How Transparent Are Agencies Wrt Review Timelines

8/11/2019 How Transparent Are Agencies Wrt Review Timelines

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How Transparent are

Regulatory Agencies with

regard to Review Timelines?

Rosanna Melchior

Sr Manager, Reg.Intelligence

THOMSON REUTERS, France

Disclaimer

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These PowerPoint slides are the intellectual property of theindividual presenter and are protected under the copyright laws

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Agenda

Tranparency: legislated timelines (timeframes to be met) vs

performance reports (timeframes actually met)

Bench mark agencies (EMA, FDA, HC, PMDA, TGA and

Medsafe)

Other Agencies in

Latin America

Middle East Africa

s a

Focus on NCE standard applications

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Preliminary Considerations

Agencys performance targets vs legislated

review/ rocedural timelines

Days, Calendar Days, Working Days (CD, WD)

Review times may include applicants time to respond

Review timelines vs time to obtain a marketing

authorization/approval


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EU/EMA: centralised procedure

ValidationD -10

Compulsory for medicinal products

derived from biotechnology, advanced

Scientific evaluation(Co)-Rapporteurs AR,

Comments from CHMP Members,

List of Questions,

Clock Stop (day 180)

Answer to Questions

Day 0

Start ofprocedure

D 210

Adopt ion of

,

substances for certain therapeutic

areas and for orphan medicinal

products.

Applications are submitted directly to

the European Medicines Agency.

At the conclusion of the scientificCHMP Opinion

Transmission of opinion (15)

Draft EC opinion (15)

Standing Committee (22)

Adoption of EC opinion (15)D 277

Adoption of ECDecision

evaluation the CHMP opinion is

transmitted to the European

Commission to be transformed into a

single Community marketingauthorisation applying throughout the

European Union.

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EMA transparency initiative

The submission deadlines and full procedural timetables are published on EMA website

The published timetables identify the submission, start and finish dates of the procedures

as well as other interim dates/milestones

The submission/start/CHMP dates are generally fixed, other dates may be subject to

adjustments until the CHMP Scientific committee proceeds to their adoption for every

individual application.

At the start of a procedure, the adopted final timetable will be formally notified in writing to

applicants.

According to EMA Annual report 2009, 99 % of applications have been reviewed within

210 days

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EU MSs: national procedures

Validation phase ranges

between 10 and 60 da s

(AT, ES, SW vs IRL, SLO)

National Authority Review

Times: 210 days (Ireland

150, Slovakia 180).

In practice it exceeds

legislated timelines for

some countries (the

longest being Spain,Norway, Turkey)

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USA According to FDAs Guidance for Review Staff and Industry : Good Review Management

Principles and Practices, FDA staff should establish and observe internal review timelines

to help ensure efficiency and consistency in the review process.

Timelines are established by the Prescription Drug User Fee Program (PDUFA).

PDUFA IV goals, as reauthorized by FDAAA of 2007, are to review and act within 10

months of receipt on 90% of standard BLAs and NDAs filed during fiscal years 2007 to

2012 and within 6 months for priority applications.


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Performances for FY 2009 and 2010

FY 2009 Submissions FY 2010 Submissions

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CANADA

There are no legal time limits for review of submissions in Canada.

The Guidance for the Management of Drug Submissions (MDSG)

outlines the way in which the Therapeutic Products Directorate (TPD)

and Biologics and Genetic Therapies Directorate (BGTD) manage

information and material submitted by sponsors in accordance with the

Food and Drugs Act and Regulations.

Time frames referred to in the guidance are the current Health Canada

Target Performance Standards

within the time shown.


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Drug Submission Performance Reports

TPD Jan-Mar 2010 Quarterly Drug

Submission Performance Report

BGTD, Jan-Mar 2010 Quarterly Drug

Submission Performance Report


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JAPAN

Following open criticism, open transparency

policy from MHLW/PMDA with regard to the

review system for drugs and devices was

Targeted review ti me in FY 2009 to 2013

adopted*:

In 2004, the Pharmaceuticals and

Medical Devices Agency (PMDA) was

founded

Substantial increase in the number of its

staff including reviewers

the process from clinical trial

consultations until reviews conducted by

the same team with the same staff

members 24

6

8

10

12

14

16

18

20

Standard

Drug

review

Standard Drugreview

Reinforcement of personnel in key

therapeutic areas

Reinforcement and improvement in the

transparency of the progressmanagement of reviews

0FY2009(*) FY2010 FY2011 FY2012 FY2013

* PMDA annual report from website

JAPAN: Standard Products

In FY 2009, the median total

review time for standard

products was shortened to 19.2

, .

months in FY 2008.

