The third annual IBC Cell Therapy Bioprocessing conference was held in Bethesda, MD, on 21–22 October 2013. It brought pioneers in the development of cell-based therapies together with companies that have enabling technologies, such as bioreactors, cell culture media, and advanced monitoring software. After the conference, I discussed the highlights and key themes coming out of the event with Dr. Phil Vanek, general manager of cell bioprocessing at GE Healthcare Life Sciences in Westborough, MA. Also an instructor for advanced…
Bioreactors
Single-Use Bioreactors and Microcarriers
Cell-based therapies hold promise for treating many acute and chronic diseases (1). Optimism surrounding that therapeutic potential has driven the initiation of multiple clinical trials in pursuit of such treatments. Procedures for preparing these therapeutic agents begin with selective isolation of cells from desired tissues. That is followed by ex vivo expansion of cells of desired phenotype and functionality. Once expanded to acceptable levels, cells are stored to preserve their viability during transportation to treatment facilities. The final step in…
Mathematical Model for Production of Recombinant Antibody 14D9 By Nicotiana tabacum Cell Suspension Batch Culture
Transgenic plants are increasingly considered a competing system for producing high-value recombinant proteins for biomedical and industrial purposes at affordable costs (1). Researchers have shown that molecular farming (or biopharming) is a secure technology that is capable of rendering valuable recombinant proteins free of toxins and animal pathogens in a relatively short time (2,3,4,5,6). Scientists have also demonstrated that most recombinant antibodies produced in plants maintain their functional properties (substantial bioequivalence) as well as do those produced in mammalian cell…
Enabling Technologies
We hear a great deal lately about the maturation of the biopharmaceutical industry — and much advancement over the past decade or so has been in business models, financing, and product pipelines. Meanwhile, regulators around the world have become more well versed in the subject matter and have adjusted their approaches to and expectations from the industry. However, the practical side of developing, characterizing, and manufacturing biotherapeutic products cannot be overlooked — nor its importance overstated. Many technological…
Enhancing Antibody Production
Increasing demand for monoclonal antibodies (MAbs) — useful as immunodiagnostic reagents in basic research applications and potential immunotherapeutics — has created a need to optimize protein production techniques. Many developers have attempted to increase MAb output from cell culture by addressing both equipment and consumables. For example, recent advances in improved bioreactor designs and bioreactor operation have increased antibody outputs by increasing cell densities and extending cell life in culture. Materials and Methods () Bioreactors can operate in batch, perfusion,…
Simpler and More Efficient Viral Vaccine Manufacturing
Human and veterinary vaccines are divided into five main categories: conjugate, toxoid, subunit, inactivated (killed), and live (attenuated) vaccines (1). The vast majority of currently licensed human and veterinary vaccines are inactivated or live (2, 3). They are produced mostly using adherent cells: primary cells such as chicken embryo fibroblasts (CEF), human diploid cells such as MRC-5, or continuous cell lines such as Vero and MDCK (4). The pioneering legacy inherited by vaccine manufacturing development has led to strategies for…
Automation of Microbioreactors
Current methodologies in genetics and microbiology enable researchers to influence metabolic pathways of microbial cells in many directions. Beside the academic interest in investigating fundamental functions in metabolic pathways, commercial production of valuable compounds by microbial hosts is state of the art. For example, such products include enzymes (lipases, proteases, phytases), therapeutic agents (insulin, antibodies), bulk chemicals (lysine, glutamate, citric acid), or the microbial cells themselves (used in brewing or milk processing), with therapeutic agents probably the fastest growing market.…
T-Cell Suspension Culture in a 24-Well Microbioreactor
Cell therapy promises revolutionary new therapeutic treatments for cancer and other serious diseases and injuries. For example, T-cell therapy response rates of >50% and durable complete response rates of 20% have been reported in patients with metastatic melanoma who had failed other therapies (1). In another example, sustained remissions of up to a year were achieved among a small group of advanced chronic lymphocytic leukemia patients upon treatment with autologous T-cells expressing an anti-CD19 chimeric antigen receptor (2). Numerous other…
Broadening the Baseline
When the editors of BPI asked us at BPSA to put together a content-rich article for the single-use supplement, we were happy to do so. Our challenge was how to bring in multiple viewpoints about the growing business of single-use that would be a “quick read” for the BPI audience. The answer: an expert colloquy (a “conversational exchange or topical dialogue”). Represented here are several of the most qualified industry spokespersons in single-use — all are members of BPSA and…
Development and Qualification of a Scalable, Disposable Bioreactor for GMP-Compliant Cell Culture
During the past decade, single-use bioreactors have become widely accepted for use in cell culture process development and clinical manufacturing. Their key benefits over stainless steel bioreactors are flexibility, cost, and time savings associated with the reduction of cross-contamination risks (1). Here, we describe our approach to development and qualification of the Biostat STR single-use, stirred-tank bioreactor. Unlike other stirred single-use bioreactors, it offers a similar design to that of well-established, conventional (stainless steel) stirred-tank bioreactors. Disposability of the single-use…