© The American Society of Gene & Cell Therapy editorial and predictability can be achieved in the process of regulatory evaluation and approval. The Glybera saga also highlights problems specific to ultra-orphan drugs—because obtaining largescale phase III data with a very limited number of patients is virtually impossible, procedures to handle these indications must be further developed.

Reapplications are not entirely uncommon during the regulatory evaluation of traditional small-molecule drugs and monoclonal antibodies. However, it is noteworthy that the first three products that have been evaluated by the CAT and the CHMP have required reapplications and reexaminations. Among these products, a chondrocyte cell therapy product was eventually approved, whereas an adenoviral thymidine kinase gene therapy for malignant glioma was not. Clearly, researchers and investors developing gene and cell therapies must be prepared for a