Illustration: Martina Bulkova/pixabay

On May 14, NITI Aayog member Vinod K. Paul shared the Centre’s new plan to procure over 2.1 billion COVID-19 vaccine doses between August and December 2021.

The plan includes eight vaccines: Covishield and Covaxin, both currently in use; Sputnik V, which India’s drug regulator has approved; and five others that are undergoing trials.

The Centre plans to obtain 1.3 billion doses of Covaxin and Covishield; 200 million doses of Novavax’s vaccine, to be produced by Serum Institute; plus 100 million doses of Bharat Biotech’s nasal vaccine. As such, the plan banks on the two existing manufacturers – Serum Institute and Bharat Biotech – to the tune of 74%.

Until today, the Centre has already ordered 266 million doses of Covishield and 80 million doses of Covaxin. State governments and private hospitals have separately ordered another 160 million doses (presumably all of Covishield since we know Bharat Biotech isn’t yet taking orders from states). The two manufacturers are expected to fulfil all these orders by July 2021.

As of May 12, India had administered 178 million doses – 160 million of Covishield and 18 million of Covaxin.

Covishield and Covavax

A simple calculation tells us that Serum Institute is expected to supply 106 million doses to the Centre and 160 million to state governments by July, which is barely three months away. This expectation far exceeds the company’s stated capacity – to produce around 65 million doses a month, and even this target the company has yet to meet.

Considering India has already exported 66 million Covishield doses, Serum Institute has thus far produced 226 million doses in four months, from mid-January to today. Remember that this company had claimed that it had stockpiled almost 100 million doses by the first week of January, a short while before India’s vaccination drive began. Assuming a lag of one month between production and supply for testing and release, the average monthly production works out to 42 million – about 65% of the stated capacity. This could be due to material constraints, as the company has also been pointing out.

In addition, its plan to increase capacity to 100 million doses per month has been delayed from May 2021 to July 2021, even as it struggles to utilise its existing capacity.

Now, the Centre expects 750 million doses of Covishield from Serum Institute from August to December, at 150 million doses per month. Serum Institute is also expected to supply 200 million of Novavax’s vaccine, ‘Covavax’, taking its total expectation to 950 million doses in five months – at the rate of 190 million per month.

In other words, this is an expectation for the company to improve its performance 5x, increase its current stated capacity by a factor of three and nearly double the capacity that the company hopes to achieve from July. This is a very, very long shot.

Serum Institute commenced bridging trials for Covavax at the end of March 2021, and delayed its launch from June to September 2021. These announcements came before the US-based Novavax said that it would file for authorisation in the US and Europe only in the third quarter of 2021. So the odds of India getting Covavax before the end of 2021 appear dim at the moment.

Indeed, Serum Institute supplying 500 million doses for Indians between August and December 2021 will be a commendable achievement – given that the company’s material constraints are yet to be resolved and its export commitments aren’t very flexible.

Covaxin and BBV154

The Centre has also ordered 80 million doses of Covaxin doses. Of this, 18 million have already been administered and another quantity must be in the pipeline. With its new plan, the Centre expects Bharat Biotech to supply 550 million doses between August and December 2021. There is reason to think this is yet another long shot.

Bharat Biotech’s actual performance has been only about 5 million doses per month in the last four months. On April 20, it announced plans to increase its capacity to approximately 700 million doses a year, but without indicating a timeline to achieve this milestone.

That said, the company’s expanded capacity would only enable 60 million doses a month, whereas the Centre’s plan already expects an output of 110 million doses a month from August.

The Centre has assumed the task of augmenting Covaxin production under a mission called ‘Covid Suraksha’. It is readying three units – Indian Immunologicals Ltd., Bharat Immunologicals and Biologics Ltd, and the Haffkine Institute – to manufacture Covaxin. The first two are expected to produce 10-15 million doses per month and Haffkine, 20 million doses per month. Haffkine has also said that it will be a year before the vaccine becomes available, although the government is pushing it to start supplies in six months.

The Centre’s plan expects an increase in manufacturing capacity from 10 million doses in April to about 60-70 million doses per month by July or August. A further increase to nearly 100 million doses by September is on the anvil.

Bharat Biotech also announced on March 14 that the Biovet plant near Pune is expected to become fully functional by the end of August. We don’t know the capacity of this plant, however.

It seems that the increased output of Covaxin will come from five different manufacturing locations, four of which were identified only recently. Technology transfer, materials and trained personnel constraints are sure to be significant in the short run. No doubt taking these steps today will help India in the longer term but the government expecting an average output of 110 million doses per month from August is just unreasonable.

It will be a great achievement even if the combined efforts of all the companies involved in this exercise generate an output of around 200-250 million doses of Covaxin in the last five months of 2021.

