'Pharmaceutical Inspectorate' and team inspections created for human, animal drugs: all Part 11 guidance, CPG revoked.

FDA plans to extend "Team Biologics"-like inspections to human and animal drugs by creating well-trained "cadres" of product specialists to join field investigators on audits, plus a new "Pharmaceutical Inspectorate" to coordinate audits with the Center for Drugs, Center for Veterinary Medicine (CVM) and Office of Regulatory Affairs (ORA).

In announcing a six-month progress report on its "Pharmaceutical GMPs for the 21st Century Initiative" at a news conference Feb. 20, FDA said that under the new Inspectorate plan, inspection teams will focus their efforts on identifying drug manufacturers that pose the greatest risk.

"We want to ensure our limited resources have the greatest impact and focus those on where FDA intervention is to happen," CDER Compliance Director David Horowitz said. He explained that the agency would concentrate its resources on drug manufacturers where non-GMP compliance has the greatest public health impact.

Thus, for the current 2004 fiscal year, FDA will be focusing audits on sterile drugs, "sites making prescription drugs" and new registrants not previously inspected. The agency hopes to develop more complex risk-based models for directing inspections for next fiscal year, he said.

CDER Director Janet Woodcock, M.D., said the new Inspectorate agreed to work together to develop a group to concentrate specialties on pharmaceutical manufacturing. Members will co-train with Center staff and the first members are anticipated to be on board by the end of fiscal year 2003. Key to this will be the inclusion of "product specialists," much like the ones already used in the biologics teams. During inspections, a specialist will be responsible for evaluating test methods and method validation, as well as reviewing and interpreting raw analytical data that may be outside the field investigators' expertise. For biological products, a specialist is key in assessing purification processes related to active pharmaceutical ingredients.

Ironically, the effectiveness of "Team Bio-logics" has never been formally evaluated, but has been criticized by industry--chiefly biotech companies--because of the difficulty of hosting so many FDAers in a plant at one time.

Asked why FDA would spread the team concept to human and animal drugs before seeing whether it has worked well for CBER-regulated products, CBER Compliance Director Steve Masiello told the press briefing that there is an ongoing re-evaluation of team inspections. "Team Biologics fits well within this [GMP] initiative, including internal quality management systems."

However, John Taylor, associate commissioner for Regulatory Affairs, said the organizational structure for inspections would not change within the agency.

Other highlights of the GMP initiative's six-month report include:

* Evaluating mechanisms to effectively and efficiently communicate inspection deficiencies: FDA will clarify the status of the observations that are noted on the 483s and highlight avenues for further discussion with FDA on the inspectional observations.

* Revoking all draft Part 11 guidance and the 1999 compliance policy guide: In making CDER the lead Center for the electronic signature/records regulation (21 CFR Part 11), FDA decided to revoke all draft guidance documents on the rule, plus the compliance policy guide. In addition, FDA decided to exempt legacy systems from most Part 11 requirements if they were in use before the regulation was enacted on Aug. 20, 1997.

* Requiring Center review of GMP warning letters: Besides a year-old requirement for all warning and "untitled" letters to be cleared by the Office of the Chief Counsel, warning letters starting this month also will have to be cleared by each Center before they are issued to firms. This means FDA has revoked direct reference authority to field districts, which already had been the case for certain kinds of GMP letters (such as for "Team Biologics" inspections and design controls for devices). FDA said: "This will help identify possible program inconsistencies and resolve them before warning letters are issued."

* Implementation of a technical dispute resolution process for GMP disputes: FDA issued a progress report from the Dispute Resolution working group. FDA is accepting comments on the issues and processes discussed in the progress report. FDA plans to consider and implement dispute resolution procedures for GMPs that allow for discussing scientific and technical issues, that bring the best technical expertise on a particular issue, and that allow for developing of best practices and policies across FDA, as well as improving transparency of the regulatory process.

* Creating a risk-management role in CDER: Effective January 27, CDER reorganized its Office of Compliance, creating a new Division of Compliance Risk Management and Surveillance to enhance the Office's capacity to implement risk management approaches.

Additional information on the initiative can be found at www.fda.gov/cder/gmp/index.htm.