Drug GMP definition high priority for Sept. MRA joint sectoral agenda committee meeting.

DRUG GMP DEFINITION TO BE ON MRA JOINT SECTORAL AGENDA as a top priority at the scheduled September meeting of the Joint Sectoral Committee established under the U.S.-European Union Mutual Recognition Agreement to assist in the implementation and monitoring of the agreement. As drafted, the MRA calls for a "tentative merging" of U.S. and European Commission "concepts to be revisited" regarding methods to be used in, and the facilities and controls to be used for, the manufacturing, processing, packing and/or holding of a drug product.

During a recent presentation at a Food & Drug Law Institute meeting, FDA Center for Drug Evaluation & Research Office of Compliance Director Stephanie Gray said the agency wants "to use our traditional definition" of Good Manufacturing Practices, and "Europe has another one. We will have to work out a definition that works for the purposes of the MRA."

The format of inspection reports is another issue that must be determined "as soon as possible" under the MRA, Gray continued. "It is possible in the context of the MRA, if there is an inspection report format, that it will, in fact, drive what is covered in an inspection," she observed.

"One of the things that we most want to avoid is a constriction of the data pipeline," Gray said, noting that although the data are used for drug approvals, "the most important part of that data is the developing and maturing of concepts" such as the need for stability testing and validation data. Without complete data, she said, "our concepts may not be as good."

Gray also acknowledged the need to "define more carefully" terms such as audit inspections, team inspections and joint inspections. "There are various fears about competing inspections, competing investigators, the issue of consistency which we hear a lot about with 21 district offices, and we are thinking what will this be like when you add in 15 different countries" and 11 languages, she noted.

FDA "will be very careful to think about the impact of the inspections themselves," the compliance director said. "We may be setting up a situation where an individual inspector or a team from one country doing the inspection in their own country may be asked to do more than what an inspection used to be -- which is a technical assessment of the ability to manufacture" or meet the specifications in an application. "It now becomes an economic and trade decision," she said.

"One way to even that out would be to have multinational team inspections which would provide better data to everyone involved, both the importing and exporting country," Gray suggested.

In May 10 comments to FDA on the agency's April 10 proposed rule on the MRA, the Pharmaceutical Research & Manufacturers of America emphasized it "does not support the concept of joint inspections and encourages more reliance on joint training, exchanges and `accompanied inspections' where the lead authority is clearly designated." The proposed rule consisted of a reprint of the MRA completed in June 1997.

The MRA "appears to mandate joint inspections as part of the equivalence assessment," PhRMA points out, adding it would "prefer language such as `may include' here to provide greater flexibility." PhRMA suggests it "may be helpful to provide...an understanding of the phrase "normally be endorsed" and its implications. The MRA provides that inspection reports "will be normally endorsed by the authority of the importing party, except under specific and delineated circumstances."

The trade group inquires about "how ongoing compliance initiatives and proposed regulatory changes...will be affected by or incorporated into the MRA transitional or operational system," citing FDA's proposed first-party audit system ("The Tan Sheet" April 20, p. 24).

PhRMA also asks FDA if recommendations on managing foreign inspections contained in a recent report by the General Accounting Office will be "factored into the MRA implementation." The report called for the agency to increase routine inspections ("The Tan Sheet" May 4, pp. 19-20). FDA is said to be attempting to make previously scheduled agency inspections in Europe joint so as to begin equivalency assessments.

Industry also is concerned about elements of a crisis "alert system" included in the MRA. "A major concern with such systems has been the lack of transparency and due process" for companies "prior to being placed in a negative regulatory status or for getting removed from such a status," PhRMA states.

The U.S./EU Transatlantic Economic Partnership may provide U.S. industry a means to raise issues with legislative initiatives under way in certain EU-member countries that pose a potential threat to the successful implementation of the MRA. USTR is seeking comments on the goals of TEP via a June 9 Federal Register notice. The comment deadline is July 6.

Announced by President Clinton, U.K. Prime Minister Tony Blair and European Commission President Jacques Santer at the May 18 U.S./EU summit in London, the TEP is aimed at exploring bilateral and multilateral approaches to negotiating the reduction or elimination of existing trade barriers and improving regulatory cooperation in industrial goods, services and agricultural products. The TEP is separate from the Transatlantic Business Dialogue, which already allows for certain issues of U.S. industry to be brought to the attention of the EC and EU member states.

Establishment of the TEP is meant to "address the recommendations of labor and non-governmental organization interests, compared to the TABD, which is focused primarily on the interests of the private sector," Commerce Department official Charles Ludolph said at a June 8 TABD meeting in Washington, D.C. "We don't expect the TABD to be other than a business dialogue," he said, but "we do expect that if recommendations are to be acted on in a timely way," there must be consensus between non-governmental organization labor and consumer interests must be taken into account.