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DRUG REGULATORY FRAMEWORKPresentation By

&NEW INITIATIVES

y

Debasish PandaJoint Secretary Ministry of Health & Family WelfareGovernment of India

INDIA

Snapshot - Indian Pharma Industry

Indian Pharmaceutical Market ~US $ 18bnImport (2008-09 )US$ 2.7 BnExport (2008-09 ) US$ 7BnExport (2008 09 ) US$ 7Bn

8% global Production & 2% of World phama Market

Bulk Drug Production > 400 API’sExport of Biotech products ~US $763M

Biopharmaceuticals ~ US $ 600 M

Manufacturing Facilities 119 US FDA ApprovedLargest Number of Manufacturing Facilities outside USg g

153 EDQM approved facilities (49 sites with CEP Approvals)Abbreviated New Drug approval Filing - 2nd to USA

DMF submissions in US (1998-2007) ~ 10% (32 out of 316)

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Final ANDA Approvals Granted in US (2008) - Countrywise

Country NumbersUSA 169India 132Israel 40Germany 25Canada 24Switzerland 19Iceland 14Iceland 14Jordan 11Other 25

Source: Thomson Scientific

Indian Vaccine & Biopharma Industry

Vaccine & BiopharmaVaccine & Biopharma400 organized pharma sector200 companies in biotech SectorGrowth rate is 37% in 2006-07Total production of biopharmaceuticals is >US $ 1Bn

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Indian Pharmaceutical Industry: EXPORTSIndian Pharmaceutical Industry: EXPORTS

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7

81980-811990-912000-012001-02 5.818

6.011

7.30

2

3

4

5

2002-032003-042004-052006-072007-082008-09

2.05

2.813.42

4.121

USD

Bill

ion

2.850

0

1

1980-81 1990-91 2000-01 2001-02 2002-03 2003-04 2004-05 2006-07 2007-08 2008-09

0.1840.009

Trade with Africa Countries

USD Bn % GrowthTotal Pharma Export 5.66 12.78Af i C t i 0 87 17 81African Countries 0.87 17.81

Share of Exports toAfrican Countries 13.53%

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TOP 5 countries Sorted by Share of Market Region Wise

Southern Africa North AfricaSouth Africa 62.08% Sudan 34.23%Zambia 12.02% Egypt 30.41%Angola 10.12% Algeria 23.69%Mozambique 4.80% Morocco 6.58%Namibia 3.72% Libya 3.33%

East Africa West AfricaKenya 36.71% Nigeria 53.37%Tanzania 19.54% Ghana 16.36%Uganda 18.58% Guinea 8.50%Ethopia 14.26% Benin 4.01%Mauritius 6.18% Senegal 3.01%

Central AfricaChad 4.18% Gabon 3.75%Cameroon 33.31% Congo Rep 0.68%

Equtl Guinea 0.28

Vaccines – Exported to 151 Countries

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• Bharat Biotech International Limited       ‐ Hepatitis B (recombinant) (Revac‐B+)

• Haffkine Bio Pharmaceutical Corp. Ltd.   ‐ OPV (from bulk supplied by Biofarma, Indonesia)

• Novatris Vaccines and Diagnostics S.r.l   ‐ Rabies India, (Formerly Chiron Behring)

WHO‐PREQUALIFIED INDIAN VACCINE MANUFACTURERS(As of June, 2009)

• Panacea Biotech ‐ DTwP  Biofarma ‐ Hib Novatris (1dose) (EASYFOUR) DTwP  Biofarma ‐ Hepatitis B  P.H.B. ( 1dose) (ECOVAC)DTwP  Biofarma‐Hep B P.H.B. ‐ Hib P.H.B. (1dose) (EASYFIVE)Hepatitis B ( Enivac B)OPV ( from bulk supplied by Biofarma, Indonesia)OPV (from bulk supplied from Chiron, Italy)

• Serum Institute of India Ltd. ‐ BCG, DT, dT, DTwP , DTwP‐Hep B, Hep B(recombinant) , Hib, TT, MR, MMR , Measles, Rubella 

• Shantha Biotechnics Private Ltd.  ‐ Hepatitis B (recombinant), DTwP‐Hep B (Shantetra),  TT (Shan TT),  DTwP‐Hepatitis B‐Hib ( Shan5) (1dose and 10 doses) 