The median regulatory review

time was shortened by 0.8

months compared with that in

FY 2008, and the median

applicants time was also

shortened by 0.7 months.

The number of approved

increased from the previous

fiscal year.

In practice: Time needed for

approval is about 19 - 21

months in total


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AUSTRALIA

The Therapeutic Goods Admini stration (TGA) is undergoing changes to the way thatthe submission and evaluation of prescription medici nes are made. Transitional

arrangements are expected to l ast until end of 2011

e s r eam ne su m ss on process cons s s o

8 phases with 8 milestones, allowing effective

planning and tracking by the TGA and sponsors.

Depending on the type of submission different

phases will be required which will affect the

overall length of time to complete the regulatoryprocess.

While the legislated TGA commitment of 40 WD

between receipt of a submission and notification

of acce tance/re ection will initiall remain, this

The streamlined submission process is designed to

take no more than 300 CD (10 months), including

the time for sponsor activities.

process will be replaced by a period of 15 CD.

The legislated TGA commitment of 255 WD *

between acceptance for evaluation through to

decision on the application will also remain forthe time being but will not be used for planning

or for target times.

(* 255 WD = 357 CD = 12 months)

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TGA Transparency init iative

Category 1 applications

Standard route of application (40 + 255 WD)

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Products that have been approved for marketing in at least two acceptable countries (UK,

Canada, Sweden, USA, Netherlands), and for which 2 independent evaluation reports are

provided (20 + 175 WD)


involving changes to the quality data of medicines already included on the ARTG (45 WD)


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NEW ZEALAND

Medsafe has made changes to new medicine application processing times and the

evaluation process. The follow ing process applies since August 2006:

The initial evaluation should be completed with 200 CD, or less.

Where a Request for Further Information (RFI) resulting from an initial evaluation is made,

the applicant has a maximum of 200 CD to provide a complete response to this letter.

The applicants RFI response will be evaluated within 120 CD or less, following

receipt by Medsafe.

If an additional RFI letter is required the applicant has a maximum of 120 CD to provide a

.

The applicants second RFI response will be evaluated within 120 CD, during which

time Medsafe will make a decision to accept, or decline the new medicine application.

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NEW ZEALAND:Processing Times

Processing times (in calendar days):

Times taken to complete the

majority (80%) of appli cations

and notifications during the 12-

month period July 1999 to June

2000.

These times are given to provide

applicants with a general guide to

the times that Medsafes

processing of the different types of

be expected to take.

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OVERVIEW

Clock stop (7 + 3)

Includes sponsors time

Includes sponsors time

Months

LATIN AMERICABRAZIL

Although Law 6.360 determines that the

registration approval should be grantedwithin a period of 90 CD days from the

date of filing, the actual time for a New

Product Registration approval is rarelyshorter than 12 months.

COLOMBIAAccording to Decree No. 677/95 the

estimated review times are:

210 WD for a new product (Includespharmacological and pharmaceuticalevaluation)

30 WD for a medicinal product includedwithin the pharmacological regulations(Only pharmaceutical evaluation)

Sponsor has 60 days to address requestfor additional information. Time for obtain a

marketing authorization is then extended toinclude 20 + 10 WD for legal checking /

ARGENTINA

Review timelines are established by

Disposition 5755/96 (8 + 69 WD). Althoughmandatory, due to the notorious gap between

workload and resources currently existing at

ANMAT, these deadlines are usually never metand the whole process may take up to 12

months and even longer.

and contents of the Product

Registration Dossier, PRD and as aconsequence the timetable for the

Approval Procedure

administrative purposes.

PERUProducts classification defines the requirements

for regulatory procedures and review timelines : Category 1 products: 60 CD

(Products whose API or associations are in theNational List of Essential Drugs)

Category 2 products: 45-90 CD (Productswhose API or associations are not in the NationalList of Essential Drugs but are registered in

countries with a high health vigilance system.) Category 3 Products:12 months (Products

whose API are not classified in Cat. 1 and 2)

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April 2011: Argentina's has developed a new

strategy to generate timely national andinternational information about the products

and processes within its remit. The so called

ANMAT Observatory is expected to strengthenthe regulator's decision making process as it

will co-ordinate for the first time such

information and activities.

