A 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
1
1
Outline
 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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22
Organization and Responsibility
3
33
Establishment 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
4
44
TFDA Organization Chart
5
55
Establish Taiwan Food and Drug
Safety Management System
Drug
Medical Drvice/cosmetics
Food
Risk
Management
And
Quality
Assurance
TFDA
Controlled
Drug
6
Center for
Regional
Administration
Research &
Analysis
66
Core Value of TFDA
From Product Center to Consumer Center
Consumer Protection
Risk Analysis
Food
Management
7
Drug
Management
7
Strategy of TFDA Reform
1. Consumer Protection
(1) Center for Consumer Protection
(2) Section of Risk Management
3. Pharmaceutical Affair
2. Food Safety
(1) Division of FS
(2) Regional Centers
(3) Risk Assessment Task Force
(1) Division of D&NBP
(2) Division of MD&C
(3) Division of CD
4. Supporting Division
(1)Division of P&RD (2) Division of R&A (3) Division of Risk
Management
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88
Division of Drugs and New Biotechnology Products
Cooperation Institute
Drug Safety and
Evaluation
New Drugs
Medical and
Pharmaceutical
Industry
Technology and
Development
Center, PITDC
Generic Drugs
Director
Deputy
Director
Center for Drug
Evaluation, CDE
Biologics and
New
Biotechnology
Products
Clinical Trial
Management
Pharmaceutical
Management
Taiwan Drug Relief
Foundation, TDRF
Roles 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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10
10
Pharmaceutical Regulation in Taiwan
Post Market
Management
Pre-Market Approvals
New Drug
Discovery
Preclinical
Testing
IND/IDE
GLP
NDA/
PMA
IRB/GCP
Market
GPvP/GPP
Quality
ADR Reporting
Insurance
ICH Based GXP
11
GMP
11
11
ADR
Drug
Injure
Relief
Statistics on Pharmaceutical Licenses
(~Sep. 2010)
Domestic API
25000
2.1%
Import API
6.4%
Domestic DP
77%
Import DP
14.5%
20000
15000
10000
5000
S1
0
Domestic API
Import API
568
Domestic DP
1752
21072
•API: active pharmaceutical ingredient
•DP: Drug Product
12
12
12
Import DP
3960
Statistics on Pharmaceutical Licenses
(~Sep. 2010)
Domestic
Import
Total
486
1104
1590
20586
2856
23442
568
1752
2320
21640
5712
27352
1:42:1.2
1:2.6:1.6
1:14.7:1.5
New Drug
Generic Drug
API
Total no. of Licenses
ratio
Domestic
13492
Import
3323
Total
16815
Non-Rx drug
7580
637
8217
Total
Rx: Non-RX
21072
1.8:1
3960
5.2:1
25032
2:1
Rx drug
13
13
13
Case numbers of IND Application in Taiwan
(~Sep. 2010)
250
200
22
18
22
150
46
100
50
25
89
4
27
183
110
112
2005
2006
146
169
141
0
2004
2007
一般案件
14
2008
Fast track案件
14
2009
2010.Q3
Distribution of Clinical Trial Applications
in Taiwan
(~ Nov. 2010)
2004
15
2005
2006
2007
2008
2009
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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15
P: protocol S: site
Milestones on Pharmaceutical Events
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
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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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Milestones on Drug Regulation
1980
2000
1990
1982 1987
GMP BA/BE
1999
cGMP
1993
1996
Local
clinical trial GCP
1998
GLP
2000
BS *
Evaluation
/ICH E5
2010
2009
DMF
2010
PIC/S
GMP
2001
Pivotal trial/
early phase trial
*Bridging Study Evaluation in accordance with ICH E5
1998
CDE
17
1983
PV/PMS
1998
ADR
2001
TDRF
2008
GPvP
2010
TFDA
Reform of Taiwan Drug
Review System
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Reform of Taiwan Drug Review System
Rationalization of the Review System
Unified, Transparent , Fast
Regulation Strategies
post-marketing surveillance
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Unified 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
★
20
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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20
Reform of the Advisory Committee
Duties of the Advisory Committee
Special case review
Clinical Trial ：First in human, Ethnic and
Ethical Concern and etc.
NDA：Global 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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Transparency 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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Transparency 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
23
Key elements of GRP
Template and tools
Reviewer training
Qualification of reviewer
24
Template 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
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design….
Reviewer’s Training and Quality Control
 Review team :
Primary
reviewer
Secondary
reviewer
supervisor
 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
26
Review Process for IND
Implement Fast Track
Hospitals、Sponsors、CRO Application
Archives
First-in Human、
Ethnic and
Ethical concern
etc.
Advisory
Committee
Technical and Administrative
Document
Assessment Report
Consultation with AC
Experts if needed
TFDA
Decision
27
TFDA
Review
Team
27
Hospitals、sponsors、CRO
27
IRB/
J-IRB
Fast-Track Review process for IND
fast-track review process for IND is issued for
those clinical trial studies that have the same FDAapproved 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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Review Process for NDA
Sponsor Application
TFDA Review Team
(TFDA Staff+ CDE)
Global New,
Botanical product,
Biosimilar product,
etc.
