Multinational Clinical Multinational Clinical Trial Review and Trial Review and
Administration in ChinaAdministration in ChinaChief of Review management , Feng Yi
Centre for Drug EvaluationState Food & Drug Administration
Legislation in ChinaLegislation in China
•• Drug Administration Law of P. R. ChinaDrug Administration Law of P. R. China–– ManufacturersManufacturers–– DistributorsDistributors–– Pharmaceuticals in Medical InstitutionsPharmaceuticals in Medical Institutions–– Drug Administration Drug Administration –– etcetc
•• Regulations for Implementation of the Regulations for Implementation of the Drug Administration Law of P. R. ChinaDrug Administration Law of P. R. China
–– Detail Requirements of the LawDetail Requirements of the Law–– Definition of New Drug, Period of monitoring for Definition of New Drug, Period of monitoring for
New Drug, New Drug, Data ProtectionData Protection–– etcetc
•• Provisions for Drug RegistrationProvisions for Drug Registration–– Definition of the Drug registrationDefinition of the Drug registration–– Category of Drug Registration ProcedureCategory of Drug Registration Procedure
•• Relevant Practise and GuidanceRelevant Practise and Guidance–– GCP/GLP/GMP Guidance
Law
Regulation
Provision
Practices & Guidance
GCP/GLP/GMP Guidance
Requirement of the Provision on Requirement of the Provision on Multinationals Clinical TrialMultinationals Clinical Trial
Before 2002No detail requirement
Some R&D trial conduct in hospital
After 2002The provision for drug registration set relevant item, make the clear
requirement to conduct multinational trial in China
Drug registration Procedure Drug registration Procedure
protocol
Responsible OrganizationResponsible Organization
Centre for Reception Receipt dossier Screen the file
Department of Drug Registration, SFDA
Issue relevant provisionIssue guidance
Make clinical and marketing Decision, etc,
Centre for drug evaluationTake charge the technical review
National Institute of China Pharmaceutical and Biological Product
Validate and test the sample ,etc
Department of drug Safety Supervision, SFDA
Supervise the clinical trial, etc
51 54
75 77
102110 114
0
20
40
60
80
100
120
1999年底 2000年底 2001年 2002年 2003年 2004年 2007年
Staff in Centre for Drug Evaluation (1)Staff in Centre for Drug Evaluation (1)
Staff in Centre for Drug Evaluation (2)Staff in Centre for Drug Evaluation (2)
BS, 39P, 34%
MS, 40P, 36% PHD,MD 30P,26%
OTH, 5P, 4%
Structure of Centre for Drug EvaluationStructure of Centre for Drug Evaluation
文秘组
资料组
Review Stream Line Review Stream Line
• Chemical Drug – Oncology, Respiration, Anti-infection, Cardio-Renal,
Gastrointestinal product, etc(13, fields)
• TCM• Oncology, Respiration, Cardio-Renal, Gastrointestinal product, etc(14,
fields)
• Biological product• Vaccine, Biological product for treatment, Diagnostic reagents in vitro
IND Review Procedure IND Review Procedure
IND review focus on IND review focus on
• Safety– Protocol and Plan– Pharmacological and toxicological data – CM&C
• Conclusion of the technical review– Submission detail data by sponsor – Disapproval (Clinical Hold)– Approval
Consult outside experts when there are some important question
Trial from submission to conduction Trial from submission to conduction
Approve By SFDA
Approve By IRBStep 1
Step 2
Conduct trial
Step 3
Type of INDType of IND
Type Amount
Multinational trial Minority
Import drug registration Middling
Domestic drug registration Majority
Multinational trial in China from 2002 to 2008Multinational trial in China from 2002 to 2008
310 13
72 74 70
19
3
31
6153
18
01020304050607080
2002 2003 2004 2005 2006 2007 2008
Year
No No of application
No of approval
Phase of trial Phase of trial
17
118
020406080
100120140
Phase Ⅱ Phase Ⅲ
NO
. of C
ase
系列1
Review time of multinational trial Review time of multinational trial ((11))
52
510
1215
6 69
1
9
3 4
18
2 1
74 5
1 1
15
1 2 4
12
4 2
05
101520
5M 6M 7M 4M 5M 6M 7M 8M 9M 11M 4M 5M 6M 7M 8M 9M 10M
11M
12M 5M 6M 7M 9M 10M
11M 7M 9M 10M
2004 2005 2006 2007 2008
Review time in different years
No
Review time multinational trial Review time multinational trial ((22))
10
87
48
0
20
40
60
80
100
<4M <7M >7M
Review time
NO
.
• The main reason of > 4M review
Protocol Not very clear, need sponsor answer question
Quality of data Not satisfy the requirement
Communication Local sponsor need get the support from the oversea headquarters
Shortage of evaluators Cde need recruit more staff
Review time multinational trial Review time multinational trial ((33))
The result of reviewThe result of review
6, 4%
139, 84%
19, 12%
Withaw by SponsorDisapprovalApproval
Need to be solved in future Need to be solved in future
Regulatory science IND function need sound establish Possibility of conduct the phaseⅠtrial
Operation and performance CDE review and IRB reviewMore evaluators
Clinical R&D process Safety report system
Guidance ICH E5
Cooperation and communication Other agency ,PMDA、KFDA,etc.Sponsor