EVOLUTION OF ETHICAL

GUIDELINES IN INDIA
BY
Dr. SIDDHARTH JAIN
M.D (Pharmacology)
Email : siddharth_jain700@yahoo.co.in
 NEED FOR EVOLUTION OF ETHICAL GUIDELINES

Following the global trend, India realized the urgent need to formulate its own
ethical guidelines specific to local conditions.

India offers unique opportunities for conducting clinical trials in view of

The large patient pool

 Qualified & well trained English speaking Investigators
 Well equipped medical institutions
 Considerably low per patient cost for trial as compared to developed countries
 CHRONOLOGY

• Govt. of India formed a Central Ethics Committee on Human Research

(CECHR) under the chairmanship of Justice Venkatchalaiah

• “Ethical Guidelines for Biomedical Research on Human Subjects” in

2000 by Indian Council of Medical Research (ICMR)

• In 2001, Central Drug Standards Control Organization (CDSCO)

published “G.C.P.: Guidelines For Clinical Trials On Pharmaceutical
Products in India”

• Revision of BE guidelines in 2003

• Schedule ‘Y’ of the Drugs & Cosmetic Act, revised in 2005

• Revision of ICMR guidelines in 2006

 DRUGS AND COSMETICS ACT 1940

• The Drugs and Cosmetics Act 1940 provides the central

legislation, which regulates import, manufacture,
distribution & sale of drugs & cosmetics in the country

• The main objective of the Act is to ensure that the drugs

available to the people are safe and efficacious and the
cosmetics marketed are safe for use

• To prevent substandard drugs, presumably for maintaining

high standards of treatment and ensuring highest quality &
purity of drugs

• The Act was enacted in 1940 has since been amended

several times

• Important rules - 122A, 122B , 122D, 122DA, 122DAA, 122E

 SCHEDULE Y

• Requirements and guidelines for permission to import and/or

manufacture of new drugs for sale & undertake clinical trials

• It was amended in Jan 2005

• Contains three main sections and 11 appendices

• It has outlined extensive study criteria in line with the globally

accepted formats such as ICH and US FDA guidelines

• The revised Schedule Y of Drugs and Cosmetic Rules devotes

significant attention to the roles and responsibilities of ECs,
Sponsor and Investigator.Composition of ECs as per the ICMR
guidelines and provides formats for the approval letter of ECs
and focuses on the conduct of clinical trials
 INDIAN GCP GUIDELINES

• Developed by CDSCO in 2001

• These guidelines have been evolved with consideration of

WHO, ICH, USFDA and European GCP and Ethical guidelines of
Biomedical Research on Human subjects of ICMR

• GCP – A shared Responsibility of Regulatory authorities,

Investigator, Sponsor, Ethics committee

• They should be followed for carrying out all biomedical

research in India at all stages of drug development, whether
prior or subsequent to product registration in India
 ICMR GUIDELINES

• As early as in 1911, the Government of India set up the Indian

Research Fund Association (IRFA) with the specific objective of
sponsoring and coordinating medical research in the country.
After independence, several important changes were made
and redesigned in 1949 as the ICMR with considerably
expanded scope of functions. The ICMR is funded by the
Government of India through the Ministry of Health & Family
Welfare

• In India, ethical guidelines were drafted by Indian Council of

Medical Research (ICMR) for conducting biomedical research in
laboratory animals and clinical trials for new drugs on human
in 2000.

• The objectives of the ICMR are in consonance with the national

health policy and aim towards improving the health of the
 QUESTIONS THAT ARISE

• Are existing guidelines and regulations sufficient and holistic

for trials to be conducted in India?

• Is there a need to develop new guidelines and regulations?

 CHALLENGES AND FURTHER REFINEMENT

Immature regulatory System

• The DCGI is severely understaffed
• Ethics committees are few in number and relatively
inexperienced
• Monitoring & Accreditation of the ethics committee--a need of
the hour
• Training of Regulators and EC members
• EC chairperson outside institute is a rarity
• Timelines for Regulatory Approval

Early phase studies in India

• Restriction of first-in-man dosing for new drug substances
discovered outside India
• No provision for micro dosing (Phase 0) studies
 CHALLENGES AND FURTHER REFINEMENT

Registration and regulation of CROs.

