In 2002, the FDA announced its new initiative called Pharmaceutical Current Good Manufacturing Practices (CGMPs) for the 21st Century. In accordance with this initiative, the Compliance Program Guidance Manual on Pre-Approval Inspections was issued, including scientific, risk-based approaches that incorporate inspection of the level of the firm's process and product understanding, an evaluation of the firm's manufacturing readiness, and verification of authenticity of submitted data. The Guidance Manual is addressed to FDA staff but gives industry a good source of information of the process of a pre-approval inspection.
The U.S. Food and Drug Administration has now revised this Compliance Program Guidance Manual on Pre-Approval Inspections. The Guidance document has been completely reworked and will be implemented on 5 December 2010. The date for completion is 5 November 2012.
The objectives are:
With the new approach, FDA won't necessarily need to cover all of the objectives (as was done in the past). This will depend upon a risk-based decision.
Here are some other major changes:
Very interesting is section 3.4 with respect to inspection coverage and techniques, defining in detail what to look for and how to proceed to determine and verify for example
In this context, also other drug products may be reviewed to evaluate the firm's capabilities and procedures.
After the inspection is conducted, investigators communicate findings primarily through establishment inspection reports (EIRs). Telephone calls, emails, or EES (Establishment Evaluation System) are often used for timely update of CDER on problematic findings. When the inspection reveals a potentially violative cGMP finding, or data integrity issues, the district should enter a "Potential OAI Alert" into EES as soon as possible. Any reportable inspection observations will be issued via an FDA-483. In the new document, examples of types of findings are listed which should appear on the FDA-483.
Attachment A of the document gives a comprehensive overview of the responsibilities of the on-site inspection team and the CDER CMC Review and Assessment.
Attachment B describes pre-approval sampling and gives examples.
The Compliance Program Guidance Manual on Pre-Approval Inspections can be found here.
At the ECA Education Course on GMP- and FDA-Compliance in Pharmaceutical Development and IMP Manufacturing (23 - 24 September 2010 in Vienna, Austria), a former FDA Investigator and Compliance Officer will give a presentation on the FDA Pre-Approval Inspection (PAI):
On behalf of the European Compliance Academy (ECA)