient(s)

4. Formulation

Comments

3.2.P.2

PHARMACEUTICAL DEVELOPMENT

3.2.P.2.1 Components of the Drug Product

3.2.P.2.1.1 Drug Substance Submitted


3.2.P.2.2 Drug Product

3.2.P.2.2.1 Formulation Development Submitted

Pharmaceutical Equivalence through Comparative Dissolution Profile

Submitted

3.2.P.2.2.2 Overages Not applicable

3.2.P.2.2.3 Physicochemical and Biological Properties Submitted

3.2.P.2.3 Manufacturing Process Development Submitted

3.2.P.2.4 Container Closure System Submitted

3.2.P.2.5 Microbiological Attributes Submitted

3.2.P.2.6 Compatibility Submitted

The firm has submitted following:

Stability of this product under various conditions has been monitored since compatibility study

was not performed. Results from stability studies proved that active ingredients and packaging

material are well suited, and do not exert any adverse impact on finished pharmaceutical

product performance.

3.2.P.3 MANUFACTURE

3.2.P.3.1 Manufacturer(s) Submitted

3. Name and full address(es) of the facility(ies)

4. Contact name, phone and fax numbers, email address

Comments

3.2.P.3.2 Batch formula Submitted

Largest intended commercial batch size

Comments

3.2.P.3.3 Description of manufacturing process and process controls Submitted

4. Description of the manufacturing process and facility

5. Master production batch record(s) for largest intended production runs

(no more than 10x pilot batch) with equipment specified

6. Master packaging records for intended marketing container(s)

Comments

3.2.P.3.4 Controls of critical steps and intermediates Submitted

Comments

3.2.P.3.5 Process validation and/or evaluation Submitted

3.2.P.4 CONTROL OF EXCIPIENTS


3.2.P.4.1 Specifications Submitted

3. Testing specifications (including identification and characterization)

4. Supplier’s COA (specifications and test results)

Comments

3.2.P.4.2 Analytical procedures Submitted

Comments

3.2.P.4.3 Validation of analytical procedures Submitted

Comments

3.2.P.4.4 Justification of specifications (as applicable) Submitted

3.2.P.4.5 Excipients of Human or Animal Origin Not applicable

3.2.P.4.6 Novel Excipients Not applicable

Comments

3.2.P.5 CONTROLS OF DRUG PRODUCT

3.2.P.5.1

Specification(s) Submitted

Comments

3.2.P.5.2


Comments

3.2.P.5.3

Validation of analytical procedures Not submitted

(if using Pharmacopoeial procedure, must provide verification of Pharmacopoeial

procedure)

You have not submitted validation of analytical procedures under control of drug

product. It is very important to submit the data as specified in 3.2.P.5.3 especially

where in-house method is developed.

3.2.P.5.4

Batch analysis Submitted

Certificates of Analysis for finished dosage form

Comments

3.2.P.5.5

Characterization of impurities Submitted


Comments

3.2.P.5.6

Justification of specifications Submitted


Comments

3.2.P.6 Reference Standards or Materials Not submitted

Comments

3.2.P.7 CONTAINER CLOSURE SYSTEM Submitted

5. Summary of container closure system

6. Component specifications and test data

7. Packaging configuration(s) and size(s)

8. Container/Closure Testing (recommended additional testing for all

plastic)

a. Solid orals: water permeation, light transmission

b. Liquids: leachables, extractables, light transmission

i. Injectables with rubber stoppers: extractables

Information in various sections from 3.2.P.5.3 to 3.2.P.5.6 as well as 3.2.P.6 of

module III is not submitted. Relevant information is required to be submitted.


3.2.P.8 STABILITY

3.2.P.8.1 Stability summary and conclusion (Finished Dosage Form) Submitted

Stability protocol submitted

Expiration dating period for marketed packaging

Expiration dating period for bulk packaging (if applicable)

Comments

3.2.P.8.2 Post-approval Stability Protocol and Stability Commitment Submitted

Comments

3.2.P.8.3 Stability Submitted

The firm has submitted stability sheets for 6 months at accelerated conditions and 24

months at real time conditions for three batches of their already marketed product Es-

Loprot 40mg IV Injection. However, the firm has not submitted raw data sheets and

chromatograms.

Sr.

No.

Observations communicated Response of the applicant

1.

Identification of Signature(s) of authorized

persons, Incharge Production, Quality Control

and Incharge Quality Assurance is not submitted.

Submitted

2.

Quantitative composition of applied formulation

contains Mannitol as mentioned in 2.3.P.1 and

3.3.P.1. However, reference product in MHRA

does not mention such excipient. Justification /

Clarification is required and also the compatibility

studies of API with this excipient is required.

The firm has submitted revised formulation which

does not contain mannitol. Accordingly firm has

submitted BMR and formulation for

Esomeprazole 40mg injection. However, firm has

just submitted template for BMR which does not

contain actual formulation development.

3.

You have not submitted validation of analytical

procedures under control of drug product. It is

very important to submit the data as specified in

3.2.P.5.3 especially where in-house method is

developed.

Not submitted

4.

Information in various sections from 3.2.P.5.3 to

3.2.P.5.6 as well as 3.2.P.6 of module III is not

submitted. Relevant information is required to be

submitted.

The firm has submitted Batch Analyses,

Characterization of impurities and justification of

finished product specifications.

5.

You have not submitted supporting documents

like raw data sheets and chromatograms against

submitted stability summary sheets of applied

formulation.

The firm has not submitted chromatograms of

initial time point of applied formulation. The firm

has submitted the data of already marketed

product Es-Loprot 40mg IV Injection of M/s

NabiQasim Industries Pvt. Ltd. karachi.

6.

Commitments as specified in sections 1.5.15,

1.5.16, 1.5.17, 1.5.19 and protocols as specified in

sections 1.5.21, 1.5.22 of module I are required to

be submitted.

Submitted

Previous Decision: Registration Board deferred the case for following observations: (M-292)

Scientific justification for the relevance of previously submitted data in section 3.2.P against recently revised

master formulation.

Submission of validation of analytical procedures as specified in 3.2.P.5.3 of module III of CTD.

Submission of chromatograms and raw data sheets of three batches of stability study data of initial time and

details of reference standards and materials as specified in 3.2.P.6.


Evaluation by PEC:

As per information from NabiQasim (contract manufacturer), they have developed the formulation of

Esomeprazole 40mg Injection as per innovator without mannitol and conducted its 06 months stability

studies. Based on satisfactory stability data, BMR of actual product is developed.

03 sets of BMRs of developmental batches of Esomeprazole 40mg Injection with their stability data, raw

data sheets and chromatograms are submitted.

For validation of analytical procedures as specified in 3.2.P.5.3, the firm has submitted following

documents:

Method validation protocol

Method validation report

For reference standard, firm has submitted following justification:

“For the analysis of Esomeprazole in lyophilized injection, Reference standard of omeprazole is used as they

are isomer of each other and contain same formula. This practice was adopted from United states

Pharmacopoea, as they are also using Omeprazole as a reference standard for the analysis of Esomeprazole

Magnesium delayed release capsules.”

Decision: Registration Board after considering the panel inspection report of M/s Nabiqasim

Industries Pvt. Ltd., 17/24, Korangi industrial Area, Karachi for Esomax (Esomeprazole) 40mg

IV Injection applied by M/s Martin Dow Limited., Plot 37, Sector 19, Korangi Industrial Area,

Karachi, decided to approve registration of ESVIN INJECTION 40mg with Innovator’s

specifications by M/s Martin Dow Marker Limited, 7- Jail Road, Quetta.


