How to Design a Cell or Gene Therapy Clinical Trial: Advice from the FDA

Abstract

Advancing new cell and gene therapies (CGTs) from the laboratory into early-phase clinical trials has proven to be a complex task even for experienced investigators. About 20 years ago, the US Food and Drug Administration (FDA) held discussions with representatives from the CGT field on what regulatory approach would best fit such products. Two types of regulation were available: similar to that used for blood banks and similar to that used for small-molecule pharmaceuticals. The pathway eventually chosen by the FDA was originally developed for small-molecule drugs, which do not resemble CGT products. The subsequent attempts to force a square peg into a round hole have been frustrating. For example, maximum-tolerated-dose determination is relatively straightforward when using a small molecule, but for CGT products the considerations are more complex and wide-ranging, and starting doses have often been tiny. Problems such as this have usually required extensive discussions between investigators and the agency’s Office of Cell and Gene Therapies.