Trends in Perfusion Bioreactors

S ingle-use bioprocessing equipment has come to thoroughly dominate precommercial biopharmaceutical production in only a decade. Yet even with this breakthrough, performance and cost pressures on biopharmaceutical facilities continue to grow. Demands for greater productivity, more efficiency, and lower costs are resulting in an unrelenting push for upstream improvements. Some people in the industry are predicting that perfusion bioreactor technologies may be the next revolution in bioprocessing (1). Perfusion may possibly become a dominant single-use bioreactor technology, with fed-batch systems taking the position as a well-proven but legacy technology. As the technology evolves, researchers are finding that perfusion may offer a number of cost and performance advantages. Data from the 2011 8th Annual Report and Survey of Biopharmaceutical Manufacturing Capacity and Production report comes from 352 bioprocessing professionals, showing that biopharmaceutical companies have uniformly increased their budgets in essentially all areas related to bioprocessing (2). Survey data also indicate that industry professionals are becoming impatient with an apparent lack of innovation in bioprocessing equipment, notably in bioreactor offerings, and that much of the industry remains unaware of recent advances in perfusion bioreactors. Results indicate that the industry is both seeking improvements in productivity and aggressively increasing budgets to invest in and adopt new technologies, particularly for upand downstream bioprocessing (Figure 1). Significant advances in clinicaland commercial-scale bioreactors have occurred in recent years, especially in single-use/disposable bioreactor-based systems. Nearly all these innovations have involved fed-batch bioreactors, usually those with plastic bags/liners dropped within a conventional fedbatch stainless steel bioreactor. Most larger bioreactor manufacturers have made substantial investments in this first-generation bag-in-a-bioreactor approach, including constructing bagmaking facilities. Although the approach works, some critics point to a lack of motivation to develop novel alternative technologies. Our annual study data indicate that the industry wants more innovations in bioreactors. Single-use bioreactors ranked along with purification as the areas in which bioprocessing innovations are most needed, with 29.2% of respondents citing bioreactors. Bioreactors were also reported as taking up the single largest portion of companies’ average ~$1 million 2011 bioprocessing budgets. This includes an average of $168,000/year for purchase of singleuse bioreactors, with contract manufacturing organizations (CMOs) reporting spending an average of $260,000 and product developers reporting $147,000. Interest in new and improved bioreactors also differed from region to region, with the highest interest (32.2%) in Europe compared with 26.9% for the United States and 31% for rest-of-the-world respondents. Among separately surveyed suppliers/vendors, single-use bioreactors was the area in which the largest portion of respondents (40.5%) reported working on new technologies and products. Thus, innovations in The Z RP perfusion bioreactor system from ZellWerk GmbH (GMP breeder, bioreactor, control unit, operation software)