As COVID-19 gained steam worldwide last spring, little was known about the disease and the havoc it would wreak on the world. A year later, vaccines offer hope in the fight against the virus, but it will be a monumental task to produce them and deliver them around the planet.
That these vaccines were invented, put through clinical testing and either have been rolled out or are nearing distribution is an accomplishment in itself, but the work is really just starting. The companies leading the charge aim to produce billions of doses to vaccinate the world's population, and encouraging real-world data from the ongoing rollouts are showing why it's such an important effort.
Meanwhile, as variants spread and experts weigh the need for boosters, more production capacity will be all the more important in 2021 and beyond.
Here, we outline the supply chains established by the five leading vaccine players and their partners over the last year.
Pfizer became the first vaccine maker to earn an FDA emergency use authorization in late 2020, and, now, its BioNTech-partnered shot is in the early stages of a worldwide rollout.
Pfizer and BioNTech aim to produce 2 billion doses of the vaccine in 2021, most of which will come from facilities owned by those companies. Aside from their own efforts to set up manufacturing capacity, Pfizer and BioNTech have partnered with at least 10 other companies that are helping the company scale up, including global pharma giants Novartis and Sanofi.
For the U.S. supply chain, Pfizer’s manufacturing process starts in St. Louis, where the company makes raw materials for the vaccine antigen. There, the company produces plasmid DNA, or the template required to produce mRNA vaccines, by using a cell culture process.
Pfizer uses its site in Andover, Massachusetts, to produce the mRNA drug substance. The substance is purified before being shipped to Kalamazoo, Michigan, where Pfizer completes the manufacturing process for stateside distribution. At the Michigan facility, the company combines mRNA drug substance and other materials to create bulk vaccine, which is then transferred to a filling line to be put into vials and capped. The vials are then inspected, labeled and packaged for shipping.
In Europe, Pfizer’s site in Puurs, Belgium, receives ingredients for the formulation process from BioNTech and other manufacturing partners. Through numerous steps, the team there creates formulated bulk vaccine and then transports it to the filling area to fill vials. Those vials are packaged into boxes that each fit around 200 units, which are then moved into the facility’s “freezer farm.”
To prepare for shipping, the company adds dry ice and a GPS temperature monitor to the crates.
Pfizer's partner BioNTech is handling the drug substance production for Europe and the rest of the country at a site in Mainz, Germany. It has also hired a contract manufacturer to purify the substance at another site in Rentschler, Germany. Two BioNTech contract manufacturers, DermaPharm in Germany and Polymun in Austria, are chipping in by manufacturing formulated lipid nanoparticle bulk.
As it was preparing for the scale-up, BioNTech purchased a former Novartis site in Marburg, Germany. The company has started production at the plant, where annual capacity is expected to be 750 million doses at peak.
Meanwhile, after Sanofi suffered a setback with its vaccine program, it teamed up with Pfizer and BioNTech to produce 100 million doses of that mRNA vaccine for the European market in 2021. The first batches will be delivered from Sanofi’s site in Frankfurt, Germany, by August. Sanofi still aims to advance its own vaccine candidates.
Novartis, which isn’t involved in COVID-19 vaccine research, has also offered to assist Pfizer and BioNTech with fill and finishing work. The Swiss pharma giant plans to receive bulk mRNA active ingredient from BioNTech at its site in Stein, Switzerland. Novartis will then fill vials and prepare them for shipment back to BioNTech for worldwide distribution. The work will begin in the second quarter, and deliveries from the site are slated to start in the third quarter.
British Big Pharma AstraZeneca has set the hefty goal of delivering up to 3 billion doses of its University of Oxford-partnered adenovirus shot globally by year-end. To see that quest through, it has locked up production capacity across 15 countries spanning 25 separate manufacturing sites.
Vaccine produced from AZ’s supply chains is typically country- or region-specific, with the drugmaker prioritizing local manufacturing “wherever possible,” Ruud Dobber, Ph.D., executive vice president and president of AZ’s biopharmaceuticals business, said (PDF) in a testimony planned for a recent hearing before the House Energy and Commerce Committee's oversight arm.
In the U.S., CDMO Emergent BioSolutions has snared a total of $261 million from AZ to crank out drug substance for the vaccine at its Baltimore Bayview facility, while Catalent produces viral vectors at its gene therapy facility in Harmans, Maryland. Catalent is also handling fill-finish services at the Anagni, Italy, facility it picked up from Bristol Myers Squibb early last year.
Meanwhile, AZ is also handling filling and packaging at its own facility in West Chester, Ohio, Dobber said in his testimony.
In Europe, AstraZeneca has tapped Halix and Novasep for shot production in the Netherlands and Belgium, respectively, and has teamed up with CDMO IDT Biologika for fill-finish services in Germany. AstraZeneca and IDT recently said they were looking at ways to hustle delivery of finished doses to Europe by the second quarter of 2021. And the companies are plotting combined investments to upgrade capacity at IDT’s Dessau, Germany, plant. The project, expected to wrap by the end of next year, will boost capacity in Dessau to the tune of “tens of millions” of vaccine doses per month, the companies said.
