Bharat Biotech founders and managing directors Krishna Ella and Suchitra Ella. Photo: Bharat Biotech
- On April 2, 2022, the WHO said it temporarily stopped UN agencies from buying Covaxin. It provided only a vague reason: “deficiencies in good manufacturing practices”.
- Last year, Bharat Biotech ran into issues with “good manufacturing practices” flagged by the Brazilian drug regulator over the company’s request to import Covaxin into Brazil.
- Despite some prodding by The Wire Science, the WHO didn’t specify what the exact issue was – but an independent expert found an operative clue in its response.
New Delhi: On April 2, 2022, the WHO issued a statement on Covaxin, the COVID-19 vaccine made by Hyderabad-based Bharat Biotech, saying it had suspended its supply to “UN procurement agencies”.
The statement followed the WHO’s first on-site inspection of Bharat Biotech’s facilities to manufacture Covaxin.
The only, and vague, reason it provided: “deficiencies in good manufacturing practices”. Neither the statement, nor the WHO since, has described the specific violations that led to this significant move – even as communications from Bharat Biotech suggest the company wishes to downplay its significance.
The Wire Science subsequently wrote to the WHO and only received the following response, again limited in the details: “Problems were detected in some parts of the manufacturing process. Some changes were made after the [emergency-use license] was granted but were not submitted to the national drug regulator and WHO for evaluation and validation.”
However, the second sentence of the reply is significant. An expert in ‘good manufacturing practices’ (GMP) who has been involved with vaccine-manufacturing at an Indian government company told The Wire Science that a vaccine maker is required to inform the WHO or the national drug regulator if it introduces any major changes in the manufacturing process after the WHO has granted an approval.
This is called a ‘change controller approval’ – and the expert said this could have been the issue. “You can’t do any major change without this.”
The WHO itself didn’t say that this was the problem. In fact, upon further prodding, it replied, “Disclosing further details will be a breach of confidentiality,” and suggested that The Wire Science ask Bharat Biotech. The Wire Science did, sending detailed questionnaires to the company as well as to the Drug Controller General of India (DCGI) on April 12. Neither has replied thus far.
The GMP expert – who didn’t wish to be named to avoid potential reprisal – speculated that Bharat Biotech could have introduced a change in the manufacturing process for a number of reasons. “One could be,” he said, “to increase the yield of the vaccine doses. The other could be a need to reduce the quantity of raw materials … required for production.”
Apart from suspending Covaxin procurement through UN agencies, the WHO’s April 2 statement also advised the countries “using the vaccine” to “take action as appropriate”. It also said “the data … indicates the vaccine is effective” and that “no safety concerns exist”.
If the vaccine is safe, what actions will other countries have to take? The WHO explained that “the inspections observation indicated that there are gaps in the quality assurance mechanisms and hence the need to take precautionary measures until the gaps have been addressed” (sic). Again, the WHO didn’t say where the gaps lay.
Neeta Sanghi, an expert in pharmaceutical supply chains, said she was baffled. “Since the WHO has said that the vaccine is safe and effective, the suspension doesn’t seem logical,” she told The Wire Science.
She also said that the WHO statement’s consequences are “very significant” and that that behooved the body to place the necessary details in the “public domain”.
As for what Bharat Biotech will need to do now to overcome the issue, the WHO said the company will need to say so in a ‘Corrective and Preventive Actions Plan’, which will be “submitted … to the DCGI and the WHO”. It didn’t specify a deadline, however.
Incidentally, a day before the WHO issued its statement, Bharat Biotech issued one of its own on April 1. This one said that the company had ‘foreseen’ a “decrease in demand” for Covaxin and was thus “temporarily slowing down” production “for facility optimisation”. It also wrote that some “upgrades” had been due at its facilities but that it couldn’t conduct them due to the pandemic.
Bharat Biotech didn’t reply to The Wire Science’s queries, four of which sought to further understand this point. But the independent GMP expert said, “This is all mumbo-jumbo to confuse the media. It is like saying one is trying to fix a plane that is already flying.”
Covaxin is the only vaccine whose supply to UN agencies the WHO has suspended during the COVID-19 pandemic. It’s also the vaccine the WHO took the longest to approve, deliberating from July to November 2021.
In addition, the current instance is the second time GMP issues related to Bharat Biotech have hit the headlines. On the previous occasion, the Brazilian drug regulator had denied Bharat Biotech a certificate to import Covaxin into the country over issues with the company’s manufacturing practices. The regulator subsequently made a conditional exception.
No impact?
PTI quoted unnamed sources, of unclear affiliation, saying the WHO’s suspension over GMP will not affect Bharat Biotech because the company isn’t participating in Covax.
‘Covax’ is the name of a coalition led by GAVI, the UN and the Coalition for Epidemic Preparedness Innovations that buys vaccines from manufacturers on behalf of countries with lower negotiating power.
“But the fact that the WHO specifically said in the statement that supply through UN procurement agencies had been halted does mean that the UN was or will be procuring through one of its agencies,” Amar Jesani, a bioethics expert, said.
In fact, the WHO statement also said that “in the interim and as a precautionary measure, [Bharat Biotech] has indicated that it will suspend production of Covaxin for export.”
It isn’t clear, however, whether Bharat Biotech will halt exports only to UN agencies or in general. Bharat Biotech itself hasn’t announced a suspension of exports. According to the UNICEF dashboard, Covaxin has received emergency approval in 18 countries.
For now, the US Food and Drug Administration has suspended an ongoing Covaxin trial in response to the WHO’s statement. But there hasn’t been a peep from the Indian drug regulator, the DCGI.
Jesani, who is also editor of the Indian Journal of Medical Ethics, wondered why. “It was the job of the DCGI to issue a statement, especially for the recipients of Covaxin in India,” he told The Wire Science.