• Zydus Cadila ‐ Rabies

India – Well defined Drug Regulatory System

Govt. of IndiaMinistry of Health & Family welfare

DGHS

Ministry of Chemicals & fertlizers

Department of

Ministry of Commerce

Patent Office

Ministry of science & Technology

ICMRDGHS

CDSCO

DCGI DTABEnforcement &

GMP audit DivQuality Control

Division CDTL

Department of Pharmaceuticals

NPPA

Controller General of patents

ICMR

DBT

CSIR Labs

Division-CDTLRegistration DivNew Drugs Div.PharmacovigilanceTrainings

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Drugs regulatory system in IndiaDrugs is in concurrent list

of Indian ConstitutionIt is governed by both

Centre and StateCentre and State Governments

Legal Enactments to Regulate Import, Manufacture & Sale of Drugs

Drugs and Cosmetics A t 1940Act, 1940

Drugs and

Drugs and Magic Remedies (Objectionable Advertisements) Act, 1954

Drugs and Cosmetics

Rules, 1945 made under

the Act

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CDSCO North Zone (Ghaziabad)

CDSCO, HQ

CDSCO – Geographical Location of 6 Zonal Offices

Mumbai

New Delhi

Kolkata.

CDSCO West Zone (Mumbai)

CDSCO South Zone (Chennai)

CDSCO East Zone (Kolkata)

* H d b d

Ahmedabad *

New Zonal Offices –Ahmedabad & HyderabadSub Zonal Office : 2

Chennai

•* HyderabadSub- Zonal Office : 2Port Offices/Airports : 7Laboratories : 6

29 States

6 Union Territories

Functions of CDSCO

Functions of CDSCO

Approval of new drugs and clinical trials

Import Registration and Licensing

Licensing of Blood Banks, LVPs, Vaccines, r-DNAproducts & some Medical Devices

Amendment to D &C Act and Rules

Banning of drugs and cosmetics

Grant of Test License, Personal License, NOCs for Export

Testing of Drugs

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Functions of State Licensing Authorities

Functions of State Licensing Authorities

Licensing of Manufacturing Site for Drugs including API and Finished Formulation

Licensing of Establishment for sale or distribution of Drugs

Approval of Drug Testing Laboratories

Monitoring of Quality of Drugs and Cosmetics marketed in the country

Investigation and prosecution in respect of contravention ofInvestigation and prosecution in respect of contravention of legal provision

Recall of sub-standard drugs

CDSCO -Number of Applications received/processedFrom Year 2005-09

20000

25000

5000

10000

15000

20000

Series 1Series 2

No.

of A

pplic

atio

ns

10160

13370

16945

1294511061

Expected applications by Year 2009 end

0

5000

2005 2006 2007 2008 2009

N

Jan-June

Year(Jan-Dec)

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S.No Subject Year

2005*

(Jan-Dec)

Year 2006*

(Jan-Dec)

Year 2007*

(Jan-Dec)

Year 2008*

(Jan-Dec)

Year 2009

(Jan-June)

1 New Drug Applications 1200 1500 1600 1750 920

2 Global Clinical Trials 100 170 300 350 130

Status of various categories of applications received/processedFrom Jan 2005 to 30th June 2009 

3 Vaccines and Biotech 10 50 40 45 58

4 Medical Devices 0 300 450 400 301

5 Diagnostic Kits

including Test License

250 350 400 850 340

6 Export NOCs 2000 2100 1800 2350 1672

7 Test License 3700 5000 5500 7200 4047

8 Blood Bank License 200 225 280 275 330

9 Import Registration 300 450 400 475 258

10 Import License / Dual

use

2300 2400 2000 1950 1935

11 BE NOC for exports 100 400 600 1300 1070

Total 10160 12945 13370 16945 11061*Approximate figures

**This does not include other applications like NOC for manufacturing of trial batches of drug, correspondence withvarious ministries/deptt. ,sate drug controller authorization ,parliament matters & other misc. letters

