One of the critical components of the US biotech firm Novavax’s COVID-19 vaccine is the adjuvant called Matrix M.
The word may remind us about the science fiction trilogy Matrix, but in reality this Matrix M adjuvant uses extracts from Soapbark trees called Quillaja Saponins (QS), grown in the foothills of Andes Mountains in Chile.
Saponins are known to Indians as Reetha, which is used for cleansing hair.
Can Serum Institute of India, which has the licence to produce Novavax’s COVID-19 vaccine in India, use extracts from Reetha? After all, its CEO Adar Poonawalla has been vocal about the shortage of raw materials such as adjuvants, and production of Novavax will be critical for India's fight against COVID-19.
The answer is not very simple.
Adjuvants are used to boost vaccine efficacy and create a stronger immune response. For years, vaccines have been using aluminum salts such as aluminum hydroxide as adjuvants. QS-21 is among a very few adjuvants approved by the USFDA for use in vaccines.
The adjuvants based on Quillaja Saponins are not just safe, but are known to boost T-Cells, boosting the efficacy of the vaccine.
Most of these adjuvants, including Matrix M, used in Novavax’s COVID-19 vaccine are patented and supplies are tightly controlled. Adding to that, the US has invoked the US Defence Production Act to preserve vaccine raw materials for its own companies.
Those restrictions are hampering efforts of companies like SII. It had entered into a licensing pact with Novavax to produce the latter's vaccine for supplies to India and other countries through COVAX.
Poonawalla, in a desperate attempt, had tried to bring in US President Joe Biden into the debate, through a tweet:
"@POTUS, if we are to truly unite in beating this virus, on behalf of the vaccine industry outside the U.S., I humbly request you to lift the embargo of raw material exports out of the U.S. so that vaccine production can ramp up. Your administration has the details," Poonawalla said.
It isn't only specific to the Novavax’s Matrix adjuvant, there is a squeeze of other adjuvants, key starting materials, enzymes and reagents that go into vaccine manufacturing. Supply challenges are also being observed across all vaccine manufacturing steps, such as bioreactor bags, single-use systems, cell culture media, filters, gamma sterilization, vials, etc.
Please read here how input material shortages may hit COVID-19 vaccine manufacturing.
Indigenisation of raw materials
Given the huge demand for COVID-19 vaccines, companies are scrambling to get as much raw materials as they can. But export restrictions aren't making life easy. So some are trying to indiginise or source it locally.
Bharat Biotech has signed up with the CSIR lab in the Indian Institute of Chemical Technology (IICT) to develop a synthetic process route for adjuvant molecule TLR 7/8 to Bharat Biotech's Covaxin, using locally available chemicals at an affordable price and with highest purity.
Covaxin is formulated with Algel-IMDG, which contains chemisorbed TLR7/8 against aluminium hydroxide gel to generate the requisite type of immune responses.
IICT managed to do this in four months, helping Bharat Biotech to scale up the production of the adjuvant.
Recently, in an interview to Moneycontrol, Rakesh Mishra, Director of CSIR's Centre for Cellular and Molecular Biology (CCMB), said that the lab is working with vaccine companies on trying to make some of the ingredients locally.
Emcure, the parent company of Gennova Biopharmaceuticals that's developing messenger RNA (mRNA) COVID-19 vaccine, said it is working on backward integration of its jab to reduce dependence on key imported raw materials, reagents and enzymes that go into its manufacturing.
"A lot of these key starting materials that go into the mRNA vaccine - Modernas and Pfizers of the world - rely on a lot of European and US suppliers. We saw that as a potential bottleneck," Vikas Thapar, President, Corporate Development & Strategy at Emcure, told Moneycontrol.
"Gennova is trying to do backward integration, solve some of these key raw material issues, reagents and enzymes that go into manufacturing. We believe that by the time we are in a position to scale up, we hopefully would have addressed a lot of critical issues," Thapar said.
While Thapar didn't specify which raw materials, enzymes and reagents, some of the critical raw materials that go into the manufacturing of Messenger RNA vaccine includes enzyme called polymerases that converts DNA to mRNA, vaccinia capping enzyme (VCE) to keep the mRNA from degrading and an oily lipid nanoparticle that coats the mRNA to give it stability.
A head of a Bengaluru-based life sciences Contract Development and Manufacturing Organisation (CDMO) company who didn't want to be named told Moneycontrol that a few components can be indiginised, but not everything.
"For some of these enzymes, reagents and components like single-use bioreactor bags, there aren't any local manufacturers, they are not easy to manufacture," the executive said.
"The lead time of procurement has increased," the executive added.