According to the US Centers for Disease Control and Prevention (CDC), the most common way of making a flu vaccine is to culture viruses in fertilized chicken eggs using methods and technologies developed in the 1940s.
To date Seqirus’ Flucelvax is the only vaccine made using modern cell culture manufacturing processes to have been approved by FDA. All other flu vaccines sold in the US are made in eggs.
Reliance on decades-old manufacturing methods is characteristic of the wider vaccines sector, says James Robinson, an industry consultant.
“Vaccines are licensed with the technologies available at the time. Technology changes may require re-licensing the product, including clinical trials. The risks of unexpected events and the regulatory hurdles do not favor keeping processes current,” he points out. “Most vaccines are not well characterized by regulatory standards, hence changes may require proof of safety and effectiveness in the field.”
Rick Stock, from BDO USA, notes that regulations discourage vaccine firms from developing alternatives to outdated cell culture methods in roller bottles or time-consuming inactivation techniques. “Some vaccine production technologies could use improvement with new technology but then the entire regulatory process would have to be gone through again to approve the product,” he explains. “Don’t fix what isn’t broke?”
However, the main reason industry has been reluctant to invest is that it does not make financial sense. According to Anthony Davies from Dark Horse Consulting, “The financial incentives in the vaccine sector are too small to stimulate investment in manufacturing.” He likens the situation to the challenges that saw the majority of large pharmaceutical companies halt development of antibiotics: namely the products do not generate sufficient revenue.
This view is shared by Rick Stock, who says “The profit margins are not fantastic in the vaccine market. Who is going to command a high profit price for something that saves millions of lives? Most vaccines are made at a slim profit. Don’t get me wrong, the US, EU and developed countries pay a high cost for vaccines but most that are supplied world-wide are not at a high profit.”
Innovation challenges
Efforts to encourage manufacturing innovation come from outside the industry. For example, the World Health Organisation (WHO) and the United Nations Industrial Development Organization (UNIDO) have called for better production systems. Likewise, the Bill & Melinda Gates Foundation (BMGF) offers grants to tech firms willing to develop more effective technologies. How effective such incentives are is a point of debate.
“These programs do provide opportunities for new technologies to emerge to face challenges normal market forces cannot drive the industry to pursue,” says James Robinson. “The BMGF generally is focused on solutions for low- and middle-income countries (LMICs) that cannot afford traditional medicine cost structures and those challenges allow newcomers to finance their innovations and apply them to these LMIC targets. What works for LMICs will also allow lower costs or higher margins in traditional markets and often those innovations can cause disruptive technology forces in the commercial sector.”
Rick Stock also sees innovation grants as positive. However, he is less convinced of the wider benefits. “Having companies compete for prizes like this is extremely effective for vaccine production,” he explains, adding “most will spend far more than the grant developing their product just to win it. However, the production is only the drug substance portion. Still need to worry about the drug product part, storage, delivery, administration, royalties and all the R&D costs that went into development, clinical trials, etc.”
For Anthony Davies innovation in vaccine manufacturing will come from outside the industry, specifically the cell and gene therapy sector. He told GEN that in contrast with low value vaccines, high value cell and gene therapies have been the focus of manufacturing R&D investment.
“The cell and gene therapy sector is under pressure to cut COGs, which has prompted a lot of companies to spend money to improve production processes,” he continues. “And, because there are some technology overlaps, vaccine firms willing to adopt new technologies could benefit significantly.”
Davies cited investments made by firms like Cellectis and Allogene as examples, pointing out that technologies developed to produce gene modified cell therapies could be directly applicable to vaccine production. “The high level of investment and innovation being seen in cell and gene therapy production technology will benefit the wider industry, with the vaccines sector being the obvious example.”
