Charting a new course

July 16, 2018 0 By CH Unnikrishnan

Shedding ambiguity, India’s clinical trial climate is evolving to be more proactive and responsive, after a long indecisive phase

In 2005 Schedule Y of Indian Drugs and Cosmetics Act was amended to permit conduct of Phase 2 and Phase 3 clinical trials concurrent with Western countries in compliance with Indian drug regulations and global standard of clinical trial conduct–Good Clinical Practice (GCP). This standard requires that all stakeholders – pharma industry sponsor, clinical research investigators, and ethics committee (EC)–ensure that rights, safety, and well-being of clinical trial participants are protected. However, frequent media stories focusing on ethical deviations and exploitation of clinical trial subjects from lower socioeconomic and educational background, and 2012 Supreme Court writ petition against clinical trials compelled the Indian regulatory authorities–Central Drugs Standard Control Organisation (CDSCO)- to strengthen clinical Trial regulations. Major changes in the regulations made in 2013 were :-

1. Rule 122DD: Regulatory requirements for registration of ECs
2. Rule 122DAB: Financial compensation and free medical management for subjects who suffer from serious adverse events – injury or death–related to clinical trial to be paid by the industry sponsor
3. Audio-visual (AV) recording of informed consent, including the procedure of providing information to the subject and his understanding, by the investigator

These changes have made ECs, investigators, and industry sponsors more responsible and accountable for protection of clinical trial participants. In addition, for clinical trial approval (CTA) the sponsor must submit assessment of a) risk vs. benefit to patients b) innovation in new therapy vis-à-vis existing therapy and c) unmet medical needs. The sponsor should give an undertaking that the company will apply for marketing authorization of new drug in India after successful completion of clinical trial and submit details of financial support to the investigator for the conduct of trial. To strengthen the review, oversight and monitoring of clinical trials, the government established a 3-tier structure – subject expert committee (SEC), technical committee, and apex committee. As these regulatory changes made CTA process long and uncertain, the number of new clinical trials dropped. In response, the government made 1) pragmatic modifications in compensation conditions, 2) limited AV consent requirements to vulnerable subject in clinical trials of New Chemical Entity /New Molecular Entity trials, and 3) empowered ECs to take decisions regarding academic trials with non-commercial objectives and concerning site issues such as number of clinical trials per investigator, need for relevant infrastructure, and addition of a new investigator. The regulatory review process has been simplified, which now requires Global Clinical Trial approval by SEC without the need for review by technical committees unless the sponsor or CDSCO disagree with SEC opinion. These changes have improved the predictability and timelines.

Indian regulatory environment for clinical trials is gradually evolving from being volatile, unpredictable, complex and ambiguous (VUCA) to proactive, unambiguous, time bound and responsive to fundamental ethical requirements of protection of rights, safety and wellbeing of clinical trial participants.


Dr Arun Bhatt

Dr Bhatt is a consultant on clinical research & development from Mumbai.