Jon Rowley

Potency assay development for cellular therapy products: an ISCT∗ review of the requirements and experiences in the industry

The evaluation of potency plays a key role in defining the quality of cellular therapy products (CTPs). Potency can be defined as a quantitative measure of relevant biologic function based on the attributes that are linked to relevant biologic properties. To achieve an adequate assessment of CTP potency, appropriate in vitro or in vivo laboratory assays and properly controlled clinical data need to be created. The primary objective of a potency assay is to provide a mechanism by which the manufacturing process and the final product for batch release are scrutinized for quality, consistency and stability. A potency assay also provides the basis for comparability assessment after process changes, such as scale-up, site transfer and new starting materials (e.g., a new donor). Potency assays should be in place for early clinical development, and validated assays are required for pivotal clinical trials. Potency is based on the individual characteristics of each individual CTP, and the adequacy of potency assays will be evaluated on a case-by-case basis by regulatory agencies. We provide an overview of the expectations and challenges in development of potency assays specific for CTPs; several real-life experiences from the cellular therapy industry are presented as illustrations. The key observation and message is that aggressive early investment in a solid potency evaluation strategy can greatly enhance eventual CTP deployment because it can mitigate the risk of costly product failure in late-stage development.

Developing assays to address identity, potency, purity and safety: cell characterization in cell therapy process development

A major challenge to commercializing cell-based therapies is developing scalable manufacturing processes while maintaining the critical quality parameters (identity, potency, purity, safety) of the final live cell product. Process development activities such as extended passaging and serum reduction/elimination can facilitate the streamlining of cell manufacturing process as long as the biological functions of the product remain intact. Best practices in process development will be dependent on cell characterization; a thorough understanding of the cell-based product. Unique biological properties associated with different types of cell-based products are discussed. Cell characterization may be used as a tool for successful process development activities, which can promote a candidate cell therapy product through clinical development and ultimately to a commercialized product.

Peak serum: implications of serum supply for cell therapy manufacturing

1The Advanced Centre for Biochemical Engineering, University College London, London, UK 2The Harvard Stem Cell Institute, Cambridge, MA, USA 3Harvard Business School, Boston, MA, USA 4London Regenerative Medicine Network, London, UK 5Harvard Medical School, Center for Excellence in Vascular Biology, Boston, MA, USA 6Future Medicine Ltd, London, UK 7Lonza Walkersville, Inc., MD, USA *Author for correspondence: david_brindley@harvard.edu ‡These authors contributed equally Peak serum: implications of serum supply for cell therapy manufacturing

Managing particulates in cellular therapy

he concept of particulates, while common to many in the pharmaceutical and blood transfusion disciplines, represents a distinct challenge in the field of cellular therapy. With newly discovered products advancing through clinical trials, the focus has shifted to ensuring products are manufactured in a reliable and safe manner. Given the unique manufacturing processes and resulting products (i.e. the cell being the active ingredient of the product), the way in which particulates are viewed and subsequently tested needs to be reviewed. No specific test or method for particulates will apply to all products, and guidance documents will be generated over time as more cell therapy products are approved. The details of the processes, testing methods used and acceptance criteria established for particulates will play a major role in generating the guidance documents. This will ultimately allow for the manufacture and administration of safe and effective products without thwarting advancement of the cellular therapy field. The intent of this review is to bring awareness to the topic of particulates with respect to cell therapy, and encourage a more open dialog and exchange of examples within the industry. We have reviewed the concept of particulates, where they originate and how they are introduced to cell therapy products, and the current methods available for their detection. We have also reviewed the relevance of current guidance documents and present potential strategies to move forward and address and control unwanted contaminating particulates in cell therapy products.

Peak MSC—Are We There Yet?

Human mesenchymal stem cells (hMSCs) are a critical raw material for many regenerative medicine products, including cell-based therapies, engineered tissues, or combination products, and are on the brink of radically changing how the world of medicine operates. Their unique characteristics, potential to treat many indications, and established safety profile in more than 800 clinical trials have contributed to their current consumption and will only fuel future demand. Given the large target patient populations with typical dose sizes of 10s to 100s of millions of cells per patient, and engineered tissues being constructed with 100s of millions to billions of cells, an unprecedented demand has been created for hMSCs. The fulfillment of this demand faces an uphill challenge in the limited availability of large quantities of pharmaceutical grade hMSCs for the industry—fueling the need for parallel rapid advancements in the biomanufacturing of this living critical raw material. Simply put, hMSCs are no different than technologies like transistors, as they are a highly technical and modular product that requires stringent control over manufacturing that can allow for high quality and consistent performance. As hMSC manufacturing processes are optimized, it predicts a future time of abundance for hMSCs, where scientists and researchers around the world will have access to a consistent and readily available supply of high quality, standardized, and economical pharmaceutical grade product to buy off the shelf for their applications and drive product development—this is “Peak MSC.”

A changing time: the International Society for Cellular Therapy embraces its industry members

The last decade has seen a dramatic rise in the development of new cellular therapeutics in a wide range of indications. There have been acceptable safety profiles reported in early studies using blood-derived and adherent stem cell products, but also an inconsistent efficacy record. Further expansion has been hindered in part by a lack of capital (both private and public) and delayed entry into the cell therapy space by large healthcare and pharmaceutical companies, those members of the industry most reliably able to initiate and maintain advanced-phase clinical trials. With recognition that the International Society for Cellular Therapy (ISCT) is uniquely positioned to serve the global translational regenerative medicine research community as a network hub for scientific standards and policy, the ISCT commissioned the establishment of an Industry Task Force (ITF) to address current and future roles for industry. The objectives of the ITF were to gather information and prioritize efforts for a new Commercialization Committee (CC) and to construct innovative platforms that would foster constructive and synergistic collaborations between industry and ISCT. Recommendations and conclusions of the ITF included that the new CC: (1) foster new relationships with therapeutic and stem cell societies, (2) foster educational workshops and forums to cross-educate and standardize practices, (3) create industry subcommittees to address priority initiatives, with clear benchmarks and global implementation, and (4) establish a framework for a greater industry community within ISCT, opening doors for industry to share the new vision for commercialization of cell therapy, emphasizing the regenerative medicine space.

Corporate profile: RoosterBio, Inc.

RoosterBio, Inc. (MD, USA) is a privately held stem cell tools and technology company focused on accelerating the development of a sustainable regenerative medicine industry, one customer at a time. RoosterBios products are high-volume and well-characterized adult human mesenchymal stem/stromal cells (hMSCs) paired with highly engineered media systems. RoosterBio has aimed to simplify and standardize how stem cells are purchased, expanded and used in the development of regenerative medicine products. To this end, RoosterBio supplies off-the-shelf cGMP hMSC working cell banks with bioprocess media that mimic the format and formulation of the research grade counterparts, radically simplifying and shortening product development and clinical translation. RoosterBios focus is to offer innovative products that help usher in a new era of productivity and standardization into the field, with a passion directed towards empowering life-saving cures to be discovered in regenerative medicine.