• Contract research organizations operating in India at close to 200
• These CROs, however, operate in a system that lacks infrastructure.
Thus, their ability to carry out their remit is of concern
• Thus to protect the Indian population it is inevitable that a mandatory
registration of CROs in a central registry should be done & some form
of regulation for CROs would be required.
Implementation of IGCP Guidelines 
• Indian pharmaceutical companies opt for fast and cheap trials
without adherence to GCP guidelines
• Urgent need for a paradigm shift from poor quality research to GCP
compliant clinical trials
• Implementation of IGCP guidelines needed for a paradigm shift
• GCP compliant trials --- tremendous impact on the industry’s clinical
trial plans and budget
 CHALLENGES AND FURTHER REFINEMENT

SOME INITIATIVES TAKEN

Pharmacovigilance
• CDSCO has initiated a well structured and highly participative
National Pharmacovigilance Programme
• Launched in November 2004
• The National Pharmacovigilance Programme at CDSCO aims
to:
• Monitor adverse drug reactions
• Review Periodic Safety Update Reports (PSURs)
• Provide information to end-users through adverse drug reaction
news bulletins, drug alerts and seminars
• But, to date, it has largely been ignored
• It remains to be seen whether the necessary technology and training
required to operate the pharmacovigilance system is actually
delivered.
 CHALLENGES AND FURTHER REFINEMENT

Trials to be registered with CTRI

• The CTRI has been set up by the ICMR's National Institute of
Medical Statistics (NIMS) which will help to
• Improve transparency and accountability
• Improve the internal validity of trials
• Confirm to accepted ethical standards
• Reporting of all relevant results of trials in India
“Single-window” and e-governance.
• A system is being developed to track and manage the complete drug
regulation process
• e-governance initiatives ---online submission of all forms, a digitalized
interactive portal, digitalization of records and online approvals with
digital sign
• By accepting e-governance no. of shortcomings like delay in review of
documents, staff shortage at DCGI can be overcome
 MORE THAN WORDS

• Formulating the Indian ethical guidelines & regulations has

been a good attempt, keeping in mind the specific Indian
conditions

• Attention must now focus on the infrastructural, resource and

ethical issues which clinical research in India must overcome.

• The answer to all these challenges lies in the 6 letter word “

ETHICS,” that comes from within and this will ensure 100%
compliance of GCP
 REFERENCES

 Lamberti MJ, Space S, Gammbrill S. Going global. Appl Clin Trials 2004;13:84-
92

 Borfitz D. Lifting India's barriers to clinical trials. Center Watch 2003;10(8):1-9

 Jayaraman KS. Outsourcing clinical trials to India rash and risky, critics warn
Nat Med 2004;10:440

 Bhatt AD. Clinical trials and regulatory tribulations. Express Pharma Pulse
2002;Nov 21:32-3

 Mudur G. Johns Hopkins admits scientist used Indian patients as guinea pigs.
Br Med J 2001;323:1204

 Indian Council of Medical Research. Ethical Guidelines for Biomedical research

on Human Subjects. New Delhi: 2000

 World Medical Association. Declaration of Helsinki

 REFERENCES

 Council for International Organizations of Medical Sciences

 Kalantri SP. Ethics of drug trials in India. Natl Med J India 2002;15 (3): 179

 Dhanya S. Nair, Health Regulatory Scenario in Clinical Trials in India

 International Biopharmaceutical Association Publication,2002

 Ganapati Mudur, India plans to audit clinical trials , BMJ  2005;331:1044

 Ezekeil J Emanuel, David Wendler,Jack Killen, Christian Grady,What makes

Clinical research in Developing countries ethical? The benchmark of ethical
research, JID, 2004 :189
THANK YOU