Year : 2021 | Volume
: 12 | Issue : 4 | Page : 177--178
Role of investigational new drug committees in propelling the drug development ecosystem in India
President, Indian Society for Clinical Research, Mumbai, India
C/O, Pfizer Limited, The Capital, 1802, 18th Floor, Plot No. C- 70, “G” Block, Bandra Kurla Complex, Bandra (E), Mumbai - 400 051, Maharashtra
|How to cite this article:|
Davis S. Role of investigational new drug committees in propelling the drug development ecosystem in India.Perspect Clin Res 2021;12:177-178
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Davis S. Role of investigational new drug committees in propelling the drug development ecosystem in India. Perspect Clin Res [serial online] 2021 [cited 2023 Mar 29 ];12:177-178
Available from: http://www.picronline.org/text.asp?2021/12/4/177/326228
To streamline and give impetus to drug discovery and development in the country, the Government of India in early part of the previous decade set up Investigational New Drugs (INDs) Committee under the chairmanship of Director General, ICMR, for the evaluation of clinical trials for INDs. The government also set up 12 Subject Expert Committees (SECs), formerly referred to as New Drug Advisory Committees, consisting of experts usually drawn from Government Medical Colleges and Institutes across India that are involved in the review and approval of clinical trial protocols. Arriving at a Go/No Go decision for continued compound development is a key milestone in the clinical development cycle. Based on my experience in clinical development in both Indian and multinational research and development (R&D) environments, companies would usually take feedback on their compound's clinical development from experts outside the country and do their early clinical development in countries such as the Netherlands, Australia, USA, Germany, and the UK. The reasoning was that you could both get advice on clinical-regulatory strategy as well as conduct early-phase studies - Phase I (first in human [FIH]) and Phase IIa (proof of concept [POC]) in a very short period and then do the larger studies in multiple countries including India.
A key motivation of Indian R&D companies, many of which initially started as spin offs from their initial avatars of being a generic player (with the exception of early-stage standalone discovery companies), would be to generate revenues quickly to offset its sunk cost in R&D. In the case of many Indian R&D organizations, the avowed development path for a compound would be to quickly out license the compound to an established pharmaceutical/biotech sponsor. This is because the costs of taking the compound into Phase III program would be a herculean task on their own (e.g. for drugs for diabetes, cardiovascular disease etc.) due to the requirement of conducting a costly phase III outcomes study. This therefore puts great stress on the need to get early and timely regulatory input on the compound development to ensure that it would meet the requirements of developing the drug globally.
Since for the firm it is important to show POC as quickly as possible, even the expedited approval of submitted protocols for the Phase I and Phase IIa studies is critical. Applications for getting input into clinical & regulatory strategy for the development of the compound as well as the clinical trial protocol go to the IND committee. The New Drugs and Clinical Trial (NDCT) Rules which came into effect in 2019 provides a clearer pathway for clinical development of compounds that are discovered, developed, manufactured and marketed in India. The rules stated that for such drugs, applications for permission to conduct a clinical trial will be processed within a period of 30 working days, from the date of receipt of application.
Raj JP et al. in this issue of the journal evaluated the minutes of the IND committee meetings available in the public domain over a 2-year period (January 2017–December 2018), with an objective to understanding the areas of drug discovery and clinical development that is occurring in India as well as types of proposals. The method they undertook was to perform an audit of the available minutes of IND committee meetings. The authors point out that there are no minutes before the period and that itself points to the lack of transparency of the IND committee review process. The minutes of these meetings would also have served as a great source of learning for future generations of drug development and regulatory science practitioners. The selected period of evaluation also introduces a recency bias with regard to the proposals submitted and/or decisions made by the committee(s).
