Single-use (disposable) technologies are gaining significant traction in biopharmaceutical manufacturing due to reductions in capital investment for plant construction, lower requirements for cleaning and sterilization, and the advantages of eliminating cross-contamination during multiproduct manufacturing (1,2,3,4). In the early days of disposables, single-use (SU) systems were used only in specific unit operations (5, 6). Recently, however, options have become more widely available throughout drug-substance manufacturing (7,8,9,10). Companies now focus on selecting the right SU technology from an array of…
Friday, June 1, 2012 Daily Archives
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.…
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 Production
Single-use technology has arguably been the biggest “story” of the past 10 years in bioprocessing. And for many people, implementation of disposable elements began soon after the turn of the century with a bioreactor (1, 2), first developed by Wave Biotech in 1996, now a mainstay of many upstream process development laboratories and sold by GE Healthcare. BPI identified the significance of such technologies early on, making them the subject of a supplement in its second year. By the fourth…
Spotting, Tracking, and Predicting Inspection Trends
Compliant companies, to paraphrase Tolstoy, are all alike. Every noncompliant company seems to find its own way to fall short of compliance with good manufacturing practice (GMP) and come, as did the writer’s famous heroine Anna Karenina, to grief. One commonality of compliant firms is that most seem to have excellent self-auditing/self-inspection programs. Indeed, many inspectors say that a primary predictor of a compliant company is a rigorous self-inspection program. Such a program is appropriately focused, adequately resourced,…
From the Publisher and Editor
At about this time of the year, 10 years ago, the four founders of BioProcess International were in arguably the most creative period of their lives. By the middle of 2002, we began designing our collaborative production and operating processes with our new Informa colleagues (then Eaton Publishing). We were assembling author and advertising contacts pretty much from scratch, trading opinions about page designs, building a manuscript pipeline, choosing fonts (something those outside of publishing might not…
Looking at the Recent FDA Biosimilar Guidelines
Small-molecule treatments are invaluable in providing symptomatic benefits for an array of illnesses. However, many serious conditions — ranging from cancer to autoimmune disorders — respond better to more sophisticated complex drugs such as therapeutic biologics and nonbiologic complex drugs (NBCDs). The latter are medicinal, nonbiological products in which the active substance is not a homomolecular structure, but rather consists of a number of different (closely related) structures that cannot be fully characterized. The US Food and Drug Administration (FDA)…
Rapid Development of Chemically Defined Media and Feeds through Replacement of Basal Hydrolysates
Protein hydrolysates are widely used in mammalian cell culture to improve cell growth and recombinant protein production. However, use of the hydrolysates can lead to significant process variability, due to the limited control of their source and final composition during manufacturing. On the other hand, development of chemically defined media and feeds requires a tremendous amount of work, including comprehensive library screening and spent media analysis.
In this educational webcast, Dr. Hao Chen, Associate Principal Scientist, BioProcess Development at Merck, describes a rapid method for developing chemically defined media and feeds for Chinese hamster ovary (CHO) cell lines from existing proprietary media and feeds by the replacement of basal protein hydrolysates with novel supplements. In the case studies presented, Dr. Chen shows that after two rounds of optimization, the protein hydrolysate was successfully replaced. The resulting cell growth, protein productivity, and product quality were similar in the chemically defined and original media. The entire development process was completed within six weeks.