FDA Adjusts Its Pre-approval Inspection Guide To Reflect ICH Q8-10 Paradigm

FDA has updated its pre-approval inspection (PAI) compliance program guidance (CPG 7346.832) to better reflect the agency’s 21st century quality initiative and the new ICH Q8-10/QbD regulatory paradigm.

The new PAI CPG represents a significant overhaul of the program guidance to reflect current agency risk-based thinking and objectives, and is the first major revision since its original release in 1994. FDA has been working on revising the program for some time and has issued interim revisions with more minor changes in the past few years.

The reach of the new version is extended to encompass large molecules, and it includes new sections to adapt the preapproval program procedures to the evolving quality regulatory approaches. For example, there is a new section on how the agency wants its internal “knowledge transfer program” to flow between reviewers and inspectors.

“CDER’s pre-market assignments and communications will now effectively transfer product and manufacturing knowledge from CDER to ORA inspections,” the new PAI guidance states. “Specifically, CDER staff will alert the inspection team to manufacturing and laboratory issues found during the pre-market application review.”

The agency has also recently released an internal directive as part of CDER’s “manual of policies and procedures” (MAPP 4730.3) that focuses on clarifying reviewer and inspector roles and responsibilities reflective of a more lifecycle-oriented regulatory approach.

The MAPP specifically breaks down the responsibilities for evaluating biotech applications between CDER’s Office of Compliance Division of Manufacturing and Product Quality (DMPQ) and the Office of Biotechnology Products (OBP).  The MAPP reflects the need for the application review and GMP compliance groups to work more closely together in advancing the ICH Q8-10/QbD objectives.

[Editor’s Note:  The May issue of IPQ includes an in-depth analysis of how the quality-by-design objectives are impacting knowledge management and transfer, and the reviewer/inspector relationship within FDA and EMA.  For subscription information, click here.]


FDA PAI Compliance Program Guidance, CPG 7346.832

CDER MAPP 4730.3