March 2014 Supplement

Many potentially therapeutic products involve the culture of stem cells. Their commercial success depends on the development of scalable good manufacturing practice (GMP) technologies that can both robustly and cost-effectively produce very large numbers of cells. Through many improvements and innovations in bioprocessing operations over the years, fed-batch suspension culture has remained the most common mode for large-scale biopharmaceutical manufacturing. However, some recent events suggest that may be changing ( 1 , 2 ). For the culture and expansion of stem cells, large-format adherent flask culture has gained significant favor. Here we investigate the potential of a new large-scale three-dimensional (3-D) cell mass expansion technology for meeting such commercial applications. It emphasizes continuous processing rather than batch production, with the mimicking of natural in vivo conditions as closely as possible. Stem cells are distinguished from other cell types by two important characteristics. F...

The list of conditions being targeted by cell therapies is rapidly growing, but commercializing cells for widespread medical use will require standardized laboratory practices. Development processes must be adapted specifically for cell-based drug products. Regulatory T-cell therapy represents a promising new frontier in the immunotherapy of autoimmune disorders, especially for patients who have been refractory to available treatments. Because of intrinsic fragility, cell therapy products can be highly sensitive to variations in manufacturing procedures. Standardization of drug-product cryopreservation and storage steps are thus key to ensuring consistent clinical trial results. Regulatory T (Treg) cells represent a cell population that can modulate immune responses and inhibit inflammatory processes in vivo. Treg cells maintain homeostasis of the immune system, preventing its unwanted activation against self-antigens (autoimmunity) or those that are normally tolerated (e.g., dietary antigens, inhaled ant...

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 academic programs at Johns Hopkins University, Vanek was in business development, innovation, and cell therapy at Lonza for six years. Before that, he worked in marketing and business development positions with BD Biosciences, Invitrogen/Life Technologies, and Trevigen. Montgomery: People are really starting to take notice of the cell therapy industry now. What is your assessment of the global impact that this wave of new therapies could have? Vanek: Solving the technological chal...

Fueled by a recent resurgence in public financing and compelling clinical data for indications as diverse as acute macular degeneration and pancreatic cancer, a growing number of cell therapies are driving toward pivotal clinical studies and commercialization. Although regulatory precedents have been set for various autologous and allogeneic products in the United States, Asia, and the European Union, regulatory guidance continues to evolve for a widening array of cell products. Adult stem cells (e.g., mesenchymal stem cells), embryonic stem cells, induced pluripotent stem cells, genetically modified somatic cells, nongenetically modified cells, and cell–device combination products all require unique measures to ensure regulatory requirements for safety and efficacy. Beyond the inherent complexity of these emerging products, the migration of processes required to produce them paired with evolving technology platforms for manufacturing at scale offer additional challenges to their sponsors. Here we touch o...

The cell therapy industry is undergoing a natural evolution from scientific curiosity into a commercially and clinically attractive opportunity ( 1 ). This evolution is by no means complete, and growing evidence suggests that its progression is driving significant developments in cell therapy bioprocessing — notably, convergence. Progressively, bioprocessing technologies primarily used in production of noncell-based products are being evaluated for cell therapy bioprocessing applications ( 2 ). Consequently, this process of convergence is leading to an increasing proportion of the total portfolio of such bioprocessing options involving technologies that have previously been used in other biomanufacturing applications — such as production of recombinant proteins. Technological convergence is not unique to cell therapy biomanufacturing (Table 1), or indeed to bioprocessing (Tables 2 and 3). This process shares similarities with technology repurposing; however, the key distinction is that convergence describ...

My sense is that we’ve come a long way and that 2013 was actually a very good year — perhaps maybe even the best year ever for regenerative medicines and advanced therapies. Clearly the financial markets have allowed us to do more in terms of raising capital to fund projects in this space, and we are seeing a growing interest in the sector in the investor community. We’ve seen a number of major financing events over the course of the past year, and we’ve seen the IPO market become an opportunity for companies to access new groups of investors to an extent that it never has been before. We just came off a panel [at the Phacilitate conference, see box below] where the bluebird bio IPO ( www.bluebirdbio.com ) was a major point of discussion. That financing came together in ways that simply couldn’t have happened just a few years ago. You could argue that the market conditions played a large role in this, but the company did an excellent job putting together the pieces that allowed it to go out and raise mo...