Computer-Based Matrix to Evaluate Optimal Medium Delivery Format for Biopharmaceutical Production

摘要

High efficiency biopharmaceutical production from eukaryotic cell culture requires significant volumes of complex nutrient media to sustain elevated biomass and biological productivity in batch, fed-batch and perfusion bioreactors. The elevated cost and complexity of animal cell nutrient media may adversely impact the projected cost-of-goods sold for large-scale bioproduction. Eukaryotic nutrient formulations historically have been commercialized in two formats: milled powdered medium or fully-diluted liquid medium. Several years ago, we applied the technology of fluid bed granulation to complex nutrient media to develop a third alternative, a granulated dry-form medium. We showed that granulated media exhibited several technical and operational advantages over the two traditional formats. Nutrient media in granulated format have already been successfully utilized for large-scale biological production. Recently, we devised a computer-based spreadsheet to facilitate comparative economic evaluation of the relative benefits and limitations of these three media formats. The multiple inputs included costs associated with purchase, qualification and storage of incoming raw materials and costs for production media kitchen conversion and quality assessment. Our analysis evaluated capital depreciation of new or renovated facilities and potential impacts of medium format on operational and culture performance factors. This paper identifies key economic drivers that prefer a particular medium format over its alternatives and provides comparative examples to illustrate bioproduction planning applications.