Registration-I Section

Case No.01: Clarification Regarding Former Approval/Permission Letters Issued by the

then Ministry of Health

Director General Health Services, Punjab has requested to clarify whether a firm/

manufacturer can quote the product in larger packs to Provincial Governments against tenders. In

this regard, a copy of following letter No. F.3-4/94-Reg-II (M-109) dated 01-11-1994 issued by

the then Ministry of Health stating “Supply of Larger Packs to Provincial Governments against

Tenders” has also been provided:

As the above referred letter dates back to almost 25 years. However, the case has

been placed before the Board for deliberation regarding rationality/requirement of such

permission in current situation. Furthermore, guidance is also requested regarding authenticity of

all such former approvals/permissions which require confirmation from old record.

Decision: Registration Board deferred the case for further deliberation.


Case No.02: Cancellation of Registration of Liquid Infusions of M/s YAS Chemicals, Swabi

Having Volumes /Packing Other Than 100ml Glass Bottle.

Registration Board in 292nd meeting (held on 1st -2nd October, 2019) noted that the

panel inspection of M/s Yusaf Ali Shah Chemical Industries, Plot No.191, Street L-10 Gadoon

Amazai, Swabi was conducted on 20-12-2018 which transpired that the manufacturing facility

has capability of producing 100ml infusion in glass bottles/vials only. Therefore, Registration

Board decided to issue show cause notice for cancellation of registrations of Liquid Infusions

having volumes other than 100ml glass bottle.

In view of the above decision the firm has been issued show cause notice (dated

26-02-2020) with respect to their following products to comply with the decision of Registration

Board and submit a compliance report within 15 days. However, till to date no response has been

received.

Sr.No. Reg. No. Brand Name & Composition Pack Size

1. 016449 Steri-Sol Dextrose 5% + Sodium Chloride 0.9% Injection

Contains:-

Dextrose Monohydrate……………….5%

Sodium Chloride …………………….0.9%

500ml

1000ml

2. 016450 Steri-Sol Ringers Solution

Each 500ml contains:

Sodium Chloride …………………….4.3gm

Potassium Chloride …………….……0.15gm

Calcium Chloride ……………………0.24gm

500ml

3. 016451 Steri-Sol Dextrose 5% Injection

Contains:-

Dextrose Monohydrate ……………….5.5gm

500ml

1000ml

4. 016452 Steri-Sol Sodium Chloride 0.9% Injection


Sodium Chloride………………………0.9gm

1000ml

5. 016454 Steri-Sol Hartmanns Solution


Sodium Chloride…………..………....3gm

Potassium Chloride……………….…0.2gm

Calcium Chloride…………………...0.135gm

Sodium Lactate………………..…....2.65gm

500ml

6. 016455 Steri-Sol Dextrose 5% + Sodium Chloride 0.45% Injection

Each 100ml contains:-

Dextrose Monohydrate……………….5.5gm

Sodium Chloride………………….….0.45gm

500ml

7. 016456 Steri-Sol Darrows Solution

Each 100ml contains:-

Sodium Chloride……………..……..0.4gm

Potassium Chloride…………..……..0.26gm

Sodium Lactate……………….…….0.59gm

500ml

8. 016453 Steri-Sol Metronidazole 0.5% Injection


Metronidazole……………………....0.5gm

Sodium Chloride…………………....0.85gm

100ml

PVC Bag.

Decision: Registration Board advised to issue reminder to M/s Yusaf Ali Shah Chemical

Industries, Swabi in the subject case.


Import & Vet. I-II Section

Case No.01: Inspection Exemption of manufacturing facility on the basis of EudraGMDP

Registration Board in 275th meeting approved 21 reference regulatory authorities

(RRAs). Further, inspection abroad is exempted for both the product and facility of said RRAs.

The subject policy is already approved by the DRAP and policy Board. The RRAs inspection

exemption are as under:

Facility (dosage form manufacturing facility or whole production facility") approved by

regulatory authorities of US FDA, EU EMA, PMDA Japan, Australia TGA, Health

Canada, Switzerland or any of regulatory authority of former erstwhile Western Europe

(United Kingdom, Germany, France, Switzerland, Netherlands, Austria, Belgium,

Denmark, Finland, Sweden, Italy, Ireland, Luxemburg, Norway, Scotland and Spain) or

minimum three stringent regulatory bodies of former erstwhile Eastern Europe may be

exempted from inspection of manufacturing facility, irrespective of the fact that the

manufacturing unit is not located in these countries.

The product pre-qualified by the World Health Organization will also be exempted from

inspection of manufacturing units abroad.

A number of firms apply for inspection exemption of manufacturing facility abroad from EU EMA

as stated above on the basis of EudraGMP. The EudraGMDP database is the Community database

on manufacturing, import and wholesale-distribution authorisations, and good manufacturing-

practice (GMP) and good-distribution-practice (GDP) certificates.The EudraGMDP database is

maintained and operated by the EMA. Access to the general public is granted in order to enhance

availability of information related to the EMA mandate. The content of the database is provided

by the National Competent Authorities (NCA) of the European Economic Area (EEA).

EMA Agency role:

EMA coordinates inspections for human and veterinary medicines authorised under

the centralised procedure or in the context of a referral, on request from the Agency's Committee

for Medicinal Products for Human Use (CHMP) or Committee for Medicinal Products for

Veterinary Use (CVMP).

EMA does not conduct inspections itself but requests that the inspection be carried out by national

authorities in the EU Member States.

Inspections:

Authorities in the EU regularly inspect sites of companies within and outside the EU involved in

developing, manufacturing and distributing medicines intended for the EU market, to verify their

compliance with the relevant standards.

These inspections ensure the reliability and integrity of the data that support the authorisation of

medicines and their quality, safety and effectiveness once on the market.

An inspection may either be 'for cause', when it is triggered by a finding of possible non-

compliance with relevant standards, or 'routine', when inspections are carried out as part of

surveillance programme.

Inspections are conducted for authorised medicines and medicines that are currently being

evaluated for authorisation.

https://www.ema.europa.eu/en/glossary/centralised-procedure

https://www.ema.europa.eu/en/glossary/referral

https://www.ema.europa.eu/en/glossary/committee-medicinal-products-human-use

https://www.ema.europa.eu/en/glossary/committee-medicinal-products-human-use

https://www.ema.europa.eu/en/glossary/chmp

https://www.ema.europa.eu/en/glossary/committee-medicinal-products-veterinary-use

https://www.ema.europa.eu/en/glossary/committee-medicinal-products-veterinary-use

https://www.ema.europa.eu/en/glossary/cvmp


EudraGMDP database provides GMP status of reference and non-reference countries. Keeping in

view above the guidance is required from Registration Board for inspection exemption of

manufacturer abroad on EurdaGMP certificate base.

Decision: Registration Board considered decision of Policy Board regarding exemption

of inspection of manufacturer abroad wherein EU EMA has been granted

exemption from inspection. Accordingly, the Board deliberated that as

EudraGMDP database is maintained and operated by the EMA thus the

Board decided to exempt inspection of manufacturer if its GMP status is

available on EurdaGMP data base irrespective of the fact that the

manufacturing unit is not located in Reference Regulatory Authorities

/countries.

Case No.02: Request of M/s Glaxo Smith Kline Pakistan Limited, Karachi For Change of

local release site of Their Registed Product.

M/s Glaxo Smith Kline Pakistan Limited, Karachichange of manufacturing site of their following

already registered products approved in 292nd as per details given below: -

S.

