Serum Institute has become the second company after Pfizer to apply for the Drugs Controller General of India (DCGI)'s approval for the emergency use of COVID-19 vaccine. Once the approvals are granted, these companies will be able to supply vaccines to the Central government to begin its multi-phase vaccination of Indian residents against the virus. Which application will pass the DCGI scrutiny first, and how quick will it be? Is there a law in India that permits such fast-track approvals? Will it compromise the safety? The announcements by these companies have generated a long list of questions in the minds of lay persons. Let's try to clear the doubts.
To be fair, both the companies have been following an international pattern in making their submissions. AstraZeneca, the company that has tied up with Serum Institute to make 'Covishield' in India, is expecting a similar emergency use authorisation request being considered in the UK. Pfizer has already received such an approval for its mRNA COVID-19 vaccine in the UK and is expecting the same from other jurisdictions. While Serum has generated data from local clinical trials, Pfizer is yet to do it and will be relying completely on the clinical trial data generated from other countries. The emergency approval will depend on both - the quality of data generated elsewhere and the credibility of the foreign regulator that has given such approval for that jurisdiction, as well as results on trials conducted within India. Pfizer has the strength of the UK approval, while Serum has locally-generated clinical trial data. Evenly poised they both appear, at least for now.
V G Somani, DCGI gives us an overview of the regulatory requirements any vaccine maker will have to follow if they market their products in India. In a webinar organised by the health ministry last week , Somani said that there is no ambiguity in the Drugs and Cosmetics Act about the regulatory pathways one needs to follow in such an emergency situation.
"On March 19, 2019 we came out with a new regulation which is in harmony with the global regulations. It has robust patient safety and data integrity mechanisms," Somani said. The accelerated (drugs/vaccine regulatory approval) review process happens according to this new rule. "The rule contains various provisions for ensuring ethical conduct of clinical trials, provisions for inspections for sites, compensation etc. Had this not been there, we would not have been in a position to do interim analysis and complete accelerated review of vaccines which are being developed in our country. These rules give provision for accelerated review which we also call as a rolling review," Somani said, explaining the current fast-track regulatory process being followed by the regulator.
The New Drugs and Clinical Trials Rules, 2019 which DCGI is talking about says that accelerated approval process may be allowed to a new drug for a disease or condition, taking into account its severity, rarity, or prevalence and the availability or lack of alternative treatments, provided that there is a prima facie case of the product being of meaningful therapeutic benefit over the existing treatment.
This accelerated approval can either be based on data generated in clinical trial in India, which is the case with Serum Institute, or can be on the basis of data from outside. The rule says that local clinical trial may not be required if the new drug is approved and marketed in countries specified by the Central Licencing Authority (DCGI) and if no major unexpected serious adverse events have been reported. A post-marketing Phase IV clinical trial as per Indian rule will be the requirement. The regulator has been allowed to relax this condition if the drug (vaccine) is indicated in life threatening or serious diseases or diseases of special relevance to Indian health scenario or for a condition which is an unmet need in India. There is also a provision to allow import of unapproved new drug for the government use for unmet medical needs.
Somani says: "If some vaccines are coming from outside the country and they have generated a lot of data, have already got authorisation and have all the phases of clinical trials over there, India can evaluate the data generated outside. if that data is found compliant with the requirement of our law, it will be relied upon." In such cases the importer (which is the case with Pfizer) or the manufacturer or the technology transfer sponsor (if the technology transfer is occurring in India like the case of Serum) will be allowed to conduct a bridging trial on the Indian population for authorisation in the emergency situation. Serum has an advantage here as its vaccine is undergoing Phase III clinical trials in India. Going by the rule book, Pfizer may also be asked to carry out a bridging study as a condition to receive the emergency approval.
If that happens, and both the vaccine candidates clear the trial successfully, one can expect more or less simultaneous launches in India in the coming months.