The site will have an annual production capacity of up to 750 million doses of the Pfizer/BioNTech COVID-19 vaccine once fully operational. The first vaccines from the site are scheduled for distribution in April.
mRNA production
Having received its first authorization in December, the Pfizer/BioNTech vaccine has now been given the green light in more than 50 countries worldwide. In Europe, it is one of three vaccines currently authorized, with a total of 300 million doses on order.
BioNTech acquired the Marburg, Germany site from Novartis last year in preparation for scaling up production this year: gaining the well-established biotechnology drug substance and drug product manufacturing equipment at the site alongside an experienced team of 300 employees.
BioNTech has now started the first step of the manufacturing process at the Marburg facility: the production of mRNA, which is the active pharmaceutical ingredient of the Pfizer-BioNTech COVID-19 vaccine.
“A single mRNA batch of the current scale is sufficient to produce around eight million vaccine doses,” explains the company. “We plan to start the manufacturing of the drug substance based on the new manufacturing license granted from Darmstadt Regional Administrative Council for the amended facility in Marburg.”
Once the mRNA has been produced, it needs to be purified and concentrated.
“After completion of mRNA production, Lipid Nanoparticles (LNP) are formed by combining mRNA and a mixture of lipids. Following further purification, the newly created drug product will then be transported to a partner site for fill and finish under sterile conditions.”
A panel of quality tests will be performed to confirm the quality of the product prior to release. The quality of the final product will be analyzed by two independent laboratories: BioNTech’s quality control laboratory in Idar-Oberstein and the official medicinal batch laboratory (Paul-Ehrlich-Institute in Germany).
Production processes at the facility will need to be approved by the European Medicines Agency (EMA).
“Data from the first production batches including from process validation will be assessed via the centralized variation procedure coordinated by the EMA. This validation, as well as the submission of data and other required information, will take place in February and March. Based on approval by the EMA, first drug product batches of the vaccine can then be delivered to partner sites for sterile fill and finish, before distribution to vaccination sites in line with established agreements with governments.”
This means the first doses from the facility are set to be distributed in April; with 250 million doses expected to come from the facility in the first half of 2021.
Further initiatives to boost production
Pfizer and BioNTech are working to expand global production of the vaccine: having increased its production goal from 1.3 billion doses to 2 billion doses for 2021.
This target is based on continuous process improvements, expansion at current facilities and adding new suppliers and contract manufacturers, and the updated six-dose labelling (allowing an extra dose to be obtained from each vial).
In Europe Pfizer’s Puurs, Belgium facility is already producing the vaccine and recently received an upgrade to production lines; while BioNTech says the set-up of the new Marburg site is a ‘key factor’ in expanding its manufacturing network.
Meanwhile, various manufacturing partnerships are increasing production. For example, BioNTech recently announced a partnership with France’s Sanofi, with the latter agreeing to support the manufacturing and supply of 125 million doses for the EU from its Frankfurt plant from July.
The Marburg facility
The Marburg manufacturing site, named Behringwerke, was established in 1904 by Emil von Behring, who developed the antitoxin for Diphtheria and Tetanus. It was built with the award money von Behring received from the Nobel Prize in Medicine in 1901.
The facility situated in a life science industry park near Frankfurt which is home to more than 10 companies – among them GSK, CSL Behring, and Siemens Healthcare Diagnostics Products - with 6,000 employees in total.
The site is a Good manufacturing practice (GMP) facility: a prerequisite for the validation of the vaccine manufacturing process by the EMA.
Novartis has ‘significantly invested’ in the site over the last five years: and as a result it is fully equipped for the production of recombinant proteins as well as cell and gene therapies, and holds cell culture labs and viral vector production capabilities.
While its immediate role is focused on COVID-19 vaccines, BioNTech says the site also holds potential for long-term growth and expansion. In the future, BioNTech plans to manufacture additional therapeutic and vaccine drug candidates at the facility: such as other mRNA vaccine, antibody, and cell and gene therapy product candidates in BioNTech’s cancer and infectious disease product pipeline.
Picture/video credits: BioNTech