PT  - JOURNAL ARTICLE
AU  - Garcia, Fernando Antonio
AU  - Vandiver, Michael W
TI  - Throughput Optimization of Continuous Biopharmaceutical Manufacturing Facilities
AID  - 10.5731/pdajpst.2016.006882
DP  - 2016 Jan 01
TA  - PDA Journal of Pharmaceutical Science and Technology
PG  - pdajpst.2016.006882
4099  - http://journal.pda.org/content/early/2016/12/13/pdajpst.2016.006882.short
4100  - http://journal.pda.org/content/early/2016/12/13/pdajpst.2016.006882.full
AB  - In order to operate profitably under different product demand scenarios, biopharmaceutical companies must design their facilities with mass output flexibility in mind. Traditional biologics manufacturing technologies pose operational challenges in this regard due to their high costs and slow equipment turnaround times, restricting the types of products and mass quantities that can be processed. Modern plant design, however, has facilitated the development of lean and efficient bioprocessing facilities through footprint reduction, and adoption of disposable and continuous manufacturing technologies. These development efforts have proven to be crucial in seeking to drastically reduce the high costs typically associated with the manufacturing of recombinant proteins. In this work, mathematical modeling is used to optimize annual production schedules for a single-product commercial facility operating with a continuous upstream and discrete batch downstream platform. Utilizing cell culture duration and volumetric productivity as process variables in the model, and annual plant throughput as the optimization objective, 3-D surface plots are created to understand the effect of process and facility design on expected mass output. The model shows that once a plant has been fully debottlenecked it is capable of processing well over a metric ton of product per year. Moreover, the analysis helped to uncover a major limiting constraint on plant performance, the stability of the neutralized viral inactivated pool, which may indicate that this should be a focus of attention during future process development efforts.