No

Reg.

No.

Name & Composition

(as per approval)

Existing approved Site

Manufacturing Site

(as per approval)

New approved site / Manufacturer

/ MAH (as per COPP)

1. 027381 Seretide Evohaler 25/50mcg.

Each actuation contains:

Salmeterol Xinafoate 36.3ug

Fluticasone Propionate 50ug

M/s Glaxo

SmithKline Australia

Pty Limited,

Australia.

Manufacturer

Glaxo Wellcome Production Zone

Industrielle No.2, 23 rue Lavoisier

27000 Evreux-France.

Marketing Authorization Holder:

Laboratoire GlaxoSmithKline 23 rue

Francois Jacob 92500 Rueil-

Malmaison-France.





-do- -do-





-do- -do-

The firm has submitted the following supporting documents: -

a) Fee of Rs.300,000/- for above three products.

b) Application on Form-5A and Form-5F.

c) Copy of initial registration letter & Post Registration renewal trail.

d) Original & legalized COPP.

e) Site master file for new manufacturing site.

f) Undertakings that provided information are correct.

Decision of 292nd meeting of Registration Board:

Registration Board approved the above changes in respect of registered products Seretide Evohaler

25/50mcg (Reg.No. 027381), Seretide Evohaler 25/125mcg (Reg.No. 027382) and Seretide


Evohaler 25/250mcg (Reg.No. 027383) subject to policy for imported finished drug registration.

Other terms and conditions remain the same.

During processing of post registration variation letter it was observed that Drug Sales License of

applicant is not valid. Now, applicant submitted Rs.15,000/- fee and apply for change of applicant

site along with copy of old and new Drug Sales License.

Approved DSL name & address Applied DSL name & address

GlaxosmithKline Pakistan 35-Dockyyard

Road, west wharf Karachi

Valid till 18-Aug-2017

GlaxosmithKline Pakistan Limited F-268

S.I.T.E Karachi

Valid till 19-Feb-2022

Decision: Keeping in view the valid Drug Sale License, Registration Board approved the

change in address of importer of above products from GlaxosmithKline

Pakistan 35-Dockyyard Road, west wharf Karachi to GlaxosmithKline

Pakistan Limited F-268 S.I.T.E Karachi. Approval letter shall be issued after

storage facility verification of new site.


Post Registration-I Section

Case No.01: Registration of Drug(s) of M/s Swiss Pharmaceuticals (Pvt) Ltd, A/159,

S.I.T.E Super Highway, Karachi for Export Purpose Only.

Firm has applied for registration of drug(s) only for export purpose as per following details:

Requirements As Per SOP Submitted Documents

Application on Form-5/ Form 5-D with required fee as per

relevant SRO.

Form5D submitted

Copy of DML (Renewal status) along with approval of

relevant sections verified by licensing Division or

inspection report for renewal of DML before 2005.

Copy of DML provided

Approval of relevant section verified from DML

renewal inspection report dated 30.12.2014.

GMP Status. Copy of Inspection report/GMP certificate. GMP status verified from GMP inspection report

dated 18.10.2018

Undertakings that the applied product is exclusively for

export purpose and the proposed names/ label/ colour do

not resemble with already registered brands in importing

country.

Provided

Detail of the products is given below:

Sr.# Name of Drug(s) with composition Generic/RRA Status Diary No. date & Remarks.

I II III IV

1. Oragel adult 16+ Gel

Each 100gm contains:

Choline Salicylate …….8.7% w/w

Cetalkonium Chloride …..0.01% w/w

Lidocaine………………...0.2 %w/w

Me too status/ RRA

status not available

Purchase order from

Kenya

Dy. No1413/ 2020-PE&R-

(EFD) 06-04-2020.

Rs.50000/- dated 18-03-2020

Decision: Regitration Board deferred for further deliberation.

Case No. 02: Registration of Drug(s) of M/s Sigma Pharma International (Pvt) Ltd plot

No.E-50, NWIZ Port Qasim, Karachi for Export Purpose Only.




relevant SRO.

Form5D submitted


relevant sections verified by Licensing Division or



Approval of relevant section verified from CLB

letter No. F.6-6/14-Lic(M-237) dated 17-10-2014

GMP Status. Copy of Inspection report/GMP certificate. GMP status verified from GMP inspection dated

18.09.2018




country.

Provided


Detail of the product is given below:


I II III IV

1. Preminbay Capsule


Pregabalin….75mg

Methylcobalamine…500mcg

Me too status/ RRA status

not available

Purchase order from

cambodia

Dy.No.1383 /19-EFD (PE&R)

dated 09-02-2020

Rs.50000/- dated 02-03-2020

Decision: Registration Board approved above mentioned product of Sigma Pharma

International (Pvt) Ltd plot No.E-50, NWIZ Port Qasim, Karachi for export

registration. Since applied formulation is neither registered for local use nor

approved by any RRA (as adopted by Registration Board in 275th meeting)

hence manufacturer and importing country shall be responsible for safety,

efficacy and quality of drug product.

Case No. 03: Registration of Drug(s) of M/s English Pharmaceuticals Industries Link

Kattar Band Road, Thokar Niaz Baig, Multan Road, Lahore for Export

Purpose Only.




relevant SRO.

Form5D submitted





Approval of relevant section verified from CLB

letter No. F.1-11/92-Lic(Vol-III) dated 09-03-2015

GMP Status. Copy of Inspection report/GMP certificate. GMP status verified from GMP certificate based on

inspection dated 17th and 18th January 2019


export purpose and the proposed names/ label/ colour do not

resemble with already registered brands in importing

country.

Provided


Sr.# Name of Drug(s) with composition Generic/RRA

Status

Diary No. date & Remarks.

I II III IV

1. Essentiallite-H Injection

Each 5ml ampoule contains:

Phosphatidylcholine……….250mg

Benzyl Alcohol ……………45mg

Deoxycholic Acid…………126.5mg

Riboflavin(vitamin B2)……0.5mg

Sodium chloride……………12mg

Sodium Hydroxide………...13.40mg

Me too status/

RRA status

not available

Purchase

order for

Uzbekistan

Dy.No.1414 /19-EFD (PE&R) dated 07-04-2020

Rs.20,000/- dated 01-01-2020

Rs.30,000/- dated 11-02-2020

Clinical use: Use for acute and chronic hepatitis

, cirrhosis, necrosis of liver cells, fatty

degeneration of liver.

2. Essentiallite Forte Capsule

Each capsule contain;

Phosphatidylcholine…..300mg

VitaminB1(Thiamine Mononitrate)

…………………..6mg

Me too status/

RRA status

not available

Dy.No.1415 /19-EFD (PE&R) dated 07-04-2020

Rs.20,000/- dated 01-01-2020

Rs.30,000/- dated 11-02-2020

Clinical use: use to relieve symptoms of liver

damage


Vitamin B2(Riboflavin)…….….6mg

Vitamin B3(Nicotinamide)…….6mg

Vitamin B6 (pyridoxine HCl)….6mg

Vitamin B12 (cynocoblamine)…60mcg

Vitamin E (Tocopheral Acetate)...6mg

Purchase

order for

Uzbekistan

Decision: Registration Board approved above mentioned product of M/s English

Pharmaceuticals Industries Link Kattar Band Road, Thokar Niaz Baig,

Multan Road, Lahore for export registration. Since applied formulation is

neither registered for local use nor approved by any RRA (as adopted by

Registration Board in 275th meeting) hence manufacturer and importing

country shall be responsible for safety, efficacy and quality of drug product.