AstraZeneca’s complex supply chain has cast a shadow over its vaccine rollout in Europe, which is now set to receive some 40 million doses in the first quarter, down from the 80 million it originally expected.
AstraZeneca tied that shortfall to reduced manufacturing yields at a former Novasep plant in Seneffe, Belgium, which Thermo Fisher recently took over in its $878.2 million buyout of the company’s viral vector manufacturing business. While production capacity there has “drastically” increased, according to EU industry commissioner Thierry Breton, AstraZeneca’s heated—and often public—beef with the EU has prompted the 27-member bloc to seek supplies beyond its own borders.
Early in the kerfuffle, the EU urged AstraZeneca to divert doses from the U.K., where vaccination efforts are running more smoothly. But CEO Pascal Soriot told the Italian newspaper la Repubblica it owed the U.K. first, since the country had placed its order three months before the EU. That extra time also gave the company a runway to work through potential manufacturing issues in that supply chain, Soriot added.
AstraZeneca recently offered to tap facilities outside the EU to supply doses there, with one EU official pegging its Indian partner, the Serum Institute of India, as a potential source, according to Reuters. But about a week later, Serum Institute CEO Adar Poonawalla said his company had been told to focus on domestic doses first.
Now AstraZeneca has flagged potential problems with its second-quarter deliveries to the EU, but it’s drawn up a plan to bring in doses from abroad. AZ will source about half of its 180-million-dose order from its European operations, “while the remainder would come from its international supply network,” a company spokesperson told Fierce Pharma.
Last June, AZ tapped Serum Institute to supply 1 billion doses for other countries. As with Novavax, WHO’s Covax facility is on the hook to distribute those doses outside of India.
Russian drugmaker R-Pharm is also producing the shot on license from AZ, which it will export to markets in the Commonwealth of Independent States—a nine-country economic group comprised of Russia and post-soviet Republics, the Middle East and the Balkans.
Meanwhile, AZ has penned licensing deals with the Oswaldo Cruz Foundation, also known as Fiocruz, in Brazil and BioKangtai in China, while Mexico and Argentina have pledged to make between 150 and 250 million doses of the vaccine for Latin American countries starting in the first half of 2021.
Like other companies involved in the COVID-19 race, Moderna—which had the second mRNA vaccine to win a U.S. authorization after Pfizer—spent nearly a year getting ready for its global rollout. The company has enlisted five partners so far in the global manufacturing and distribution push, aiming to deliver more than 2 billion doses over the next 2 years.
As Moderna's vaccine, mRNA-1273, progressed through early stages of testing last year, the company entered a worldwide, 10-year collaboration with Switzerland’s Lonza to help scale up the program and others that could follow. Soon after, the biotech entered a fill-finish partnership with Catalent to help deliver on the U.S.’ big supply order of 100 million doses. That pact sought to utilize a Catalent site in Indiana. And since that original U.S. order, government officials have tripled down on the shot, scooping up a total commitment of 300 million doses.
The "vast majority of the U.S. production will be done in Massachusetts," Moderna co-founder Noubar Afeyan told Boston-based GBH News. In 2018, the company opened a 200,000-square-foot site in Norwood, Massachusetts. Lonza sites in New Hampshire and Switzerland are also helping produce vaccines, Fast Company reported.
In December, the shot scored its FDA authorization and the U.S. rollout got underway. So far, Moderna has shipped 60 million doses worldwide. Most of those have gone to the U.S. Overseas, the supply chain is "in the process of ramping up," Moderna said in late February.
A month after inking its Catalent deal in the U.S., Moderna brought on Spain’s Rovi to complete fill--finish tasks for doses destined to be shipped outside the U.S. That deal incorporates Rovi's site in Madrid.
In an effort to further bolster its ex-U.S. supply chain, Moderna in late 2020 enlisted Swedish CDMO Recipharm for a separate fill-finish partnership on doses destined for ex-U.S. markets. That work will take place at a Recipharm site in France.
Lastly, in early 2021, Moderna partnered with global logistics company Kuehne+Nagel to support deliveries to countries in Europe, Asia, Middle East and Africa, and parts of the Americas. The doses will come from Moderna’s international supply chain, which Kuehne+Nagel said is based in Europe.
During its most recent supply update, Moderna bumped up its “base case” for 2021 production to 700 million doses, up from an initial estimate of 500 million doses. The company aims to make up to 1 billion doses of its mRNA-1273 in 2021 and 1.4 billion doses in 2022. Already, Moderna has booked $18 billion in supply orders for 2021, and it’s in the process of negotiating more deals for this year and next.
Moderna's 1.4 billion-dose estimate for 2022 is based on the assumption that boosters will require a 100-μg dose. The company is testing various booster doses, and if boosters require less than 100-μg, the company could potentially turn out more than 2 billion doses next year, CEO Stephane Bancel said in a statement.
