Regulation and Views on Drug Clinical Trials in China - Apec-ahc.org

<strong>Regulation</strong> <strong>and</strong> <strong>Views</strong> on Drug
Clinical Trials in China
Dr. Li Jinju
Director, Division of Drug Research Supervision,
Dept. of Drug Registration, SFDA
Sep. 14, 2010 Seoul, South Korea
STATE FOOD AND DRUG ADMINISTRATION

Outline
� Approval of drug clinical trials
� Implementation of Multi-regional Clinical
Trials
� GCP implementation
� Future trends
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STATE FOOD AND DRUG ADMINISTRATION

Approval of drug clinical trials
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STATE FOOD AND DRUG ADMINISTRATION

Legislation
1. Drug Administration Law
2. <strong>Regulation</strong>s for Implementation of the Drug
Administration Law
3. Provisions for Drug Registration
4. Good Clinical Practice
5. Provisions for Accreditation of Drug Clinical
Trial Institutes
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STATE FOOD AND DRUG ADMINISTRATION

Drug Administration Law
� Article 29 The dossier on a new drug research <strong>and</strong> development
including the manufacturing process, quality specifications, results of
pharmacological <strong>and</strong> toxicological study, <strong>and</strong> the related data <strong>and</strong>
the samples shall, in accordance with the regulations of the drug
regulatory department under the State Council, be truthfully
submitted to the said department for approval, before clinical trial is
conducted. Measures for verifying the qualifications of clinical study
institutions for drugs shall be formulated jointly by the drug regulatory
department <strong>and</strong> the administrative department for health under the
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State Council.
� Article 30 The institutions for non-clinical safety evaluation <strong>and</strong> study
<strong>and</strong> clinical study institutions shall respectively implement the Good
Laboratory Practice for Non-Clinical Laboratory Studies (GLP) <strong>and</strong>
Good Clinical Practice (GCP).
The GLP <strong>and</strong> GCP shall be formulated by the department designated
by the State Council.
STATE FOOD AND DRUG ADMINISTRATION

Approval Procedure
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Applicant
Office for Acceptance
of Applications
Center for Drug
Evaluation
Evaluation report
Dept. of Drug Registration
approval of clinical
trials
Ethics Committee
Clinical trial starts
Submission of documents
Reject
STATE FOOD AND DRUG ADMINISTRATION

Different clinical trials
�clinical trials for local innovative drugs
�clinical trials for local generics
�clinical trials for import drugs
�Multi-regional clinical trials
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STATE FOOD AND DRUG ADMINISTRATION

Requirement for applicant
Local applicant:legally registered <strong>and</strong> able to
take the civil liability independently
International applicant:legal drug company
overseas, an agent in China must be identified by
the applicant
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STATE FOOD AND DRUG ADMINISTRATION

Requirement for sponsors
•qualified hospitals accredited by SFDA <strong>and</strong> MoH
based on SOP <strong>and</strong> relevant requirements
•261 drug clinical trial institutes
•clinical pharmacology institutes jointly inspected
by SFDA <strong>and</strong> MoH
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STATE FOOD AND DRUG ADMINISTRATION

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Control over samples
� manufactured in GMP-compliant
facility
� with appropriate scope for trials
� free supply to subjects
STATE FOOD AND DRUG ADMINISTRATION

Highlights of regulation on trials in China
•all clinical trials must be approved by SFDA
prior to the approval by the ethics committee
•clinical trials must be conducted in
designated clinical hospitals
•clinical hospitals jointly selected by SFDA
<strong>and</strong> MoH as clinical pharmacology institutes
• Chinese GCP as the guideline
• lots of trials for generics
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STATE FOOD AND DRUG ADMINISTRATION

Approvals in 2009
2009:1105 trials have
been approved,
including 785 local
applications,320
international applications
indications include
common disease, e.g.
tumor, cadiovascular
diseas, <strong>and</strong> orphan
diseases, e.g. Fabry
disease
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pharmace
utical
Local application
TCM Biolo
gics
STATE FOOD AND DRUG ADMINISTRATION
Internatio
nal
applicatio
Number 658 101 26 320
compound or
formula
267 91 / 171
n

