Investigational drug product liability laws, rules and associated instructions have for a long time not been clear in India, despite directives from the highest court on the contrary. This year, the Ministry of Health and Family Welfare (MoHFW) made considerable steps updating the New Drugs and Clinical Trials Rules, 2019 (NDCT Rules) under the auspices of the Drugs and Cosmetics Act, 1940. (D&C Act).
Recently, full-service Indian law firm Cyril Amarchand Mangaldas nicely summarized the changes to Indian law. TrialSite News, for the benefit of our readers, breaks down material changes. We include links to the attorney authors for those seeking counsel in India.
Clinical trials were traditionally conducted under Schedule Y of the Drug and Cosmetic Rules, 1945 (D&C Rules). These rules left investigational product liability issues direction open-ended. In a 2012 public interest litigation, the India Supreme Court established clinical trial approval parameters, which included A) factoring in all relevant aspects of safety and efficacy, B) focus on risk versus benefit to patient, and C) innovation as compared to existing therapeutic options and unmet medical need in the country. By 2013 D&C Rules were amended including the insertion Rule 122DAB—introducing compensation in case of injury or death during a clinical trial. The clinical trial subject was eligible for financial compensation over and above free medical management and the Licensing Authority would determine the compensational impact.
Moreover, Rule-122DAC was inserted into the D&C Rules listing the conditions for conduct of clinical trials, including A) complying with Schedule Y of the D&C Rules, B) obtaining Ethics Committee (EC) approval, C) registration of the trial with the Registry of India, and D) reporting serious adverse events. Importantly, the EC guidelines as to composition and registration were updated.
Deficiencies in the regulation of clinical trials was observed in the 59th Report of the Parliamentary Standing Committee on Health and Family Welfare on the functioning of the Central Drugs Standard Control Organization (CDSCO). After governmental delays to update, the High Court exerted pressure leading to the MoHFW to ratify changes to law March 19, 2019.
Relevant Summary of New Drugs and Clinical Trials Rules (NDCT) of March 2019
In the NDCT Rule 2(w) defines a “new drug” and it establishes the scope of applicability (e.g. not just trials but bioequivalence studies, etc.). Rule (d) defined adverse event while the Drugs Controller of India appointed by the Central Government in the MoHFW was designated as the Central Licensing Authority to act as the nexus entity for licensing and approvals under the rules (Section 3).
ECs must be set up and a trial cannot proceed without their approval. The EC registration with the Central Licensing Authority is valid for 5 years. The EC must analyze any serious adverse event arising during a trial and notify the Central Licensing Authority (Chapter III).
When applying to conduct a clinical trial, the sponsor must submit Form CT-04 to the Central Licensing Authority along with documents and other relevant information specified by the Second Schedule and Fee as specified in the Sixth Schedule (Rule 21).
Deemed Approval: as it appears Indian authorities seek to make it easier to run clinical trials there. The Central Licensing Authority will respond to an investigatory new drug application within 30 days and if the sponsor/applicant doesn’t hear back from the Authority the clinical trial is deemed to have been granted. One of the most important changes brought by the change in NDCT was compensation. Chapter VI of the NDCT Rules centers on injury or death occurring in a clinical trial. The amount of compensation is calculated based on a formula specified in the Seventh Schedule of the NDCT rules.
Manufacturing of investigational drug for the clinical trial involves the securing of permission by the Central License Authority. If permission granted it is valid for 3 years—labeling and other associated requirements delineated in NDCT Rules (Chapter VIII). Moreover, for the Import of new drugs for a clinical trial, the sponsor must secure a license from the Central Licensing Authority—valid for 3 years.
Analysis & Conclusion
The Cyril Amarchand Mangaldas’ authors note that the NDCT Rules replace Part XA and Schedule Y of the D&C Rules. The previous rules was based on “multiple stop gap measures” and the Indian attorneys believe that the updated rules lead to a more solid, comprehensive framework to regulate clinical trials in India.
However, they believe there are still matters of concern. For example, the observation that the prescribed system of compensation for clinical trial participants could be perceived as an attempt of executive branch government to surpass its mandate and engage in the domain of the judiciary. D&C Act provisions preclude payment for compensation in such cases. This, exacerbated by the fact the Central Government is not empowered to make any rules prescribing compensation, as the relevant chapters where compensation rule-making apply silent on compensation.
The net takeaway from this law firm: The D&C Act is silent on the issue of compensation and the formula established in the NDCT Rules appear to expand beyond the actual D&C Act scope (e.g. encroaching into the terrain of the Judiciary). For the time being, this is the new legal reality governing the conduct of clinical trials in India.
Cyril Amarchand Mangaldas Authors