Risk of cell-culture contamination is a common concern whenever materials are added to or removed from a bioreactor. It is essential to maintain a sterile barrier and provide containment against intruding organisms during such operations. Many R&D and pilot-scale manufacturing tasks involve flexible, single-use processes with presterilized containment systems in nonclassified laboratory areas. Here, we examine a process that requires substantial manipulation of a culture — first completely removing and later returning the culture to a bioreactor during media exchange…
Bioreactors
Measuring kLa for Better Bioreactor Performance
Knowledge of kLa (the volumetric mass-transfer coefficient that describes the efficiency with which oxygen can be delivered to a bioreactor for a given set of operating conditions) is not new. Here I provide information for those who are unfamiliar with the measurement method and/or issues that must be considered when making these measurements. Advances in this area now make it advisable to run kLa measurements routinely in many bioprocesses. The Importance of Measuring kLa Before examining the process theory and…
Trends in Perfusion Bioreactors
Single-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…
A Brief History of Perfusion Biomanufacturing
Today’s renewed interest in perfusion culture is due to an increased awareness of its advantages, some general improvement in equipment reliability, and a broadening of operational skills in the biomanufacturing industry. Some misperceptions persist, however, according to a 2011 review by Eric Langer (1). Our view here of the history of perfusion and fed-batch processes includes some discussion of technological process improvements and challenges that the bioprocess industry faces. A team of authors at Serono in Switzerland wrote…