oct 06 ethical and regulatory approval process in hiv vaccine clinical research india experience hiv...
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Oct 06
Ethical and Regulatory Approval Process in HIV Vaccine Clinical Research
India Experience
HIV Vaccine Clinical Research Ethical and Regulatory Issues
Brasilia, October 4-5, 2006
Dr. Sonali Kochhar
Senior Medical Project Manager International AIDS Vaccine Initiative, India
Oct 06
Approval Process in India
• Well-delineated pathway with published guidelines and forms for
regulatory and ethical bodies available
• Regulatory Agency - Drug Controller General of India (DCGI)
(www.cdsco.nic.in)
• Drugs and Cosmetics Act 1940 was to prevent sub-standardization in
drugs.
• Drugs and Cosmetic Rule 1945 provided rules to Act. In latest
amendment in January 2005, existing Schedule Y substituted.
• Schedule Y – Provides specific guidelines for permission to import or
manufacture new drugs for clinical trials
• No separate guidelines for vaccines
Oct 06
Approval Process in India
Phase I trials with imported product
• Normally no Phase I with new product if not first tested outside
India.
• Need to submit Phase I data generated outside India, obtain
permission to repeat Phase I trials and /or Phase II trials followed
by Phase III trials concurrently with other global trials for product.
• Phase III trials must be conducted in India before permission to
market product in India is granted
• Exceptions on case-by-case basis for vaccines or drugs targeting
diseases of major public health threat or life threatening/serious
diseases e.g. HIV, Malaria, TB, Cancer
Oct 06
Export Permit from USA to India
• India is not on US FDA list for export of investigational products
without IND
• Two scenarios are possible:
• India is site of joint trial with countries where dossier was
approved by European agency (A001 trial, Pune)
• Obtain export approval from FDA
• Submit abbreviated dossier and letter to FDA providing
evidence that all steps have been taken to get approvals
from Indian regulatory authorities and ethics committees
(D001 trial, Chennai)
Oct 06
Approval Process in India
Mandatory, transparent
• Institutional Scientific Committee
• Ethics committees
• Institutional
• National
• Import permit of vaccine (DCGI) – MOH&FW
• National Regulatory Authority (DCGI) - MOH&FW
• Genetic Engineering Approval Committee
• Ministry of Environment & Forest
• Health Ministry’s Screening Committee
Oct 06
Preclinical Data
Institutional Scientific Committee •Protocol •IB
Institutional Ethics Committee•Protocol & IB•Toxicology Report Summary•Clinical documents
DCGI• Reviews standard clinical documents• Schedule Y with Form 44 (IND equivalent)• Form 12 (Import of test vaccine)
Central Ethics CommitteeProtocol & IBToxicology Report SummaryClinical documents
DCGI: Drug Controller General of India HMSC: Health Ministry Screening CommitteeGEAC: Genetic Engineering Approval Committee
LetterPermission to use material for clinical trial
HMSC•TRC cover letter•Special HMSC form•All approvals
Regulatory Process in India
GEAC GEAC dossier
1
2
3
3
Approval Steps
4
TK-02-24-05
Oct 06
Institutional Ethics Committee
At least 7 members including Chairperson (from outside
institution)
• Basic medical scientist
• Clinician
• Legal Expert
• Social Scientist/ representative of NGO
• Lay person from community
Sch Y requirement that committee function according to
• Good Clinical Practice Guidelines issued by Central Drugs
Standard Control organization
• Ethical Guidelines for Biomedical Research on Human Subjects, issued by Indian Council of Medical Research
Committee to have SOP’s and maintain record of proceedings
Oct 06
Genetic Engineering Approval Committee
Genetically Engineered Products
• If vaccine is manufactured locally by using recombinant DNA technology, approval of Review Committee for Gene Manipulation (RCGM) and GEAC is mandatory.
• If vaccine is imported into country, approval required from GEAC.
• Consists of members from Dept. of Biotechnology, Agricultural Research, Pollution Control, Food Technology etc.
• Need to confirm that product is free of contamination
• Measures taken to avoid release or damage of environment by product.
Oct 06
Heath Ministry’s Screening Committee
• Provides final approval for foreign-funded and/or collaborative
project submitted by Indian collaborator.
• Proposals are considered for review and approval after ICMR’s
technical review.
• In the case of projects on HIV/AIDS, review by National AIDS
Control Organization required.
• Information collected on
– Role/Status/Expertise of the Indian Principal Investigator.
– Type of infrastructure and manpower in institution
– Sources of foreign collaboration and funding.
