In anticipation of a roundtable at CPhI North America we spoke with Fiona Barry, Associate Editor, PharmSource – GlobalData, to discuss her view on the future potential of mRNA and vaccines, where these facilities are located and the impact they have on viral vector capacity shortages. The analysis also identified which contract manufacturing organizations (CMOs) have emerged as the biggest winners from the surge in demand.
 
To watch the session again, please visit HERE.

Contract Pharma: With 37 COVID vaccines currently in Phase III or later, what would you consider to be the most promising pipeline vaccines?

Fiona Barry: When evaluating the most promising pipeline vaccines, I think it’s important to evaluate them based on trial data and the stage of development. As such, I would say the subunit vaccines in development from Sanofi/GlaxoSmithKline, Novavax, Clover, and Medicago are promising, as is the inactivated vaccine in development by Valneva. They are all in phase III or II/III and have strong investor interest. Recently, Novavax’ phase III trials showed efficacy of 90%, and the company has initiated a pediatric expansion of the phase III trial. The vaccines from Sanofi/GSK and Novavax are under EMA rolling review.

CP: Are vaccine developers outsourcing to Asia and India for low-cost, high-volume production of vaccines or are they selecting CMOs closer to home?

Fiona Barry: Definitely closer to home. A lot of the COVID vaccine manufacturing agreements that have been publicly announced are going to the United States and quite a few to Germany too. I believe this mirrors current vaccine contract API capabilities.
 
There are approximately a dozen contract manufacturing sites in India and China that are approved to make vaccine API for developed markets. That is a relatively small number, especially when compared to the United States which has around 70 sites and a similar number when you add all the sites from across Europe, with Germany, Belgium and the Netherlands playing a large role. Another country that houses many vaccine contract API manufacturers is the UK, partly due to the increased investment in advanced manufacturing from Innovate UK. It makes sense that the countries that house the most vaccine API manufacturing sites are the countries that are getting the most contracts. The only caveat here is we are talking about number of contracts, not volume of doses to be manufactured.
 
Another factor is vaccine developers are also looking to diversify their supply chain; they are no longer looking to rely on just one supplier. This is partly due to supply chain security and avoiding potential difficulties in sourcing raw materials from a single country, for example if an export ban is imposed, but also out of necessity due to the sheer volume of doses required to be made. Naturally you are going to be contracting with multiple companies using multiple sites. So holistically, if you look at those reasons, maybe it’s not quite as surprising that the vaccine innovators have chosen to be closer to home as opposed to using lower cost options.

CP: What companies have emerged as the leading CMOs for vaccine development? Why is that so?

Fiona Barry: In terms of the number of contracts (rather than the number of doses contracted), Catalent leads the way with five publicly announced COVID-19 contract service agreements in place, with Polymun Scientific (four) and ACG Biologics (three) also doing really well. Had you asked me this question maybe six months ago, I would have definitely said Emergent was a big winner from the contract manufacturing of COVID-19 vaccines, with their Baltimore site responsible for the manufacturing of Johnson & Johnson and AstraZeneca vaccines. However, after quality issues were discovered and millions of doses were scrapped, all vaccine production was stopped at the site until last week when it restarted manufacturing for J&J.

CP: When looking for the ideal CMO, what are vaccine developers looking for? i.e. what services are they actively looking for?

Fiona Barry: We are seeing that the majority of CMOs are securing work from vaccine developers due to their specialised API services. The pandemic has ushered the use of two new technologies: the recombinant vector vaccine, with J&J, AstraZeneca and Sputnik all using the technology for their COVID vaccines; and mRNA technology used by Pfizer/BioNTech and Moderna for theirs. So definitely, vaccine developers are looking for these specialised services.
 
More broadly, we are also seeing a surge in demand for supply chain services from vaccine developers, especially cold chain storage. As you know, the most important component of a vaccine is the API. If the vaccine is not stored correctly i.e., if it gets too hot, the active ingredients can degrade and the batch will have to be discarded.

CP: A shortage of viral vectors existed even prior to the pandemic – why is that the case? What are CMOs doing to combat this shortage?

Fiona Barry: With fewer than 90 CMO sites worldwide with capabilities to produce viral vectors, there is certainly a shortage of manufacturers with the required capabilities to manufacture viral vectors. However, CMOs began recognizing coming demand even prior to the pandemic, with a wave of gene therapies and gene modified cell therapies approved in the last couple of years, and as a result have started to build capacity in recent years.
 
While building facilities is already underway, it won’t be enough to just build due to the sheer number of viral vectors needed. CMOs will need to improve the manufacturing processes which is currently very inefficient. We are currently now where the industry was in the 90s when making monoclonal antibodies: making mAbs was a very slow process, quite laborious and almost manual. What will need to happen now is improvements in both upstream and downstream processing, and we certainly need to take a look at potential regulatory changes as well. Standardised viral vector platforms that are recognised and approved by the regulators would really speed up development and manufacturing. You certainly wouldn’t have to go through as many hoops and it would be significantly better for CMOs as they would be familiar with the platform and have a ready-made set-up to make viral vectors. These solutions were already in the works pre-pandemic, but the pandemic has certainly accelerated this and really intensified the need for these improvements.

CP: Currently, there are 12 approved vaccines for emergency use. What type of molecule type and vaccine is most dominant in developed pharma markets? In the developing world?

Fiona Barry: To no one’s surprise, the big four of Pfizer, Moderna, AstraZeneca and J&J are the most popular vaccines in the developed pharma markets. In the developing pharma markets, COVAX is helping to supply some of the same vaccines approved in the developed countries—especially J&J’s and AstraZeneca’s—but there’s also a strong reliance on ‘home-grown’ vaccines such as CanSino Biologics’ Convidecia and Sinopharm’s BBIBP-CorV vaccine in China, and Russia’s Sputnik V, EpiVacCorona and KoviVac, and Bharat Biotech’s Covaxin in India.
 
In terms of molecule type, half of the twelve vaccines approved (or given emergency use authorisation) in developed markets are either recombinant vector vaccines or mRNA, with only 25% of vaccines approved for emergency use being inactivated vaccines. Certainly, in the developed pharma markets, mRNA and vector vaccines dominate.

CP: Almost 300 COVID vaccines are in the pre-clinical stages, have they missed the boat on this?

Fiona Barry: Possibly, and we’re going to see a lot of attrition now unless it’s for something that provides benefits above and beyond the currently available vaccines in providing protection against a wide variety of variants.