Shortage of key chemical from US hits Covaxin ramp-up plans

'In case of shortage of other raw material, like filters and bags, one can try to develop another vendor. However, for chemicals as critical as adjuvants, this is not possible'

With Hyderabad-based vaccine maker Bharat Biotech in the midst of ramping up its capacity for Covaxin, sources said the biotechnology company is facing challenges in procuring the adjuvant used in the vaccine.

The unsung hero of vaccines is a component called the adjuvant. It puts a 'red flag' on the antigenic component of the vaccine -- an inactivated whole or part of a virus or bacteria -- and instructs the immune system to mount a defence against that antigen whenever it is encountered.

"One of the reasons for the sluggish pace of the Covaxin production scale-up is the firm facing issues in sourcing the adjuvant from the US," said a source.

Bharat Biotech is trying to ramp up capacities of Covaxin to 12 million doses per month by July, from the current 5 million doses per month.

Bharat Biotech is using Kansas-based ViroVax's adjuvant to boost the immune response to its Covaxin.

The company did not comment till the time of going to press.

Adjuvants are pharmacological or immunological agents that improve the immune response of a vaccine. They may be added to a vaccine to produce more antibodies and longer lasting immunity, thus minimising the dose of the antigen needed. 

An antigen is any substance that causes the immune system to produce antibodies against it. It can be any substance like chemicals, viruses, bacteria that the immune system does not recognise and tries to fend off. 

ViroVax's Alhydroxiquim-II adjuvant is used in Covaxin, which is an inactivated Sars-CoV-2 virus vaccine. The inactivated virus is formulated with ViroVax's adjuvant to produce the vaccine candidate. 

"In case of shortage of other raw material, like filters and bags, one can try to develop another vendor. However, for chemicals as critical as adjuvants, this is not possible. The vaccine, which is tested on volunteers and gets approved, is made with this adjuvant. Therefore, any change to this would lead to fresh clinical trials and fresh approvals," said a source.

Krishna Ella, chairman and managing director, Bharat Biotech, had said earlier that the widely used adjuvant aluminium hydroxide in the development of Sars-CoV-2 vaccines is known to induce Th2-biased immune response. However, Th2-biased response has a theoretical risk of VAERD (vaccine-associated enhanced respiratory disease) or ADE (antibody-dependent enhancement).

"We have used imidazoquinoline class of adjuvants (TLR7/8 agonists). They are known to induce Th1-biased response, which further reduces the risk of ADE," Ella had said at the time of announcing Bharat Biotech's partnership with ViroVax.

A few days ago, Adar Poonawalla, chief executive officer of Pune-based Serum Institute of India (SII), had indicated that the shortage of raw material was holding back production scale-up of the Novavax vaccine. 

Novavax has pushed back the timeline for hitting its production target of 150 million vaccine doses per month until the third quarter due to supply shortages, including bags used to grow cells.

"Stockpiling of Novavax will happen to the tune of 50 per cent more if we have access to US raw material," he said, adding, "The US has invoked the Defense Act and banned the export of raw material. This is as good as banning the vaccines."

SII is now working on developing new vendors for raw material it imports from the US like filters, bags, cell culture media, etc.

Bharat Biotech, too, announced a tie-up with the Council of Scientific and Industrial Research (CSIR) last month to work on technologies and platforms for novel vaccines, drugs, and even raw material. The collaboration will work on developing novel platform technologies for biotherapeutics and vaccines to support indigenous, affordable health care solutions for humans and animals.

Ella had said that several raw materials to make vaccines were imported. Preservatives for vaccines are imported from Germany and some raw material from the US. 

"India is not self-reliant in some of these vaccine raw material. We will work with CSIR-Indian Institute of Chemical Technology to develop these products, new drugs, and even new platforms," Ella had said.