CMC Regulatory Paradigm Shift To Be Reviewed By PQRI

FDA will look to the Product Quality Research Institute to help with the manufacturing science issues involved in reshaping the agency's NDA chemistry, manufacturing and controls regulatory paradigm.

The role of PQRI in helping the agency make the shift from a "CMC review" to a "quality assessment" paradigm has been stressed by agency officials following FDA's release of the two-year status report on its good manufacturing practices initiative (¹ (Also see "FDA Creates Four New Drug Chemistry Divisions For CMC Evaluation" - Pink Sheet, 4 Oct, 2004.), p. 18).

At a recent Consumer Healthcare Products Association meeting, FDA Office of Pharmaceutical Science Associate Director-Policy Development Jon Clark discussed the need for PQRI in streamlining the agency's approach to manufacturing changes - a key component in reaching the initiative's goal of supporting innovation and continuous improvement in pharmaceutical manufacturing.

Four areas cited by Clark where PQRI could help facilitate manufacturing changes are site, components, technology and container closures.

PQRI is currently assessing the science involved with the forthcoming FDA guidance on bulk active postapproval changes (BACPAC II).

The PQRI effort could help FDA compare its guidance to comments from the Pharmaceutical Research & Manufacturers of America and the Generic Pharmaceutical Association, Clark said.

The institute is also planning to explore postapproval changes for aseptic processes, as well as the implementation of process analytical technology.

PQRI, a collaborative effort among academia, industry and FDA intended to conduct research to support regulatory policy, has created a manufacturing technology committee specifically to pursue a number of projects aimed at helping implement aspects of the agency's 21st century drug quality initiative.

The manufacturing committee is one of the largest within PQRI, with many member trade associations including both a quality expert and a manufacturing specialist on the panel. Currently, it includes 19 representatives from 11 trade associations and FDA.

At the CHPA meeting, Pfizer Tech Services Senior Director Bruce Bird, who co-chairs the committee, outlined how the committee developed its work plans using four focal points of the drug quality initiative: manufacturing changes without prior approval, integrating CMC review with inspections, risk-based cGMPs and manufacturing science.

The committee decided to concentrate its efforts on comparability protocols, product technologies, integrated inspections, manufacturing science and risk assessment, he explained.

The manufacturing committee is also focusing on projects involving aseptic processing issues and process robustness for oral dosage forms.

Specifically, a process robustness working group is designing definitions for critical process parameters and critical quality attributes, Bird noted.

"One of the important things from the FDA point of view," Clark stressed, is that PQRI is part of the effort to make "our policy decisions in the open."

"I am particularly sensitive to that point because I am of the personal belief that one of the great successes of American government is its openness: the fact that we do not make decisions without good rationale and without good input, and even if we fail in that, at least it is in the open," he added.

PQRI will also be sponsoring workshops to provide additional input on regulatory issues related to the quality initiative.

The institute plans to hold a session to discuss risk assessment from Jan. 31 through Feb. 2 in Washington, D.C., and another on specifications March 15-18 at a location yet to be decided.

[Editor's note: The NDA regulatory paradigm shift from "CMC review" to "quality assessment" and the role of PQRI in the process is addressed in depth in the November issue of ² "The Gold Sheet." For a sample copy, call customer service at 800-332-2181.]