(522f) FDA Review Chemist’s Participation in Pre-Approval Inspections: Case Study from Drug Substance Facility

In 2014, FDA initiated a new approach to incorporate review chemistâ??s expertise in the inspection of drug substance/product manufacturing facilities. A pilot was launched with the objective to evaluate the feasibility, effectiveness, and efficiency of Office of Pharmaceutical Qualityâ??s vision for the integrated team-based quality assessment of A/NDAs. A risk analysis was conducted jointly by the compliance officer, drug substance, drug product, and facility reviewers to determine the need for a pre-approval inspection (PAI) and prioritize the issues to be covered on the inspection. The integrated team-based approach resulted in improved knowledge sharing among the reviewers and compliance officers, and in better identification and evaluation of high-risk areas during the application review. These high-risk areas identified by the review team were covered during the PAI. Collaboration between the review chemist and investigators helped uncover significant issues and resulted in the issuance of deficiencies to the firm.

Based on outcomes of the Agencyâ??s pilot integrated PAI program, other inspections were conducted using this paradigm including the recent PAI of a complex drug substance manufacturing facility. Participation on this inspection provided the reviewer with an opportunity to examine the equipment and process closely, to gain a better understanding of the development and optimization of manufacturing process and controls, and in turn allowed the inspection team to identify the CMC-related observations. Furthermore, the firm provided positive feedback regarding the presence of a review chemist on inspection deemed particularly helpful to better understand and improve regulatory submission of future applications. In summary, implementation of this new integrated approach for conducting a PAI has enhanced the efficiency and quality of review process, and improved communication between FDA and industry.