Planning Split-Apheresis Designs for Demonstrating Comparability of Cellular and Gene Therapy Products.

A recent FDA draft guidance discusses statistical considerations for demonstrating comparability of cell and gene therapy products and processes. One experimental study described in the guidance is the split-apheresis design. The FDA draft guidance recommends a paired data analysis for such a design. This paper demonstrates that the paired analysis is under powered for some quality attributes for practical sample sizes of three to five donors unless a significant portion of variability is attributed to donor. Addition of historic lots from the pre-change process can increase the power for these attributes. This paper provides appropriate statistical methods for including this information.