Cell/Gene Therapies

Top 10 Regenerative Medicine Stories of 2011

    Geron Ends Stem Cell Programs in November: Big hope for a spinal cord injury trial, big loss for a field — the most discussed news of the year. Despite the company’s official comment citing a “purely business decision,” many professionals think that a “lack of impressive preliminary results” also played a role. The company is now seeking a partner to take over that trial. The effect on the cell therapy industry remains to be seen — but for…

Emerging Challenges in Cell Therapy Manufacturing

    The introduction of recombinant proteins and monoclonal antibody (MAb) products revolutionized the treatment of many diseases, including diabetes, rheumatoid arthritis, multiple sclerosis, Crohn’s disease, cardiac disease, and cancer. These highly specific biologic therapies provide patients with life- saving approaches that are not possible with small molecules. MAbs in particular are a unique class of biopharmaceutical products that interact with and activate components of the immune system to provide such therapeutic benefits as tumor destruction by antibody-dependent cell-mediated cytotoxicity…

Meeting Regulatory Challenges for Cell-Based Therapies

    Many companies follow a general rule when assembling regulatory packages for presenting new biologics: Accentuate the aspects of your new biologic that mimic approved therapies. For companies working on cell-based therapies, however, that is a challenging task. The industry lacks established models, and the current European Medicines Agency (EMA) regulatory definition of a cell-based therapy is simply “an advanced therapy medicinal product” (ATMP) (see EMA guidance box). Regulations for cell therapies cannot always be compared directly with those…

Mastering Industrialization of Cell Therapy Products

    Incomes currently generated by the global cell therapy market are estimated to be ~US$400 million. That value represents 10 main products, some of which have been on the market since the late 1990s (e.g., Dermagraft and Apligraf, with >$100 million yearly revenues each). Cell therapy product revenues are low compared with those of the biopharmaceutical market (~$100 billion). But the market’s growth potential and clinical pipeline are leading to higher expectations. The sector’s compound annual growth rate (CAGR),…

Meeting Lot-Size Challenges of Manufacturing Adherent Cells for Therapy

    Adherent cells such as adult primary cell lines and human multipotent (MSCs) and pluripotent stem cells (hPSCs) present a manufacturing challenge as lot sizes increase from 109 (billions) to 1012 (trillions) cells (1). Typically, manufacturing platforms are good for one log of expansion. So new methods will be required to achieve commercially relevant lot sizes. Traditional two-dimensional culture methods have been used to grow anchorage-dependent cell types. Although such methods are reliable and well defined, they are very…

Streamlining Cell Therapy Manufacture

    The cell therapy industry (CTI) is no longer a cottage industry; it is a distinct and sustainable component of the global healthcare sector (1). Today, CTI prospects are strong, with annual revenues exceeding US$1 billion/year, supported by improving investor sentiment and public support (1,–3). The next phase of CTI growth — toward a multibillion-dollar global industry — will depend on the biomanufacturing community innovating to meet growing market demands and providing products at affordable costs to healthcare payers.…

Small–Batch-Size Production

    After coexisting as close cousins in the world of life sciences, the bioprocessing and cell therapy industries now find themselves as possible allies in the pursuit of solutions to small–batch-size production technology. As cell culture titers continue to increase and biotherapies become more “personalized,” pressure is increasing on the bioprocessing industry to find more cost-effective and flexible technologies for producing smaller batch sizes than before. At the same time, the cell therapy industry (renowned for its small–batch-size production)…

Transfer of Hepatic Progenitor Stem Cell Culture Process from multiple-tray stacks to the Xpansion Multiplate Bioreactor.

Scale-up a stem cell process may be challenging: small variations in physicochemical parameters (surface characteristics, pH and dissolved oxygen) can heavily impact stem cell growth and behavior. The Integrity® Xpansion™ multiplate bioreactors have been designed to enable an easy transfer from multiple-tray stacks process by offering the same cell growth environment: stacked hydrophylized polystyrene plates in a compact and closed system (from 10 to 200 plates per bioreactor equivalent respectively to 6120cm² and 122400cm²). As there is no headspace between…

Recommendations for Cell Banks Used in GXP Assays

Cells and cell-derived reagents form the basis of an operationally challenging class of test methods used in execution of product potency testing (stability and lot release), assessments of pharmacokinetic/ pharmacodynamic (PK/PD) profiles, detection of antidrug antibodies (ADAs) or neutralizing antibodies (NAB), and characterization and comparability testing of biopharmaceutical products. Frequently, cell-based assays provide the only measurement of the tertiary/quaternary structure of each batch of product at the time of lot release and during stability testing to assist in determining product…

Toward Defined Culture Conditions for Pluripotent Stem Cells, Part 2

    At the UK National Stem Cell Network ‘s annual meeting in York, UK on 31 March 2011, a workshop organized by STEMCELL Technologies workshop addressed defined media for human stem cell culture. As illustrated in Part 1 (October 2011), it is critical to understand the pathways that maintain genetic stability during hES self-renewal, which is a prerequisite for all clinical applications. Because physiological DNA damage can take place during normal cellular proliferation, and accumulation of unrepaired DNA could…