USFDA Guidance: Manufacturing Changes & Comparability for CGT Products, Good Cause for Noncompliance

Last Week (13th & 14th July 2023) the United States Food & Drug Administration's Center for Drug Evaluation and Research, and Center for Biologics Evaluation and Research released updated guidances on "Manufacturing Changes and Comparability for Human Cellular and Gene Therapy Products" and "Postmarketing Studies and Clinical Trials: Determining Good Cause for Noncompliance with Section 505(o)(3)(E)(ii) of the Federal Food, Drug, and Cosmetic Act".

Guidance: Manufacturing Changes and Comparability for Human Cellular and Gene Therapy Products

Human cellular therapy or gene therapy (CGT) products have a complex manufacturing process, so managing these changes can present many challenges. In addition to ensuring product safety and quality, it allows for necessary manufacturing modifications.

Manufacturing and control of CGT products can often be affected by unique factors, such as a limited understanding of product quality attributes, limited manufacturing experience, a limited and variable number of starting materials, a limited amount of product, a complex manufacturing process, and a limited product shelf life.

The purpose of this guidance is to provide FDA’s current thinking on

1) management and reporting of manufacturing changes for CGT products based on a lifecycle approach

2) comparability studies to assess the effect of manufacturing changes on product quality

Guidance: Postmarketing Studies and Clinical Trials: Determining Good Cause for Noncompliance with Section 505(o)(3)(E)(ii) of the Federal Food, Drug, and Cosmetic Act

According to the draft guidance, FDA considers several factors in determining whether an applicant has demonstrated good cause for failure to complete studies or clinical trials in a timely manner.

Post Marketing Requirements (PMR) milestones are in the timetable to measure the progress of studies and clinical trials. A timetable with milestone dates is usually proposed by the applicant, and the FDA review team assesses whether the proposed timetable will provide for the timely completion of the study or clinical trial.

This guidance describes relevant procedures, including how applicants should communicate with FDA regarding compliance with these required studies and trials, as well as the actions FDA may take for non-compliance.