Facility Size Requirements for Manufacturing Billions of Vaccine Doses

Fairly large facilities are needed to manufacture billions of vaccine doses. The exact size depends on the specific vaccine type, production techniques, and efficiency of the cell lines used. Existing infrastructure and human elements also play a significant role. In this article, we will break down the requirements based on the adenovirus vaccine modality and other key factors.

Initial Considerations and Background

Large-scale bioprocessing, particularly for vaccines, requires substantial facilities to handle the enormous volume needed. Storing vaccine doses is less problematic compared to producing them. For storage, a couple of storage facilities the size of a supermarket dairy case per state would be sufficient. Storing initial vaccines often involved unconventional methods.

To get a better understanding, I conducted some back-of-the-envelope calculations and confirmed my numbers at bioprocessing conferences like BioProcess International and ACS BIOT. These initial technical details of the vaccines give us a clearer picture of the required facility size.

Adenovirus Vaccine Modalities

The adenovirus modalities, such as the AZD1222/ChadOx1-nCoV and Ad5-nCoV vaccines, are more well-understood and have similar technical challenges. The JnJ Ad26 vaccine uses a different approach and has unique properties. The details around mRNA vaccines remain largely trade-secret, differing significantly between companies.

Viral Production and Purification

For viral production, most teams are using Vero or HEK293 production cell lines, with JnJ using its proprietary Per.C6 cell line. Typical viral purification yields are around 20, meaning one liter of culture can produce around 2E14 viral particles. For the AZD1222 vaccine, this translates to approximately 4000 doses per liter of viral culture.

Single-Use Bioreactors

The standard single-use bioreactor being used for viral vector manufacturing is the 2KL system. For clinical manufacturing, many teams are using smaller 500L systems, such as Halix Oxford BioMedica, while commercial sites prefer the 2000L system. The 2000L bioreactor can produce around 1E15 viral particles/L, supporting the production of up to 8 million doses per lot.

Production Scheduling and Lot Requirements

Assuming 4000 doses per liter of culture and 2000L reactor, we can produce roughly 8 million doses per lot. To meet the demand for 1 billion doses, we would need 125 of these lots, requiring 5 2000L bioreactors running 365 days a year. Given a 2-week run rate and an 85% utilization, we can run a maximum of 25 production lots per year.

Impact of Clinical Trials and Vaccine Types

Specific factors, such as the number of doses required and the concentration of viral particles, heavily influence the number of production lots needed. For instance, CanSino’s Ad5-nCoV vaccine requires two doses at a higher concentration, thus needing 4 times the amount of material. JnJ’s Ad26 vaccine, on the other hand, uses a Per.C6 cell line, which is twice as productive, potentially reducing the number of production lots required.

Human and Facility Factors

Facility size requirements are not solely determined by the practical capacity of the equipment. Human elements, such as staff and infrastructure, also play a significant role. New facilities are being built specifically for vaccine production, but the theoretical maximum production rate might not always be achieved due to competing demands and other logistical challenges.

Future Trends and Flexibility

In the long term, there could be a shift towards larger facilities similar to those used for monoclonal antibody manufacturing. However, as of now, many of these larger facilities are being allocated to COVID-19 therapeutics, and vaccine manufacturing technologies might not be advanced enough to fully utilize these larger production spaces.

Conclusion

The scale of facilities required for manufacturing billions of vaccine doses is a critical consideration in the global fight against infectious diseases. While the technical details and specific challenges vary between vaccine types, the foundational understanding provided here can help guide facility planning and scalability strategies. The key is to balance between feasible production capacity and the practical limitations imposed by the biological science and manufacturing processes.