TL61: Some Design Issues in Biologic Product Applications
*Shiowjen Lee, FDA\CBER\OBE\DB 


In some biologic product applications, patients’ cell is used to manufacture products. For product approval, clinical trials of this type of applications usually randomize patients prior to taking cells from patients for product manufacturing purpose. For patients randomized to the experimental treatment, their cells would go to manufacturing process to produce product. For patients that are allocated in the control group (e.g. vehicle group), their cells would be discarded through a proper procedure. It is however unfortunate that not all patients’ cells produce product successfully (i.e. some not at all and some produce insufficient product). Two issues are usually raised: a. Potential risk to un-blind the study if re-taking cells from patients who had manufacturing failure (i.e., did not produce product successfully) at the 1st round. b. Intent-to-Treat (ITT) principle in data analyses – the manufacturing failure rate can be as large as more than 10%. This differs and is in addition to missing data occurred later during the course of the trial.

This round table will discuss the issues.