Draft pilot program to reduce warning letters

Additional device standards recognized

HIMA wants FDA to use entire standards

FDA needs more device review prototypes

HIMA seeks further-expanded MRA

Ruling satisfies Myo-tronics—for now

Medical device manufacturers may have felt alienated by David Kessler's FDA, but his successor-designate and former deputy, Jane Ellen Henney, MD, has been making deliberate if measured efforts through government channels to show a more friendly countenance to the industry.

On September 23, Henney's appointment was approved in a voice vote by the Senate Labor and Human Resources Committee and subsequently approved by the full Senate. In the days leading up to her confirmation hearing, Henney answered 140 written questions that had been put to her in advance by committee chairman James M. Jeffords (R–VT). Sixty-seven of the questions were about medical devices—far more than about any other subject.

The questions purportedly originated with Jeffords and his colleagues, but the content was heavily influenced by the medical device industry. Similarly, most of the information in Henney's answers appeared to have been provided by FDA officials and their overseers in the Department of Health and Human Services.

It could hardly have been otherwise, given Henney's four-year absence from the agency and the intricate nature of some of the questions. For example, she could hardly have been expected to know whether a senator's constituent should be able to get a 510(k) for a laser based on another laser's approved use with a slightly different kind of tissue—one of the questions posed to her.

Despite the fact that Henney may have been repeating the party line, the nominee took advantage of numerous opportunities to show that she is personally sensitive to many industry concerns. These include issues to which FDA had seemed unresponsive during and since the time Henney last served at the agency (1992–1994).

For instance, Henney was at CDRH when the center—in the wake of the generic drug scandal—choked off many channels of communication between device sponsors and reviewers. In her answers to Jeffords, however, she emerges as a champion of open communication. To a question about industry-FDA interaction prior to publication of a guidance document, Henney maintained that, if confirmed, she would "work diligently to continue to improve the communication between the agency and the regulated industry. . . ."

Other responses showed Henney to be an advocate of equal time and access to briefing packages for sponsors at FDA advisory committee meetings; a supporter of fair treatment for sponsors in administrative appeals, including freedom from reprisals when officials make unfavorable decisions; and a voice for continued grassroots dialogue with industry. "I believe there is always value in communication, particularly when it is undertaken at a stage where it can guide the parties in making appropriate decisions," Henney said in answer to a question about early FDA meetings with potential premarket approval (PMA) applicants.

Henney's answers showed considerable sympathy for manufacturer positions in other areas as well. She said, for example, that FDA should require "only such data as are necessary" and not default to requiring the most burdensome type of clinical studies. She also gave a cold shoulder to the oft-recurring plea for device user fees, despite being nominated by a White House that seeks them every year. Historically, Henney said, "user fees have succeeded only when they result from consensus among the agency, the Congress, industry, and consumers."

Henney supports third-party reviews of medical devices and will give them her top priority, applauds CDRH reengineering efforts, favors requiring only the minimal amount of information needed to demonstrate substantial equivalence, and favors reliance on harmonized international device standards. She also endorses the "reasonable assurance" standard for device effectiveness rather than the "substantial evidence" standard applied to drugs and will encourage FDA reviewers to rely on information in approved PMAs when it is available and relevant to the evaluation of a newer device.

On the issue of whether CDRH should consider possible off-label uses when reviewing a device as opposed to confining itself to the sponsor's requested indications, Henney said she agreed with the solution found in the FDA Modernization Act of 1997—that off-label uses should be considered only after the rest of the review is done.

Asked whether FDA should issue warning letters to companies that are implementing corrections to GMP problems found during an inspection, Henney showed how well she knows the agency. Even though she was not privy to the information that FDA would, within the following week, propose a pilot program for device manufacturers eliminating such warning letters in good-faith situations, Henney told Jeffords she believes that "in the case where a firm responds to an inspection finding and the agency deems the response to be adequate, a warning letter usually is not warranted."

In responding to a question that might have been inspired by the publicity hound reputation of her predecessor, Henney implied that she would be just the opposite. The question asked in what circumstances FDA should use publicity to achieve a consumer protection result. "I believe," Henney replied altruistically, "that FDA should use publicity wisely to provide the American people with critical, useful public health information in an accurate and timely manner. I think that some circumstances in which publicity is effective are announcements of recently approved products that may provide significant new clinical benefits and options to patients; warnings about adulterated or misbranded foods, drugs, and devices that are being withdrawn or recalled from the market because they may pose serious or life-threatening health risks; and continuing education efforts such as FDA's Office of Women's Health 'Use Medicines Wisely' campaign."

This answer might be indicative of Henney's like-mindedness with the people she will be leading at FDA. As physical security barriers have increasingly shielded them in their daily work from outsiders and voice mail has freed them from many past intrusions on their time—especially from the media—Henney's FDA may see itself more in charge of its own publicity than has been the case in the past. And whereas David Kessler enjoyed a love affair with the media and was able to manage it to his and the agency's advantage, this is a rare skill, and Henney may not be so fortunate.