Case No. 04: Registration of Drug(s) of M/s Ophth Pharma (Pvt) Ltd. Plot No. 241, Sector

24, Korangi Industrial Area, Karachi for Export Purpose Only.




relevant SRO.

Form5D submitted





Approval of relevant section verified from Panel

inspection for renewal of DML dated 04-08-2016.

GMP Status. Copy of Inspection report/GMP certificate. GMP status verified from GMP Inspection dated 27-

09-2019




country.

Provided



I II III IV

1. Ophth Atropine 0.01% Eye Drops

Each ml contains:

Atropine Sulphate…0.1mg

Me too status/ RRA status

not available

Purchase order for

Afghanistan

Dy.No.1416 /19-EFD (PE&R)

dated 07-4-2020

Rs.20,000/- dated 20-11-2019

Rs.30,000/- dated 08-01-2020

Decision: Registration Board approved above mentioned product of M/s Ophth

Pharma (Pvt) Ltd. Plot No. 241, Sector 24, Korangi Industrial Area, Karachi

for export registration. Since applied formulation is neither registered for

local use nor approved by any RRA (as adopted by Registration Board in

275th meeting) hence manufacturer and importing country shall be

responsible for safety, efficacy and quality of drug product


Item No. III Division of Biological Evaluation & Research

Sr. No. Details of application No. of Cases

A Miscellaneous cases 01

Total 01

Sr. No. Assistant Director Designated No. No. of Cases

a. Mr. M. Zubair Masood AD-III 01

A: Miscellaneous Cases

Case No.01: Exemption from the Drugs Labelling & Packaging Rules, 1986 for Actemra

(Tocilizumab) 200mg Vial (Reg No. 083135) at the time of import applied by

M/s Roche Pakistan Limited, Karachi.

M/s Roche Pakistan Limited, Karachi applied for the exemption from the Drugs Labelling &

Packaging Rules, 1986 at the time of import for their already registered product Actemra 200mg

(Reg. No. 083135). The firm submitted that we all are informed that there is no targeted drug for

COVID-19 and it is only being treated symptomatically and supportively. The “Clinical

Management Guidelines for Covid-19 Infections” (issued by NHSRC, Govt. of Pakistan) has

mentioned one of their registered products, Actemra (tocilizumab), as an important drugs for

COVID-19 management, which has exponentially increased its demand and they have been

receiving the requests for the said drug from miscellaneous medical institutions and hospitals (pf

which some notable are SIUT, AKUH and DOW) for the urgent supply of it.

Since, the said product is imported from their principal F. Hoffmann-La Roche Ltd., Basel,

Switzerland and due to high demand of this product from all over the world, it will take us at least

six months to import the shipment on local (Pakistan make-up) label, which includes Urdu text,

local MRP and local registration number. The shipment will be received in parts.

The firm has submitted the following documents:

a. Fee challan of Rs. 5000/-

b. Copy of clinical management guidelines for COVID-19 infections issued by MNHSR&C

which indicates the following:

“These medications have considerable adverse effects, have limited available and unclear

efficacy. Consultation with an Infectious Disease Specialist is mandatory prior to

prescribing.”

c. Prints of emails from Agha Khan University and SIUT indicating demand of Actemra for

COVID-19.

d. Copies of invoices of Agha Khan Hospital, Indus Hospital and SIUT for Actemra.


In this context, it is submitted that the aforementioned product has already been registered

on 28-04-2017 as per following details:

Reg.No. Name of Manufacturer Brand Name & Composition Pack Size

083135 M/s Utsunomiya Plant of

Chugai Pharma Manufacturing

Co., Ltd., 16-3, Kiyohara

Kogyodanchi, Utsunomiya-

city, Tochigi, Japan

Actemra 200mg

(Concentrate for Solution for

Infusion)

Each vial(4ml) contains:

Tocilizumab (Genetical

Recombination)…….80 mg

1’s Vial

Prescribing information available on official website of FDA indicates following indications for

above product (https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/125276s114lbl.pdf):

i. Rheumatoid Arthritis (RA)

ii. Giant Cell Arteritis (GCA)

iii. Polyarticular Juvenile Idiopathic Arthritis (PJIA)

iv. Systemic Juvenile Idiopathic Arthritis (SJIA)

v. Cytokine Release Syndrome (CRS)

Moreover, the online available news show that Roche has announced that the US Food and Drug

Administration (FDA) has formally approved its phase 3 trial of Actemra in severely ill COVID-

19 patients, who have been hospitalised with pneumonia. The trial – named COVACTA – will

recruit around 330 patients around the world, with an expected start date sometime in early April.

The primary and secondary endpoints will include assessing clinical status, mortality, mechanical

ventilation and intensive care unit variables in the patient population. Despite a number of clinical

trials evaluating Actemra already ongoing across the world, Genentech has maintained that the

COVACTA study is pivotal because there are still no well-controlled studies and limited published

evidence on the safety or efficacy of the drug in COVID-19.

(https://www.pmlive.com/pharma_news/fda_approves_roches_actemra_covid-19_trial_1329887)

The firm has requested to grant them exemption from the Drugs Labelling & Packaging Rules,

1986 for Actemra (Tocilizumab) 200mg Vial (Reg No. 083135) at the time of import.

Decision: Registration Board deliberated the case in light of prevailing COVID-19

emergency situation and considered Clinical Management Guidelines for

COVID-19 Infections issued by M/o NHSR&C, requirements of Actemra

200mg by leading medical institutions of the country (AKUH, SIUT, Indus,

HMC, DOW etc) for management of their COVID-19 patients and Rule 3 of

Drugs (Labeling & Packing) Rules, 1986 and decided as under:

a. Acceded to request of the firm for import of registered Actemra 200mg, Reg.

No. 083135 in Standard Export Packs.

b. The firm shall make necessary arrangement for local printing of MRP and

Registration Number at least on secondary packing before sale of drug, at any

licensed premises having. Firm shall be responsible for providing requisite

cold chain facility during local printing process under supervision of relevant

experts of manufacturing and Quality Assurance. Complete batch processing

record shall be maintained for aforementioned process.

c. Actemra 200mg, Reg. No. 083135 shall be supplied only to medical institutions

for use under strict medical supervision of relevant experts / Registered

https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/125276s114lbl.pdf

https://www.pmlive.com/pharma_news/fda_approves_roches_actemra_covid-19_trial_1329887


Medical Practitioner and shall not be sold either to retail pharmacies or whole

sale market.

d. Complete import, sale / supply and printing record shall be maintained and

will be provided if required by DRAP.

e. This permission shall be valid for three (03) months only. During this period,

M/s Roche shall make efforts for future import of finished product as per

requirements of Drugs (Labeling & Packing) Rules, 1986.

Case No.02: Change in address of Importer and renewal of already registered drugs

applied by M/s Marush Pvt. Ltd., Lahore approved in 292nd meeting of

Registration Board.

Requests of M/s Marush Pvt. Ltd., Lahore for change in address of importer and grant of

renewal of registered drugs were considered in 292nd meeting of Registration Board wherein the

Board decided as follows:

“Registration Board granted the renewal of above products as per following details subject

to submit an undertaking on notarized stamp paper that the valid authorization of below

mentioned products in their name is true & correct, nothing has been concealed and that

if at any stage any discrepancy / misinformation is detected / observed the firm/ company

will be held responsible as per relevant laws:……..”

