GMP implementation of a hybrid continuous manufacturing process for a recombinant non ‐mAb protein—A case study

AbstractAdvances in manufacturing technology coupled with the increased potency of new biotherapeutic modalities have created an external environment where continuous manufacturing (CM) can address a growing need. Amgen has successfully implemented a hybrid CM process for a commercial lifecycle program. In this process, the bioreactor, harvest, capture column, and viral inactivation/depth filtration unit operations were integrated together in an automated, continuous module, while the remaining downstream unit operations took place in stand-alone batch mode. CM operations are particularly suited for so-called “high mix, low volume” manufacturing plants, where a variety of molecules are manufactured in relatively low volumes. The selected molecule fit this mold and was manufactured in a low-capital micro-footprint suite attached to an existing therapeutic production facility. Use of a hybrid process w ithin an already operating facility required less capital and minimized complexity. To enable this hybrid CM process, an established fed-batch process was converted to a perfusion process with continuous harvest. Development efforts included both process changes and the generation of a novel cell li ne adapted to long-term perfusion. Chromatography resins were updated, and purification processes adapted to handle variable inputs due to the fluctuations in harvest titer from the lengthy production process. A novel automated single-use (SU) viral inactivation (VI) skid was intr...
Source: Biotechnology Progress - Category: Biotechnology Authors: Tags: RESEARCH ARTICLE Source Type: research