A presentation by Don Parsons, PhD, VP, Early Technical Development and LNP Process Development at Moderna Therapeutics, Inc.
Biotech writer David Orchard-Webb revisits a popular presentation on the rapid development of a mRNA vaccine which was given by Don Parsons, PhD, VP, Early Technical Development and LNP Process Development, Moderna Therapeutics, Inc. at TIDES Europe in 2020.
Don Parsons reflected upon Moderna’s efforts to develop and deploy mRNA1273, which is an mRNA-based vaccine against SARS-CoV-2 and how Moderna’s long term vision made it possible.
Entering 2020 Moderna was beginning their tenth year of operation. The company had over 900 employees and just over 400 of those were in CMC related areas.
Twelve clinical trials were ongoing, two of which were in phase II, and the teams were working very hard to prepare for the first phase III trial with their vaccine candidate against cytomegalovirus.
The company had already established an internal GMP manufacturing facility which supplies its clinical trials. Importantly, it had scaled the manufacturing processes to approximately the gram scale. Eight months into 2020, it had almost doubled the number of employees in CMC functions.
Moderna was able to supply material for the COVID-19 vaccine in the fastest ever phase I start Parsons had ever witnessed, and was well into a 30,000 patient phase III with over 18,000 patients enrolled at the beginning of September.
Moderna has executed agreements with manufacturing partners in the US and Europe, which will enable the production scale needed for a global supply of the vaccine and the company has been able to scale its manufacturing processes very significantly. While a lot has been achieved, there are many challenges ahead.
The CMC for the COVID-19 vaccine mRNA1273 benefited greatly from Moderna’s experience with personalized cancer vaccines. The second critical capability was an established in-house GMP manufacturing facility.
It is not common for an emerging biotech company, however it was vital in the context of the pandemic because they had control over the facility’s priority and were able to respond to the level that the crisis deserved. A previous focus on a reliable supply chain was likewise invaluable.
This strong starting position with respect to phase I, however, was only the starting point for Moderna’s next challenge; phase III, which it had never conducted before and needed to implement fast to shift its CMC efforts to a laser focus on a single product.
Key to that understanding was the need for major scale up, approaching 500x, in only a couple of months.
This was needed to extend across multiple processes from raw materials, to mRNA, to lipid nanoparticles, to drug product. That scale up would not have been valuable without the manufacturing capability to go along with it.
Moderna needed to very quickly identify partners with global manufacturing presence to assist. And of course, they were operating during the pandemic with all the associated challenges.
Certain long-term features of Moderna made the challenge of the pandemic less daunting.
Firstly, they have always been committed to a scientific understanding of their products and processes. However, finding the resources for this as an emerging biotech was not always straightforward.
Secondly, manufacturing processes were defined with scaling explicitly in mind.
Finally, Moderna has a focus on vertical integration of the supply chain and Parsons credits the company’s internalization of much of that supply chain as a key enabler of the rapid pandemic response.
Three major challenges remain:
Despite the thermal lability of mRNA, Moderna has been able to design a product that can be stored long-term at -20℃.
Obviously, such a storage condition will nonetheless require careful and rigorous cold chain management, even though it is a common capability within most jurisdictions.