AND

“Keeping in view the valid Drug Sale License; Registration Board approved the change of

address of importer from M/s Marush Pvt. Ltd., Khoti No. 123-K First Floor, Model Town

Lahore to M/s Marush Pvt. Ltd., 117-A, Ahmad Block, New Garden Town Lahore for above

products subject to cold storage facility verification of their godown.”

During processing the cases for issuance of letters, the comments of QA&LT Division were

sought regarding the pending inquiries against the firm and following response was received:

“It is submitted that the Central Licensing Board in its 262nd meeting has granted the permission

for registration of 03 FIRs against following accused persons, 1. M/s Marush International Pvt.

Ltd., Karachi 2. Muzamil Husain Shah 3. Muhammad Usman Ali Shah to Area FID, Karachi.

That the FID Karachi vide letter No. SAA.F. 1-1/2019-FID-V(K) dated 03rd December,

2019 informed that he visited the office of FIA and met with the investigation offiocer Mr. Abdul

Jabbar Mendhro to seek the current status, the inspector verbally informed that the accused

persons have already been penalized for issuing forged/ fake documents and the same accused

persons cannot be penalized with similar allegations due to “double jeopardy”. As per letter of

area FID, no written communication has been made by inspector FIA, Karachi which is required

to be verified after seeking legal opinion in this regard.

Furthermore, the Central Licensing Board in its 263rd meeting has granted permi8ssionms

for registration of 03 FIRs against following accused persons, 1. Syed Muzamil Husain Shah 2.

Syed Usman Ali Shah 3. Muhammad Ziauddin 4. Ansar Mehmood to Area FID, Karachi.

That Assistant Director/ Ex-area FID, Lahore vide letter 9595/2019-DRAP(AD-PEC)

dated 12-07-2019 informed that FIR No. 158/2018 has been registered in FIA, Lahore against the


following accused persons, 1. Syed Muzamil Husain Shah 2. Syed Usman Ali Shah 3. Muhammad

Ziauddin.”

After the above comments from QA&LT Division, it was decided to take the opinion of Legal

Affairs Division whether the approval letters should be issued or not. In response, the legal Affairs

Division submitted the following:

“It is submitted that there are many inquiries pending against the firm as mentioned by QA&LT

Division. Furthermore, for the purpose of issue of summons/ warrants or process by the court or

Investigation agency, the already provided address will be used. Therefore, the Division is opined

that the concerned Division may not process the case for change in address of importer while the

division may process the case of renewal in accordance with the law.”

In this context, it is submitted that while processing the case for issuance of renewal

certificates on old DSL address it was observed that the old DSL is no more valid. Meanwhile, the

firm informed that the case no. 158/2018 registered by FID Lahore against M/s Marush Pvt. Ltd.

Lahore has been closed and same information has already been forwarded to Additional Director,

DRAP Lahore. The firm requested to issue them the pending registration letters along with renewal

certificates and approval of change in address of importer.

The case was then referred to QA&LT Division for the verification of above claim of the

firm and Director QA&LT advised that as the case of M/s Marush Pvt. Ltd., is long pending with

various aspects requiring clarifications. It would be appropriate if the whole case with all

comprehensive detail be put up before Registration Board for further disposal/ necessary action.

Decision: Deputy Director, Legal Affairs Division apprised the Board that as the address

of importer has already been changed on DSL therefore, approval letters may

be issued on new address and the concerned inquiry agencies may be informed

regarding said change. Keeping in view the said opinion, Registration Board

advised DBER to issue pending registrations and renewal certificates along

with approval of change in address of importer to the firm on new address as

already approved in previous Registration Board meetings. Registration

Board further advised to inform the concerned inquiry agencies regarding the

change in address of the firm for their future communications.


Item No. IV Division of Quality Assurance & Laboratory Testing

Case No. 01: DRAP REVIEWING DRUGS CONTAINING RANITIDINE

FOLLOWING FDA / EMA ALERTS ON DETECTION OF

PROBABLE CARCINOGENIC IMPURITY.

In a letter received on 16-09-2019 with subject “NOTIFICATION OF GLOBAL REVIEW

INTO RANITIDINE FORMULATIONS BY GLAXOSMITHKLINE (GSK) AND

ASSOCIATED”, Dr. Gohar Nayab Khan, Director (Regulatory Affairs) GSK Pakistan Limited,

35-Dockyard Road, West Wharf, Karachi-74000, Pakistan informed as under;

“On 29 August, 2019, we were notified by Swissmedic’s Official Medicines

Control Laboratory (Swissmedic OMCL) about the initiation of a review procedure

following the low-level detection of N-nitrosodimethyamine (NDMA) impurity in

one batch of Zantac injection solution 50mg product/5ml, batch 669A. The value of

NDMA found was in the 0.3ppm range relative to the active substance.

The product is manufactured and packaged at GSK’s site in Pharma, Italy,

using API produced by the supplier, Dr. Reddy’s Laboratories Ltd., India (DRL).

We have provided the information requested by Swiss medic and suspended

the distribution of Zantac injection solution 50mg product/5ml batches in

Switzerland as a precautionary action, based on their instructions and pending our

own investigations.

On 12 September 2019, GSK was also notified by Health Sciences

Authority (HSA), the Singapore regulatory authority, that it had tested all locally

available ranitidine products for the presence of nitrosomine compounds and

found most of the Zantac products contained NDMA. Consequently,

HSAinstructed GSK to suspend the whole supply of the above products and conduct

a Class 2 retail level recall of the Zantac products.

Based on the instructions received from the HSA and as a precautionary

action, GSK has made a decision to suspend the release and supply of all Zantac

products to the Singapore market and to implement the Class 2 retail level recall

of the Zantac products which will be initiated on 16 September, 2019.

GSK is continuing with investigations into the potential source of the

NDMA. These investigations include continued engagement with the API suppliers.

GSK have engaged with external laboratories to conduct tests on API and

finished product batches of Zantac IV. Test results are expected by the end of

September 2019. The testing is being extended to include batches of tablets and

potentially other dose forms if required.

Based on information received to date and correspondence with the

regulatory authorities, GSK has made the decision to suspend the release and

supply for all dose forms of Zantac products to all markets, including Pakistan,

as a precautionary action pending the outcome of the ongoing tests and

investigations.

GSK is committed to supplying high-quality products to patients and we are

actively working with the regulatory authorities to address their concerns.


In Pakistan, Zantac products (Tablets 150mg & 300mg & Injection 50mg/5mL)

are locally manufactured and not imported/supplied from overseas sites.”

03. Following are the international scenarios on the subject matter:

Source Brief contents

THE

HINDU-

BusinessLine

Some countries in the European Union are recalling ranitidine containing an

active ingredient made by India-based manufacturer, Saraca Laboratories Ltd,

said Germany’s Federal Institute for Drugs and Medical Devices in a statement

HBW insight Ranitidine Recalls Begin In Europe As Regulators Take Action:

“[…] Germany, Switzerland and Austria are the first European countries to

initiate recalls of ranitidine-based drugs after tests showed that certain products

contained N-nitrosodimethylamine, a probable human carcinogen.[…]

THE

HINDU-

BusinessLine

Europe, Canada start recall of Zantac drug versions after carcinogen scare:

FDA –

MedWatch

Safety alert

The FDA safety information and Adverse Event Reporting Program alert on

Zantac (Ranitidine) Safety information – NDMA Found in Samples of Some

Ranitidine Medicines.

