THE government is persisting with its arbitrary and non-transparent decision-making on approval and deployment of Covid vaccines and medicines, playing ducks and drakes with official regulatory procedures and even with its own government-appointed expert groups set up specifically to tackle the pandemic.  It is now crystal clear that, far from being one-off or even occasional decisions by-passing existing procedures and institutional mechanisms due to the urgency and exigencies posed by the pandemic, they are part of a deliberate and considered practice of the political executive brushing aside evidence-based decision making and asserting its total authority by superseding all expert groups and regulatory bodies.

The latest example is the emergency use approval recently granted to the Corbevax two-dose vaccine, again without published or peer-reviewed data from Phase-3 clinical trials, and the subsequent go-ahead given to roll out vaccination of 12-14 year-olds exclusively with Corbevax without approval from the National Technical Advisory Group on Immunisation (NTAGI) or recommendation from the National Expert Group on Vaccination Administration for Covid-19 (NEGVAC). No explanation has been given by government or the concerned expert groups or regulatory bodies, which have obviously been steamrollered into giving their consent or have simply been by-passed by the faceless yet all-powerful executive, except to tell people to trust the decision-makers!

Readers will well remember the painfully long and tortuous saga of the indigenously developed Covaxin which had similarly been steamrollered in India, wherein the government could coerce all institutions to grant it approval and then include it in the vaccine rollout programme, but ran up against a more rigorous scrutiny procedure for global approval in the WHO. The world body had to repeatedly ask for Phase-3 clinical trial data which the manufacturer Bharat Biotech and its partner Government of India had till then neither published nor subjected to peer review, despite promising to do so “very soon” over many months! This prolonged episode was not only embarrassing for Indian science, and damaging for the reputation of India’s drug regulatory system, but also triggered much vaccine scepticism within the country. Despite what should have been a salutary experience, the government has decided to continue to cut corners on the approvals process and to take rollout and related decisions based not on scientific basis but, as argued in this piece, on the basis of dubious administrative convenience and political messaging.

CORBEVAX    

Let us look at the vaccine itself first.

Corbevax is a different type of vaccine compared to either Covishield or Covaxin used in India so far. Corbevax is a protein sub-unit vaccine where the spike protein of Sars-CoV-2 is directly injected with stabilising chemicals and adjuvants (substances that enhance immune response) in order to raise antibody levels in the recipient. On the other hand, Covaxin uses a full inactivated Sars-CoV-2 virus and Covishield uses a genetically modified adenovirus vector to introduce the DNA coding for the spike protein into cells, a technique used by several other vaccines against Covid-19.

Corbevax is manufactured by Hyderabad-based Biological E. While much has been made by the government and also by BE of this vaccine being one among three indigenously-developed vaccines, the fact is that Corbevax was developed by Texas Children’s Hospital and Baylor College of Medicine’s commercialisation arm, which then licensed it to Biological E for manufacture. The Hyderabad-based company has also received funds from the US International Finance Development Corporation for scaling-up production up to one billion doses by end 2022. Undoubtedly, Biological E must have contributed to the productionisation of the vaccine which would have involved some adjustment or adaptation of process protocols. But this is a far cry from the claim repeatedly made by government ministers and high-ranking officials that the vaccine has been “indigenously developed.”

The US team has dubbed Corbevax “the world’s Covid-19 vaccine” because the manufacturing technique is relatively simple and the vaccine can be stored at refrigerator temperatures. Most importantly, the vaccine carries no patent, is open-source and is therefore, in theory, available for manufacture by any entity in any developing country. However, as with the issue of patent waiver for vaccines, an imperfect international agreement belatedly reached after much haggling and resistance especially from European countries, with numerous conditionalities including exclusion of India, patents are not the only obstacle to effective technology transfer from developed to developing countries. Vaccine manufacture involves production processes, specialised machinery and numerous other aspects other than patents.

