India Proposes Safeguards For Gene Therapies
Executive Summary
India has proposed establishing a Gene Therapy Advisory and Evaluation Committee that will comprise independent experts to monitor all GTP clinical trials.
The deadline is nearing for stakeholders to comment on India’s proposal to establish a national guideline to support the research and development of gene therapy products (GTPs). The proposal clarifies that any GTP of foreign origin, or its modified variants, that is first-in-human use is not permissible for direct first-in-human trials in India.
The Indian Council for Medical Research has developed a draft guideline on the “nascent” field of GTPs “emerging in India” and is accepting comments from stakeholders until 1 August.
The guideline, when finalized, will help close a gap in the regulatory framework, which came to light when industry and scientists started approaching regulators for advice and directions regarding requirements for preclinical studies and clinical translation of GTPs.
The guideline clarifies that as per the New Drugs and Clinical Trial Rules (2019), GTPs fall under the definition of a “new drug” and shall always be deemed to be a new drug. (Also see "India's New Trial Rules Tick Right Boxes, Shed Interim Compensation Clause" - Pink Sheet, 31 Mar, 2019.) “Thus as per these rules ‘academic trials’ are not applicable to clinical trials using GTPs,” it states.
The draft guideline recommends, among other things, establishing a multi-disciplinary Gene Therapy Advisory and Evaluation Committee (GTAEC) under the aegis of the health ministry’s Department of Health Research. The GTAEC would be responsible for, among other things: advising sponsors on how to design GTP trials; monitoring all first-in-human or existing GTP trials; providing pre-investigational new drug (IND) consultation if required by the applicants; and periodically reviewing and updating GTP guidelines.
The guideline proposes a number of measures to ensure that the necessary safeguards are in place involving GTP research. It recommends:
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- Making it mandatory for all institutions and entities engaged in the development of GTPs to establish an Institutional Bio-Safety Committee (IBSC), constituted as per the Regulations and Guidelines on Biosafety of recombinant DNA Research and Biocontainment 2017. Research involving the development of new GTPs should be approved by the IBSC and the institutional ethics committee.
- Requiring additional approval of the Institutional Committee for Stem Cell Research (IC-SCR) if GTP research involves stem cells.
- Requiring prior approval from the Review Committee on Genetic Manipulation (RCGM) for all GTPs.
- Ensuring that all clinical trial applications for GTPs are evaluated by the GTAEC before these are submitted to the Central Drugs Standard Control Organisation.
- Making it mandatory for sponsors to obtain approval from the institutional ethics committees of the participating sites/institutions before initiating a GTP trial.
For an imported GTP or its modified variants, the guideline states that these must undergo preclinical animal model studies and receive approval from the RCGM followed by the GTAEC and the CDSCO for permission to begin first-in-human trials in India. Moreover, for international collaborative projects/global clinical trials it is mandatory to have prior approval from the Health Minister’s Screening Committee (HMSC) and this information should also be made available to the GTAEC.
The guideline explains the responsibilities of investigators, institutions, sponsors and institutional ethics committees involved in GTP research. It also outlines considerations for chemistry, manufacturing and control, quality assurance and product attributes for human gene therapy products. In addition, it specifies requirements for good manufacturing practice, preclinical evaluation of investigational strategies/products for gene therapy, and clinical trials.
The ICMR explained that it has proactively developed the draft guideline in consultation with the experts in the field and government agencies, including the Department of Biotechnology and the CDSCO. When finalized, the guideline is expected to promote further research and streamline regulatory processes for future clinical trials using GTPs.