Technical and
administrative document,
GMP/PMF
Assessment report
Consult with AC experts for
special concern
Advisory
Committee
Decision
★ GMP: 29
Good manufacturing practice
PMF: Plant master file
GMP
/PMF
29
Sponsor
Fast-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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30
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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Regulation 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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Regulation 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, GCRC：11 sites
Center of Excellence：5 sites
Cancer Center of Excellence ：8 sites
Site Management Organization, SMO
 Qualified clinical trial sites for IND：
 108 teaching hospitals
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Regulation Strategies for NDA
NDA
Standard Review
Non-CPP
Accelerated Review
1-CPP
Abbreviated Review
2-CPP
(FDA + EMA)
Full technical dossier
+
CT in Taiwan
+
REMS
Full technical dossier
+
REMS if necessary
Full technical dossier
Early development
in Taiwan
GCP GLP GMP
preapproval inspection
REMS
34
34
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34
Regulation 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)
35
35
35
Regulation 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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36
Regulation 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
37
37
37
Regulation 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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38
Regulation 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
39
39
Reform of Taiwan Drug Review System
Rationalizeation of the Review System
Regulation Strategies
post-marketing surveillance
40
40
Post-marketing Surveillance System
Post-marketing surveillance system
Post-approval
changes
Pharmacovigilance
Quality
surveillance
PICS/GMP
Post-approval
commitment
ADR
reporting system
Product quality
defect reporting
system
Compliance
Testing
Inspection
Review
Surveillance
reporting
41
Post-marketing
Safety and Quality Surveillance
-Risk Management
Passive
Quality
surveillance
Surveillance
Post-marketing
product quality
and safety
surveillance
Safety
surveillance
Active
National Quality surveillance
Program
Passive
ADR reporting system
Active
Manufacturer：Drug safety
report on a regular basis
Government：ADR active
Monitoring Network
Reassessment / Inspection
Labeling change
 Withdrawal/Recall
42
Drug Product quality defect
reporting system
42
Pharmacovigilance in Taiwan
 Taiwan MedWatch
(http://adr.doh.gov.tw/default.asp )
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
43
43
43
Taiwan MedWatch
 http://adr.doh.gov.tw/default.asp
 Provide update safety information to the public
 On-line report an ADR
44
44
44
Website of Pharmacovigilance in Taiwan
(http://adr.doh.gov.tw)
45
45
45
Drug Safety information for Consumer
http://drug.doh.gov.tw/
46
46
46
Product Quality Defect Reporting System
http://recall.doh.gov.tw
47
47
47
Taiwan Drug Injury Relief System
TFDA
Drug Injury Relief
Review Committee
Request for Review
Drug Injury Relief Fund
Review and
Determine Results
Relief Fund
Payment
Levies
Taiwan Drug Injury Relief Foundation (TDRF)
Drug Injury Relief
Application
Review Notification,
Relief Fund Payment
Drug Hazard Victim
48
Levies Collection,
Verification, Request,
Return and Claim
Licensed Holders
48
48
Quality 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
49
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49
Milestones of Pharmaceutical GMP
Development in Taiwan
GMP
600
500
cGMP
PIC/S GMP
number of domestic pharmaceutical manufacturer
550
400
300
211
200
230
163
165
100
0
◆
1982
◆
1988
◆
1999
◆
2005
21 pharmaceutical
manufacturers are in
compliance with
PIC/S GMP
◆
2010.11
Overseas Inspection since 2002
50
GMP International Harmonization
1999
1982
Implement Upgrade to Current GMP
(Validation)
GMP
Control
Quality
by
Testing
1970s
Building
Quality
into
Product
1980s
Design
Quality
into
Product
1990s
2007
adopt to International
GMP (PIC/S GMP)
Quality
Systems
2000s
GMP Inspectorate in TFDA
• The Pharmaceutical
GMP Inspectorate and
Licensing Quality
System had been
established.
Risk
Management
Branch
Taiwan FDA
Div. of Risk Management
GMP Audit
Branch
GTP Audit &
Licensing
Branch
Domestic &
Oversea
GMP Inspection
GMP
Licensing &
Certificate
GMP Inspectorate
Laboratory
management
Branch
GMP 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 (API’s 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.
The distribution of Domestic
Pharmaceutical Manufacturers in Taiwan
4
• 166 pharmaceutical
manufacturers
• 9 pharmaceutical
distributors involved in
packaging activities
• 19 of 166 pharmaceutical
manufacturers are in
compliance with PIC/S
GMP.
1
3 19+2
11
14
14
4
3
2
1
7
18
3
1
Data collection until Sep. 15, 2010
25+6
3
1
20+1
3
International Cooperation
55
55
55
International 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.3~6)
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56
International Cooperation
 Harmonization on regulation and review process
with international standard
 Application of PIC/S membership
 Observership
 USP
 WHA
International 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
58
58
58
Future Prospects
59
59
59
Initiatives
Pharmaceutical Affair Reform
Regulation harmonization
Modern Review System
Quality assurance
Cross Strait Cooperation
Food Safety Management
New Drug Development and Clinical Trial
Cooperation
60
60
60
Action 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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Future 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.
62
Quality
Efficiency
International
Transparency
Harmonization
62
Thank You
for Your Attention
http://www.fda.gov.tw
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