India may open doors to multinational pharma firms for first-in-human Phase I trials

Mumbai: India is planning a major overhaul of its pharmaceutical regulatory framework to bring its drug oversight system in tune with the best global practices. One of the key decisions being discussed is to cautiously open the doors to multinational companies to conduct first-in-human Phase I clinical trials in the country.

India has significantly strengthened its manufacturing compliance over the last two years and is looking to bolster its specialist regulatory capacity, according to top government and industry officials aware of the matter.

The government has already initiated informal discussions on allowing multinational pharmaceutical companies to conduct early-stage clinical trials in India, a move that could make the country more attractive for global drug innovation and development. Having phase one data also helps faster approvals for new products against a lag of two years or more for regulatory reviews of dossiers.


“There is a demand from international companies...discussions have started,” said a top government official who requested anonymity. A formal decision would require working out the entire process and safeguards, the person added.

As per current rules, for new drug substances discovered or developed in countries other than India, Phase I data should be submitted along with the application.

Clarity on Foreign-origin Molecules

After submission of Phase I data generated outside India to the Central Licensing Authority, permission may be granted to repeat Phase I trials or to conduct Phase II trials and subsequently Phase III trials concurrently with other global trials for that drug.

A government official also said that the existing framework for Phase I trials by Indian companies could potentially be extended to multinational companies. “The system is there. We just have to extend it,” said the official.

Australia has emerged as an attractive destination for clinical trials. The country clears applications in 4-6 weeks besides doling out financial incentives like tax credits for Phase I studies. “Not just MNCs and Chinese companies, a few Indian companies are conducting first-in-human studies in Australia,” the official noted.

Another senior industry official said for Phase 1 studies, having skilled personnel and well-equipped infrastructure and clinical capabilities is an important prerequisite. “For MNCs, India can be an important destination for new drugs research due to its population size and can be aligned with China, Australia and US,” she noted. But she cautioned that for a maximum of 20-25 subjects that may be needed for Phase I data, MNCs will take a very close look before making strategic decisions.

Kausik Maiti, vice president, Safety Medical Sciences at Parexel, one of the leading clinical research organisations, said India needs more detailed and publicly available guidelines outlining the pathway for FIH (first-in-human) studies involving molecules discovered outside the country. A risk-based approach that clearly defines the circumstances under which such studies may be permitted would help the industry. “While the pathway for Indian-origin molecules is relatively clear, there is a need for greater clarity around foreign-origin molecules,” he noted.

While sponsors or companies can discuss proposals with the drug regulators, a formal, structured and time-bound scientific advice process for early-phase programs would give greater predictability, Maiti said. Global companies should be encouraged to engage Indian regulators from the start of their development plans, which could help India join global Phase I programs, including simultaneous studies, where appropriate.

Importantly, the Indian Council of Medical Research (ICMR) has set up a national network of academic Phase I centres to build early-phase capacity. Its focus so far has been Indian-origin molecules of national health priority. Experts say this network could be extended, in a carefully defined way, to also take selected foreign-discovered molecules. Candidates could include molecules whose development would benefit the Indian population, such as those addressing diseases of high local burden.

Over a decade ago, a few alleged unethical clinical trials had forced an exodus of early stage or Phase I studies conducted by global drug makers and research institutions.

Regulatory Overhaul

The government has also initiated parallel internal efforts towards membership of the Pharmaceutical Inspection Co-operation Scheme (PIC/S), a government source said. PIC/S is a global arrangement for cooperation among pharmaceutical inspection authorities. The process is expected to take six to seven years and will involve upgrading the broader regulatory system.

“The processes have been initiated. But PIC/S is a long-term process. It takes about six-seven years,” the official said. Discussions with subject experts and other stakeholders have begun, the person added.

India is also seeking to move from observer status to the core group of the International Council for Harmonisation (ICH), a process expected to take 18 months to two years.

“Everything (PICS and ICH) must move parallelly. You cannot move in series,” the official said. “A lot of things will happen in parallel for the next five-six years, which will actually converge and culminate into PIC/S.”

The government is also looking to strengthen the regulatory workforce through 1,500 proposed recruitments.

“The file is in the final stage of approval. We should get it any time now,” the official said, adding that the hiring process could begin within three months. The positions are expected to require people with backgrounds in drug development and regulatory affairs.

Another part of the overhaul involves bringing more industry expertise into regulatory decision-making. The regulator said 21 external experts, with experience in drug development, are already participating in discussions of Subject Expert Committees (SECs), particularly in areas such as investigational new drugs, cell and gene therapies and oncology.

The push comes alongside tighter enforcement of revised Schedule M good manufacturing practices (GMP), which has triggered a fresh round of inspections and compliance action across pharmaceutical manufacturing units. Of the roughly 8,000 units in the regulator’s records, more than 1,400 have been audited so far.

The inspections have resulted in action ranging from licence cancellations to improvement notices and orders to undertake remediation.