– If material to be sent abroad; purpose/need of transfer; nature
of investigation to be conducted
– Material Transfer Agreement (MTA)
Oct 06
AIDS Vaccine Research in India
• First ever AIDS Vaccine trial being conducted in India raised lot of First ever AIDS Vaccine trial being conducted in India raised lot of
apprehensions amongst Regulatory and Ethics committees and apprehensions amongst Regulatory and Ethics committees and
investigatorsinvestigators
• Institutional committees required numerous meetings to address Institutional committees required numerous meetings to address
concerns (e.g. for first trial, four meetings of Institutional Scientific concerns (e.g. for first trial, four meetings of Institutional Scientific
Committee held before members satisfied)Committee held before members satisfied)
• Committees gained confidence with experience with trial process Committees gained confidence with experience with trial process
(e.g. for second trial, members from the first trial site’s Ethics (e.g. for second trial, members from the first trial site’s Ethics
Committee invited to attend meeting. Shared experience and Committee invited to attend meeting. Shared experience and
concerns with second ethics committee members. Process was concerns with second ethics committee members. Process was
faster).faster).
• National Ethics Committee reviewed trial because of public National Ethics Committee reviewed trial because of public
significancesignificance
Oct 06
AIDS Vaccine Approval Process Timelines - India
Task Name
Nari Ethic Committee
Nari Scientific Committee
Central Ethics Committee
Meeting with ICMR, NACO, DCGI, Secretary of Health, IAVI
Drug Controller of India
Genetic Engineering Approval Committee
Health Ministry's Screening Committee
Form 11
11/10
Jun '04 Jul '04 Aug '04 Sep '04 Oct '04 Nov '04 Dec '04 Jan '05 Feb '05
Task Name
TRC Ethics Committee
TRC Scientific Committee
Central Ethics Committee
Meeting with ICMR, NACO, DCGI, Union Minister of Health, Secretary of Health, TRC and IAVI
Drug Controler General of India
Genetic Engineering Approval Committee
Health Ministry's Screening Committee
Form 11
6/22
Nov '04 Dec '04 Jan '05 Feb '05 Mar '05 Apr '05 May '05 Jun '05 Jul '05 Aug '05 Sep '05 Oct '05 Nov '05 Dec '05 Jan '06
D001 Clinical Trial, TRC, Chennai
A001 Clinical Trial, NARI, Pune
Oct 06
AIDS Vaccine Trial Approval Timelines
Approval Timelines in India
0 50 100 150 200
EC
SAC
CEC
DCGI
GEAC
HMSC
Import Permit
Days from Submission to Letter of Approval
A001
D001
Oct 06
IAVI’s Clinical Research in India
• Institutional and Central Committee’s should have procedures Institutional and Central Committee’s should have procedures
and maintain record of proceedings as per GCPand maintain record of proceedings as per GCP
• Committees should provide approval letters according to GCP Committees should provide approval letters according to GCP
requirements. requirements.
• Committees are often overworked and understaffedCommittees are often overworked and understaffed
• Committee's might lack technical expertise amongst Committee's might lack technical expertise amongst
members. Simple and coherent presentations by investigators members. Simple and coherent presentations by investigators
and sponsors asked to attend sessions to answer questions.and sponsors asked to attend sessions to answer questions.
Oct 06
IAVI’s Clinical Research in India
• IAVI in partnership with Government of India and trial sites in IAVI in partnership with Government of India and trial sites in
Government institutions. Distrust amongst committees for Government institutions. Distrust amongst committees for
private agencies (e.g. CRO’s). Need to address concerns. private agencies (e.g. CRO’s). Need to address concerns.
• IAVI built capacity amongst trial investigators and staff on IAVI built capacity amongst trial investigators and staff on
GCP (via basic and advanced GCP courses) including on GCP (via basic and advanced GCP courses) including on
submissions and correspondence with committees. submissions and correspondence with committees.
• Framework and learning's useful for future HIV vaccine and Framework and learning's useful for future HIV vaccine and
Vaccine research conducted in India. Vaccine research conducted in India.
Oct 06
Key Learning’s from AIDS Vaccine Research in India*
• Importance of working with local experts/ agentsImportance of working with local experts/ agents
• Be aware of cultural differences and sensitivitiesBe aware of cultural differences and sensitivities
• Deal with long approval process & bureaucracy
• Discuss development plans and dossiers with regulatory Discuss development plans and dossiers with regulatory
agencies and scientific committees when possibleagencies and scientific committees when possible
• Understand local concerns and address them even if not Understand local concerns and address them even if not
scientifically valid scientifically valid
• Despite ICH and WHO, technical requirements and capacities Despite ICH and WHO, technical requirements and capacities
varyvary
• Global dossiers not still a reality. Need to prepare documents Global dossiers not still a reality. Need to prepare documents
according to local requirements according to local requirements
• Prepare well in advance and be prepared to be flexiblePrepare well in advance and be prepared to be flexible
*Acknowledgment Jim Ackland