Increased pace of biologics development in order to reach the clinic faster has led to tremendous pressure on first in human (FIH) drug substance manufacturing plants. Even though innovations in single-use cell culture and purification technologies have aided faster clinical entry, our current efforts are directed to efficiency gains through improved plant cadence and utilization. As a contract development and manufacturing company using disposable technologies, we have investigated techniques to reduce overall cell culture process duration to enable introduction of more products in the plant. The main goal for an inoculum train is to adapt cells out of thaw and generate enough viable cells to initiate the production-stage. Traditional approaches such as 100-200 million cells/mL vials or bags of frozen cells can be used for directly inoculating seed bioreactor bags, but due to long-term cell bank stability concerns these may not be readily implemented for all FIH products. We have assessed and implemented use of 30-50 million cells/mL vials and use of multiple cell bank vials to initiate the seed train. High volume culture vessels (1.5-2.5 L working volume) have also been successfully used to limit the number of subcultures required. These approaches have led to over 30% reduction in inoculum train duration for the platform process and have been implemented even for expedited process development projects. Apart from maintaining a strict seed train schedule, production perfusion cell culture (ATF) can also been used for process intensification. Use of perfusion production processes can lead to 20-30% higher volumetric productivity. Results from two cell lines comparing perfusion performance with fed-batch will be presented. These efforts toward intensifying seed train and production stages can lead to improved plant cadence by adding more manufacturing runs or reducing the number of runs required per year for each molecule.

Improving plant cadence and utilization through cell culture seed train and production process intensification

Macromolecular Chemistry: The Second Century

[Author Benefits](https://scimeetings.acs.org/?utm_source=pubs_content_marketing&utm_medium=website&utm_campaign=0320_MCF_NPI_Launch_Spring_Homepage&ref=pubs_content_marketing)

[How to use SciMeetings](https://storage.googleapis.com/dl.morressier.com/acs/SciMeetings-ACSSpring2020-HowToGuide_M3020-Final.pdf)

[Frequently Asked Questions](https://storage.googleapis.com/dl.morressier.com/acs/SciMtng_ACSNMSp2020_FAQ_M3120_Final.pdf)

ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.