Spring Release Expected for Revised GMP and Guidances

Medical Device & Diagnostic Industry
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Originally published November 1995

Spring 1996 is now the new target date for promulgation of FDA's long-awaited revision of its good manufacturing practices
(GMP) regulation, but the agency has yet to determine how and when the new GMPs will take effect. In the meantime, FDA is
also turning its attention to the development of crucial guidance documents that it hopes to release shortly after publication of
the final regulation.

Final work on the revised GMP regulation follows the recent meeting of the agency's GMP Advisory Committee, which
gathered in Gaithersburg, MD, on September 13-14 to hear industry testimony about the agency's July draft of the regulation
and to offer advice on key areas of concern to industry. The meeting was the first in three years for the nine-member
committee, which had to be reconstituted after nearly being eliminated by government bureaucracy busters. Among the issues
under consideration were the applicability of the GMP regulation to component manufacturers, how it should define and
regulate servicing and remanufacturing operations, and whether it should be phased in or made effective all at once.

The committee was in full agreement on the issue of component manufacturers, voting nine-to-zero to recommend that the
GMP regulation not be extended to apply to them. "This vote wasn't too surprising," said device industry consultant Anita
Thibeault of Anita Thibeault and Associates (Rogers, AR), who is serving as one of the two industry representatives on the
committee. "No one who thought about this from a purely logical standpoint would conclude that component manufacturers
should be subject to the GMP regulation."

On issues related to servicing, however, the committee was divided along a number of lines. In testimony from third-party
service organizations, the committee was urged to make hospital service technicians subject to the regulation in order to
provide a level playing field for all servicing organizations. "The biggest question was whether this regulation should be applied
to third-party servicers and hospital personnel that it didn't seem intended for, that had not previously been under the
regulation, and for whom it would be an unusual burden," noted Thibeault.

While several committee members expressed the view that FDA regulation of hospital service technicians was an essential
public health issue, "there was no clear-cut consensus," said Thibeault. "Other members argued that applying the regulation to
hospitals and third-party servicers would burden the health-care system by forcing users to go to the original manufacturer for
parts and service, thus making it more expensive for them to buy and maintain equipment than if they were able to use
third-party servicers with less overhead."

Despite FDA's admission that it does not have the resources to enforce the servicing requirements in hospital and other clinical
settings, in the end the committee voted five-to-four to recommend that user-facility service technicians be subject to the
regulation.

On related issues regarding the responsibility of manufacturers to provide service manuals for use by third-party servicers, the
panel expressed a variety of views. "FDA had proposed language requiring manufacturers to 'ensure that the device's safety
and performance specifications, as set forth in service manuals or literature,' be made available to servicers," noted Thibeault.
"I felt that language was too general and didn't deal with the fact that companies that make instruments often have separate
technical or service manuals that include such details as schematics, board design, and circuitry - all the things that go into
servicing a device. In some instances, these manuals reveal the design of the product, and that information is proprietary,
intellectual property. As written, the regulation requires manufacturers to give that information away 'at a cost not to exceed the
cost of preparation and distribution,' despite the protections for intellectual property provided by copyright and patent laws. I
felt there needed to be a balance in FDA's approach; patient safety is the primary part of this equation, but protection of
intellectual property also has to be a factor," Thibeault added.

According to Kimberly Trautman, acting chief of the Cardiovascular/Neurology Branch in the Office of Compliance of FDA's
Center for Devices and Radiological Health, the agency's proposed language was not meant to apply to proprietary
information, but only to such manuals as manufacturers had already released for distribution outside their companies. "The
intent was to ensure that if a manufacturer was already providing information to one group of servicers, such as its hospital
customers, it would also supply that same information to all other service organizations," Trautman said. In the end, the panel
voted to retain FDA's proposed language, even though some committee members recommended that it be carefully scrutinized
to determine exactly what it would require manufacturers to give away.

Trautman expects that revision of the new GMP regulation to meet the committee's recommendations will take several months,
and that the final version will be promulgated next spring. Release of GMP-related guidance documents will take place during
the months intervening between promulgation and the final date for the statute to go into effect.

"The first guidance document that FDA wants to produce is one on design control, because that area is going to be new for
almost everyone," said Thibeault. Trautman confirmed that the agency's Harmonization Task Force is now working on a
guidance for design control, and that a second draft - still not ready for public circulation - is expected very shortly. A second
guidance on process validation is expected to be included in a horizontal guidance on validation now being prepared by
European members of the task force. Other documents being planned include a guidance on human factors, which is being
compiled by the device center's Office of Health Industry Programs, and a compliance guidance on software validation.

Thibeault suggested that FDA might need to issue a compliance guide on servicing for the use of agency investigators, and that
industry may need additional GMP-related guidances in areas such as the handling of nonconformances, and corrective and
preventive actions. "Statistical techniques might be another area of interest, since companies are having a hard time
understanding what they're supposed to do in that area," she noted.

In the wake of the citizen petition submitted by the Indiana Medical Device Manufacturers Council (IMDMC) to halt FDA's
use of "improper" methods in creating industry guidances, it is unclear what process the agency intends to use for soliciting
comment on the planned GMP-related guidances. "At this stage, FDA would probably not put out any guidance that would
affect industry in an important way without first conducting a public review," noted Thibeault.

Although the GMP Advisory Committee has in the past been called upon to assist the agency in the compilation of guidances
and conduct of public hearings, Trautman doubts that it will play a major role in the development of new GMP-related
guidances. Bradley Merrill Thompson, an attorney with the firm of Baker & Daniels (Indianapolis) and counsel for the
IMDMC, observed that "by itself an advisory committee hearing is not a very complete way of getting industry comments.

"The membership of FDA's advisory panels is usually not reflective of industry," added Thompson. "The members tend to be
academics with little or no industry experience, and the panel meetings do not offer much opportunity for comment by industry,
patients, or other stakeholders. In addition, the members are chosen by FDA, and subject to self-selective bias. In any case,
holding advisory committee hearings would not fully address the concerns that are raised in the IMDMC petition."

Trautman agreed, noting that better channels for soliciting industry input might be found among such groups as the
Harmonization Task Force and the International Organization for Standardization (ISO) Technical Committee 210, which is
working on the application of quality systems standards to medical devices.

The burning question of how and when the revised GMP regulation should be implemented escaped from the September
committee meeting without firm resolution. FDA presented several options for putting the full regulation into effect, with time
frames ranging from 180 days to 18 months after promulgation. The agency also put forward an option that would have made
the full regulation effective 180 days after promulgation, but with an unspecified phase-in period for design control issues.
During that period, the agency would forego writing form FDA-483s for design control observations, but would issue
"feedback reports" to help manufacturers learn what FDA expects in terms of design control.

The panel reviewed all of those options - and a lot of variations along the same lines - and we just could not agree," said
Thibeault. "The most we got to support any one option was two people. So there was never any vote, no consensus, nothing.
Now we don't know what will happen; FDA will have to make a decision based on what it thinks is best."

- Steven Halasey

(This article originally appeared in the November 1995 issue of Medical Device & Diagnostic Industry. © 1995 CanonCommunications, Inc. All rights reserved.)

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