India’s Expanded Trial Waiver Proposal Sets R&D Site Inspection Clause

India has proposed expanding its clinical trial waiver clause to permit such exemption for drugs already approved in ICH countries, subject to certain conditions – a move which potentially augurs well for applicant firms and could improve patient access to some critical medicines.

India’s Drugs Technical Advisory Board (DTAB) has proposed that a waiver of clinical trials for medicines already approved in International Conference on Harmonisation (ICH) countries be considered subject to two specific conditions, including an inspection by India’s Central Drugs Standard Control Organization (CDSCO) of R&D facilities for “batches manufactured for regulatory approval” of the drug.

The other rider stipulates that bioavailability/bioequivalence studies be conducted for new drugs including parenteral preparations manufactured for the first time in India where local clinical trials have been waived.

“It may also be ensured that the drug [for which a waiver is sought] is being marketed in the country of origin,” the DTAB said, as per details in the minutes of its 75th meeting held on Jan. 3, 2017.

The DTAB, the highest technical body under India's Drugs and Cosmetics Act, is chaired by Dr. Jagdish Prasad, Director General of Health Services, with the Drugs Controller General of India, Dr. G N Singh, as member secretary.

A waiver of clinical trials in the Indian population for new drugs, which have already been approved outside India, is currently permitted in cases of "national emergency, extreme urgency, epidemics and for orphan drugs for rare diseases and drugs indicated for conditions/diseases for which there is no therapy".

The proposed expanded rules for trial waivers are expected to garner interest from innovator firms seeking to introduce their products in India – it could reduce launch timelines significantly - and improve access for patients to some critical drugs, though much will depend on how these norms are implemented, if and once they are cleared by India’s Ministry of Health and Family Welfare.

Early Access

Industry experts told Pink Sheet that the DTAB appears ready to go a little beyond the original trial waiver provisions if there is enough robust global data available for a new drug, especially in ICH countries, and if there are no specific concerns per se in the Indian patient context. A blanket waivers approach is unlikely, though, they suggested.

“The thinking appears to be why not allow the company to market the drug so that patients can have early access to new medicines but at the same time also ensure that we get India specific data with post marketing studies to understand how the drug is behaving in the Indian population,” Suneela Thatte, president of the Indian Society for Clinical Research told Pink Sheet. The ISCR’s members include several large multinational firms and clinical research organizations.

Thatte noted that the proposed trial waiver conditions are not “add-on processes” but supplement those already in place.

“They are an important step towards enhancing the robustness of the drug approval process. These steps must be seen against a recent comment by the minister of health and family welfare that India-specific diseases need focused attention,” Thatte explained.

Importance Of Trials, PMS

India’s health minister, Jagat Prakash Nadda, was recently reported in the local media as underscoring the significance of the clinical trials segment. The minister noted that with an increasing disease burden and emergence of new disease variants, some of which are specific to India, trials become “all the more” important.

An industry expert in the trials segment told Pink Sheet that he was unsure of the additional value that the inspection of innovator R&D sites would bring under the proposed new trial waiver clause given that most of the data would have probably been vetted by reputable regulators; such plans could also require a more coordinated effort with foreign regulators.

The expert also suggested that India should focus on making its postmarketing surveillance efforts robust, backed by a more standardized approach.

India's clinical research sector has, in general, been dented amid uncertainties and delays caused by evolving regulations and ongoing trial-related litigation among other factors. There have, however, been concerted efforts over the recent past to streamline the regulatory process. (Also see "Indian Clinical Research Sector: Hope And Despair Amid Shutdowns" - Scrip, 26 Aug, 2016.)

Last year, Informa’s Trialtrove noted how the “rosy view” of India as a location for relatively low-cost clinical trials with a readily available, treatment-naïve patient population became shaded over the past five years by an untenable time to approval.

Previous Recommendations

The latest trial waiver proposal appears to be an outcome of certain previous DTAB recommendations in the area, though ISCR’s Thatte cautioned that they are still recommendations and not part of the legal framework/regulations yet.

“We will need to see how these are further crystallized in legal requirements,” Thatte maintained.

The DTAB had opined, in a meeting in February 2015, that if a new drug is approved and marketed in a “well-regulated” country, the waiver of clinical trials in the Indian population for marketing approval of the new drug may be granted, provided “evaluation of safety, efficacy, effectiveness and need of the drug is found favorable” and the plan for postmarketing surveillance of the drug is approved.

“The DTAB further advised that the evaluation of such new drugs should be made scientifically in consultation with the subject experts in the specific therapeutic area,” details in the minutes of the DTAB’s Feb 16, 2015 meeting stated.

The minutes also referred to the recommendations of the government-appointed expert committee for reforms in drug regulation and clinical trials chaired by Professor Ranjit Roy Chaudhury (who passed away in October 2015). The committee, details in the minutes said, had recommended that drugs which have already been on the market in “well-regulated” countries with “good” PMS for more than four years, and that have a “satisfactory” report, may be granted a marketing license, subject to “strict” postmarketing surveillance for four to six years.