#4: Who are the CDMOs? For whom is their capacity being deployed to produce COVID vaccines?

by Öner Tulum, William Lazonick, and Ken Jacobson

In responding to the COVID-19 pandemic, the global pharmaceutical industry has done something unprecedented: In less than one year, it has developed several vaccines and obtained regulatory approval for some of them. The rollouts of the newly authorized vaccines, however, have been far from smooth. The global pharmaceutical industry is beset by a structural problem: Its capacity to produce vaccines lags its capacity to develop them.

This lag exists because over the past two decades the capacity to develop vaccines has become concentrated among relatively young, R&D-intensive biopharmaceutical companies  whose focus on innovative drug development has precluded their investing in facilities for mass producing the drugs that they develop. That job has been left to long-established pharmaceutical companies—known as Big Pharma—as well as to a host of specialized contract manufacturers.

Big Pharma, however, has itself shown an increasing reluctance to invest in vaccine manufacturing over the past half-century. Coming into the COVID-19 pandemic, only four of their number—Merck (USA), Pfizer (USA), GSK (UK), and Sanofi Pasteur (France)—had significant capacity for producing vaccines of any type.

Fortunately, the world has a large number of other vaccine producers, known as “contract manufacturing organizations” (CMOs) and “contract development and manufacturing organizations” (CDMOs). The trade publication Genetic Engineering & Biotechnology News calls CMOs/CDMOs “the sleeping giants of vaccine production.”

The contractors became significant actors in global pharma beginning in the early 2000s, in the wake of a rapid increase in biotechnology startups during the high-tech boom that peaked in 2000. Encouraging and enabling this new-venture formation in biotech was a doubling between 1998 and 2003 of life-sciences spending by the National Institutes of Health, focused in particular on the National Institute of Allergy and Infectious Diseases (NIAID). These new firms were essentially research labs seeking to develop novel medicines. As some of them succeeded, they turned to CMOs to produce the drugs. Since then, several CMOs have evolved to become “one-stop shopping” destinations for young biotechnology companies, to which they provided not only contract manufacturing of pharmaceutical products but other services as well.

The leading CMOs worked with the biotechnology startups, beginning in the development process, helping to ensure the formulation and manufacturability of the drug design.   CMOs that expanded into these development services became known as “contract development and manufacturing organizations” (CDMOs). Following a series of recent acquisitions, including some that have occurred during the SARS-CoV-2 pandemic, a number of CMOs, such as Cambrex, Thermo Fisher Scientific, Catalent, and Lonza, expanded the range of productive activities in which they engage. Now operating as fully integrated CDMOs, these companies can handle a wide array of specialized services, broadly classified as a) manufacture of active pharmaceutical ingredients (APIs), b) manufacture of finished dosage form (FDF), and c) drug discovery, process development, and scale-up (DPS), which makes a company a CDMO rather than a CMO. Table 1 identifies the main CMOs/CDMOs producing COVID-19 vaccines around the world, including the nation in which they are headquartered and recent acquisitions, and the categories of services that they provide.

If these CMOs and CDMOs had not existed coming into the SARS-CoV-2 pandemic, it would have been impossible to even contemplate the manufacture of billions of doses of COVID vaccines in 2021: Big Pharma’s manufacturing capacity would have been insufficient. Nevertheless, some large pharmaceutical companies offer the same services as independent CDMOs to meet the industry’s growing contract-manufacturing demand. One of the world’s oldest producers of specialty chemicals and pharmaceuticals, Merck Group (a German company not to be confused with US-based Merck & Co.), has gradually moved into the CDMO market, becoming one of the largest suppliers of contract services to the global life-sciences industry, with some of its capacity being used for COVID vaccines. Similarly, Baxter Biopharma Solutions (USA) and Bayer (Germany) are significant contract manufacturers for COVID vaccines.

Note that while the US-based Merck is one of the four Big Pharma companies that has vaccine-manufacturing capacity, until very recently it had not made that capacity available to other companies on a contract basis. The Biden administration, however, has invoked the Defense Production Act to oblige Merck to manufacture the vaccine developed by J&J, which does not have its own in-house capacity for vaccine mass production.

Developers of the five COVID-19 vaccines listed in Table 2 have announced plans to make available by the end of this year 8.8 billion doses, most of which will be produced in partnership with CMOs and CDMOs. AstraZeneca aims to produce three billion doses of the Oxford vaccine through a network of over two dozen contract manufacturers, spread across the world. A number of specialty pharma companies such as the Serum Institute of India, the world’s largest producer of vaccines; Emergent BioSolutions, based in the United States; and the Australian company CSL have joined the Oxford/AstraZeneca global production network, and nearly half of the three billion doses of the Oxford vaccine will be produced by these three partners.

Even after partnering with Pfizer, which is one of the world’s largest pharmaceutical companies with a significant legacy of vaccine production, BioNTech has had to enlist more than a dozen contract manufacturers to ramp up the production of its vaccine. J&J, the only large pharmaceutical company to develop a COVID vaccine, uses several contract manufacturers and had already partnered with US-based Emergent BioSolutions before entering into its manufacturing agreement with Merck.

Whereas Oxford and BioNTech have turned to Big Pharma companies to manufacture and market their COVID vaccines, Moderna has chosen to partner with Swiss-based Lonza, one the world’s largest CDMOs. Lonza already possessed a large vaccine-manufacturing plant in New Hampshire located, conveniently for technology transfer, a mere 90-minute drive from Moderna’s Massachusetts facility for manufacturing clinical-trial doses. Using Lonza’s capacity in Switzerland as well, Moderna plans to produce up to one billion doses in 2021.

Maryland-based Novavax, which has developed a COVID vaccine that is in late-stage clinical trials, has signed partnership agreements with several CDMOs, including AGC Biologics, Fujifilm, and Baxter—as well as with a number of specialty pharma companies, including Serum Institute of India, Emergent BioSolutions, and Endo Pharmaceuticals—to produce up to two billion doses in total if and when its vaccine obtains authorization. Like other vaccine developers, Novavax has had to be aggressive in lining up manufacturing capacity in advance of vaccine approval: If a COVID-vaccine developer were to wait for approval, there would likely be little if any capacity to be had. Indeed, during the development phase, manufacturing capacity must be equipped for COVID-vaccine production to provide doses for clinical trials and to enable a rapid rollout once the vaccine receives authorization for use.

Will Moderna, Pfizer, AstraZeneca, J&J, and Novavax be able to deliver the 8.8 billion doses that they have promised in 2021? The capacity to produce a certain quantity of doses does not automatically translate into the scale of production that is ultimately achieved. Now that we know who the players are, let’s see how they do as they step up to the mass-production plate. Even the best ballplayers fail to reach base most of the time. Welcome to the CVP ballpark, where, over the course of the 2021 season, we will track the batting averages of the companies upon which the world is relying to deliver the COVID vaccines.

 

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