13 new chemical compounds,1 new TCM
compound <strong>and</strong> 48 new TCM formula have
been approved for clinical trials in 2009.
28 trials for innovative drugs were reviewed
<strong>and</strong> approved according to the special
procedures, with SFDA’s communication with
applicants at key stages, which encourages the
R&D of innovative drugs
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STATE FOOD AND DRUG ADMINISTRATION

Professional background of CDE
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STATE FOOD AND DRUG ADMINISTRATION

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CDE
� Highly professional team
� focus on drug evaluation, while also involved
with drug clinical trial regulatory system
� Take the lead in introducing international
evaluation system <strong>and</strong> concepts
� Heavy workload, lack of human resources
� st<strong>and</strong>ardized, independent, science-based <strong>and</strong>
transparent
� Active in international activities, e.g. dialogue
with US FDA, EMA
STATE FOOD AND DRUG ADMINISTRATION

Implementation of Multi-regional
Clinical Trials(MRCT)
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MRCT
� Main sponsors: big international
pharmaceutical companies
� Try to conduct MRCT in different
countries simultaneously
� compressed R&D timeline so as to
speed up commercialization
STATE FOOD AND DRUG ADMINISTRATION

China’s strength for MRCT
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Talents
Cost
Market
� 。
Resource
STATE FOOD AND DRUG ADMINISTRATION

Challenges
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Approval timeline
Import <strong>and</strong> export of samples
ADR reporting
IPR
Lack of institutions
Infrastructure & personnel
Incentive policy
STATE FOOD AND DRUG ADMINISTRATION

MRCT in Asia:
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MRCT in China: 2002 - 2008
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China is being included into the
synchronized global research.
Among 320 approved international
applications in 2009, 132 are MRCT
application.
STATE FOOD AND DRUG ADMINISTRATION

Risk-benefit Analysis
� Benefits
� provide new therapy to patients
� complete safety data on Chinese population
� facilitate best practice for treatment on Chinese population
� attract foreign investment in R&D
� Training for R&D talents, improve GCP implementation
� establish world-class R&D system <strong>and</strong> platform for global
competition
� Facilitate an R&D industry
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STATE FOOD AND DRUG ADMINISTRATION

Risk-benefit Analysis
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� potential concerns <strong>and</strong> risks
� how to protect rights of the subjects <strong>and</strong> ethics?
� how to avoid <strong>and</strong> reduce risks associated with the
uncertainty of the research?
� how to evaluate ethnic difference?
� how to protect the safety of healthy subjects?
� how to avoid the unfairness for allocation of
medical resources?
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GCP Implementation
STATE FOOD AND DRUG ADMINISTRATION

History
1998: GCP for trial implementation by MoH
1999: GCP by SDA
2003: GCP by SFDA
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STATE FOOD AND DRUG ADMINISTRATION

Accreditation
by Jun. 1, 23 Notice for Accreditation of Drug Clinical Trial
Institutions issued by SFDA
� 298 drug clinical trial institutions in 27 provinces, autonomous
regions or municipalities
� 3 hospitals in HK
� For relevant information: www.sfda.gov.cn
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STATE FOOD AND DRUG ADMINISTRATION

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Clinical trial institutions
wide-spread in 31 provinces, autonomous
regions <strong>and</strong> municipalities.
e.g. Beijing(32), Guangdong(28)
,Shanghai(26), Jiangsu(26)
STATE FOOD AND DRUG ADMINISTRATION

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Clinical trial institutions
about 132 disciplines(56 TCM disciplines,
77 allopathic disciplines)
� Endocrine, respiratory, cardiovascular, gastro enterology,
neurosurgery, internal neurology, oncology: >100 institutions
� Gynecology & Obstetrics <strong>and</strong> other 8 disciplines: >50 institutions
� Thoracic surgery <strong>and</strong> other 33 disciplines:

