Originally published June, 1996
James G. Dickinson
Two major developments in March signaled an overall rebuilding of the way this country regulates medical devices.
The first development was the announcement from both industry and FDA sources of a new consensus-developed approach to FDA inspections. Until the end of this year, firms without a violative history that continue to make individuals and documents involved in previous preannounced inspections "reasonably available" will receive notice of inspections at least five days in advance. Corrective actions taken or promised by these firms will be noted on their FDA-483 forms; however, specific observations made during the inspection will not be deleted when the company has corrected them. FDA will also send formal compliance status letters after each inspection where conclusions of no action indicated (NAI) or voluntary action indicated (VAI) were reached by the district office.
Although these may seem fairly modest accomplishments to industry reform-seekers, they actually constitute the tip of an iceberg. Last August, a collaborative grassroots process began in Denver between FDA's Southwest regional management and an industry task force spearheaded by the Colorado Medical Device Association and its president, Cobe Laboratories senior vice president Wendell Gardner.
The second major development was a legislative breakthrough on both sides of Capitol Hill, defying all earlier predictions that time had virtually run out for meaningful FDA reform to be passed this year. On the Senate side, the Labor and Human Resources Committee marked up a reform bill sponsored by committee chairwoman Senator Nancy Kassebaum (RKS). In addition, House Commerce Oversight and Investigations Chairman Joe Barton (RTX) unveiled his bill on FDA medical device reform; two other regulatory reform bills, one on drugs and biologics and the other on food, were announced at the same time.
Kassebaum's bill, which appeared headed for Senate floor debate in the second half of May, was strengthened by markup session amendments that would:
* Allow firms at their own election to have new products reviewed for marketing clearance by a non-FDA third party at company expense. FDA would have only 15 days (for a Class I or Class II device) or 45 days (for a Class III device) to reject this approval recommendation.
* Force FDA to approve or reject within 30 days products already approved in Europe if the agency fails to meet one of its approval deadlines and the sponsor wishes to press the issue; rejections could be appealed.
* Allow Class III device approval on the basis of only one clinical trial, instead of two.
* Require that FDA collaborate with the sponsor in designing investigational device research.
* Limit the terms of FDA commissioners to five years.
Barton's bill, which was given the most chance to be acted on of the three House FDA reform bills, parallels much of the Kassebaum bill with respect to devices; unlike Barton's bill, Kassebaum's bill covers all FDA-regulated product categories. Scheduled to be the subject of May 12 hearings and "early" markup after that, Barton's bill includes provisions turning good manufacturing practices (GMP) inspections over to third parties, allowing manufacturers to cite non-FDA standards of safety and effectiveness, and eliminating the need for filing many 510(k)s for postapproval product changes.
Conveniently, these developments coincided with a blizzard of media publicity criticizing FDA's management of device issues. On March 28, the Washington Post attacked the device approval process in an in-depth critique of the agency's performance on pedicle screws.
The next day, Jack Anderson's syndicated column impaled Commissioner David Kessler with the criticism by former aide Jim Phillips, now a Senate committee staffer with no FDA responsibilities, who charged that Kessler is mismanaging every issue faced by the agency except tobacco.
The next day, as Congress adjourned for its 15-day Easter recess, the Investor's Business Daily blasted the agency with a front-page story headlined "Have FDA Officials Gone Rogue? Agency Leaked Papers, Lost Records, Critics Say." The article focused on an unidentified court case from which court-sealed documents, clearly stamped as such, were allegedly leaked by FDA. In another incident, an FDA-leaked inspection report on Epitope, Inc. (Beaverton, OR), allegedly hurt the device manufacturer's stock prices for a securities short-seller. The article also said that FDA concealed documents on Commissioner Kessler's contacts with Ralph Nader's Public Citizen Health Research Group.
Set against the background of furious legislative activity, this torrent of anti-FDA publicity did not bode well for the agency. The House and Senate bills, which would sharply diminish the potency of FDA's activities in the device area, seemed increasingly likely to succeed. With major party conventions and a presidential election campaign looming after the congressional recess, time was running short, and both House and Senate proponents were mustering bipartisan support for FDA reform, especially for devices.
The only discordant note was struck by the venerable Edward Kennedy (DMA), who left the Kassebaum markup clearly unhappy with the changes made. Some observers predicted he might lead a filibuster on the Senate floor, effectively delaying a vote until time for passage had actually run out.
It's likely that by the time this column is read, all such scenarios will have been exhausted, and the outcome will be known. But regardless of the outcome, it's clear that forces have been set in motion that will radically alter the style and substance of medical device regulation in this country --sooner or later.
FDA's Center for Devices and Radiological Health (CDRH) investigated "more than 38" medical device marketing application integrity cases under its Application Integrity Program (AIP), formerly known as the "Fraud Policy," during fiscal year 1995 (ending last September 30), according to the Office of Device Evaluation's annual report.
"Integrity issues were based, in part, upon internal inconsistencies within the submission, scientifically implausible data, contradictory information provided by scientific/clinical researchers, data inconsistent with the scientific and professional literature, information provided by employees of the applicant, and information obtained from legal documents," the report says.
Four letters were issued under AIP last year that suspended the review of all pending and future filings until the firms in question performed internal audits and implemented an FDA-approved corrective action plan.
The report acknowledges that ODE's own integrity was under scrutiny last year; 37 instances of ethics and conflict-of-interest problems at the office were brought to light. Several were attributed to manufacturers' claims of unequal treatment during the review process. Other questionable activities cited in the report included "receipt by ODE staff of free training, travel expenses, meals, cash honoraria, and other things of value from persons outside the government."
