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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
The views and opinions expressed in the following PowerPointslides are those of the individual presenter and should not be
, . ,directors, officers, employees, volunteers, members, chapters,councils, Special Interest Area Communities or affiliates, or anyorganization with which the presenter is employed or affiliated.
These PowerPoint slides are the intellectual property of theindividual presenter and are protected under the copyright laws
of the United States of America and other countries. Used bypermission. All rights reserved. Drug Information Association,Drug Information Association Inc., DIA and DIA logo areregistered trademarks. All other trademarks are the property oftheir respective owners.
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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
3
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.
5
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)
15
TGA Transparency init iative
Category 1 applications
Standard route of application (40 + 255 WD)
16
Category 2 applications
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)
Category 3 applications
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.
23
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
Products that have not been approved
by any drug regulatory agency at the
time of submission
Products that have not been approved
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?
27
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)
29
THANK YOU
30