Donald G. Phinney, PhD Senior Editor Department of Molecular MedicineUF Scripps Biomedical Research Jupiter, FL, USA
In this issue of Cytotherapy Corner I want to highlight a white paper authored by Fink et al., published in the June 2022 issue of Cytotherapy, and contributed by the ISCT Process Development & Manufacturing Committee (formerly the Process and Product Development Subcommittee) that provides guidance on optimizing the economics aspects of cell and gene therapy (CGT) product development to ensure a successful launch of affordable products with broad patient accessibility. This guidance is critically needed as the high cost of recently approved CGTs limits patient access despite their remarkable clinical benefit. The paper focuses on post-production procedures, including product stability, storage, shelf life, distribution, handling logistics, ownership, liability, and compliance issues and discusses their potential impacts on commercialization success and patient access. For example, the authors recommend establishing a compliant method to track the product from manufacturing to patient and to start this tracking early in the clinical trials stage. This process is essential to ensure a proper chain of identity and chain of custody of the product, which is required by regulatory agencies. It also stresses the importance of maintaining high-quality data across the supply chain to facilitate timely and accurate delivery of the product. The authors also discuss issues related to product configuration and stability and how changes in these parameters between clinical testing, manufacturing and commercialization may impact cost and suitability for patient administration. Issues related to shipping temperatures, containers, and product shelf lives are also discussed, as these may also have significant cost implications if changes are necessitated at patient administration or commercialization stages. Lastly, the authors provide a robust discussion on the distribution supply chain and the importance of developing a sound strategy that encompasses all facets of the process, such as product modality and configuration, operational complexity, ownership/liabilities, and compliance requirements. Since lack of anticipation or improper planning for additional product processing by clinical staff may limit patient access, planning for these processes and establishing who is responsible for training, costs, and liability issues is necessary to ensure broad patient access. The authors provide case studies and scenarios to highlight these issues and illustrate their complexity. I found the paper to be highly informative and believe it will serve as a useful resource for anyone involved in the development, manufacture, commercialization, and administration of CGTs.
In the July 2022 issue, I want to highlight an Editorial contributed by Renesme et al. that describes a broad collaborative effort to establish an international consensus definition for mesenchymal stem/stromal cells (MSCs). This effort involves consulting a diverse group of MSC stakeholders across various disciplines to establish a basis for the definition, and then employing the Delphi method to arrive at a consensus opinion by engaging experts through several rounds of surveys. While I firmly believe the quality and rigor of the science undertaken to describe the biology and therapeutic potential of MSCs surmounts issues surrounding the “MSC” acronym, the field’s reputation has been tarnished and funding significantly diminished by those who find the acronym flawed and inaccurate. Therefore, establishment of a consensus definition of MSCs, together with efforts by the International Standards Organization’s (ISO) to adopt standards for the bio-banking of cells from different tissues is anticipated to bring greater clarity and consistency with respect to reportability of data to the field. There is also an effort underway to establish a patient registry for MSC-based clinical studies, which would provide access to large amounts of patient data for analysis. This effort is desperately needed to bridge the gap between basic scientists working to identify biomarkers of MSC potency and clinicians searching for biomarkers of patient responsiveness. Access to complete data sets will greatly aide in efforts to develop predictive models of MSC outcomes, which can be used to create therapies tailored to specific disease indications or patient populations. Achieving the latter will elevate MSC-based products to commercialization success, and by doing so validate the decades of scientific inquiry devoted to these cells. If you have been invited to complete the Delphi survey, I strongly urge you to do so to support this effort. Also, if you have an interest in supporting an MSC patient registry, please reach out to members of the ISCT MSC committee to learn more about this endeavor.