New Delhi: The Covid-19 vaccine process in India has suddenly been accelerated after three manufacturers — Pfizer, Serum Institute of India and Bharat Biotech — applied for emergency use authorisation. The move has spread cheer by boosting hopes of the vaccination process beginning soon, and speculation is rife that there might even be a vaccination ‘event’ before the year ends, possibly on late PM Atal Bihari Vajpayee’s birth anniversary, 25 December.
The National Expert Group on Vaccine Administration for Covid (NEGVAC) has met at least nine times since its inception in August, and there have also been multiple meetings with states and political parties, chaired by Prime Minister Narendra Modi, to discuss the modalities of vaccine administration.
However, crucial questions about the vaccine rollout remain unanswered, including funding options, geographical distribution of vaccines, and the extent of regulatory discretion. ThePrint lists out five such questions.
Of the three vaccine candidates that have moved for emergency approval, two are currently being manufactured in India and are in Phase-III clinical trials. The Serum Institute of India (SII) claims to have readied four crore doses of the vaccine it is manufacturing, which was developed by Oxford University and then put on trial in various countries by AstraZeneca.
India’s vaccination plans have identified about 30 crore people as ‘priority groups’, who will likely be the first recipients of the vaccine. This includes doctors, other healthcare workers, the elderly and those with co-morbidities. That alone would require 60 crore doses, since all these vaccine candidates require two doses. Budgeting for some wastage in transit etc., India would need at least 70-80 crore doses to complete vaccinating just these priority groups — a demand that no one company would be able to meet.
So, the question of choice of vaccine arises — does a recipient or even a state get to choose which vaccine s/he wants, or would the choice of which state gets what vaccine be made by the central government?
This question has been debated in the NEGVAC, but there are no clear answers yet. A small subgroup that has been involved with India’s vaccination programme for years, including some members of the National Technical Advisory Group of Immunisation (NTAGI), has deliberated on this and sent its recommendations to the NEGVAC.
“Two things have been highlighted by the expert group in the context of multiple vaccines being approved for public health use. The first, and very important, thing is that since most of these are two-dose vaccines, it has to be ensured that every person gets two doses of the same vaccine. They have also said that logistics and geographical considerations need to be respected,” a senior official told ThePrint.
The easiest solution, sources say, is to limit one type of vaccine to one geography rather than mixing them up. There is also a precedent — old-timers in the health ministry recall that when the Japanese Encephalitis vaccine was being rolled out in 2013 (only for endemic districts and not the whole country), the NTAGI had deliberated on the question of how to choose between a live attenuated vaccine and a killed vaccine. It had recommended to the government that the two kinds of vaccines should not be mixed, and there should be only one kind of vaccine given to a particular location.
Whether to procure at different prices
Government procurement rules usually go by the lowest bidder principle. However, the three vaccines that have sought emergency-use authorisation are likely to be priced differently.
SII has already said that it would sell to the government at a price of $3 or Rs 225 per dose. For individual buyers, though, it may cost double that amount. Pfizer has not said how much its vaccine will cost in India; it is selling for about $20 per dose abroad (approximately Rs 1,460).
NEGVAC sources claim there has been no conversation with Bharat Biotech on prices. Its MD Krishna Ella had said the vaccine would cost “less than a bottle of water”, but it is yet to come out with a number.
Officials are divided on whether procurement rules allow purchase of products at such widely varying prices. “We can probably ask the L2 (second lowest bidder) whether they will give at L1 (lowest bidder) rates. Or maybe, because vaccines are proprietary items, we can procure at different rates,” said one health ministry official.
Another official said: “Financial rules allow for such procurement of vaccines. But you have to also understand that once Indian vaccines hit the market, all these airy-fairy $10-20 prices will crash. There will be a significant disruption in the market.”
That, at least, has been the case with Covid testing kits — the initial price ceiling of Rs 4,500 was brought down to Rs 800 within just 10 months with more and more indigenous manufacturers producing them.
There have been multiple meetings between the Centre and states since the start of the pandemic, and at least three, including one chaired by PM Modi himself, have been to discuss the modalities of vaccine administration. There have also been multiple official communications from the Centre to the states on the need to prepare to monitor adverse reactions, on the guidelines for vaccination etc.
However, officials say there has been no discussion so far on the funding pattern. Congress-ruled states too have now started to raise the issue, asking for more clarity. It is a question that will have bearing on a lot of issues, including the choice of the vaccine.
