Increased demand for higher product yield in biologics requires optimal use of existing manufacturing capacity. Process intensification is one way a facility can meet increased demand as it allows for fewer or smaller batches to provide the same amount of product in the same timeframe. Approaches for cell culture intensification may include addition of perfusion in seed train or production stages and modification of growth and production media to support cell densities not achievable in a standard fed-batch process. Perfusion requires specialised equipment such as tangential or alternating tangential flow (TF or ATF) controllers which require additional training and increase manufacturing costs.

Installation of this equipment may be limited by existing manufacturing site capabilities and could require costly expansion to accommodate their use. For facilities designed for fed-batch processes, the implementation of perfusion is too costly or impractical. Alternatively, significant gains in cell growth and productivity can be achieved by modification of media and feeds, capturing many of the benefits of perfusion without the additional costs related to equipment, facility upgrades, and training.

This poster shows a significant gain in growth and yield with similar product quality is achievable by modifying media and feeds. Intensification of the seed train was first assessed in these studies to allow for seeding a production vessel at a higher initial cell density. Multiple designs of experiments were executed. First, to intensify the seed train to deliver sufficient cell density for the production stage. Second, to evaluate the impact of production stage parameters on an intensified cell culture process in terms of growth, productivity, and product quality. Harvest studies were performed to ensure feasibility of processing the intensified cell culture at the manufacturing scale.