Direct reference authority for drug GMP letters taken away from FDA districts.

Centers must decide to issue warning letters

Dear Reader,

FDA District Offices no longer have direct reference authority for issuing human and animal drug GMP warning letters and must have them cleared through the appropriate Center in addition to clearance by the Office of Chief Counsel, according to a six-month progress report on the agency's "Pharmaceutical GMPs for the 21st Century Initiative," released Feb. 20.

While certain types of GMP letters--such as letters from "Team Biologics" inspections and letters involving device design controls--have been free of District Office direct reference authority for some time, the rescission was officially extended to all drug GMP warning letters effective March 1.

Previously, District Offices had the authority to issue warning letters directly to firms when inspectional observations did not meet GMP regulations.

The impetus for such a move comes from the agency's desire to "identify possible program inconsistencies and resolve them before warning letters are issued," FDA announced.

Asked to explain what inconsistencies the agency is trying to eliminate, FDA replied: "As innovative manufacturing and control technologies are adopted in the pharmaceutical industry, it is important that FDA regulate them in a consistent way. Some of these technologies will be first encountered in FDA's inspection program and Center review of warning letters will help assure that FDA responds to any deficiencies in a consistent manner."

Additionally, the Centers will be evaluating the inspectional information supporting proposed warning letters, the agency stated. Regular analysis of this data will aid the Centers in identifying trends used to further develop a risk-based strategy towards GMP enforcement practices, FDA continued.

The agency hopes to use this analysis "to enhance policy, provide guidance, and establish training for the FDA field staff and regulated industry."

To provide guidance under the Initiative, the review of warning letters has its own working group, chaired by CDER's Fred Blumenschein. But unlike some other working groups under the Initiative, the Warning Letter Review Working Group has yet to issue a progress report.

Blumenschein told a Feb. 20 press briefing that the Center review will examine "two issues--technical competency and significance" of the violations. "The idea is ensure consistency both from a technical realm and significance."

The rescission of direct reference authority was one of the "first steps" of the Initiative to improve regulation of pharmaceutical manufacturers to be completed.

Other completed steps of the Initiative's short-term goals included clarifying the agency's 21 CFR Part 11 electronic submission and recordkeeping requirements, and "clarifying the language used to communicate deficiencies observed" during GMP inspections.

This latter step was addressed by the "483 Communications Working Group." The Group came up with the following language that will be added to FDA's website where any 483s and warning letters are posted in order to clarify the purpose and effect of the 483 and alert the recipient about how to object to an observation or how to bring new information to the agency's attention. The language reads:

"This document lists observations made by the FDA representative(s) during the inspection of your facility. They are inspectional observations, and do not represent a final Agency determination regarding your compliance. If you have an objection regarding an observation, or have implemented, or plan to implement, corrective action in response to an observation, you may discuss the objection or action with the FDA representative(s) during the inspection or submit this information to FDA at the address above. If you have any questions, please contact FDA at the phone number and address above."

Complete details on the GMP Initiative six-month progress reports can be found at: http://www.fda.gov/cder/gmp/index.htm

Sincerely,

The Editors