EMA communication vide no. EMA/503622/2019 dated 13.09.2019 bearing title

“EMA to review ranitidine medicines following detection of NDMA”

In response to the mentioned scenario, a nationwide recall alert was issued vide letter F. No. 13-

1733/2019-QC dated 23-09-2019 with the approval of Chief Executive Officer, DRAP. In greater

public interest and in order to protect patients from probable risk associated with detection of low

levels of NDMA in Ranitidine containing products as per alert of FDA & EMA, the manufacturers

of Ranitidine containing products were advised that following regulatory actions shall be initiated

on immediate basis;

i. Suspension of production for all dosage forms of ranitidine containing drugs till further

orders;

ii. Stoppage of release/distribution of all dosage forms of ranitidine containing drugs till

further orders; and

iii. Stoppage of sale/supply/utilization of all dosage forms of ranitidine containing drugs till

further orders.

That Mr. Nawaz Ahmed, Secretary General/Executive Director of PPMA vide letter No.

PPMA/CEO/DRAP/2019/110 dated 26th September 2019 regarding the matter of Ranitidine

HCL and the Detection of NDMA-A Carcinogenic Impurity addressed the CEO, DRAP Islamabad

wherein informed & reproduced as under:-

“With reference to the subject cited above news circulated by the US Media

the initiation of the probe by the USFDA on Ranitidine HCL containing medication

and the subsequent Letter No.12208/2019-DRAP (L-VII), dated September 2019

from the office of Ms. Aisha Irfan FID DRAP Lahore titled recalled alert under the

direction of the Directorate of Quality Assurance and Lab Testing letter No.01-

20/2019-FID-I (K) dated 23rd September 2019 from the office of Dr. Najam Us-

Saquib FID DRAP Karachi Letter Dy.No.40/2019-FID-III dated 23rd September

2019 from the office of Hasan Afzal FID III DRAP Islamabad and letter No.F.13-

173/2019-QC from the office of Arslan Tariq AD QC- I DRAP Islamabad kindly

note that we would like to bring to your knowledge that PPMA has discussed the

matter amongst its member firms and after studying the global information


available and a through concrete discussion the PPMA members have unanimously

arrived to the conclusion that it is too early for the Drug Regulatory of Pakistan

(DRAP) to issue a Recall Alert.

2. Before stating our point of view we would like to inform your office that

Ranitidine HCL containing medication is commonly used in treatment of peptic

ulcer disease gastroesophageal reflux disease, and Zollinger-Ellison syndrome.

Ranitidine HCL is part of not only the NEML 2018 issued by DRAP but is also

included in the WHO Model List of Essential Medicine 2019.

3. The Ground for the conclusion stated in Para 1 lies in the facts that though

the USFDA has initiated a probe on the Ranitidine HCL containing medication it

has not directed the Manufactures for a recall and neither have the health officials

of the USFDA directed the patients to stop medication. The only Recall reported

was voluntary Recall.

It may also be noted that the UAE Ministry of Health & Prevention via Circular

No. (2) 2019 dated 23rd September 2019 has clearly mentioned that the said

Circular is not a Recall Circular and the Existing Stocks of Ranitidine products

currently available in the Pharmacies or at Retails stores may continue to be sold.

4. Furthermore, it may also be mentioned that NDMA is found in portable water

meat and certain foods consumed by us in minute quantities.

For the same it is concluded that consuming large quantities of Ranitidine HCL

containing medication may lead to the higher risks of Carcinogenic effect not at

the prescribed doses and dosages.

5. The summary of the Toxicology assessment ICH M7 aligned limits of NDMA in

Drug products, is mentioned below in Tabular Form.

According to the below information 1 out of 100,000 theoretical risk of cancer is

present if 0.0959mcg/day or 95.9ng/day NDMA is consumed for a period of 70

years. This is a worst case scenario.

The class of medication that Ranitidine HCL belongs to is not prescribed as part of

a long duration of therapy.

Number of

doses

1 7 31 84 365 2190 3285 3650 7300 25550

Duration 1 day 7 days 1

Month

12

week

1

year

6

years

9

years

10

years

20

years

70

years

NDMA

Daily intake

mcg/day

2450.24 350.035 79.04 29.17 6.713 1.12 0.746 0.671 0.336 0.0959

Table 1 :- ICH M7 aligned less that lifetime limits of NDMA for drug products

associated with a theoretical 1 in 100,000 excess lifetime risk of cancer.

6. For the same we request that the Drug Regulatory Authority of Pakistan

(DRAP) taking a decision on technical grounds and in light of the actions taken by

the USFDA and other Global Regulatory Authorities may take the following steps.

i. Withdraw the Recall Alert.

ii. Directions may be given to the manufacturers of Ranitidine HCL containing

medication to immediately initiate the testing of the Ranitidine HCL API

irrespective of the source of the API and also initiate the testing of all the


batches of the Finished product marketed which are within the labeled shelf

life of the product and currently manufactured and planned for marketing

and confirm that the results are within the USFDA stated acceptable limits

of 0.0959mcg/day or 95.9ng/day of NDMA.

The batches with values within the acceptable limit may be un seized and

permitted to be distributed sold freely and the batches that are out of

specifications may not only be reported of Drug Regulatory Authority of Pakistan

DRAP but the batches may also be voluntarily recalled.”

That in their update issued on 04-12-2019, Food and Drug Administration, USA (US FDA)

stated as under; (https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-and-press-

announcements-ndma-zantac-ranitidine)

“Update [12/4/2019] Over the past several weeks, FDA has communicated about

the detection of an impurity known as N-nitrosodimethylamine (NDMA) in common

heartburn medications (ranitidine, commonly known as Zantac, and nizatidine)

available over the counter or by prescription. We have launched an investigation

to understand the cause of this impurity in these drugs and to provide information

for patients and consumers who take them. As part of this investigation, we have

asked manufacturers to conduct their own laboratory testing to examine levels of

NDMA in ranitidine and nizatidine and to send us samples to be tested by our

scientists.

Today, we are announcing that we have asked manufacturers of ranitidine and

nizatidine products to expand their testing for NDMA to include all lots of the

medication before making them available to consumers. If testing shows NDMA

above the acceptable daily intake limit (96 nanograms per day or 0.32 parts per

million for ranitidine), the manufacturer must inform the agency and should not

release the lot for consumer use [………].

Proceeding and Decision of the 293rd meeting of Registration Board.

The board deliberated about the identification of NDMA a carcinogenic impurity in Ranitidine

containing products which poses threat to the consumers if found above the prescribed limits.

Keeping in view risk the Board decided as under:

i. That every manufacturer holding registration of ranitidine containing products are

under obligation of law to provide testing facilities of this impurity for every

consignment (API and finished) imported and brought into Pakistan. The consignments

(API and finished) should be accompanied with the certificates of analysis by the

manufacturers. Meanwhile the manufacturers/importers may temporarily avail testing

facilities of the any public sector institutions till the establishment of their own facility

for testing of ranitidine API and finished Pharmaceutical Products. However sampling

will be done by the area AD, DRAP and meanwhile the consignment (API and

finished) will be released with the restriction that it could only be used if it has qualified

requisite tests from the public institutions/testing laboratories and the certificate has

been endorsed by the DRAP.

ii. The Board further decided to allow resumption of production of ranitidine containing

products, with direction that manufacturers/registration holders of ranitidine

https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-and-press-announcements-ndma-zantac-ranitidine



containing products shall expand their testing for NDMA to include all lots of the

medication before making them available to consumers.

iii. If testing shows NDMA above the acceptable daily intake limit (96 nanograms per day

or 0.32 parts per million for ranitidine) both for API and finished products, the

manufacturer must inform the DRAP and should not release the lot of ranitidine API

for production and finished Pharmaceutical Products for consumer use. Board

constituted following panel for destruction of such batches of ranitidine containing

products:

i. The Additional Director.

ii. Area Federal Inspector of Drugs.

iii. Assistant Director I&E.

