Speedy approval vs safety?

June 10, 2019 0 By FM

Recently released new Indian drug rules have been hailed as allowing fast and time-bound approval within 30 calendar days for clinical trials of “Indian new drugs”. This step can improve “ease of business”, support “Make in India”, and will encourage innovation in drug discovery. But this is a major shift from the uncertain and long regulatory approval process of the last few years. Hence, the concern is how Indian health authorities (HA) plan to implement this. Will the expedited approval be at the cost of ensuring protection for Indian clinical trial participants?

The rules define an “Indian new drug” as 1) a drug discovered in India, or (2) its research and development (R&D), manufacture, and marketing are done in India. Current Indian cost of R&D, extrapolated from Dr Mashelkar committee’s 1999 estimate of Rs 150 crores, would be Rs 500 crores. In contrast, the US R&D cost estimate of $ 2.6 billion (Tufts Center 2016) or Rs 19,500 crores is 39 times higher! Considering the tremendous cost advantage, quicker approval and faster completion of clinical trials, western companies would find it commercially attractive to develop a new drug in India in collaboration with an Indian partner. Such collaborations will boost Indian drug research capabilities.

New drug development begins with phase I trials. In this first-in-human (FIH) trial, serious adverse events (SAE) can jeopardize the safety of clinical trial participants. In 2006, TGN1412 resulted in life-threatening multiorgan failure in all 6 healthy volunteers who received the first dose of the drug. In 2016, BIA 10-2474 caused the death of a healthy volunteer and SAEs in 4 participants who received the drug. Hence, thorough risk-benefit assessment of an investigational new drug (IND) is essential before approving FIH clinical trial.

US Food and Drug Administration (FDA) allows a pharma company to initiate phase I trial 30-days after receiving IND application. But FDA can place the trial on-hold if it finds that human subjects would be exposed to unreasonable and significant risk. FDA has an in-house team of pharmacologists, toxicologists and clinical pharmacologists to review IND application. Indian HA depends on IND committee for review and approval of the phase I trial.
This committee, consisting of ICMR experts and other consultants, meets at intervals of 2-3 months to review pre-clinical data – animal pharmacology, pharmacokinetic, and toxicity – and decide whether the phase I trial should be approved. The committee may ask for additional pre-clinical data or modifications in the clinical trial protocol. For Indian R&D based pharma companies, which have complained about long and unpredictable IND review process, the new 30-day clinical trial approval is a dream come true. However, unless Indian HA develop in-house expertise or establish a fast track IND committee process before the 30-day approval rule and have well-defined post-approval oversight process and clinical hold rules, Indian clinical trial participants will be at high risk from investigational new drugs.


Writer is a consultant on clinical research & development from Mumbai