Multinational Clinical Trial Review and Administration in ChinaIND review focus on •Safety – Protocol and Plan – Pharmacological and toxicological data –CM&C • Conclusion

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