MURKY APPROVALS

Corbevax is nowhere near obtaining approval from the US FDA and is probably not even pursuing that goal.

Here in India, approvals for Corbevax were rushed through the system with little or no transparency and, as with Covaxin earlier, with very little relevant clinical trial data. Corbevax received Emergency Use Approval (EUA) from the Drugs Controller General of India (DCGI) on December 28, 2021 for adults based on partial results from combined Phase-2/Phase-3 trials, with data mostly on safety and immunogenicity, with little data on efficacy. Interestingly, the union government had already placed an order with Biological E for 300 million doses on August 21, 2021, well before DCGI approval had been obtained! It seems clear that unnamed and top-ranking government officials had already decided to clear Corbevax, which then received formal approvals from concerned authorities afterwards. Later, after some more partial results from further small studies in the 5-18 years age group, Corbevax obtained DCGI approval on February 21, 2022 for use in children between 12 and 18 years of age. However, it subsequently received EUA from DCGI for the 12-14 years age group on March 17, 2022!

The above raises all kinds of questions about the integrity of the decision-making process of the drugs controller and its scientific basis. None of the data are available in the public domain. In fact, the clinical trial data have not been peer-reviewed or published even in pre-print form.  When queried about this by the press, different high authorities and even Biological E have only said either that these would be available “soon,” or that the DCGI and its decisions should simply be trusted. This is a repetition of the Covaxin saga all over again, with government now clearly having decided that it is accountable to nobody, and that it can take any decision it wants without having to provide any justification.

The very issue of vaccines for adolescents and children also comes under scrutiny for a total lack of transparency as regards decision-making.

First Covaxin received approval from DCGI for administration to 12-18 year olds, restricting a subject expert committee recommendation for approval for the 2-18 age group. However, during roll-out, this was later revised to the 15-17 years age group. NTAGI is believed to have reviewed this decision, but has been more cautious as regards vaccination of adolescents and younger children. For instance while another indigenous vaccine Zycov-D was given DCGI approval for adolescents, NTAGI wanted to wait and assess results of vaccination of adults before considering extension to younger cohorts.

BY-PASSING NTAGI & NEGVAC    

At the time of announcing the rollout of Corbevax for 12-14 year olds, the government said, it had been decided “after due deliberations with scientific bodies.” However, it has since come to light that the matter was never brought before NTAGI and NEGVAC as it should have before the health ministry ordered its roll out to the arbitrarily defined 12-14 age group. Thus today, nobody knows the basis for the DCGI approval nor the government’s decision to administer the vaccine to the 12-14 age group.

Bypassing of NTAGI is an extraordinary decision that could only have been taken under orders from, or with the acquiescence of, the highest government authorities.  If NTAGI and NEGVAC are to be by-passed in this manner, then why set them up at all? The entire handling of this matter calls into question evidence-based decision-making by government on vaccines and other Covid-related treatments etc, and the now firmly established tendency of this government to either cherry-pick expert recommendations or coerce expert bodies to decide on issues on pre-determined lines or, as in this case, to simply by-pass expert bodies. Government is even taking the position, as in an on-going case in the Supreme Court on this very question, that it may not be in the public interest to make clinical trial data public, thus going against established scientific practice the world over!

It is also extraordinary that, as a result of the above non-transparent and apparently arbitrary approvals process, Bharat Biotech’s Covaxin and Biological E’s Corbevax have been granted exclusive monopolies over the 15-17 year age group and the 12-14 year age group. No other vaccine has been allowed to be administered to these exclusive cohorts, even though DCGI approvals may have been given for a wider 5-18 years age group.  In effect, the government has taken it upon itself to allot market-shares to different companies through some collusive agreement. As more vaccines get approvals, perhaps new age-group divisions will get created to “accommodate” the new entrants and ensure that each manufacturer gets at least some section of the Covid vaccine pie. Strange goings-on indeed in atmanirbhar India!