In 2008:
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Clinical trial institutions
� 731 pharmaceutical trials on 642 drugs;
� 262 TCM trials on 247 drugs;
� 277 biologics trials(272 for therapeutic biologics <strong>and</strong> 5
for preventive biologics) on 220 products ( 215
therapeutic biologics <strong>and</strong> 5 preventive biologics)
p.s. all conducted in 168 institutions with more than 3 years of
operation after the accreditation
STATE FOOD AND DRUG ADMINISTRATION

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Clinical trial institutions
Approved institutes can basically meet current
needs for trials. However,there’re still unmet
needs for special diseases.
� HIV
� Pediatrics
� Vaccine
� Orphan drug
STATE FOOD AND DRUG ADMINISTRATION

Highlights of Chinese GCP
� GCP implementation is specified in Chinese legislation
� Procedures <strong>and</strong> st<strong>and</strong>ards in place for medical institute
accreditation
� growing awareness of GCP implementation among
medical institutes, drug manufacturers <strong>and</strong> dug regulatory
authorities at various levels; quality of trials being
improved
� increase in MRCT
� conformity with international GCP requirements
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STATE FOOD AND DRUG ADMINISTRATION

Comparison between China <strong>and</strong> other countries
� Similarities
1. conformity with fundamental GCP spirits <strong>and</strong> principles internationally
2. generally in line with GCP internationally
3. conformity with drug laws <strong>and</strong> regulations
4. conformity with national conditions
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STATE FOOD AND DRUG ADMINISTRATION

� Differences
1.clinical trial of new drug shall be approved in written form by drug regulatory
authorities
2、Trials must be done in institutes accredited by SFDA
3、A single department in a drug clinical trial institute cannot conduct trials on the
same drug from different sponsors , <strong>and</strong> shall not conduct too many studies
4、ethics committee is subordinated to medical institutes.
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STATE FOOD AND DRUG ADMINISTRATION

Inspections
� Supervisory inspection on institutes
Inspection for accreditation <strong>and</strong> follow-up inspections(
comprehensive inspections)
� Validation of clinical trials
site-inspection for drug clinical trial registration(regular inspection)
for-cause inspection in evaluation( for-cause inspection )
inspection for potential non-compliance( for-cause inspection )
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STATE FOOD AND DRUG ADMINISTRATION

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Next steps
STATE FOOD AND DRUG ADMINISTRATION

1. improve legal <strong>and</strong> regulatory systems
2. science-based selection of reference drug in clinical
trials
3. coordination between DRA <strong>and</strong> EC
4.reinforce process control over clinical trials (SAE
monitoring, risk-control plan, site inspection,
enforcement)
5.consistent quality of drug clinical trials
6.compensation for damages to the subjects
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STATE FOOD AND DRUG ADMINISTRATION

Generics
� Adhere to “strict control over both entrance <strong>and</strong>
exit”
� Clarify responsibilities, risk-control measures <strong>and</strong>
obligations of all participants in the trials
� Provide detailed guidelines for evaluation <strong>and</strong>
approval of clinical trials for generics
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STATE FOOD AND DRUG ADMINISTRATION

Innovative drugs
� While focusing on safety <strong>and</strong> process control,
-have full communication among reviewers, sponsors <strong>and</strong>
researchers;
-provide support under safety supervision system;
-define responsibilities of all stakeholders <strong>and</strong> risk control.
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STATE FOOD AND DRUG ADMINISTRATION

� capacity-building for reviewers, researchers <strong>and</strong>
sponsors through ongoing training
� Exchange <strong>and</strong> cooperation with international
regulators
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STATE FOOD AND DRUG ADMINISTRATION

Targets
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set up a team of GCP inspectors
including full-time <strong>and</strong> part-time
professionals
four systems:
1. legal system
2. inspection system
3. information system
4. technical support system
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Targets
� Three mechanisms
1. seamless linkage from pre-trial, in-trial to
post-trial regulation;
2. coordination <strong>and</strong> interaction between
administrative control <strong>and</strong> technical
supervision
3. interaction between SFDA <strong>and</strong>
Provincial FDAs
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Thank you!
STATE FOOD AND DRUG ADMINISTRATION