CHILE

Review timelines are identified by

Decree 1876/95 (Art. 47): the PublicHealth Institute has 90 WD to approve

or reject a MAA. Time for review can

be extended of 30 additional days ifthe application includes a new API.


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MIDDLE EAST AFRICAExpected Review Time for MAA Standard Review

ISRAEL 360 Medicinal Products are evaluated and registered within 360 days, except for:- Generics which have been approved by the FDA/EMA (70 days).

- Additional dosages of registered products (180 days).

There are some contradictions in Guidelines timetables and it is advisable to clarify the

s ua on w e par cu ar c er ea ng w e spec c pro em.

EGYPT 255 WD(357 CD)

Drug Registration process depends on the status of the product (Brand or generic; imported,

locally or Toll manufactured). Generally, MA procedure takes around 12-18 months as an

average. It includes: Pre-inquiry Notification (15), Pricing file Submission (60), Scientific

Committee Review (60), Registration file Submission (15), Stability file Submission (60),

NODCAR file Submission (45 ).

SAUDI

ARABIA

10 + 245

WD

Target performance timeline from the date of acceptance to SFDA decision is of 290 days

(10 days validation + 245 days assessments "pricing +testing + dossier review" + 35 days

licensing). Applicant has 30 days to answer to inquiries raised during evaluation.

UAE 365 There is no official text dealing with registration timelines. The registration procedure in theUAE is a long process lasting usually 6 to 12 months. It can be shortened to 3 to 6 months

for New innovative drug, New therapeutic class, Products manufactured by GCC countries or

having GCC certification.

SOUTH AFRICA

Registration timelines are sub-optimal.

Delays are however not only caused by the

.

trial applications are substandard.

The MCC has committed to improve the

evaluation time of applications and the

Minister of Health appointed a task team to

address the current back log at the MCC.

A newly proposed process (adapted from

us ra an an ngapore mo e s a ms toconduct a full r eview in 210 WD (+ 60 for

regulatory decision making).

In practice, lengthy process up to 40

months


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ASEAN COUNTRIES *THAILANDThe timeframe for

new drugregistration is

approximately210 WD + 70 ifsubmitted to

VIETNAMWithin 6 months from the date of

receiving the full legitimate dossier,the Ministry of Health shall issue

registration number for the drugsregistered for the first time

MALAYSIA12 months for

hard copysubmissions,6

months for onlinesubmissions.

Average length

subcommittee.The estimated

actual time spentfor registration is

ranging from 10-24 monthsdepending on the

quality of theinformation and

the completenessof the documents.

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is 6 to 12 months.

(not officiallystated)

* Excluding: Myanmar, Cambodia, Laos, Brunei DarussalamSINGAPORE INDONESIA PHILIPPINESHave adopted a registration system that relies on product assessment

and approval of other competent Drug regulatory Agencies

INDONESIA SINGAPORE PHILIPPINES3 dist inct review processes and timelines

INDONESIA SINGAPORE PHILIPPINES

-

Products that have not been approved

by any competent regulatory agency


by any drug regulatory agency at the

time of submission


by any agency

Path II 150 days

Products that have been already

approved by one of the competent

regulatory agencies with whom

Indonesia has signed the mutual

recognition agreement and other

agreements

Abridged dossier 180 (NDA) or 240

days (GDA)

Products that have been evaluated and

approved by at least one drug

regulatory agency

150-180 working days

Products that have already received

approval from other agencies with

whom the Philippines signed a MRA

Path I 100 days Verification dossier 60 (NDA) or 120 130 to 210 working days.

For generic products/copy drugs(essential drug for Government

program) that do not required non-

clinical and clinical data to establish

safety and efficacy

days (GDA)Products that have been evaluated and

approved by HASs reference drug

regulatory agencies, which include EMA

(for CP), US FDA, Health Canada,

TGA, and UK MHRA (for MRP/DCP)

For generics products/copyproducts/similar products which do not

require clinical and non-clinical data

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ASIAN COUNTRIES

Expected RA Review Time for MAA Standard Review

CHINA 30 + 250 WD Legislated MAA review timelines are of 250 days, however time for obtaining adecision from the authority varies from product to product. The total time to approve

a dru is estimated to ran e between 26 to 40 months. Recentl March 2011 , the

Guideline on Principles and Procedures for Drug Scientific Review introduced the

principles of openness and transparency to be applied to pharmaceutical product

review (Art. XLV). The information on review procedures (status reports on products

reviews, the targeted review time) will be made public on government website.

