An FDA analysis of clinical hold deficiencies affecting investigational new drug applications for oncology products.

ABSTRACT

A systematic analysis of new commercial investigational new drug applications (IND) submitted to the FDA's Office of Hematology and Oncology Products (OHOP) in the Center for Drug Evaluation and Research was conducted to quantify the most common reasons INDs for oncology indications go on clinical hold. In OHOP, less than 10% of INDs went on hold or were withdrawn within the 30-day safety review period. Of INDs that were placed on hold, deficiencies were mainly clinical, followed by concerns related to pharmaceutical quality and nonclinical development. INDs were also characterized based on phase of development, product type, sponsors' regulatory experience, and occurrence of a pre-IND meeting. INDs that were placed on hold were mostly for first-in-human trials or submitted by sponsors with limited regulatory experience. INDs that went on hold or were safe-to-proceed had pre-IND meetings with comparable rates but sponsors with substantial experience appeared to benefit more from pre-IND meetings compared to those with limited experience. The time interval between the pre-IND meeting and the IND submission was longer for INDs that went on hold. To obtain useful FDA feedback on product development, it is essential to provide focused questions and supporting information in pre-IND meeting packages.