Title: A New Paradigm for Pharmaceutical Regulation in Taiwan: TFDA Establishment
1A New Paradigm for Pharmaceutical Regulation in
Taiwan TFDA Establishment
- Taiwan Food and Drug Administration
- Director, Division of Drugs and New Biotechnology
Products - Meir-Chyun Tzou, Ph.D
- Dec. 10, 2010
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2Outline
- Organization and Responsibility
- Reform of Taiwan Drug Review System
- Rationalization of Review System
- Regulation Strategies
- post-marketing surveillance
- International Cooperation
- Future Prospects
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3Organization and Responsibility
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4Establishment of Taiwan FDA
- Taiwan FDA (TFDA) was inaugurated on Jan. 1, 2010
- TFDA supersedes the following 4 bureaus of
Department of Health - Bureau of Food Safety
- Bureau of Pharmaceutical Affairs
- Bureau of Food and Drug Analysis
- Bureau of Controlled Drugs
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5TFDA Organization Chart
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6Establish Taiwan Food and Drug Safety Management
System
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7Core Value of TFDA
- From Product Center to Consumer Center
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8Strategy of TFDA Reform
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9Division of Drugs and New Biotechnology Products
Cooperation Institute
Drug Safety and Evaluation
Medical and Pharmaceutical Industry Technology
and Development Center, PITDC
New Drugs
Generic Drugs
Center for Drug Evaluation, CDE
Deputy Director
Director
Biologics and New Biotechnology Products
Taiwan Drug Relief Foundation, TDRF
Clinical Trial Management
Pharmaceutical Management
10Roles of Regulatory Authorities
- Public Health Protection
- Gate-keeper
- Prudent evaluation based on Good Review Practice
- Drug quality, safety and efficacy
- Health Industry Promoter
- Consultation mechanism
- Efficient and transparent review process
- International harmonization
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11Pharmaceutical Regulation in Taiwan
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12Statistics on Pharmaceutical Licenses(Sep. 2010)
3960
568
1752
21072
- API active pharmaceutical ingredient
- DP Drug Product
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13Statistics on Pharmaceutical Licenses (Sep.
2010)
Domestic Import Total
New Drug 486 1104 1590
Generic Drug 20586 2856 23442
API 568 1752 2320
Total no. of Licenses Total no. of Licenses 21640 5712 27352
ratio ratio 1421.2 12.61.6 114.71.5
Domestic Import Total
Rx drug 13492 3323 16815
Non-Rx drug 7580 637 8217
Total 21072 3960 25032
Rx Non-RX 1.81 5.21 21
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14Case numbers of IND Application in Taiwan(Sep.
2010)
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15 Distribution of Clinical Trial Applicationsin
Taiwan ( Nov. 2010)
2004 2004 2005 2005 2006 2006 2007 2007 2008 2008 2009 2009 2010 2010
P S P S P S P S P S P S P S
Phase I 8 12 14 26 12 20 10 18 11 14 18 19 18 21
Phase II 22 57 33 78 32 98 46 158 46 120 60 167 43 135
Phase III 85 237 69 242 86 300 106 391 132 527 95 407 102 475
Phase IV/others 4 10 4 5 3 4 6 14 16 21 14 19 18 27
Total 119 316 120 351 133 422 168 581 205 682 187 612 181 658
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P protocol S site
16Milestones on Pharmaceutical Events
- 1982 Good Manufacturing Practice (GMP)
- 1987 Bioavailability / Bioequivalence Guideline
(BA/BE) - 1993 Safety monitoring system-the requirement of
local clinical trial - 1996 Good Clinical Practice (GCP)
- 1998 Good Laboratory Practices (GLP)
- 1999 Establishment of Adverse Drug Reaction
reporting system - 1999 Amendment of current GMP (cGMP)
- 2004 Implementation of bridging study evaluation
(BSE) - 2005 Revision of Pharmaceutical Affairs Act (Data
Exclusivity compulsory requirement of serious
ADR reporting) - 2008 Good Pharmacovigilance Practice (GPvP)
- 2008 Guideline for Biosimilar Product Review and
Approval - 2009 Drug Master File (DMF)
- 2010 Implementation of PIC/S GMP
- 2010 Amendment of Guideline for Biosimilar
Product Review and Approval (in process) - 2010 Develop strategies for review guidelines of
tNCE and Botanical New Drug (in process) - 2010 Relaxation of CPP requirement (in progress)
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17Milestones on Drug Regulation
1980
2000
2010
1990
1982 GMP
1987 BA/BE
1999 cGMP
2009 DMF
2010 PIC/S GMP
1993 Local clinical trial
1996 GCP
1998 GLP
2000 BS Evaluation /ICH E5
2001 Pivotal trial/ early phase trial
Bridging Study Evaluation in accordance with ICH
E5
1998 CDE
2001 TDRF
2010 TFDA
1983 PV/PMS
1998 ADR
2008 GPvP
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18Reform of Taiwan Drug Review System
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19Reform of Taiwan Drug Review System
- Rationalization of the Review System
- Unified, Transparent , Fast
- Regulation Strategies
- post-marketing surveillance
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20Unified Drug Review System
- TFDA Review Team
- TFDA staff CDE ? reviewers
- Responsible for drugs and medical devices review
- General cases fast-track review process
- Advisory Committee (AC)
- Committee members from academics, research
organizations and health institutes - Provides TFDA related consultation and advices
- Special cases review
- ? Center of Drug Evaluation (CDE) was
Established by the DOH (Department of Health)
in1998 as a NGO, NPO. - Its mission is to assist DOH to evaluate new
drugs and new medical devices for regulatory
requirements and offer related consultation
services.