ODE and another CDRH branch, the Office of Compliance, jointly created a highly unusual seminar for center staff entitled "RS Medical: A Case Study--Lessons Learned." This seminar examined regulatory activities against RS Medical that led to "major civil litigation in which FDA was found to be responsible for improper conduct." The judgment against FDA entered two years ago awarded over $390,000 to the plaintiff, attorney fees included. The case, International Rehabilitative Sciences dba RS Medical v. David Kessler, involved a dispute over whether the company's powered muscle stimulator device required a 510(k), and credible charges were made that agency employees engaged in retaliation against the firm.
The report says that 1995 industry submissions to ODE continued a relatively flat three-year trend with 16,978 received, 73 more than in 1994. However, the number of major submissions--premarket approvals (PMAs), investigational device exemptions (IDEs), PMA supplements, IDE amendments, and 510(k)s--decreased for a third consecutive year--by 104 to 10,189 in 1995. This reduced inflow probably allowed ODE to substantially increase its work output; the office processed 12,013 major submissions last year, up from 11,045 in 1994. An "all-time record" of 7948 510(k) reviews, 813 more than in 1994, were performed with total average review time declining from 216 days in 1994 to 178 days in 1995.
"FDA is soliciting comment on how best to communicate to its own staff and to the public the principle that guidance is not binding." That is one of five key issues that were discussed at an April public meeting convened in response to an Indiana Medical Device Manufacturers Council (IMDMC) petition last year. The document proposed that FDA make a policy of seeking public input on guidance document development.
Four other issues that FDA is soliciting public input on are: (1) The value of a standardized nomenclature for guidance documents, and what to do with existing nomenclature; (2) whether to adopt a three-tiered approach to public input (input before guidance is issued, input after guidance is issued, or public notification without formal input after guidance is issued); (3) the adequacy of FDA's current document access programs and any improvements to access; (4) whether the public is sufficiently aware of current appeals mechanisms and whether the mechanisms are sufficient for appealing decisions relating to guidance documents.
In a March 7 Federal Register notice, FDA narrowed the scope of what is meant by "guidance." IMDMC's petition broadened the definition to cover any documents used to convey "regulatory expectations," but FDA's notice says guidance covers "(1) [d]ocuments prepared for FDA review staff and applicants/sponsors relating to the processing, content, and evaluation/approval of applications and relating to the design, production, manufacturing, and testing of regulated products; and (2) documents prepared for FDA personnel and/or the public that establish policies intended to achieve consistency in the agency's regulatory approach and establish inspection and enforcement procedures."
Specifically excluded from the scope, FDA says, are agency reports, consumer information, documents relating solely to internal FDA procedures, speeches, journal articles and editorials, media interviews, warning letters, or "other communications or actions taken by individuals at FDA or directed to individual persons or firms."
On the vexed issue of FDA employees who take guidance documents as binding and seek to enforce them, the agency says it will begin an educational effort, inserting the following cautionary language within each guidance document: "Although this guidance document does not create or confer any rights for or on any person and does not operate to bind FDA or the public, it does represent the agency's current thinking...." In addition, FDA says it will attempt to ensure that all guidance documents use language that clearly conveys that they are nonbinding, avoiding the use of "compulsory language such as 'shall' and 'must,' except when referring to a statutory or regulatory requirement."
Two new guidances have been developed to provide understanding of human errors as they relate to medical device design and preproduction quality assurance design control. Entitled "Medical Device Design Control Guidance" (document number 995) and "Do It by Design" (document number 994), they will both complement and "aid in the implementation" of the soon-to-be-published final rule on current device GMPs, according to CDRH's Office of Compliance GMP expert Kimberly Trautman. Both guidances are available from FDA's Fax-on-Demand at 800/899-0381.
The costs of FDA medical device regulation would revert to 1991 levels, or $40 million less than current costs, if CDRH were relocated elsewhere within the Department of Health and Human Services, according to an analysis released in March by American Enterprise Institute (AEI) resident scholar John Calfee.
Calfee based this assessment on a likely reversal of CDRH's Kessler-era "drug culture," which he says is inappropriate because "drugs are unchanging entities surrounded by rapidly changing information," while devices "are continually changing because they are technology-based tools."
"Sounds like they're living in fantasyland," CDRH director Bruce Burlington commented on the AEI report. He said all of CDRH's work over the past three years has been "diametrically opposed" to the so-called "drug model" cited in the report. A recent CDRH analysis of PMAs reviewed since 1987 shows no increase in double-blind, randomly controlled clinical trials or in the size of subject groups studied (average 600 patients). "Science drives the type of testing you have to do," Burlington said.
A bipartisan bill that would liberalize export restrictions on drugs and devices not having FDA marketing approval was loosened even more in an amendment introduced on March 15. If the amendment passes, any U.S. human drug, biologic, veterinary drug, or device that is approved in one of 24 countries named or those in the European Economic Area would be permitted to be exported to any country willing to receive it. In addition, the product would have to comply with the laws of the country and be labeled for export only; it could not be sold or reimported into the United States.
The list of countries whose approval qualifies products as exportable would be subject to continuing update.
In March, the April 11 effective date for FDA's Medical Device User Facility and Manufacturing Reporting rule was extended to July 31, based on industry requests for more time to comply.
James G. Dickinson is a veteran reporter on regulatory affairs in the medical device industry. *