Abstract
Manufacturing cell and gene therapy (CGT) products derived from donor cells may involve genetic and other testing that identifies unexpected findings of potential donor origin. Testing may be done to assess the safety of the product or manufacturing process and to assess gene transduction efficiency or aspects of cell expansion, and also may be performed in recipients of CGT products following infusion to monitor the effects of treatment. Tests that may identify unexpected findings in donor cells include chromosomal karyotyping, targeted tests for specific gene mutations or rearrangements, and large gene panels or whole genome sequencing to detect mutations or cytogenetic abnormalities of relevance to donors. Deciphering whether variants are of donor origin as opposed to introduced via manufacturing processes is key, as is having a framework for protecting donors that includes procedures for ensuring robust donor consent and appropriate pathways for disclosure of clinically relevant and actionable results. Building on recent recommendations from the World Marrow Donor Association regarding unexpected findings of potential donor origin following allogeneic hematopoietic cell transplantation, an expert group was assembled to review available evidence and develop a framework to apply to healthy volunteer donors who provide cells for the manufacturing of allogeneic CGT products. These guidelines aim to provide recommendations for predonation consenting, as well as a framework for informing and managing the care of donors when findings of potential donor origin are identified. Since many cellular therapies remain under development, donors who provide cells for any aspect of research and development of CGT products require special consideration. Realizing that cellular therapy may involve commercial entities and donors that are recruited within conventional stem cell registries or through other mechanisms, we provide suggestions on how recommendations can be adapted.