The NDA Government’s hallmark ‘Make in India’ programme can potentially be a game-changer in fulfilling Prime Minister Narendra Modi’s dream of transforming the currently anaemic $2 trillion economy into a $20 trillion power house.

Achieving this vision would necessitate a sustained, year-on-year growth of 9 per cent going forward. The pharmaceuticals and biotechnology sectors can play a significant role in this growth story if the government institutes a single-window clearance system for regulatory licenses.

The growth targets set for India’s healthcare sector are nothing new. The drivers of this growth – low-cost labour, technical skills and scientific excellence, all backed by a robust product patent regime – have existed for decades. Yet, the sector has not been able to actualise its innate potential. One of the major reasons is the contradictions built into the regulatory system.

The need of the hour is a top-to-bottom restructuring of the convoluted framework that regulates the introduction and manufacture of novel and generic drugs in India. This step is critical to get newer, cheaper and more effective medicines to the market much faster than what is possible now. It is instructive to take a look at how the system currently works.

Three futile steps

Only those drugs get licensed which have been established as safe and effective in clinical trials for defined therapeutic actions. Safety and efficacy of a drug is first tested in animals, then on healthy volunteers and, lastly, in actual patients. A drug typically goes through three phases of human clinical trials – Phase I to III – before it gets manufacturing and marketing authorisation from the regulator, the office of the Drugs Controller General of India (DCGI).

An application to DCGI, whether it is to start a clinical trial or review its results, undergoes several rounds of written queries and responses between the regulator and the developer. This scrutiny usually takes months. A go-ahead by DCGI is not a grant of permission to start the clinical trial or, based on its results, to move to the next phase.

It is instead a referral to the New Drugs Advisory Committee (NDAC) or Investigational New Drugs Committee (IND).

Both of these have several external experts who are expected to study about ten DCGI proposals for every meeting, each consisting of hundreds of pages of study and research. NDAC and IND typically take less than half an hour to evaluate an issue that DCGI has pored over for months, and the developers have worked on for years.

All recommendations of the NDAC and IND are reviewed by a Technical Committee and approved by an Apex Committee, which consists of ministry officials. In actual practice, these two committees rarely challenge an NDAC decision, while NDAC is known to regularly turn down or amend DCGI referrals.

The appellate process for the cumbersome three-tier review remains unclear. It applies to each phase of a clinical trial: before commencing the study and subsequently to review its results.

The advice of DCGI is based on months of investigation by full-time experts within the agency. When this is overturned by NDAC/IND, it undermines the authority and credibility of the institution. It is also confusing and demoralising for the scientists who may have been doing research for years based on DCGI’s advice. The country and industry can ill-afford such wastage of time and resources.

The procedure elsewhere

Consider a hypothetical situation in which DCGI approves a comparative, two-arm clinical trial involving 112 patients. The NDAC may mandate to drop one arm of the study. This would mean that the protocol has to be revised by the developer and reviewed again by DCGI.

The process could take months. It would instead be more sensible to make NDAC’s evaluation a part of the initial review by DCGI. Asking for an evaluation after the event is counter-productive for all concerned.

In developed nations, the process is far more efficient. The US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) finalise the regulatory pathway for all clinical trials upfront.

The entire pathway, from Phase I to III, is discussed and agreed upon by everyone involved in development and regulation of drugs before the clinical trials start.

Protocols submitted before the commencement of clinical trials have deemed clearance if they are not challenged within a stipulated time period, which is about thirty days. There are platforms available for continuous interaction between the regulator and the developer for course correction. At the end of the Phase III study, a dossier is submitted to the regulator.

It is thoroughly reviewed by several teams of domain experts within the office of the regulator before the manufacturing and marketing authorisations are given.

In stark contrast, our three-tier reviews are counter-productive because they are post-facto . There is a need to expand the office of the DCGI to include teams of full-time specialists at least in areas like chemistry manufacturing and control, pre-clinical, clinical, statistics, data management, medical writing, toxicology, quality, pharmaco-kinetics and pharmaco-vigilance.

The DCGI must be the final authority for the licensing process with a similar model of single-window clearance as the EMA or FDA.

This will speed up the regulatory process and establish much-needed predictability in the various steps involved in developing and licensing drugs in the country.

The writer is International Director, Bharat Serum and Vaccines

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