Building vaccine capacity on a global scale

The rush to find effective vaccines against the coronavirus is only one part of the story. How is the pharmaceutical industry addressing the difficult issue of ensuring there will be enough manufacturing capacity to roll them out on a global scale?

The biopharmaceutical industry was quick to react to the pandemic. According to the World Health Organisation (WHO), at least 10 SARS-CoV-2 vaccines have entered clinical development in the past six months and a further 121 have started preclinical studies [1].

Developers range from academic institutions and biotechnology firms to global biopharma companies and national Governments. Many of the partnerships involve CDMOs, although the specifics of each scale-up effort differ significantly.

CDMO surge

Fiona Barry, associate editor at GlobalData’s PharmSource market intelligence unit says there is very significant activity among CMOs preparing for COVID-19 vaccine manufacturing. 

“The GlobalData Deals database shows more than 20 contract service agreements announced between biopharma companies and CMOs for COVID-19 vaccine candidates since the start of the year,” she says. “These vaccine candidates are in their early stages of development - the majority of these outsourcing agreements are for preclinical vaccines - which reflects the progress of COVID-19 therapies and vaccines generally.”

Partnerships

Biotech firm Moderna was one of the first developers to initiate trials of a SARS-CoV-2 vaccine, mRNA-1273, manufacturing the first clinical trial batch within 25 days of receiving the virus sequence from Chinese authorities [2].

Production was carried out at Moderna’s facility in Norwood, Massachusetts with the Oslo, Norway-based Center for Epidemic Preparedness and Innovations (CEPI) providing financial support.

Moderna has said it plans to invest in in-house production capacity as mRNA-1273 progresses through clinical trials. In May, the firm partnered with Swiss CDMO Lonza with the aim being to make 1 billion doses a year [3].

Tech transfer to Lonza plants in Switzerland and the US is due to start in June, with production scheduled for the following month.

The 10-year agreement will also result in a major scale-up of Lonza’s manufacturing operations, according to Barry: “The capacity expansion is partly funded by BARDA's USD 483 million award.”

J&J is also working with contractors to scale up production of its vaccine candidate, Ad26. In March, the US drug firm announced it plans to start trials of the jab in September [4] and shortly after, announced partnerships with Emergent Biosciences [5] and Catalent [6] to increase vaccine production capacity.

Emergent will provide drug substance production and will reserve capacity to “potentially support” commercial manufacturing using Janssen’s AdVac and PER.C6 technologies.

Under the latter deal Catalent’s Biologics unit will prepare for large-scale commercial manufacturing at its Bloomington, Indiana plant. The CDMO said it will hire 300 staff in July to “meet operational readiness and 24x7 manufacturing schedules by January 2021.”

Pharma capacity

One of the most advanced SARS-CoV-2 vaccines is being developed by researchers at the University of Oxford.

The vaccine – which entered a Phase I clinical trial in April – is made from a weakened chimpanzee virus that cannot replicate in humans, which is used to deliver a SARS-CoV-2 protein that induces a protective immune response.

In May the University announced it had partnered with Anglo-Swedish drug firm AstraZeneca to scale up production of the vaccine, which was renamed AZD1222.

Under the deal AstraZeneca will use its own manufacturing capacity to support clinical trials and potential commercial supply. The firm also said it would set up “several parallel supply chains” in collaboration with partners.

In late May, cell and gene therapy CDMO, Oxford Biomedica, said it will make multiple batches of the vaccine and grant AstraZeneca access to its OxBox manufacturing centre [7].

AstraZeneca is in talks with the Serum Institute of India to increase production and distribution [8].

Academic support

The first SARS-CoV-2 vaccine to enter trials is being developed by CanSino Biologics [9].

The product – which is made using the Admax system from Microbix Biosystem - comprises an adenovirus vector filled with material encoding the spike protein of the Wuhan-hu-1 virus strain.

Production of trial supplies was conducted by CanSino and development partner, the Beijing Institute of Biotechnology.

According to data published in the Lancet the majority of the 108 participants in the Phase I study developed immune responses to the vaccine [10]. CanSino has not disclosed how it plans to scale-up production if the vaccine progresses.

Facility repurposing

Pfizer is also working on a SARS-CoV-2 vaccine. The candidate – called BNT162 – is an mRNA-based vaccine created by German firm BioNTech, a developer of personalized cancer medicines.  It is currently in Phase I/II studies in the US [11].

Pfizer joined the project in mid-March, when it teamed up with BioNTech to collaborate on development, manufacture and commercialization of the vaccine if it proves effective [12].

Under the agreement BioNTech and Pfizer will manufacture the vaccine for trials. The firms will collaborate on scale-up if it is approved.

Pfizer CEO Albert Bourla shared more details of the manufacturing plan during the firm’s Q1 conference call in April [13].

