With an aim to fast-track approvals for foreign manufacturers to market their Covid-19 vaccines in India, the government on Tuesday announced that vaccines that have been granted emergency approvals by US, UK and Japanese regulators, and those listed by the World Health Organization (WHO), may be granted emergency use approvals in India.
The move comes at a time when vaccine shortages are being reported from various parts of the country. The Centre said the decision will facilitate quicker access to foreign vaccines in India. India’s current vaccination programme involves two vaccines — Covishield (Serum Institute of India) and Covaxin (Bharat Biotech) — while the expert body of the national regulator has recommended emergency use approval for Russia’s Sputnik V.
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What are the rules on regulatory approvals for foreign Covid-19 vaccines?
The New Drugs & Clinical Trials Rules, 2019 mandate that whenever a foreign manufacturer applies for emergency use authorisation of vaccines, it has to submit the result of local clinical trials. These trials are called bridging trials, in which the manufacturers conduct phase 2/3 studies to collect safety and immunogenicity data. Since the efficacy data is already established at a foreign site, limited participants are enrolled (around 1,000) and a clinical trial is conducted to ascertain if the vaccine is safe in the Indian population.
On the basis of this rule, Serum Institute conducted a bridging trial of Covishield, which is a version of the vaccine developed by the University of Oxford and AstraZeneca, and Dr Reddy’s conducted an bridging trial of the Sputnik V vaccine from Russia.
The Rules also empower the regulator to relax the rules if the vaccine has been approved by the national regulator of another country. These relaxations are invoked if there “no major unexpected serious adverse events have been reported” in the vaccine; and if the vaccine is indicated “in life-threatening or serious disease” or “special relevance to Indian health scenario”; and for an “unmet need in India”.
This clause has now been invoked; India has technically waived the pre-condition to conduct phase 2-3 trials at Indian sites.
What does this mean for foreign manufacturers?
Any vaccine manufacturer whose Covid-19 vaccine has received approval for restricted use by the foreign national regulators USFDA, EMA, UK MHRA or PMDA Japan, or which are listed in WHO (Emergency Use Listing), can come directly to India and get emergency approval for the vaccine. It fast-tracks the process for approval.
How will the regulator then assess the safety of these vaccines?
It has introduced a special condition, under which foreign manufactures have to assess the first 100 beneficiaries for seven days for safety outcomes before it is rolled out for further immunisation programmes in India.
After approval, a parallel bridging clinical trial will continue and the manufacturers have to submit the safety data to the regulator.
What are the implications of the changes?
The decision will facilitate quicker access to such foreign vaccines. Second, it will be the first time that India starts importing foreign vaccines for Covid-19; currently, only vaccines manufactured domestically are being used in the vaccination drive ((Sputnik V is being manufactured in India under collaborations with the Russian developers). Third, local manufacturers can import these vaccines in bulk from foreign companies, and utilise their domestic infrastructure to fill these in India.
Since India is considered the vaccine capital of the world, it can utilise the third option to ramp up vaccine production.
Which companies are likely to benefit?
US pharma giant Johnson & Johnson, the only manufacturer with a single-dose Covid-19 vaccine, has communicated to the Indian regulator that it will soon begin bridging clinical trials in the country. With Tuesday’s decisions, it can directly use this route to introduce its product in India.
The J&J vaccine has run into a hurdle in the US, where the regulator has temporarily paused its use following reports or blood clots. This does not affect the company’s application to India, as it received approvals from the WHO on March 12.
The new move may also see Pfizer reapply for emergency use authorisation for its mRNA Covid-19 vaccine, which it had earlier withdrawn after the regulator sought more data. India could also see the US-based Moderna entering the market.
The move opens up a door for Serum Institute to seek speedier approval for Covovax, its version of the Covid vaccine developed by Novavax. The American vaccine maker had said in March that it could file for authorisation for this vaccine in the UK, and for EUA nod in the US, by the early second quarter of 2021.
How much will the doses cost?
In the absence of any vaccines having been approved by this route yet, Health Ministry officials said it would be speculative to discuss costs now. As of now, Covaxin and Covishield are being administered at Rs 250 a dose in private hospitals. In January, the Ministry had cited the price of a single dose of the Pfizer vaccine at Rs 1,431 (not including overhead cost and taxes). The price of a single dose was Rs 2,348-2,715 for Moderna’s vaccine, Rs 5,650 and Rs 1,027 respectively for Chinese vaccines from Sinopharm and Sinovac, and Rs 734 for Sputnik V. The price of the single-dose vaccine developed by J&J was cited as Rs 734.
Can India import Chinese vaccines, when China is not on the list of regulators recommended?
This is possible, through the WHO Emergency Use Listing. The EUL pathway involves a rigorous assessment of late phase 2 and 3 trial data as well as substantial additional data on safety, efficacy, quality, and a risk management plan. These data are reviewed by independent experts and WHO teams who consider the current body of evidence, the plans for monitoring the vaccine’s use, and plans for further studies.
As part of the WHO’s EUL process, the vaccine manufacturer continues to generate data to enable full licensure and WHO prequalification of the vaccine. The WHO prequalification process assesses the additional clinical data generated from trials and deployment on a rolling basis to ensure the vaccine meets the necessary standards of quality, safety, and efficacy for broader availability.
In fact, on December 31, WHO issued its first emergency use validation for a Covid-19 vaccine: Pfizer/BioNTech’s mRNA vaccine. On February 15, WHO listed for emergency use two versions of the AstraZeneca/Oxford vaccine (including Covishield; the other is a South Korean version), giving the green light for these vaccines to be rolled out globally through its COVAX programme.
On March 12, the WHO listed Johnson & Johnson’s Ad26.COV2. for emergency use in all countries and for a COVAX rollout.
Which newer vaccines are expected to figure in the WHO EUL list?
One is a vaccine developed by Chinese state-owned company Sinopharm, called BBIBP-CorV. Another is a vaccine developed by Beijing-based biopharmaceutical company: CoronaVac.
In both these vaccine, the WHO has held a pre-submission meeting and a final decision is expected at the end of April.
There are other vaccines whose expressions of interest have been accepted, and whose pre-submission meetings are still to be held. These are EpiVacCorona, developed by Vector State Research Centre of Virology and Biotechnology; and a Chinese vaccine developed by Zhifei Longcom, IMBCAMS, and Clover Biopharmaceuticals.
Will vaccines be now made available in the commercial market?
Not yet. Currently, the decision is only with respect to approvals for foreign vaccine manufacturers. No decision has been taken by the Centre on if, or when, vaccines will be made available to the private market. The outcome of that decision will largely depend on how many foreign vaccine manufactures are willing to seek approvals to commercially market their products in India.
One should also remember that most of the promising candidates, including Pfizer, Moderna and Johnson & Johnson, have made advance commercial commitments to supply millions of doses to other countries.