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,…
Analytical
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.…
A Decade of Microbial Fermentation
Microorganisms play a vital role in modern life — with applications ranging from wine fermentation to biofuel production to solutions for complex mathematical problems (1). During the past decade, microbial fermentation for protein production reached a higher level of sophistication and wider adoption. When BPI was first published in 2003, the physical and biological characteristics of many microbial cells and the attributes of their fermentation processes were well known. Nonetheless, the economic environment at that time created immense pressure on…
Approaches to Debottlenecking and Process Optimization
Two major challenges associated with optimizing biomanufacturing operations remain unresolved. The first is variability: how to understand and improve manufacturing with significant variation in process times throughout all unit operations. The second is complexity: modern biomanufacturing facilities are complex and interconnected, with piping segments, transfer panels, and valve arrays, as well as water for injection (WFI) and other shared resource constraints. That complexity is becoming even greater with the need for process standardization and processing of higher (and…
Large-Scale, Single-Use Depth Filtration Systems
Clarifying cell culture broth is the first downstream unit operation in an elaborate sequence of steps required to purify a biological therapeutic. A combination of centrifugation, depth filtration, or tangential-flow filtration (TFF) is used for that operation. The availability of largescale, single-use, depth filtration technology in the recent years, however, has given process developers the capability to improve and simplify downstream processes. Clarification of Cell Culture Streams The main purpose of clarification is to efficiently separate…
An Emerging Answer to the Downstream Bottleneck
Biotechnology companies have invested billions of US dollars in new manufacturing infrastructure, expanding the industry’s total mammalian cell culture production capacity from 670,000 L in 2002 to 2,550,000 L in 2010 (Figure 1) (1). This capacity expansion is estimated to have cost the industry about $20 billion (Figure 2) (1). Figure 1: Macroporous structure of Natrix chromatography media (see () Figure 1: () Figure 2: () That production capacity (and the investment it represents) is…
Integrity Testing of Sterilizing-Grade Filters
Integrity testing of sterilizing-grade filters is necessary to reliably prevent damage to these sterile barriers from compromising the production of biopharmaceuticals. Documented integrity test results are essential to a manufacturing audit trail for releasing pharmaceutical products (1, 2). Accordingly, problems encountered during this testing can lead to considerable financial damages and substantial delays or even entirely prevent a production lot from being released to the market. Therefore, filter integrity testing is a critical step with high economic importance…
Retention of Highly Penetrative A. laidlawii Mycoplasma Cells
Mycoplasma are infamous for contaminating cell culture lines at rates as high as 80% (1,2,3,4,5). For biopharmaceutical processes, the inadvertent use of contaminated culture medium or medium components can lead to contamination of an aseptic process-validation media fill or cell culture medium for a bioreactor (6,7,8,9,10,11). Thoroughly testing medium components before use is generally impractical because of the large volume of material in use. Frequently, culture media cannot be autoclaved (because of the presence of heat-sensitive components or…
Designing the Ideal Bioreactor with Single-Use Technology
Bioprocessing companies are hoping for a brighter future in biologics manufacturing that will include ever-higher titers of vaccines and therapeutic proteins grown in cell culture. It would also facilitate bioprocess operations without the recurring challenges that stem from process scale-up and human error. Moreover, that future would also comply with increasingly stringent regulatory and current good manufacturing practice (CGMP) requirements while providing better cost controls than we see today. How far away is this future? Perhaps not too…
Large-Scale, Insect-Cell–Based Vaccine Development
Vaccines are among biotechnological products characterized by continuous growth over the past decade. According to a 2011 report, the global vaccine market is expected to reach US$34 billion in sales by 2013 (1). Much development can be ascribed to vaccine treatments for cancer, autoimmune, and infectious diseases (which have risen significantly) as well as the growing worldwide population and emergence of new pandemics. Although to date the main health impact of vaccines is still in disease prevention, the…