Manufacturing

A US soldier holding the Pfizer–BioNTech vaccine

Pfizer and BioNTech are manufacturing the vaccine in their own facilities in the United States and in
Europe. The license to distribute and manufacture the vaccine in China was purchased by Fosun,
alongside its investment in BioNTech.[26][115]
Manufacturing the vaccine requires a three-stage process. The first stage involves the molecular
cloning of DNA plasmids that code for the spike protein by infusing them into Escherichia
coli bacteria. For all markets, this stage is conducted in the United States, [116] at a small Pfizer pilot
plant in Chesterfield, Missouri[117][118] (near St. Louis). After four days of growth, the bacteria are killed
and broken open, and the contents of their cells are purified over a week and a half to recover the
desired DNA product. The DNA is bottled and frozen for shipment. Safely and quickly transporting
the DNA at this stage is so important that Pfizer has used its company jet and helicopter to assist. [119]
The second stage is being conducted at a Pfizer plant in Andover, Massachusetts,[120] in the United
States, and at BioNTech's plants in Germany. [116] The DNA is used as a template to build the desired
mRNA strands,[119] which takes about four days.[116] Once the mRNA has been created and purified, it
is frozen in plastic bags about the size of a large shopping bag, of which each can hold up to
10 million doses. The bags are placed on trucks which take them to the next plant. [119]

A Pfizer employee putting dry ice in a box to protect the COVID-19 vaccines during transport at the Puurs
factory
Boxes containing the COVID-19 vaccines at the Pfizer factory in Puurs

Inside view of Pfizer factory in Puurs

The third stage is being conducted at Pfizer plants in Portage, Michigan[121] (near Kalamazoo) in the
United States, and Puurs in Belgium. This stage involves combining the mRNA with lipid
nanoparticles, then filling vials, boxing vials, and freezing them. [119] Croda International subsidiary
Avanti Polar Lipids is providing the requisite lipids. [122] As of November 2020, the major bottleneck in
the manufacturing process is combining mRNA with lipid nanoparticles. [119] At this stage, it takes only
four days to go from mRNA and lipids to finished vials, but each lot must then spend several weeks
in deep-freeze storage while undergoing verification against 40 quality-control measures. [116]
Before May 2021,[123] the Pfizer plant in Puurs was responsible for all vials for destinations outside the
United States.[116] Therefore, all doses administered in the Americas outside of the United States
before that point in time required at least two transatlantic flights (one to take DNA to Europe and
one to bring back finished vaccine vials).[116]
In February 2021, BioNTech announced it would increase production by more than 50% to
manufacture 2 billion doses in 2021,[124] raised again at the end of March to 2.5 billion doses in 2021.
[54]

In February 2021, Pfizer revealed that the entire sequence initially took about 110 days on average
from start to finish, and that the company is making progress on reducing the time to 60 days.
[125]
 More than half the days in the production process are dedicated to rigorous testing and quality
assurance at each of the three stages. [125] Pfizer also revealed that the process requires 280
components and relies upon 25 suppliers located in 19 different countries. [116]
Vaccine manufacturers normally take several years to optimize the process of making a particular
vaccine for speed and cost-effectiveness before attempting large-scale production. [125] Due to the
urgency presented by the COVID-19 pandemic, Pfizer and BioNTech began production immediately
with the process by which the vaccine had been originally formulated in the laboratory, then started
to identify ways to safely speed up and scale up that process.[125]

Syringes containing Pfizer COVID-19 vaccine doses

BioNTech announced in September 2020, that it had signed an agreement to acquire a

manufacturing facility in Marburg, Germany, from Novartis to expand their vaccine production
capacity.[126] Once fully operational, the facility would produce up to 750 million doses per year, or
more than 60 million doses per month. The site will be the third BioNTech facility in Europe that
produces the vaccine, while Pfizer operates at least four production sites in the United States and
Europe.[126]
The Marburg facility had previously specialized in cancer immunotherapy for Novartis.[127] By the end
of March 2021, BioNTech had finished retrofitting the facility for mRNA vaccine production and
retraining its 300 staff, and obtained approval to begin manufacturing. [127] Besides making mRNA, the
Marburg facility also performs the step of combining mRNA with lipids to form lipid nanoparticles,
then ships the vaccine in bulk to other facilities for fill and finish (i.e., filling and boxing vials).[127]
On 23 April 2021, the EMA authorised an increase in batch size and associated process scale up at
Pfizer's plant in Puurs. This increase is expected to have a significant impact on the supply of the
vaccine in the European Union. [128][129]
At the end of April 2021, it was reported that Pfizer had started to export vaccine doses to Mexico
and Canada from the Kalamazoo plant, which is much closer geographically to both countries than
the Puurs plant.[123]