Continuous Cell Culture for Viral Vaccines

Development of a mechanistic model of vaccine production for the development and demonstration of the continuous operation of an upstream cell culture process for the production of a model vaccine.

Project status

100% Completed

Industry Need

The biopharmaceutical industry has shown significant interest in developing continuous manufacturing processes for therapeutic protein production.
Despite some progress, continuous manufacturing approaches have yet to be widely applied to cell-culture based vaccine manufacturing.
The production of viral vaccines is more biologically complex than the production of recombinant protein therapeutics because of the infection and replication cycle of the virus.
The development of a first principles/mechanistic model of the manufacturing process could be a key element in the design of a manufacturing process and feedback control system that will allow for extended operation of the production system and consistent effluent of virus titer of high quality.

Solution

MIT and participating organizations aimed to create a mechanistic model of vaccine production for the development of the continuous operation of an upstream cell culture process to produce a model vaccine. This approach could be generalizable to a variety of vaccine production systems based upon the characteristics of the host cell line being used and the vaccine being produced.

Impacts

Demonstrated automatically controlled production of a viral vaccine over a 20-day continuous culture at process development scale at an FDA-licensed manufacturer of vaccines.

Advanced continuous processing and mechanistic models applied to vaccines

Demonstrated the suitability of novel PAT in vaccine manufacture

Positively correlated changes in cellular biophysical characteristics with viral vaccine production and measured in two flow-through systems, the Ovizio iLine F and MIT SMR; leveraging these technologies will allow for continuous monitoring of cellular biophysical attributes during viral vaccine production.

Enabled a platform approach for the rapid development and commercialization of viral therapeutics

Developed a mechanistic model that describes the production of a viral vaccine in mammalian cell culture, allowing greater understanding of viral production in continuous cell culture.