Johnson & Johnson
J&J’s vaccine is made in several stages, starting with the creation of drug substance by growing cells in a controlled environment. The material is then taken to production sites that convert the raw substance into large batches of vaccines. Lastly, fill-finish sites fill and package vials for final distribution.
In addition to using its relatively new vaccine production site in Leiden, the Netherlands, J&J has brought on partners for to help in various stages of the process, both in the U.S. and around the world.
In the U.S., the company has partnered with Emergent BioSolutions to produce the initial substance, as well as Catalent and Grand River Aseptic Manufacturing to assist with vaccine production and fill-finish services. Emergent has also partnered with AstraZeneca in the U.S.
In Europe, the company is working with Catalent and Reig Jofre on vaccine production and fill-finish services. Catalent will use a site in Italy, while Reig Jofre's facility is located in Spain. J&J’s Leiden site is handling the initial step of making drug substance in Europe.
Global vaccine players are also getting involved to help boost supply of the one-dose shot. In February, J&J inked a vaccine manufacturing deal with fellow biopharma giant Sanofi. Under that agreement, Sanofi will provide J&J access to its vaccine production site in Marcy l’Etoile, France, where workers will formulate vaccines and fill vials. The work is expected to start in the third quarter of this year, and Sanofi's facility will turn out around 12 million doses per month.
In March, J&J unveiled the Merck collaboration after that company bowed out of the vaccine race.
Elsewhere, in India, J&J has partnered with Biological E on all three phases of the manufacturing process. Biological E plans to make 600 million doses of the J&J shot, Reuters reported in February. And in South Africa, J&J has enlisted Aspen Pharmacare to tackle drug product and fill-finish services.
“Due to the global interconnectivity of our production and supply chain processes, one batch of the J&J COVID-19 vaccine will likely visit multiple countries through the course of various manufacturing stages in its journey from drug substance to a finished vial for injection,” the company says.
At a Congressional hearing in late February, a J&J exec said the company is in good shape to deliver 20 million doses of its vaccine to the U.S. by the end of March, and 100 million in total by the end of June. With help from its partners, J&J is aiming to produce 1 billion doses this year.
J&J is still looking to boost available supplies, though. In a Bloomberg interview after the FDA authorization, CEO Alex Gorsky said the company was "leaving no stone unturned" in its push to deliver more doses.
Novavax, which expects to hit annual capacity of at least 2 billion doses this year, cranks out its phase 3 candidate NVX-CoV2373 at its own facilities in Maryland, Sweden and the Czech Republic. For now, product made in the U.S. will remain stateside, while the company’s ex-U.S. operations will fill the rest of the world’s orders, a Novavax spokesperson said via email.
The company has signed on Japanese contract development and manufacturing organization AGC Biologics to scale up and produce the Matrix-M adjuvant for its shot at facilities in the U.S. and Denmark, while Polypeptide Group is on deck to make two key intermediaries for the vaccine component at American and Swedish sites. Novavax also cranks out the adjuvant at its plant in Uppsala, Sweden.
Novavax has never scored a vaccine authorization in its three-decade history, but it appears poised to change that in 2021. CEO Stanley Erck told CNBC this week his company is eyeing a potential FDA authorization in May.
Another partner, Fujfilm Diosynth, is handling antigen production at sites in Texas, North Carolina and the U.K. Elsewhere, Biofabri is making the component in Spain, while Serum Institute of India is helping in India, SK Bioscience in Korea and Takeda in Japan. Novavax also does this work itself at its plant in the Czech Republic, which it snared in its $167 million buyout of local manufacturer Praha Vaccines last May.
Serum Institute of India and Takeda also have licenses to deploy Novavax’s shot in India and Japan, respectively, while Serum Institute has pledged to manufacture doses of NVX-CoV2373 for the World Health Organization’s equitable vaccine distribution effort Covax, which the facility itself will distribute outside India.
Novavax earlier this month revealed a memorandum of understanding with Gavi, the Vaccine Alliance, to supply 1.1 billion doses of its shot to Covax, which aims to distribute some 2 billion COVID-19 vaccine doses to low- and middle-income countries this year.
The final fill-finish step of Novavax’s production process will be managed by Par Pharma and Jubilant in the U.S., with Baxter and Siegfried wrapping up doses in Germany and Switzerland, respectively.
Novavax last summer bagged a massive $1.6 billion Operation Warp Speed deal to support late-stage vaccine testing and production, pledging a minimum of 100 million doses to the U.S. Earlier this month, Reuters, citing two unnamed EU officials, reported the company was homing in on a supply deal with the EU to provide an initial 100 million doses, with the option to sell 100 million more in the future.
Editor's note: This story was corrected to reflect that Catalent performs drug substance manufacturing for AstraZeneca's vaccine at its Harmans, Maryland facility.