The plan also includes 100 million doses of Bharat Biotech’s adenovirus nasal vaccine, BBV154. The company co-developed the vaccine with Biologics Therapeutics Centre, the Washington University School of Medicine, St. Louis., and is currently reviewing interim safety and immunogenicity data from a phase 1 trial involving 175 participants. Bharat Biotech is also evaluating the need for a booster dose. For now, it is not clear if India’s drug regulator will approve it for use before phase 3 clinical trials.

In September 2020, the company had revealed an intention to manufacture a billion doses a year of the single-dose nasal vaccine at its Hyderabad facility.

Sputnik V

Next, the Indian government expects 156 million doses of Sputnik V between August and December this year. The first dose of this vaccine was administered on March 14, at a cost of Rs 995, from the 1.5 lakh doses that Dr Reddy’s Labs has imported from Russia.

Sputnik V is an adenovirus-vector vaccine that needs to be stored at -18º C, which presents a challenge for India, a country that lacks the corresponding refrigeration infrastructure. Another peculiarity is that the two doses of Sputnik V have different composition.

Although Dr Reddy’s has an arrangement to distribute 250 million doses in India, it is not clear if this requirement will be met from imports or from local manufacturing – and right now both options appear tough.

Russia has administered fewer than 23 million doses of Sputnik V in its own population. And as of May 12, Russia had produced only 66 million doses of Sputnik V and had exported fewer than 30 million.

A Moscow based biotech firm called R-Pharm had planned to produce 10 million doses of Sputnik V every month – but by late March had not produced even a million doses. As such, Russia seems stumped about scaling up production at the moment. And against this context, it is hard to see how India can get 156 million doses by December 2021.

Biological Evans’ vaccine candidate

The Centre expects 300 million doses of a two-dose vaccine candidate to be manufactured by Biological Evans in India. This protein-based vaccine uses an antigen developed by the Texas Children’s Hospital Center for Vaccine Development.

On April 24, Biological Evans received permission to start a 1,268-participant phase 3 clinical trial in India, as part of a larger, global study. The company has also said it will apply for emergency use authorisation based on government advice and directives. Will the Indian regulator grant its approval without results from the global trials? From the public healthcare point of view, it should not.

Anyway, Biological Evans plans to produce 75-80 million doses a month from August 2021, so capacity should not be an issue.

Zydus Cadila’s vaccine candidate

The Centre’s plan includes 50 million vaccine doses of a three-dose DNA vaccine candidate being developed by Zydus Cadila. This company began recruiting participants for the phase 3 trials around January 20, 2021.

The company plans to submit interim data to seek ’emergency use’ approval this month and to start supplying vaccine doses from June, with an intended production of 20 million doses per month.

A fortnight earlier, Zydus Cadila managing director Sharvil Patel had said that the company would produce 10 million doses at an in-house facility and contracted manufacturers would produce the remaining 10 million; the company is already in talks with them.

Of all the vaccine candidates in the plan, this one appears the most doable, at least based on the available information. Note, however, that the quantities in play are relatively small.

Gennova’s vaccine candidate

Pune-based Gennova Biopharma and Seattle-based HDT Bio are jointly developing an mRNA vaccine candidate. And the Centre plans to have 60 million doses of this shot by the end of this year. Gennova commenced phase 1 and 2 trials this month, after a delay of six months. It already has the capacity to produce 200 million doses a year, and which it plans to increase to a billion.

The bigger question with this product is if the Indian regulator will approve it sans phase 3 trial data.

§

In sum, of the 1.3 billion doses of Covishield and Covaxin that the Centre expects by December, it is more likely to receive 750 million between August and December – although even this will be challenging. The Centre is also unlikely to have 200 million doses of Novavax’s Covavax and far fewer than 156 million doses of Sputnik V.

The remaining 510 million doses are expected to be made up of four vaccines that are still undergoing trials, some still in phases 1 and 2. Three of them are being developed together with foreign companies and/or institutions, and the data from their trials abroad isn’t available yet. In this context, there is a risk of the Indian regulator approving these vaccines without adequate efficacy and safety data, under pressure from the Centre to expedite supply.

Of course, it’s a relief to find the India government exiting its inertia and making some efforts to throw light on its vaccine strategy. The plan it has come up with however does not bear the stamp of careful thought, meticulous planning and in-depth evaluation of capacities. This said, its announcement could buy the Centre some respite from the flak it has been receiving continuously for India’s vaccine shortage.

Or was this the purpose anyway?

The author has no affiliations at the moment with, nor has she worked in the past for, any of the companies named in this article. All statements about vaccines in this article are based on current information in the public domain, to the best of her knowledge.

Neeta Sanghi has over three decades’ experience in managing pharmaceutical supply chains. She is currently working on a book about the industry.



Source link