CMOs are expanding their capabilities to make the viral vectors needed to make COVID-19 vaccines, gene therapies, and gene-modified cell therapies, according to a report from GlobalData PharmSource. But compared to monoclonal antibody therapies, there are relatively very few viral vector contract manufacturing sites around the world: 87 facilities, owned by 62 companies in 15 countries, according to The Outlook for Viral Vector Contract Manufacturing: Gene Therapies, Cell Therapies and COVID-19 Vaccines (May 2020).

A shortage of viral vectors exists due to insufficient manufacturing capacity, inefficient manufacturing process and the requirement of complex specialized facilities. This shortage will be exacerbated by an upcoming wave of gene therapies and genetically modified cell therapies, and by the huge number of doses to be manufactured of certain COVID-19 vaccines requiring a viral vector (recombinant vector vaccines), especially those made by Vaccine. Covishield from AstraZeneca (Cambridge, UK) and Johnson & Johnson (New Brunswick, NJ).

The majority of the world’s outsourced and excess capacity manufacturing facilities capable of manufacturing viral vectors are in the United States. The United States has 45 such sites, compared to 32 in Europe. There are only seven locations in Asia. This contrasts with the manufacture of other types of molecules. The majority of small molecule API manufacturing facilities are located in China and India, and Asia has increased its manufacturing of biological proteins and peptides in recent years, but has yet to catch up with other regions in cell and gene therapy manufacturing material.

After the United States, the United Kingdom has the most viral vector sites. The UK government funded the manufacture of viral vectors through Innovate UK and the Industrial Strategy Challenge Fund, notably by establishing the non-profit Cell and Gene Therapy Catapult (London, UK).

A dedicated contract manufacturing model is offered by CMOs who only offer outsourced contractual services and who do not hold a marketing authorization (MAH) for a drug. An excess capacity manufacturing model is offered by pharmaceutical companies that produce their own products and also offer contract services using their excess production capacity, but are also MA holders. There are far fewer excess capacity viral vector manufacturing facilities than those owned by dedicated CMOs. This relationship is much more pronounced than that of biological protein and peptide manufacturing, where excess capacity manufacturing is common. In the case of viral vectors, few pharmaceutical companies with their own facilities have the capacity to subscribe to external contracts, with a few notable exceptions: Novartis (Basel, Switzerland) announced in March 2021 the closure of its manufacturing plant in Zolgensma, Colorado (see B / POR, March 2021). Additionally, cell and gene manufacturing, in its current form, does not have the same level of interchangeable platforms as monoclonal antibody production, which means that it will be more difficult to manufacture the product d. ‘another company. Vasily Medvedev, Development Manager at CDMO Exothera (Brussels, Belgium) told us that “many pharmaceutical companies producing vaccines are quite reluctant to invest in their own facilities, which risk becoming redundant once the pandemic has receded”. The production of viral vectors requires an inherently high level of manufacturing expertise and expensive installation requirements. CMOs who have made this high CapEx investment will benefit from this significant opportunity.

The production of viral vectors requires a biosafety level 2 (BSL2) facility, which has more constraints than the BSL1 facilities used to produce monoclonal antibodies. BSL2 facilities may have the same equipment as for other biological products, but they have greater containment needs so that the virus does not escape: for example, there is a pressure difference between the production area of viral vectors and other areas of installation, and a retention area in the event of a leak. These constraints mean that viral vector installations cost more and take longer to build.