#6. Scaling of COVID vaccine manufacturing: Does the CEO understand the extraordinary complexities involved?

by Öner Tulum, William Lazonick, Ken Jacobson, and Ellen Chappelka                             

During an interview on December 18, 2020, Moderna CEO Stéphane Bancel revealed his “Never Again Plan,” which called for action to prepare for future pandemics. Bancel argued that Moderna could have made “300 million doses available in the fall [of 2020]” if, beginning that March, the company had had at its disposal “a factory cranking 50 million doses a month” of its COVID vaccine. In making this statement, Moderna’s CEO seriously misrepresents the challenges that a company faces in scaling production of a novel vaccine, especially when the underlying technology platform–in this case, mRNA–is novel as well.

Under pressure to scale production of Moderna’s mRNA vaccine, which had received emergency use authorization (EUA) from the US FDA on the day of the interview (see the table below), Bancel was probably seeking to preempt criticism of the pace at which Moderna would actually be able to deliver doses. The fact is, however, that in early 2020 Moderna had possessed only a small manufacturing plant in Norwood, MA, designed to produce small batches of doses for clinical trials of non-COVID medicines it already had in the process of development. It would not be until the beginning of March 2020 that the company commenced conversion and expansion of its manufacturing facilities to produce doses for use in the COVID vaccine’s clinical trials. 

The following table shows the clinical trial start dates and emergency use authorization dates of four COVID vaccines, developed by BioNTech, Moderna, Johnson & Johnson (J&J), and Oxford University, that are important milestones on the vaccine-production timeline. 

COVID-vaccine manufacturing partnerships, key dates

[Click image to enlarge]
* First emergency use authorization (EUA) obtained in the United Kingdom; EUA not granted in the United States

OWS: Operation Warp Speed 

Moderna began phase I trials in mid-March and completed enrollment of 30,000 participants in phase III trials toward the end of October. The company required at most 50,000 doses to carry out all phases of its trials, relying upon its own manufacturing facilities to produce just a few thousand doses per month, with the rest being manufactured by a contract development and manufacturing organization, Lonza, with which Moderna entered into a production contract on May 1 (see the table above). It was Lonza, not Moderna, that possessed the capacity, capability, and commitment to scale to tens of millions of doses per month of the Moderna vaccine.

With Lonza scaling production in its plant in Portsmouth, NH, and beginning large-scale production for commercial use in September 2020, Moderna was able to supply 104 million doses to the US government by the end of March 2021. The Lonza plant produced an average of 5.3 million doses per month in the third quarter of 2020 and 29.3 million per month in the first quarter of 2021. That’s a far cry from the 50 million doses per month that Bancel, in his alternative reality, had argued Moderna could have been producing from a year earlier, when its clinical trials had just begun.

Scaling COVID vaccines is a difficult process that, given the pressure of the pandemic, has been proceeding in hothouse fashion, carried out, as we detailed in an earlier post, at specialized manufacturing sites around the world. It was not until mid-February 2021 that the global output of COVID vaccines reached 300 million doses. By mid-April, global output had jumped to more than three times that amount, at one billion doses, and the consulting firm Airfinity predicts that another one billion doses will be added by May 27, 2021.

The scaling of COVID-vaccine production has been an extraordinary bioproduction-engineering undertaking on a global scale. The essence of this feat is a process of “organizational learning”, in which large numbers of professionals with different hierarchical responsibilities and functional specialties work collectively to solve a myriad of productivity problems. As we explained in post #5, this organizational learning has spanned a series of sequential activities from pre-manufacturing design and setup to fill-and-finish operations. In subsequent posts, we will highlight the key transformations in supply chains, manufacturing processes, and quality control required to enable a manufacturing facility to produce and deliver tens of millions of doses of safe and effective COVID vaccines on a consistent monthly basis.