A senior health ministry official said: “This has not been discussed yet. So far, the understanding is that we are supplying the states with three things — syringes, vaccines and the existing cold chain setup. On the long-term funding pattern of vaccines, there has not been any discussion yet.”
Under the Universal Immunisation Programme, the cost of vaccines is borne by the Centre and states in a 60:40 ratio respectively. Officials do not rule out such an arrangement at least at a later stage, and also the possibility of states being allowed to procure vaccines on their own, as was done for testing kits.
“I can assure you that the Department of Expenditure has kept aside a sizeable sum for the procurement of vaccines,” said another senior official.
Regulatory discretion: How much is too much?
Although all three vaccines have applied for emergency use authorisation, the phrase itself does not appear in the New Drugs and Clinical Trial Rules, 2019. However the rules allow the regulator enough discretion to make exceptions, based on the guidance of the relevant expert committees.
According to the Central Drugs and Standards Control Organisation: “The requirement of non-clinical and clinical data may be relaxed, abbreviated, omitted or deferred under life threatening or serious disease conditions or rare diseases and for drugs intended to be used in the diseases of special relevance to Indian scenario or unmet medical need in India, disaster or special defence use e.g. haemostatic and quick wound healing, enhancing oxygen carrying capacity, radiation safety, drugs for combating chemical, nuclear, biological infliction etc. However, such relaxation, abbreviations, omission or deferment of data will be evaluated on case-by-case basis depending on the nature of the new drugs, proposed indication, etc.”
For the three vaccines in question, only one — Pfizer’s — has been approved abroad. India has a provision for clinical trial waiver for products approved in some countries, including the UK. But since the UK too has given only emergency use authorisation, which means that the full process of approval was not completed, it makes the decision tricky for the Indian regulator.
The approval by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK has already been criticised by Dr Anthony Fauci, director of the US National Institute of Allergy and Infectious Diseases, as not having been “rigorous” enough. The Pfizer vaccine, after conclusion of the Phase-III trial, was found to be 95 per cent efficacious.
The SII is still conducting Phase-III trials in India, and is also caught up in a controversy over two doses versus one-and-a-half doses that the international trial anchored by AstraZeneca got embroiled in. AstraZeneca had found the one-and-a-half-dose model more efficacious.
The SII has included Phase-III trial data from Brazil and also from India in its application, sources say, but for the regulator, the key question would be how much to trust that data. In India, the trial was approved for two doses and that is what it is proceeding with.
Bharat Biotech is the most recent entrant into the Phase-III trial arena — as late as 16 November, and just two days before Pfizer announced the conclusion of its Phase-III trials. The fact that Bharat too has moved for emergency use authorisation has set India’s pharma firmament abuzz with speculation about whether it would get preferential treatment, being the sole indigenous contender. Bharat’s vaccine was developed in association with the Indian Council of Medical Research, unlike Pfizer’s which is wholly foreign and SII’s, which is only manufactured in India, but not developed.
What lent credence to this speculation was the alacrity with which the government responded to Haryana Health Minister Anil Vij testing positive after the first does of Bharat Biotech’s Covaxin, against its prolonged silence on a SII volunteer’s legal notice to the company, apparently after having suffered a serious adverse event. In the first case, the government responded within hours; in the second, it took many days and many media queries.
Phase 3 clinical trial of COVAXIN™️ takes off as the largest efficacy trial ever conducted in India, with about 26,000 participants. pic.twitter.com/qyCkoOkUl9
— BharatBiotech (@BharatBiotech) November 16, 2020
“All countries give emergency use authorisation. But there is obviously a grey area there because it is not out laid in black and white, and is open to interpretation. We will have to wait and see what the Indian regulator decides,” said a senior health official.
What to do about refusals?
There are apprehensions that even among the first batch of priority recipients, there would be people unwilling to take the shot.
“We cannot force anybody. It is not mandatory,” a senior health official clarified.
In an article for ThePrint, Dr Kabir Sardana from Delhi’s RML Hospital had argued against universal vaccination unless it is free for all; his main argument being that after the pandemic has run its course for so long in the country, many Indians already have a viable T-cell response that make the vaccine redundant and needlessly expose them to side-effects.
India has already made it clear that it is not looking at free universal vaccination.
While states have been asked to step up communication to counter vaccine hesitancy, India will also need to take a call on whether it can allow doctors and healthcare workers in particular — who are constantly in touch with vulnerable, immune-compromised patients — to go about their job without getting vaccinated as and when the product is available.