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21Reform of the Advisory Committee
- Duties of the Advisory Committee
- Special case review
- Clinical Trial First in human, Ethnic and
Ethical Concern and etc. - NDAGlobal New, NCE not approve by US FDA and
EMEA, Botanical product, Biosimilar, t-NCE and
etc. - Ethics, Public Health and Public awareness issues
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22Transparency of the Review System
- 2000 Present to AC meeting for Appeal Case
- 2001 Use bar code to trace review status
- 2005 Announce AC meeting schedule on website
- 2006 Release of AC meeting results to applicants
- 2009 Announce AC members/experts name on
website - Aug. 2010 announce the NCE assessment report on
website
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23Transparency and Quality Assurance
- Implementation of Good Review Practice (GRP)
- Review quality assurance QA/QC task force
- On-line Roadmap for tracking review progress,
starting from May 2010
24Key elements of GRP
- Template and tools
- Reviewer training
- Qualification of reviewer
25Template and Other Tools of GRP
- Template
- points to consider
- Content and format of assessment report
- template for IND, BSE and NDA assessment report
- CMC, Pharm/Tox, PK/PD, Clinical, Statistics
- Other tools
- SOP, guidelines, primary endpoint for different
indication, special protocol design. -
26Reviewers Training and Quality Control
- Review team
- Consultation with a group of 100 domestic experts
and 5 oversea contracted consultants with FDA
experience - Regular case discussion, review guidance
discussion and drafting - Structured training and evaluation program for
primary and secondary reviewers - Internal/external QA/QC task force
Primary reviewer
Secondary reviewer
supervisor
27Review Process for IND Implement Fast Track
Hospitals?Sponsors?CRO Application
TFDA Review Team
Archives
Technical and Administrative Document
IRB/ J-IRB
Assessment Report
Consultation with AC Experts if needed
Advisory Committee
TFDA Decision
Hospitals?sponsors?CRO
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28Fast-Track Review process for IND
- fast-track review process for IND is issued for
those clinical trial studies that have the same
FDA-approved IND number as in the US. - (Apr. 09, 2010)
- fast-track review process for multi-national IND
is issued for those clinical trial studies that
have been approved by advanced countries. - (Aug.18, 2010)
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29Review Process for NDA
Sponsor Application
TFDA Review Team (TFDA Staff CDE)
GMP /PMF
Technical and administrative document, GMP/PMF
Global New, Botanical product, Biosimilar
product, etc.