Any two of the above with the permission of Additional Director.

iii. The above mentioned panel will make coordination with the respective

manufacturer for the destruction of stocks and will prepare destruction

certificates for the consideration of the Drug Registration board. It shall be

ensured that destruction /incineration is conducted in the presence of panels

and incineration certificates from the environment protection agency are also

accompanied with the panel report.

iv. Board further directed to bring details of seized and/or order not to dispose of stocks

of ranitidine API as well as finished products by FIDs through Pakistan to decide its

fate.

Meanwhile, USFDA issued a press release dated 1st April, 2020 and requests removal of all

ranitidine products (Zantac) from the market, the contents are reproduced as under:

“FDA Requests Removal of All Ranitidine Products (Zantac) from the Market

FDA Advises Consumers, Patients and Health Care Professionals After New

FDA Studies Show Risk to Public Health

The U.S. Food and Drug Administration today announced it is requesting

manufacturers withdraw all prescription and over-the-counter (OTC) ranitidine

drugs from the market immediately. This is the latest step in an

ongoing investigation of a contaminant known as N-Nitrosodimethylamine

(NDMA) in ranitidine medications (commonly known by the brand name Zantac).

The agency has determined that the impurity in some ranitidine products increases

over time and when stored at higher than room temperatures and may result in

consumer exposure to unacceptable levels of this impurity. As a result of this

immediate market withdrawal request, ranitidine products will not be available

for new or existing prescriptions or OTC use in the U.S.

“The FDA is committed to ensuring that the medicines Americans take are safe

and effective. We make every effort to investigate potential health risks and

provide our recommendations to the public based on the best available science.

We didn’t observe unacceptable levels of NDMA in many of the samples that we

tested. However, since we don’t know how or for how long the product might

have been stored, we decided that it should not be available to consumers and

patients unless its quality can be assured,” said Janet Woodcock, M.D., director

of the FDA’s Center for Drug Evaluation and Research. “The FDA will



continue our efforts to ensure impurities in other drugs do not exceed acceptable

limits so that patients can continue taking medicines without concern.”

NDMA is a probable human carcinogen (a substance that could cause cancer). In

the summer of 2019, the FDA became aware of independent laboratory testing

that found NDMA in ranitidine. Low levels of NDMA are commonly ingested in

the diet, for example NDMA is present in foods and in water. These low levels

would not be expected to lead to an increase in the risk of cancer. However,

sustained higher levels of exposure may increase the risk of cancer in humans. The

FDA conducted thorough laboratory tests and found NDMA in ranitidine at low

levels. At the time, the agency did not have enough scientific evidence to

recommend whether individuals should continue or stop taking ranitidine

medicines, and continued its investigation and warned the public in September

2019 of the potential risks and to consider alternative OTC and prescription

treatments.

New FDA testing and evaluation prompted by information from third-party

laboratories confirmed that NDMA levels increase in ranitidine even under

normal storage conditions, and NDMA has been found to increase significantly in

samples stored at higher temperatures, including temperatures the product may

be exposed to during distribution and handling by consumers. The testing also

showed that the older a ranitidine product is, or the longer the length of time since

it was manufactured, the greater the level of NDMA. These conditions may raise

the level of NDMA in the ranitidine product above the acceptable daily intake

limit.

With today’s announcement, the FDA is sending letters to all manufacturers of

ranitidine requesting they withdraw their products from the market. The FDA is

also advising consumers taking OTC ranitidine to stop taking any tablets or liquid

they currently have, dispose of them properly and not buy more; for those who

wish to continue treating their condition, they should consider using other

approved OTC products. Patients taking prescription ranitidine should speak with

their health care professional about other treatment options before stopping the

medicine, as there are multiple drugs approved for the same or similar uses as

ranitidine that do not carry the same risks from NDMA. To date, the FDA’s testing

has not found NDMA in famotidine (Pepcid), cimetidine (Tagamet), esomeprazole

(Nexium), lansoprazole (Prevacid) or omeprazole (Prilosec).

In light of the current COVID-19 pandemic, the FDA recommends patients and

consumers not take their medicines to a drug take-back location but follow the

specific disposal instructions in the medication guide or package insert or follow

the agency’s recommended steps, which include ways to safely dispose of these

medications at home.

https://www.fda.gov/news-events/press-announcements/statement-new-testing-results-including-low-levels-impurities-ranitidine-drugs

https://www.fda.gov/news-events/press-announcements/statement-new-testing-results-including-low-levels-impurities-ranitidine-drugs

https://www.fda.gov/drugs/drug-safety-and-availability/medication-guides

https://www.fda.gov/drugs/safe-disposal-medicines/disposal-unused-medicines-what-you-should-know


The FDA continues its ongoing review, surveillance, compliance and

pharmaceutical quality efforts across every product area, and will continue to

work with drug manufacturers to ensure safe, effective and high-quality drugs for

the American public.

The FDA encourages health care professionals and patients to report adverse

reactions or quality problems with any human drugs to the agency’s MedWatch

Adverse Event Reporting program:

Complete and submit the report online

at www.fda.gov/medwatch/report.htm; or

Download and complete the form, then submit it via fax at 1-800-FDA-

0178.

The FDA, an agency within the U.S. Department of Health and Human Services,

protects the public health by assuring the safety, effectiveness, and security of

human and veterinary drugs, vaccines and other biological products for human

use, and medical devices. The agency also is responsible for the safety and security

of our nation’s food supply, cosmetics, dietary supplements, products that give off

electronic radiation, and for regulating tobacco products.”

Proceeding and decision of 294th meeting:

The Board deliberated the matter considering the facts of the case and decided as under:

i. Registrations of all Ranitidine containing products shall remain suspended.

Meanwhile status of ranitidine containing products will be reviewed in Reference

Regulatory Authorities and a comprehensive case shall be submitted before

Registration Board for its consideration. However during suspension period, the

manufacturers/importers shall submit the prescribed product renewal fee as and

when applicable to them.

ii. Manufacturer/importer of ranitidine containing product(s) shall

withdraw/remove all stocks from the market immediately.

iii. Cases pertaining to any seizures / not to dispose of / withheld shall be placed

before Registration Board if required.

Case No.02: REQUEST OF M/s NOVARTIS PHARMA (PAKISTAN) LTD, FOR

EXEMPTION OF NDMA TESTING IN VALSARTAN DUE TO

UNAVAILABILITY OF THE PRODUCTS IN THE MARKET.

The firm has requested that it has received the following consignments of valsartan. The firm

informed that the assistant director I & E has restricted the utilization till testing from the lab as

per decision of 291st meeting of DRB. The firm added that in the current scenario there is a chance

that the local testing may not be possible or delayed, which will delay the access of medicine to

the patients. Firm has provided CoA confirming testing of NDMA and NDEA in valsartan APIs

with assurance that valsartan of same batches has been used in manufacturing of following finished

products. The firm has requested to issue directions to lift the utilization restriction of the following

batches of Valsartan containing products;

Sr.

No.

MAT.

Code

Description of Item Batch

No. QTY(PC) SAP PO. Invoice No.

Received at

warehouse on

https://www.fda.gov/about-fda/forms/medwatch-fda-safety-information-and-adverse-event-reporting-program-mandatory-html




1.