In any case, Henney is the first nominee for commissioner to be subjected to such a grueling, intense, and diversely detailed senatorial screening process.

Her answers to Jeffords's 140 questions show a deft blending of reliance on institutional data, political acumen, philosophical caution, and native reserve. All of these qualities will serve her well as commissioner.

Few FDA behaviors have aggravated industry more than the agency's past penchant for issuing publicly embarrassing warning letters when the matters complained of have already been cooperatively cleaned up by the subject company.

The situation has arisen out of two tendencies within FDA. The first is a lawyer-driven perceived need to "put the firm on official notice" to the effect that problems have been found and duly reported and that the agency is poised to administer heavy punishment if it becomes necessary (courts like to see this sort of thing). The second tendency is a bureaucracy-driven inclination to issue warning letters later rather than sooner (sometimes many months later).

Now comes an FDA draft pilot program under which much of this kind of delayed enforcement could become a thing of the past. Constrained to do more with much less money, FDA said in an August 27 Federal Register notice that—for medical device companies only—it wants to pilot test an 18-month program under which warning letters for quality system, 510(k), and labeling violations will not be issued in the following circumstances:

1. The firm responds adequately and within 15 days to the FDA 483 notice of inspectional observations.

2. The violation(s) are not found in "non–quality system" inspections such as for mammography, radiological health, or bioresearch.

3. The establishment does not manufacture drugs as well as devices.

4. The establishment does not manufacture devices that are regulated by the Center for Biologics Evaluation and Research.

5. The establishment does not have a "recidivous" history with FDA.

6. The inspection did not uncover quality system, 510(k), or labeling deficiencies that could cause serious adverse health consequences.

7. The inspection was not a compliance follow-up inspection to a previous one that resulted in a warning letter or regulatory action for quality system, 510(k), or labeling violations.

8. The inspection did not disclose other significant device violations—in addition to quality system, 510(k), or labeling violations—that warrant the issuance of a warning letter or other regulatory action (e.g., medical device reporting or premarket approval infractions).

9. The firm's management did not fail to make available to FDA personnel all requested information and records required by regulations or laws enforced by FDA.

10. The violations do not involve advertising and promotion issues.

11. The inspection uncovered no devices that were never cleared by FDA via a 510(k), unless they were exempt from this requirement (section 807.81(a)(1) or (a)(2)).

12. There was no major change or modification in the intended use of the device(s).

13. The device(s) are not electronic products that emit radiation.

The draft pilot program—which won't begin before FDA has evaluated public comments it is receiving until October 13, 1998—will be applicable to all medical device inspections except those conducted under FDA contracts by the states of California, Colorado, and Texas.

An additional 241 consensus standards for use in the CDRH "510(k) paradigm" submission process have been recognized by FDA. Under the paradigm, device manufacturers can submit declarations of conformance to recognized standards in lieu of submitting data that ordinarily would be evaluated by FDA reviewers. The complete list of FDA-recognized standards is available on the Internet at http://www.fda.gov/cdrh/modact/recstand.html.

FDA should recognize relevant national and international consensus standards in their entirety unless the agency has valid scientific reasons for deviating from such standards, the Health Industry Manufacturers Association told FDA in a recent letter. Specifically, HIMA cited the ASTM standard PS 77-97 that FDA didn't fully incorporate in its May 4, 1998, draft guidance "Testing for Skin Sensitization to Chemicals in Latex Products." In the guidance, FDA proposes setting the sample size at 300 subjects when the standard recommends 200; the agency also calls for a 1 x 1-in. test patch while the standard suggests a 2 x 2-cm patch.

FDA should publish a flowchart of internal processes for all device submissions, HIMA told CDRH on August 18 at a FDA Modernization Act stakeholders meeting in Washington, DC. In addition, more templates, prototypes, and examples of successful submissions should be made available. For inspections, HIMA suggested that "FDA should consider ISO certifications in prioritizing and should ultimately harmonize" with ISO. HIMA also called for joint training with FDA investigators so that device manufacturers could have a better understanding of inspection criteria.

In August 3 comments, HIMA urged FDA to widen its mutual recognition agreement (MRA) with the EU to allow third-party review of even more medical devices than are covered by its recently expanded list. All eligible devices other than permanently implanted or life-sustaining/supporting devices or those requiring clinical data should be eligible for review by EU conformity assessment bodies (CABs), HIMA maintained, and FDA should accept international standards in its reviews rather than write new guidances.

Despite FDA advance submission of allegedly "biased" information against its products to the Dental Products Advisory Panel in August, Myo-tronics, Inc., president Roland Jankelson said afterward that the company "got what we wanted"—namely, a recommendation for Class I classification of its jaw-tracking and sonography monitoring devices. Jankelson, who has been battling what he calls a "flawed" process at CDRH since 1994, when a panel decision against his products had to be vacated because it was tainted by membership conflicts of interest, says he expects more trouble from FDA in the future.

Copyright ©1998 Medical Device & Diagnostic Industry