Why did India’s drugs regulator seek more data from Serum Institute and Bharat Biotech?
The story so far: The Pune-based Serum Institute of India and Bharat Biotech of Hyderabad, frontrunners among Indian vaccine makers, have been advised by India’s drugs regulator — the Drugs Controller General of India (DCGI) — to furnish more evidence that their vaccine candidates were safe and capable of preventing COVID-19. Neither company has finished testing its vaccines, but they chose to approach the drug regulator seeking ‘emergency use’ provisions.
What is emergency use authorisation (EUA) for drugs and vaccines?
The conventional process to approve new drugs or vaccines is to subject them to a clinical trial process. This means that after a prospective drug has been determined safe in animals, it is progressively tested in larger groups of people — healthy ones, if it is a vaccine — or patients, in case of a new drug.
The trials in phase 1, 2 and 3 are designed to establish the drug’s safety and efficacy, and promoters of the new drug or vaccine must furnish data from each phase to a country’s drugs regulators to satisfy them that the results are promising enough to move to the next stage. This process and the logistics of execution and evaluation are long, and it often takes years for a new entity to be commercially approved.
However, there may be several situations when the approval process must be hastened — for instance, a potential drug may be available to treat an extremely debilitating and rare disease, but there are too few potential patients to devise appropriate clinical trials; or there is an outbreak that is putting several lives at risk and no proven drugs or vaccines are at hand; or a drug or vaccine has been properly tested in one country and known to save lives and will evidently be useful in another country which has neither the resources nor expertise to subject it to a similar evaluation. It is under such circumstances that health regulators allow accelerated approvals under EUA. The latter is terminology specific to the United States Food and Drug Administration — it has just given emergency approval to a vaccine developed by Pfizer and BioNTech, the first vaccine to prevent COVID-19 approved in the U.S. — but several countries have similar provisions under similar names.
What is the process in India?
India does not have an explicit EUA provision. However, a section in the rules governing the use and regulation of drugs that came into effect in 2019 — called the New Drugs and Clinical Trials Rules, 2019 — mentions an ‘accelerated approval process’. Depending on the severity of the disease, urgency, rarity or the lack of alternative treatments, the regulator has the right to waive local clinical trials if a drug has been approved elsewhere. Also, in the case of a new drug, the medical benefits of the drug are evaluated based on the first two phases of the testing and the larger — usually more time-consuming and expensive —phase 3 trial can be deferred. It is under such provisions that first pharmaceutical companies, and then vaccine firms, were able to offer drugs such as hydroxychloroquine, Remdesivir and Favipiravir to COVID-19 patients, even though there was little evidence to show that they worked.
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Vaccine makers such as Serum Institute of India (SII), Bharat Biotech (BB), and Zydus Cadila, too, have been allowed to rely on the efficacy of data from other countries, or limited human trials to accelerate their testing process.
Why did India’s drugs regulator seek more data?
The DCGI has a Subject Expert Committee (SEC) which evaluates technical data from trials. At its meeting on December 9, the committee said that in the case of SII, it would need “updated” safety data from the company’s ongoing combined phase-2/3 trial on 1,600 volunteers in India. Because the SII’s vaccine, ‘Covishield’, is a version of the Oxford-AstraZeneca ChAdOx1 vaccine candidate, whose early results from its phase 3 trials are being scrutinised by the United Kingdom’s drugs regulators, the Indian committee also wanted to evaluate this data as well as wait for that country’s decision on the vaccine. In the case of Bharat Biotech, the regulator wanted to see data from the company’s ongoing trial on 28,500 volunteers across India.
The committee has not laid bare its reasoning, but the rules say it is free to ask for any data it terms necessary to evaluate the risk-benefit ratio of approving an untested vaccine candidate.
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What lies ahead?
Drugs regulators are not enjoined to approve a drug just because there is a pandemic. However, this is a rare historic moment when drugs and vaccines anywhere, even with the slightest promise, are being given unprecedented leeway and are nudged by the government to rapidly bring an effective vaccine to market. Companies are allowed to furnish ‘interim’ data — they do not have to wait for trials to end before approaching the regulator. In the case of SII, the approval of the ChAdOx1 vaccine in the United Kingdom could potentially mean almost immediate approval in India.
Another factor would be the frequency of adverse events and reactions. While there have been reports of volunteers in global trials — and in India too — experiencing severe reactions, none has been definitely linked to the administration of the vaccine. Being convinced that Indians, if not significantly benefit, would not come to harm at least, will be a key factor influencing the committee’s decision.