The authors point out that there is no separate policy or guideline that explains the structure and functioning of the IND committee in the public domain even though it is now almost two decades since the inception of IND committees. While the committee was set up with the intent to inform/advise the CDSCO on the applications submitted for clinical trials of the new drug, there was always the opaqueness about the how the experts were constituted, the structure and functioning, etc. In the case of early clinical development studies reviewed by the committee, it would have been a great addition to the body of literature in India if the experts views on risk versus benefit, innovation, unmet medical need, appropriateness of FIH dose, and safety monitoring were available in the minutes. While this would not be too much of an issue if the application was for only a clinical trial permission, the same would not evoke any confidence in the IND committee for an R&D organization which wants to primarily engage with the experts in a discussion on the development strategy for a compound from regulatory, clinical efficacy, and safety perspective. Even in the case of applicants requesting for clinical trial approval, it was seen that if the committee pushes back the proposal in one meeting, there would be new IND committee members in the subsequent meeting to re-deliberate on the proposal leading to the situation where the applicant has to start all over again. The same scenario when repeated for a proposal submitted to get IND committee feedback on compound development strategy can lead to loss of time, effort, and resources if the proposal is for a compound which is either going into clinical phase FIH or if in early clinical trials and is planning to move from Phase II to late development stages.
The authors bring out in their analysis that while FIH and POC studies are the ones which commonly end up for deliberation in the IND committee; there were still 12 out of 35 submitted trials (34%) which belonged to the Phase I and Phase III Clinical Trials (CTs). When an applicant raises a CT application in the regulatory system, there is no prediction as to which pathway the application would take – i.e., whether it would be considered under the IND committee or the SEC committee. There are no separate pathways in the system that guides the applicant. This has been a long-standing issue with regard to the application process that needs to be rectified and even with the advent of online application system this deficiency continues.
The level of preparation when facing an IND committee versus a SEC is entirely different. In the case of IND committee meetings in mature regulatory organizations, these meetings require the development of a “briefing book” with data being arranged in a highly standardized format on the discovery, preclinical and clinical sections with sufficient data for the reviewer. The document will also contain specific questions that the applicant would like to get answers on for the compound's development. There has been some redemption in the process within the NDCT Rules as provisions for a pre- and post-submission meeting with CDSCO are included.
The experience till date on the outcome of the pre-submission meetings has been varied with applicants not getting the in-depth feedback/nonbinding recommendations that they were looking for from a meeting of this nature. An applicant would want these meetings to have a high degree of interaction and appropriate review of the materials (submitted prior) by the experts on the panel. Sadly, the meetings are sometimes very perfunctory in nature with the committee neither well prepared with review of the submitted dossier nor having the right level of expertise in drug discovery and development, thereby defeating the original intent of these meetings which is to guide small- and mid-sized Indian R&D companies.
My wish list, as a clinical development scientist for the IND committee, would be: “A committee whose meetings are calendarized, are publicly available, are conducted in a professional ambience, which has availability of experts who have good a good mix of experience and expertise in drug R&D and most importantly has a mindset which is to nourish and support drug discovery and development ecosystem in the country.”
|1||New Drugs and Clinical Trial Rules, 2019, G.S.R. 227(E), Central Drugs Standard Control Organization, Ministry of Health and Family Welfare. Available from: https://cdsco.gov.in/opencms/export/sites/CDSCO_WEB/Pdf-documents/NewDrugs_CTRules_2019.pdf [Last accessed on 2021 Sep 03].|
|2||Raj JP, Gogtay NJ, Thatte UM. A two-year evaluation of the minutes of Investigational New Drug committee meetings. Perspect Clin Res 2021;12:199-202.|
|3||Gogtay NJ, Renju R, Thatte UM. Regulatory requirements for Clinical Trials in India: What academicians need to know. Indian J Anaesth 2017;61:192-9.|
|4||Gupta NV, Reddy CM, Reddy KP, Kukarni RA, Shivkumar HG. Process of approval of new drug in India with emphasis on clinical trials. Int J Pharm Sci Rev Res 2012;13:17-23.|