HONG KONG 1 + 180 WD The Pharmaceutical Service has a performance pledge to approve applications forregistration of pharmaceutical products within 5 months (Agency website) . The

whole process is 6 months (including the evaluation and decision delivery)

INDIA 270 CD India's new draft guidance on test licence applications aims to shorten reviewtimes. The Indian Central Drugs Standard Control Organization has issued revised

draft guidance explaining the content and format of applications that companies

need to submit for obtaining a licence to import drugs for examination, analysis and

u . u u , w

in turn would shorten the application processing time and facilitate uniform decisions

by examiners/reviewers.

SOUTH KOREA 203 CD 203 days as per regulation (60 days for S/E review, 120 for CMC).

TAIWAN 10 + 360 CD According to the current practice, market authorization is granted within 90 to 270days. In Nov 2010 and in order to shorten the evaluation timeline, the Dept. of

Health (DOH) has decided that a Letter of Approval will be issued as soon as the

application has satisfactorily passed the review process without waiting for the

results of the package insert review.25

WHAT MAKES AGENCIES REVIEW

TIMELINES SO DIFFERENT ?

Agencys maturity and experience

Reliance u on assessment conducted b bench mark

agencies (FDA, EMA, etc) for several agencies (TGA,

Asean, etc)

Distinct evaluation processes (CTA + CMC + samples +

pricing in parallel or sequential)

Type of producttype of dossiertype of review

. For each Agency/Country the granularity of information

varies


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Conclusion

How Transparent are Regulatory Agencies with regard to

Review Timelines?

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Conclusion

Information on legislated review timelines is available for

most of the Agencies considered

Explicit information for some countries, customers practice-

based for others

Information on review performances is available for few

countries

Agencies willing to increase transparency and improve

, ,China, CDSCO India, ANMAT Argentina, South Africa)

How much do legislated/target and experienced/actual review

times concorde?

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References

Argent ina: Disposition 5755/96 (Marketing Authorization Application Procedure for New Medicinal Products, 03-Feb-1997, as amended,29-Nov-2000); ANMAT Disposition 907/2011, Boletn Oficial de la Repblica Argentina, No 32.092, 15 February 2011

Austr alia: Guideline: Transitional Prescription Medicine Streamlined Submission Process (Applicable to pre-submission planning forms

received by the TGA from 1 March 2011 and submissions lodged under the streamlined submission process and received by the

rom arc , an- ; erapeu c oo s egu a ons , onso a e ers o n as o - c -

Canada: Guidance for Industry: Management of Drug Submissions, 16-Mar-2011; Agencys performance reviews info available through

quarterly/annual submission performance reports, HC Website

China: Guideline: Principles and Procedures for Drug Scientific Review, 23-Mar-2011, SFDA Order No. 28: Regulations on Drug

Registration Administration, Revision, 10-Jul-2007

Colombia: Decree 677: Regulates the Process of Registration, the Granting of Licences, Quality Control and Sanitary Surveillance of

Medicinal Products, Cosmetics, Herbal Medicinal Products, Personal Hygiene Products and Other Products for Domestic Use, 26-Apr-1995

Israel: Title Guideline 72: Medicinal Products Approval Schedule, 30-Jul-2007

Mexico: Regulation of Health Sector Products, 03-Feb-1998 (Drug Law)

New Zealand: Guideline: New Zealand Regulatory Guidelines for Medicines, Volume 1, Part F: Medsafes evaluation procedures,

edition 6.13, Mar-2011

- - - , ,

2009

Saudi Arabia: Guideline: Regulatory Framework for Drugs Approvals, Version 4, Jun-2009

South Africa: Report Of The Ministerial Task Team On The Restructuring Of The Medicines Regulatory Affairs and Medicines ControlCouncil and Recommendations For The New Regulatory Authority For Health Products Of South Africa, 25-Feb-2008

Singapore: Guidance on Medicinal Product Registration in Singapore, Revised version, Apr-2011

USA: FDAs Guidance for Review Staff and Industry: Good Review Management Principles and Practices; The Food and Drug

Administration Amendments Act of 2007 (FDAAA)

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THANK YOU

[email protected]

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How Transparent Are Agencies Wrt Review Timelines