There are more than 1,000 vaccines and therapies in development for Covid-19, and more than 30 have been approved (or granted Emergency Use Authorisation) for Covid-19. The GlobalData Pharma Intelligence Centre shows that 230 contract manufacturing agreements for Covid-19 vaccines and therapies have been publicly disclosed to date. This is just the tip of the iceberg, as many more exist and will be disclosed retrospectively.
The scale of Covid-19 vaccine doses required means that sponsor companies are turning to contract manufacturing organisations (CMOs) to fulfil orders. This is true even for the largest multinationals, which ordinarily might have chosen to manufacture some of their innovative drugs in-house. At the beginning of the pandemic, slightly more than half of these agreements were for vaccines. According to GlobalData’s Covid-19: Contract Pharmaceutical Development and Manufacturing Relationships report, this proportion has risen and continues to rise, as several vaccines have proven their safety and efficacy, received approval and are being ordered in billions of doses by numerous governments (GlobalData, September 2021).
Some of these manufacturing contracts are for a huge number of doses and can span a decade, but nonetheless, Covid-19 manufacturing contracts are spread between a great number of CMOs. There are more than 150 CMOs involved in publicly disclosed contract manufacturing agreements. Many of these contracts are for messenger ribonucleic acid (mRNA) based or recombinant vector vaccines, both of which are novel molecule types. Relatively few service providers are capable of certain steps in their production, such as viral vector production or mRNA production, which requires specialist equipment.
Near and long-term developments will increase the size of existing vaccine manufacturing contracts and create new ones. The prospect of administering the vaccine in paediatric populations or administering one or more extra vaccine doses to all populations, both of which are currently under study, will further raise manufacturing volumes and bring CMOs more highly specialised work in making these novel molecules. For more information about this issue, see GlobalData’s BIO 2021: mRNA Vaccine Booster Shots for Covid-19 and Increasing Uptake Will Offer CMOs Lucrative Opportunities (Bio/Pharmaceutical Outsourcing Report, GlobalData, July 2021).
On 18 August, the US Centres for Disease Control and Prevention (CDC) and FDA announced a plan to offer the US general public a third shot of either Pfizer (New York, NY)/BioNTech SE’s (Mainz, Germany) or Moderna’s (Cambridge, Massachusetts) Covid-19 vaccines from 20 September (FDA OKs Third Dose for Pfizer and Moderna Covid-19 Vaccines: What Does It Mean for Manufacturing?, Bio/Pharmaceutical Outsourcing Report, GlobalData, August 2021). The US is already administering a third dose to immunocompromised people, with Israel also rolling out a third dose. Many European countries are also expected to offer a third dose to vulnerable groups.
Under the FDA’s plan, a third shot of the Pfizer/BioNTech or Moderna vaccines will be given eight months after the second dose. The agency says it is also likely that people who received the one-shot Johnson and Johnson (New Brunswick, New Jersey) vaccine will need a second shot. It is possible that these extra doses will not be the last. If future data support a regular, seasonal immunisation program in response to the Delta Covid-19 variant or future variants, this will further increase manufacturing demand. The rate of manufacturing and distribution is, however, limited. The World Health Organisation (WHO) has called for a moratorium on ‘booster’ shots until at least the end of September so that at least 10% of the population of low-income countries can receive a first dose.
It is also probable that one or more vaccines currently in clinical development will be approved. These will require commercial-scale contract manufacturing. So far, vaccines have won over therapies in the fight against Covid-19. Several highly efficacious vaccines are now available, but significant room for improvement remains in Covid-19 treatments. The scale of Covid-19 vaccine production now dwarfs that of therapies, which are only indicated for sick patients and then only in certain circumstances.
There is still the possibility of a breakthrough in Covid-19 therapies. If one such therapy is found to be safe and efficacious, there will likely be a flurry of contract manufacturing agreements. There are still unmet needs in this area, as vaccine distribution takes time, vaccine efficacy is not 100%, and certain parts of the population will not receive a vaccine or will not have a strong immune response. Many of the promising clinical-stage therapies and marketed therapies are monoclonal antibodies (often repurposed from development in other indications). Their manufacture requires CMOs with specialised biologic capabilities.
Top CMOs strike vaccine and drug deals
The CMOs benefiting most from Covid-19 vaccine development so far, by the number of contracts disclosed, are Catalent (Somerset, New Jersey), Lonza (Basel, Switzerland) and Emergent BioSolutions (Gaithersburg, Maryland). Other large contract development and manufacturing organisations (CDMOs) have also benefitted. Emergent’s contracts skew toward vaccine manufacture, whereas Catalent and Lonza’s contracts are more evenly split between vaccines and therapies.
CMOs that only have outsourced contract services and are not the Marketing Authorisation Holder (MAH) of a drug offer a dedicated contract manufacturing model. 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 MAHs.
In the top three spots for disclosed contract manufacturing agreements, Catalent and Lonza are well-known CMO industry leaders. Catalent’s 11 publicly disclosed Covid-19 contracts to date are each for a different product, and are split between six therapies and five vaccines. The company has one contract each for Moderna’s, AstraZeneca’s (Cambridge, UK) and J&J’s vaccines. Lonza’s contracts include a ten-year active pharmaceutical ingredient (API) manufacturing contract with Moderna, which was signed last May and for which it is building commercial production lines in Portsmouth, New Hampshire, Visp, Switzerland, and Geleen, Netherlands.
Emergent has been one of the largest winners from the contract manufacturing of Covid-19 vaccines and therapies, but this is poised to change following disasters at Emergent’s plant in Baltimore, Maryland, where the company ruined up to 30 million Covid-19 vaccine doses. An FDA inspection found cross-contamination between AstraZeneca’s and J&J’s vaccines, as well as problems in the facility with cleanliness and overcrowding with materials. The company performs contract manufacturing and markets and develops products for public health threats, including infectious diseases and chemical weapons. Last June, Emergent invested $75m in viral vector and gene therapy production up to a 1,000l scale at its facility in Canton, Massachusetts. The company has nine manufacturing sites in total.
Most CMOs with contracts for Covid-19 vaccines and therapies are privately owned. This reflects the general make-up of the dedicated CMO industry, as more than 90% of dedicated CMOs are privately owned, although several of the largest are public. Private equity firms now own many of the world’s leading CMOs, such as Recipharm (Stockholm, Sweden), Cambrex (East Rutherford, New Jersey) and PCI Pharma Services (Philadelphia, Pennsylvania). Private CMOs are more likely to have vaccine contracts than therapies, but no single private company dominates; 120 different private CMOs have Covid-19 contracts.