Dr Siddharth Jain

EVOLUTION OF ETHICAL GUIDELINES IN INDIA BY Dr. SIDDHARTH JAIN M.D (Pharmacology) Email : [email protected]

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

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“Ethical Guidelines for Biomedical Research on Human Subjects” in 2000 by Indian Council of Medical Research (ICMR)

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In 2001, Central Drug Standards Control Organization (CDSCO) published “G.C.P.: Guidelines For Clinical Trials On Pharmaceutical Products in India”

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Revision of BE guidelines in 2003

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

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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

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It was amended in Jan 2005

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Contains three main sections and 11 appendices

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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