“We expect that we will have in the last quarter of this year, millions of doses basically ready. And then, for ‘21, we could ramp up to hundreds of millions of doses available.”

Pfizer told Reuters it would outsource production of more products and repurpose some manufacturing capacity for SARS-CoV-2 vaccine production [14].

According to a Michigan Business Network report, Pfizer’s sites in Andover, Massachusetts, Chesterfield, Missouri, and Kalamazoo, Michigan will be involved in producing the vaccine for trials [15].

BioNTech’s agreement with Pfizer does not include China. Instead, commercialization in China will be conducted with Shanghai Fosun Pharmaceutical which teamed up with the German firm in March [16]

Under that agreement BioNTech is supplying the vaccine for clinical trials from GMP manufacturing facilities in Europe along with Austrian CDMO Polymun.

Similarly, AveXis has agreed to redeploy capacity and technology to support manufacture of a vaccine – called AAVCOVID – being developed by Massachusetts Eye and Ear and Massachusetts General Hospitals [17].

According to Bioprocess Insider, production will take place in a suite at Catalent’s facility in Maryland that AveXis had reserved to produce Zolgensma (onasemnogene abeparvovec) [18].

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"Biopharma companies and CMOs are already thinking well ahead to commercial manufacturing, as they should be: producing and packaging the billions of doses needed will be a huge bottleneck to getting the winning vaccine or vaccines to patients worldwide"

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Forward planning

The positive thing about all the vaccine development deals is that manufacturing scale-up planning is happening now. Such efforts are vital according to Barry, who says it is the only way to ensure the products are widely available.

“Biopharma companies and CMOs are already thinking well ahead to commercial manufacturing, as they should be: producing and packaging the billions of doses needed will be a huge bottleneck to getting the winning vaccine or vaccines to patients worldwide, and it's vital to plan for this today, before approval.”

The question of how long it is likely to take before there are enough coronavirus vaccines to dose billions of people and constitute a global game changer still prevails but there are is no firm answer. What is known that pharma’s multi-pronged initiative is well underway and operating at – relatively – breakneck speed.

References:

[1] https://www.who.int/who-documents-detail/draft-landscape-of-covid-19-candidate-vaccines

[2] https://investors.modernatx.com/news-releases/news-release-details/moderna-announces-progress-prophylactic-vaccines-modality-cmv

[3] https://investors.modernatx.com/news-releases/news-release-details/moderna-and-lonza-announce-worldwide-strategic-collaboration

[4] https://www.jnj.com/johnson-johnson-announces-a-lead-vaccine-candidate-for-covid-19-landmark-new-partnership-with-u-s-department-of-health-human-services-and-commitment-to-supply-one-billion-vaccines-worldwide-for-emergency-pandemic-use

[5] https://www.jnj.com/johnson-johnson-announces-collaboration-to-expand-manufacturing-capabilities-for-its-covid-19-vaccine-candidate-in-support-of-the-companys-goal-to-supply-more-than-one-billion-vaccine-doses-globally

[6] https://www.catalent.com/catalent-news/catalent-signs-agreement-with-johnson-johnson-for-lead-covid-19-vaccine-candidate/

[7] https://www.oxfordbiomedica.co.uk/news-media/press-release/oxford-biomedica-signs-clinical-commercial-supply-agreement-astrazeneca

[8] https://in.reuters.com/article/us-health-coronavirus-india-serum-insigh/how-one-indian-company-could-be-worlds-door-to-a-covid-19-vaccine-idINKBN22Y2BI

[9] https://clinicaltrials.gov/ct2/show/NCT04313127

[10] https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31208-3/fulltext

[11] https://clinicaltrials.gov/ct2/show/NCT04368728?term=vaccine&cond=covid-19&draw=3

[12] https://investors.biontech.de/news-releases/news-release-details/pfizer-and-biontech-co-develop-potential-covid-19-vaccine

[13] https://seekingalpha.com/article/4340748-pfizer-inc-pfe-ceo-albert-bourla-on-q1-2020-results-earnings-call-transcript?part=single

[14] https://www.cnbc.com/2020/05/08/pfizer-to-outsource-some-drug-production-focus-on-coronavirus-vaccine.html

[15] https://www.michiganbusinessnetwork.com/blog/governor-whitmer-statement-on-pfizers-clinical-trial-for-covid-19-vaccine

[16] https://investors.biontech.de/news-releases/news-release-details/biontech-and-fosun-pharma-form-covid-19-vaccine-strategic

[17] https://www.newswise.com/coronavirus/aavcovid-vaccine-program-from-mass-eye-and-ear-and-mass-general-enters-manufacturing-agreement-with-gene-therapy-leader-avexis-a-novartis-company/?article_id=732213

[18] https://bioprocessintl.com/bioprocess-insider/facilities-capacity/avexis-redeploying-cdmo-gene-therapy-capacity-to-support-covid-19-project/