Assessment report
Consult with AC experts for special concern
Advisory Committee
Decision
? GMP Good manufacturing practice PMF
Plant master file
Sponsor
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30Fast-Track Review Process for NDA
- Fast Track (Priority and Abbreviated) Review
- Priority
- For Un-met medical Needs and with clinical
advantages, expected to shorten the review
processing time up to 2/3. - Abbreviated
- For New chemical entity (NCE) approved by USFDA
and EMA , expected to shorten the review
processing time up to 1/2. - Fast track
- for value added drugs, to expand global market
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31-
- Reform of Taiwan Drug Review System
- Rationalization of the Review System
- Regulation Strategies
- IND, NDA, New Biotechnology Products, Generics,
API - post-marketing surveillance
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32Regulation Strategies for IND
- Establishment of a Modern Clinical Trial
Environment in Taiwan - Preclinical GLP inspection
- GCP inspection
- Enhancement of the quality of IRB
- Training for clinical trial professional,
including CRO. - Improvement of clinical trial Infrastructure
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33Regulation Strategies for IND
- Improvement of Clinical Trial Infrastructure
- Goal
- Establishment of software and hardware to meet
international standard - Promote early phase multi-national multi-center
trial, global drug development - Strengthen quality of clinical trial
- Government funding Research Centers
- Grant 22 million (2010)
- Good Clinical Research Center, GCRC11 sites
- Center of Excellence5 sites
- Cancer Center of Excellence 8 sites
- Site Management Organization, SMO
- Qualified clinical trial sites for IND
- 108 teaching hospitals
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34Regulation Strategies for NDA
NDA
Standard Review Non-CPP
Accelerated Review 1-CPP
Abbreviated Review 2-CPP (FDA EMA)
Full technical dossier Early development in
Taiwan GCP GLP GMP preapproval inspection REMS
Full technical dossier REMS if necessary
Full technical dossier CT in Taiwan REMS
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35Regulation Strategies for NDA
- Relaxation of the requirement of Certificate of
Pharmaceutical Product (CPP) - Risk Evaluation and Mitigation Strategy (REMS) or
Risk Management Plan (RMP) - Strategies for Special Categories of New Drugs
- Botanical product
- Biosimilar
- T-NCE
- ? approved the first domestic botanical product
(Apr. 2010)
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36Regulation Strategies for New Biotechnology
Products
- Regulation strategy in supporting the development
of - new biomedical innovation
- stem and somatic cells
- engineered tissue products, and etc.
- biosimilar medicine
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37Regulation Strategies for Biosimilar medicine
- Regulation Strategies for Biosimilar medicine
- Points to consider for common technical document
(CTD) in review and approval of biosimilar
medicine - (Draft announced on Aug. 27. 2010 )
- including CMC, Non-clinical, Clinical, RMP
- ? Incentive abridged data submission if NDA
application before Dec.31.2013
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38Regulation Strategies for Generic Drug and API
- Establishing the review strategies for DMF of API
and CTD of Generic Drugs - Time-line and action plans for DMF and CTD
- Communication with the industry association
- Training /Education
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39Regulation Strategies for Post-Approval Changes
- Regulation strategies for post-approval
changes - Establish DMF database of API
- Monitor and inspect API changes
- Revise guideline for Scale-Up and Post Approval
Changes (SUPAC) - Regulation Strategy for management of
product license
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40Reform of Taiwan Drug Review System
- Rationalizeation of the Review System
- Regulation Strategies
- post-marketing surveillance
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41Post-marketing Surveillance System
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42Post-marketing Safety and Quality
Surveillance-Risk Management
Passive
Drug Product quality defect reporting system
Quality surveillance
National Quality surveillance Program
Active
Surveillance
Post-marketing product quality and safety
surveillance
Passive
ADR reporting system
Safety surveillance
ManufacturerDrug safety report on a regular
basis
Active
GovernmentADR active Monitoring Network
- Reassessment / Inspection
- Labeling change
- Withdrawal/Recall
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43Pharmacovigilance in Taiwan
- Taiwan MedWatch (http//adr.doh.gov.tw/default.as
p ) - Website of Pharmacovigilance in
Taiwan(http//adr.doh.gov.tw) - Drug Safety information for Consumer
- Product Quality Defect Reporting System
- From Voluntary reporting to Active surveillance
- Establish Taiwan VAERS for Vaccine Safety
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44 Taiwan MedWatch
- http//adr.doh.gov.tw/default.asp
- Provide update safety information to the public
- On-line report an ADR
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45Website of Pharmacovigilance in
Taiwan(http//adr.doh.gov.tw)
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46Drug Safety information for Consumer
http//drug.doh.gov.tw/
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47Product Quality Defect Reporting System
http//recall.doh.gov.tw
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48Taiwan Drug Injury Relief System
TFDA
Drug Injury Relief Review Committee
Drug Injury Relief Fund
Relief Fund Payment
Request for Review
Review and Determine Results
Levies
Taiwan Drug Injury Relief Foundation (TDRF)
Levies Collection, Verification, Request, Return
and Claim
Drug Injury Relief Application
Review Notification, Relief Fund Payment
Licensed Holders
Drug Hazard Victim
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49Quality Assurance for Drug Manufacturing
- Good Manufactory Practice (GMP)
- Documentations, SOP, QC, QA
- Current GMP (c-GMP)
- Validations- analytical method, process, data
treatment - PIC/S GMP by 2014
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50Milestones of Pharmaceutical GMP Development in
Taiwan
PIC/S GMP
cGMP
GMP
number of domestic pharmaceutical manufacturer
21 pharmaceutical manufacturers are in compliance
with PIC/S GMP
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1982
1999
2010.11
1988
2005
Overseas Inspection since 2002
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51GMP International Harmonization
1999Upgrade to Current GMP (Validation)
1982ImplementGMP
2007adopt to International GMP (PIC/S GMP)
Quality Systems
Design Quality into Product
Building Quality into Product
Control Quality by Testing
1980s
1990s
2000s
1970s
52GMP Inspectorate in TFDA
- The Pharmaceutical GMP Inspectorate and Licensing
Quality System had been established.