709626 Exforge FCT

160/10mg Alu 2x14

PK

BPA63 10,000 4701504472

200153273 18-03-2020

2. 709648 Exforge FCT 80/5mg

Alu 2x14 PK BPD05 26,000 4701504474

3. 708615 Co-Diovan 80/12.5mg

FCT 2x14 PK TCY62 15,208 4701504470

2001529227

4.

725698 Co-Diovan FCT

160/12.5mg Alu

(2x14) PK

TAJ39 959

4701504482


160/12.5mg Alu

(2x14) PK

TAX31 987


160/12.5mg Alu

(2x14) PK

TCJ88 568


160/12.5mg Alu

(2x14) PK

TCX86 35,170

5. 709637 Exforge FCT 160/5mg

Alu 2x14 PK BNY90 11,918 4701504473

2001529218 18-03-2020

6.

717700 Exforge HCT FCT

160/25/10 mg Alu 2x7

PK

BPA14 14,000 4701504476

7. 725693 Diovan FCT 80mg Alu

(2x14) PK BPC18 34,000 4701504480

8. 725695 Diovan FCT 160mg

Alu (2x14) PK BPC89 40,000 4701504481

9. 709626 Co-Diovan 160/25mg

ALU 2x14 PK TDE03 8984 4701504483 2001531245 19-03-2020

M/s Novartis Phrma Karachi further requested to exempt requirement of local testing if APIs and

finished goods imported from SRA approved sites and CoAs stating clearly levels of impurities

NDMA within limits.

Background of the case:-

Valsartan is an orally active antihypertensive drug developed in the 1990s and is a selective

angiotensin II receptor blocker (ARB)

1. It relaxes the blood vessels and thus reduces blood pressure; it is also used for treating patients

with congestive heart failure and post myocardial infarction.

2. There are eight other ARBs that patients may be switched to if they discontinue their valsartan therapy

(1.Valsartan, 2.Telmisartan, 3. Losartan 4.Irbesartan 5.Irbesartan, 6.Azilsartan, 7.Olmesartan and

8.Olmesartan).

N-nitrosodimethylamine (NDMA) AS SAFETY ISSUE IN VALSERTAN

1. On 5 July 2018 the European Medicines Agency (EMA) reviewed medicines containing

valsartan following detection of an impurity, N-nitrosodimethylamine (NDMA), a probable

human carcinogen, in medicines from Zhejiang Huahai Pharmaceutical Co Ltd, Linhai, China.

Since the batches manufactured from this valsartan-active substance have been administered to

https://en.wikipedia.org/wiki/Valsartan

https://en.wikipedia.org/wiki/Telmisartan

https://en.wikipedia.org/wiki/Losartan

https://en.wikipedia.org/wiki/Irbesartan

https://en.wikipedia.org/wiki/Azilsartan

https://en.wikipedia.org/wiki/Olmesartan


many patients, the EMA’s review focused on investigating the levels of NDMA in the products

and the potential impact on patients who have been taking them. The agency further issued

advisory notices on their website for patients not to stop taking their medicine.

2. The US Environmental Protection Agency found an association between NDMA and liver

toxicity, which could lead to liver cancer: NDMA exposure may be associated with bladder,

renal, pancreatic, intestinal, colon, and stomach cancers.

3. Immediately following the EMA’s review, 24 countries recalled approximately 2300 batches

of valsartan products (Germany, Norway, Finland, Sweden, Hungary, The Netherlands, Austria,

Ireland, Bulgaria, Italy, Spain, Portugal, Belgium, France, Poland, Croatia, Lithuania, Greece,

Canada, Bosnia and Herzegovina, Bahrain, and Malta.

4. Hong Kong recalled 5 products of 2 companies and Canada recalled drug products of 5

companies.

5. The Drug Regulatory Authority of Pakistan on 12 July recalled valsartan-containing drugs

of nine manufacturers becoming the first developing country to announce separately the recall as

a precautionary measure to protect patient health.

6. The US Food and Drug Administration (FDA) on 13 July announced the voluntary recall of

five valsartan-containing products.

ACTION TAKEN BY DRAP:

The Drug Regulatory Authority of Pakistan on 12 July recalled valsartan-containing

drugs of nine manufacturers becoming the first developing country to announce separately the

recall as a precautionary measure to protect patient health. Accordingly the case was placed before

291st meeting of DRB held on 02-04 September 2019. Wherein, the board decided as under;

“Decision of the 291st meeting of Registration Board. Registration Board deliberated about

the identification of NDMA & EDMA as impurities which are carcinogenic and limits has been

prescribed by US FDA and EMA. Above the limits API as well as products poses threat to the

consumers. Keeping in view risk the Board decided as under:

i. Product registration holders shall ensure that the API as well as products containing

valsartan are within the prescribed limits impurities i.e. NDMA & EDMA. Every manufacturer

holding registration of valsartan containing products are under obligation of law to provide testing

facilities of these impurities for every consignment imported and brought into Pakistan. The

consignments should be accompanied with the certificates of analysis by the API manufacturers.

Meanwhile the manufacturers/importers may temporarily avail testing facilities of the any public

sector institutions till the establishment of their own facility. However, sampling will be done by

the area AD, DRAP and meanwhile the consignment will be released with the restriction that it

could only be used if it has qualified requisite tests from the public institutions/testing laboratories

and the certificate has been endorsed by the DRAP.

ii. Board constituted standard panels comprising of following for destruction of seized

stocks of valsartan API as well as finished products containing NDMA manufactured from the raw

material of M/s Zheijhiang Huahai pharmaceuticals, China/any other manufacturer contaminated

batches as the API has been withdrawn and banned internationally. a) Area Additional Director.

b) Area Federal Inspector of Drugs. c) Assistant Director I&E. Any two of the above with the

permission of Additional Director.

iii. The above mentioned panels will make coordination with the respective manufacturer

for the destruction of stocks and will prepare destruction certificates for the consideration of the


Registration Board. It shall be ensured that destruction /incineration is conducted in the presence

of panels and incineration certificates from the environment protection agency is also accompanied

with the panel report”

Due to the safety issue NDMA and NDEA testing in valsartan is internationally made

mandatory because of its carcinogenic activity has been established. DRAP in its 291st meeting

of DRB held on 02-04 September 2019 made the NDMA and EDMA test compulsory for every

consignment of valsartan before utilization. The request of the firm for exemption of local N-

nitrosodimethylamine (NDMA) testing of valsartan is placed before the board in view of the

decision taken in 291st meeting of Registration Board.

Proceeding of 294th Meeting:

The Board deliberated on the matter in detail. At the time when Registration Board decided to

make NDMA and NDEA testing compulsory for every consignment of valsartan before utilization,

there was no arrangement of worldwide testing of said impurities before in their country of origin.

The Board further deliberated that as M/s Novartis Pharma Pakistan has provided CoA of API

confirming testing of NDMA and NDEA and results are within acceptable limits. The Board also

considered M/s Novartis statement apprehending delay of the access of medicine to the patients

due to current scenario due to non or delayed local testing.

Representative of PPMA also informed that after emergence of NDMA and NDEA impurities

issues, now other API manufacturers have also started testing NDMA and NDEA in APIs.

Decision: After thorough deliberations and discussion by the Board and considering

documents submitted by M/s Novartis Pharma Pakistan, the Board decided as

under;

i. The imported finished products of above products containing Valsartan of

M/s Novartis (Pakistan) Limited shall be allowed for utilization.

ii. A comprehensive proposal will be presented in forthcoming meeting

regarding future strategy for testing of NDMA and NDEA in valsartan

containing products and API.

The meeting ended with vote of thanks to and from the Chair.