Timelines for ApprovalsS.NO. APPLICATION FOR TIME IN WORKING

DAYS

A. EXPORT RELATED CLEARANCES

1. EXPORT NOC 10

2. BE NOC FOR EXPORTS 28OC O O S 8

B. OTHER CLEARANCES

3. DUAL USE, RULE 37 & NEUTRAL CODE 20

4. ADDITIONAL INDICATION ETC.(1ST RESPONSE) 45

5. FORM 10 30

6. TEST LICENCE 30

7. A. NEW DRUGS & CLINICAL TRIALS APPLICATIONSFOR OTHER THEN BIOLOGICALS (1ST RESPONSE) 45

B. NEW DRUGS (MARKETING AUTHORIZATION) APPLICATION FOR BIOLOGICALS (1ST RESPONSE) 90

C. CLINICAL TRIAL APPLICATION FOR BIOLOGICALS AS PER GUIDANCE DOCUMENT TO INDUSTRY (1ST RESPONSE) 45

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S.NO. APPLICATION FOR TIME IN WORKING DAYS

8. FDC (1ST RESPONSE) 45

Timelines for Approvals Condt.

9. ENDORSEMENT OF ADDITIONAL PRODUCTS ON REGISTRATION FOR MEDICAL DEVICES

60

10. ENDORSEMENT OF ADDITIONAL PRODUCTS ON REGISTRATION FOR OTHER THAN MEDICAL DEVICES

90

11 REGISTRATION 120*

12. REGISTRATION (1ST RESPONSE) 45

*Subject to all clearances including testing by CDTL/CDL as applicable.*Subject to all clearances including testing by CDTL/CDL as applicable.

Countries Timeline (Days)

China 300

Brazil 120-140

India 60-80

Comparison Of Regulatory Timeline Approvals - Clinical Trials

Czech 80-100

Poland 100-120

Australia/ NZ 70-90

South Africa 70-80

Russia 70-90

Taiwan 80-90

Korea 60-80

Honkong 50-75

Singapore 20-40

USA 20-40

Ernst & Young

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Myth – Reality About Spurious drugs in India

The figures quoted by media range from 10% to 25% of drugs in country being spurious / counterfeit drugsspurious / counterfeit drugs

A study of a samples of drugs tested all over the country in last 4 to 5 years, reveals that about 0.3% to 0.4% of y , % %around 40,000 samples fall within the category spurious drugs

Facts and FiguresYear

(2001-2008)SamplesTested

SpuriousDrugs

% age Spurious

Drugs Detected

2007 2008 39 117 46 0 1172007-2008 39,117 46 0.117

2006-2007 34,738 58 0.166

2005-2006 43,138 152 0.352

2004-2005 49,287 144 0.292

2003-2004 40,862 118 0.288

Figures from the StateDrug Controllers -spurious Drugsdetected year wise

2002-2003 43,138 129 0.299

2001-2002 38,824 96 0.247

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Country wide Survey (Year 2008-09)- Spurious Drug

Study to assess the extent of spurious drugs in countryStudy designed by Indian Statistical Institute, HyderabadSamples of 61 various popular brands from 9 therapeuticp p p pcategories like anti-TB, Anti allergic, Ant-infective, Anti-Malarial, Antihistamines etc. were targeted for this study.Samples from various parts of the country have beencollected.24,136 samples collected from different parts of country.Analysis of 3000 samples drawn randomly is underwayAnalysis of 3000 samples drawn randomly is underwayand results are expected by October 2009 end.

Initiatives taken by Govt. of India

Definition of spurious drugs and penal provision for its manufacture wereintroduced in the D&C Act in 1982.

Recently under the D& C Act (Amendment 2008)Recently under the D& C Act (Amendment 2008)

Penalties for violation of provisions of D & C Act have been enhancedMaximum penalty has been enhanced to life imprisonment & fine of Rs 1 Million.Certain offences have been made cognizable & non bailableGuidelines for implementing the D&C amendment have been circulated to StateDrugs Controllers

Revised Schedule M became effective from 30th June 2005 to assure thatquality drugs are produced in the country.

Whistle Blower policy is in process of being implemented

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Definition of IMPACT

A medicinal product is counterfeit when there is a falserepresentation in relation to its identity, history or source.This applies to the product, its container, packaging orThis applies to the product, its container, packaging orother labeling information. Counterfeiting can apply toboth branded and generic products. Counterfeits mayinclude products with correct ingredients/components,with wrong ingredients/components, without activeingredients, with incorrect amounts of active ingredientsor with fake packaging.”