Taiwan FDA
Div. of Risk Management
GMP AuditBranch
GTP Audit LicensingBranch
Risk Management Branch
Laboratory managementBranch
GMP Licensing Certificate
Domestic Oversea GMP Inspection
GMP Inspectorate
53GMP Regulation in Taiwan
- Legal System
- Pharmaceutical Affairs Act
- The pharmaceutical manufacturers shall comply
with GMP and be approved and registered after
meeting inspection standards of the competent
health authority (i.e. TFDA) - GMP standards PIC/S GMP Guide for Medicinal
Products for medicinal products for human use had
been formally adopted since Feb. 2010. - Management Activities
- Licensing activity
- Manufacturing License
- GMP certification
- Inspection activities
- Domestic and oversea inspections (APIs factory
only) - New GMP Assessment, routine inspection, for-cause
inspection - Inspections on contract laboratory
- Other activities
- Reviewing the Plant Master File of oversea
manufacturers, etc.
54The distribution of Domestic Pharmaceutical
Manufacturers in Taiwan
- 166 pharmaceutical manufacturers
- 9 pharmaceutical distributors involved in
packaging activities - 19 of 166 pharmaceutical manufacturers are in
compliance with PIC/S GMP.
Data collection until Sep. 15, 2010
55International Cooperation
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56International Cooperation
- Continuous international cooperation i.e. APEC
(LSIF, ISTWG), ICH-GCG, DIA, etc. - Initiation of APEC Industrial Science and
Technology Working Group (ISTWG) project - APEC Network on Pharmaceutical Regulatory Science
since 2000 - Engage in APEC Life Science Innovation Forum
(LSIF) - Initiation of APEC LSIF project Best Regulatory
Practice of Medical Products - Hosted the 2010 APEC Good Review Practice
Workshop on Pharmaceuticals (Nov.36)
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57International Cooperation
- Harmonization on regulation and review process
with international standard - Application of PIC/S membership
- Observership
- USP
- WHA
58International Cooperation
- Bilateral Cooperation
- Taiwan-Australia
- Pharmaceutical bilateral video-conference
- Memorandum of Understanding (2010)
- Taiwan-Japan
- The 5th Joint Seminar of Taiwan Japan
- Taiwan-EU
- Pharmaceutical bilateral video-conference
- Pre-notification of GCP, GMP inspections
- Taiwan-US
- Pre-notification of GCP, GMP inspections
- Taiwan-Korea, Singapore
- (Pharmaceutical bilateral video-conference)
- Cross strait cooperation on new drug research
and clinical trial
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59Future Prospects
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60Initiatives
- Pharmaceutical Affair Reform
- Regulation harmonization
- Modern Review System
- Quality assurance
- Cross Strait Cooperation
- Food Safety Management
- New Drug Development and Clinical Trial
Cooperation
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61Action Plans of TFDA
- Action plan to Reform Pharmaceutical Affairs
- Action plan for International affairs
- Action plan for Cross-strait affairs
- Action Plan to Reform Food Safety management
- Action Plan for Anti-counterfeiting
- Action Plan for Information Integration
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62Future Prospects
- Continuous efforts in
- Promoting public health
- Enhancing review quality, efficiency, and
transparency. - Improving consultation mechanism to facilitate
industrial development and increase international
competitiveness. - Promoting international, regional and
cross-strait drug regulatory harmonization and
cooperation.
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63Thank You for Your Attention
http//www.fda.gov.tw
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