Bioreactors

Novel Single-Use Sensors for Online Measurement of Glucose

    According to an FDA guidance document, process analytical technology (PAT) tools “are intended to support innovation and efficiency in pharmaceutical development” (1). The agency encourages manufacturers to use a PAT framework for developing and implementing effective innovative approaches in development, manufacturing, and quality assurance. The sensors described here are one possible response to the requirement of systems by analyzing and controlling critical cultivation parameters with real-time process measurements.   Working Principle   Glucose was measured using a #CITSens…

Bioreactor Design and Bioprocess Controls for Industrialized Cell Processing

It’s official: The “Age of Cell Therapy” has arrived. A robust pipeline of cell therapies, with increasing numbers of both early- and late-stage clinical trials as well as FDA-approved commercial products that have entered the market already, strongly indicates that the cell therapy industry is poised to emerge as a distinct healthcare sector (1). Renewed investor interest and recent activity among major pharmaceutical companies suggest that this industry will rapidly develop the capability and capacity to be a highly competitive,…

A Decade of Bioreactor and Upstream Technologies

A high-quality product begins with efficient upstream process equipment. Ten years ago, manufacturers were still warming up to single-use bioreactors, which were mainly rocking-bag–based solutions. The benefits relating to cleaning and validation were clear, but their use as bioreactor vessels was still new, and stainless steel systems up to 20,000 L in scale were still needed. Today’s facilities are a hybrid of sophisticated single-use components and stainless steel equipment, the mechanisms of both having undergone improvement during the past decade.…

Method for Preserving Cell Density and Viability in Two-Phase Fed-Batch CHO Culture

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…

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…