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bioRxiv · 10.1101/2021.12.22.473478

Accelerating manufacturing to start large-scale supply of a new adenovirus-vectored vaccine within 100 days

Joe, C. C.·Segireddy, R. R.·Oliveira, C.·Berg, A.·Li, Y.·Doultsinos, D.·Chopra, N.·Scholze, S.·Ahmad, A.·Nestola, P.·Niemann, J.·Douglas, A.
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Abstract

The Coalition for Epidemic Preparedness Innovations 100-day moonshot aspires to launch a new vaccine within 100 days of pathogen identification. Here, we describe work to optimize adenovirus vector manufacturing for rapid response, by minimizing time to clinical trial and first large-scale supply, and maximizing the output from the available manufacturing footprint. We describe a rapid viral seed expansion workflow that allows vaccine release to clinical trials within 60 days of antigen sequence identification, followed by vaccine release from globally distributed sites within a further 40 days. We also describe a new perfusion-based upstream production process, designed to maximize output while retaining simplicity and suitability for existing manufacturing facilities. This improves upstream volumetric productivity of ChAdOx1 nCoV-19 by around four-fold and remains compatible with the existing downstream process, yielding drug substance sufficient for 10000 doses from each liter of bioreactor capacity. Transition to a new production process across a large manufacturing network is a major task. In the short term, the rapid seed generation workflow could be used with the existing production process. We also use techno-economic modelling to show that, if linear scale-up were achieved, a single cleanroom containing two 2000 L bioreactors running our new perfusion-based process could supply bulk drug substance for around 120 million doses each month, costing <0.20 EUR/dose. We estimate that a manufacturing network with 32000 L of bioreactor capacity could release around 1 billion doses of a new vaccine within 130 days of genomic sequencing of a new pathogen, in a hypothetical surge campaign with suitable prior preparation and resources, including adequate fill-and-finish capacity. This accelerated manufacturing process, along with other advantages such as thermal stability, supports the ongoing value of adenovirus-vectored vaccines as a rapidly adaptable and deployable platform for emergency response.

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Joe, C. C., Segireddy, R. R., Oliveira, C., Berg, A., Li, Y., Doultsinos, D., Chopra, N., Scholze, S., Ahmad, A., Nestola, P., Niemann, J., Douglas, A.. 2021-12-23. Accelerating manufacturing to start large-scale supply of a new adenovirus-vectored vaccine within 100 days. https://doi.org/10.1101/2021.12.22.473478

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