Counterfeit Drugs-New Definition at Hammamet ,Tunisia

A medical product is counterfeit when there is a falserepresentation1 in relation to identity2 and/or source 3representation1 in relation to identity2 and/or source.3This applies to the product, its container or otherpackaging or labelling information. Counterfeit can applyto both branded and generic products. Counterfeit mayinclude products with correct ingredients/components4,with wrong ingredients/components, without activeingredients with incorrect amounts of active ingredientsingredients, with incorrect amounts of active ingredients,or with fake packaging.

(Contd.)

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Counterfeit Drugs-New Definition at Hammamet Tunisia(Contd.)

Violations or disputes concerning patents must not be confused withcounterfeiting of medical products. Medical products (whether generic orbranded) that are not authorised for marketing in a given country butauthorized elsewhere are not considered counterfeit. Substandard batchesor quality defects or non-compliance with Good Manufacturing Practices/Good Distribution Practices in legitimate and medical products should notbe confused with counterfeiting.

(1) Counterfeiting is done fraudulently and deliberately. The criminal intentand/or careless behaviour shall be considered during the legal proceduresfor the purposes of sanctions imposed.

(2) This includes any misleading statement with respect to name, composition,strength, or other elements

(3) This includes any misleading statement with respect to manufacturer,( ) y g p ,country of manufacturing, country of origin, marketing authorization holderor steps of distribution

(4) This refers to all components of a medical product

CDSCO Initiatives : Year 2008-2012

1. Implementation of CTD Format for biological & qualification of NRA Assessment by WHO and Introduction of CTD Format for New Chemical Entities

• Streamlining regulatory approval pathway for facilitating development of New Chemical Entities

2. Infrastructure :Shifting of CDSCO HQ, to new building(FDA Bhawan)Creation of Pharma Zones with Minilab facility at ports- Delhi, Hyderabad, Mumbai Upgradation of 2 Sub Zonal to Zonal Offices and creation of 2 new sub Zonal offices.Shifting of CDSCO West Zone office to new buildingVideoconferencing /Teleconferencing facility in HQ, Zonal offices, Sub Zonal Offices, ports & CDTL LaboratoriesCreation of Centralized state of art Archiving Facility

3. Manpower144 New posts in various categories have been sanctioned 72 new posts were sanctioned in the Year 2008This will take the number of Drugs inspectors to 169 , besides 31 assistant drugs inspectors

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4. Transparency & AccountabilityRegular posting of approvals on CDSCO website at www.cdsco.nic.inRegular posting of guidance document for industry /stakeholdersDisplay on 2 LCDs of various approvals at FDA BhawanTurn around time for various applications such as BE, NOC for export ,test licence etc. Interactive sessions with stakeholders

CDSCO Initiatives : Year 2008-2012

5. Clinical TrialMandatory registration of clinical trials in centralized clinical trial registry (www.ctri.in) w.e f. 15th June 2009Registration of CROs , Ethics Committee & Clinical Trial sitesGCP training of investigators by accredited body.Inspection of Clinical TrialsBuilding of regulatory capacity in respect of First in Man(i.e. Phase 0/Micro-dosing studies)

6. Medical devicesSchedule M III guidelines have been posted on website which are in line with GHTFMedical Devices to be taken out from the definition of Drug & Rules to be amended accordingly

7. National Pharmacovigilance ProgramAll medical colleges ,premium medical institutions ,corporate hospitals etc to have a Pharmacovigilance centre

8. Internationals Collaborations with

WHO USA FDA, Health Canada Brazil (ANVISA) ,South AfricaEMEA, AFSSAPS- FranceICH

CDSCO Initiatives : Year 2008-2012

ICHMHRA - UK

9. Nationwide survey of Spurious drugs

10. Inspections Overseas manufacturing unitsCOPP under WHO GMP Scheme to be issued by CDSCO from 1st October 2009.

11. E-GovernanceLAN / Wi-Fi connectivity, MIS ,Digitalization of recordsLAN / Wi Fi connectivity, MIS ,Digitalization of recordsOnline submission of all the forms/applicationsDigitalized interactive portalOnline approvals with Digital signatureNearly paperless office.

12. Creation of Central Drugs Authority- Bill under consideration in Parliament.

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