Continuous Bioprocessing and Perfusion: Wider Adoption Coming as Bioprocessing Matures

B atch processing has long been the predominant bioprocessing paradigm, both upand downstream. Bioprocessing f luids are processed incrementally, piped as a bolus or transferred via vessels from one process and piece of equipment to the next. This continues to work well, including a number of technological advances resulting in improvements that continue to make bioprocessing more efficient. Upstream and overall process yields are essentially doubling about every five years, with this largely driven by improved cell lines, expression systems and genetic engineering, culture media, and equipment. Among the technologies now gaining increasing adoption and market share for biopharmaceutical manufacture is continuous (bio) processing, with perfusion currently the leading technology, in terms of adoption. The use of incremental, one-step-at-a-time, classic batch processing in biopharmaceutical manufacture is different than most other major products manufacturing and high-tech industries, where processing is generally more continuous. In this context, the move toward more continuous processing in manufacturing is a common characteristic of industries starting to reach maturity. Continuous processing is exemplified by assembly lines, and petroleum refining with processing involving a rather continuous flow of the material being manufactured from one unit operation to the next. Continuous processing generally follows and eventually replaces incremental manufacturing. Continuous processing generally requires more process knowledge, equipment and technological advances than incremental manufacturing. Successful adoption of continuous processing by any industry requires each of the component processes involved to be more integrated, at least with the next process. Continuous processing requires a sufficient critical mass of technological competencies and available equipment capable of supporting process integration. For example, implementing continuous bioprocessing, such as upstream perfusion, is not practical if the next and following steps are unable to handle this output. This article reviews and details some of the key advances and trends in the bioprocessing industry that have emerged which are creating greater adoption and potential for continuous processing as the industry matures. We evaluate aspects of continuous processing, exemplified by perfusion, and the adoption of these technologies by the biopharmaceutical manufacturing (bioprocessing) industry.