Medical device regulation--then and now.

In a 1995 issue of Research Nurse, the predecessor to this journal, author Eileen Rusnak recounted the history of medical device regulation in the United States. In her fascinating review, she wove the story of how medical devices were, or were not, regulated during the many years from the end of the 19th century. Her review ended with a brief summary of 2 major pieces of legislation that affected medical device regulation, specifically the 1976 Medical Device Amendments to the U.S. Food, Drug, and Cosmetic Act, and the 1990 Safe Medical Devices Act. This article picks up from that article, and highlights the evolution of medical device regulation in the late 1980s, through the 1990s, and into the current century, and then briefly reflects on the effect politics has had on medical device regulation.

Key Words: 510(k), FDA Modernization Act of 1997, investigational device exemption, medical device, Medical Device User Fee and Modernization Act of 2002, premarket approval

Troubled waters for medical device companies

Several events occurred in the late 1980s and early 1990s that resulted in major changes in the relationship between the medical device industry and the Food and Drug Administration (FDA). As the 1980s were winding down, FDA became embroiled in a scandal concerning generic drugs. In essence, some generic drug companies were producing inferior products that did not comply with FDA's generic drug manufacturing requirements, but this was the least egregious aspect of the scandal. Several companies were submitting fabricated data to FDA for review and approval of their generic products, and a few companies submitted pharmacokinetic (PK) data for a number of commercially available innovator drugs as the results of their own not-yet-on-the-market generic equivalents. In reviewing these PK data, of course, the generic version would be deemed bioequivalent to the innovator drug, because the innovator drug had been substituted for the generic version in the testing. FDA field inspectors and criminal investigators discovered these substitutions in 1989 and the resulting investigations and legal action grew into a scandal that swept up several FDA staff reviewers and managers who had been taking industry money improperly, either in the form of illegal direct payments or prohibited gifts. Successful prosecutions of several company executives and FDA staff resulted.

The publicity surrounding the scandal put pressure on FDA to clamp down on its normal communications with industry so that neither the public nor the press would perceive FDA as too friendly with the companies it regulated. This siege mentality overtook FDA in its relationship with industry, and blocked many otherwise useful discussions between FDA reviewers and company regulatory staff on the adequacy of submissions for new products, causing product approvals to stall.

Owing to the departure of the FDA Commissioner under whose tenure this scandal occurred, then-President George H. W. Bush appointed a new FDA Commissioner in 1990. The candidate was David Kessler, a physician and lawyer who had extensive experience in medicine, law, and politics. Dr. Kessler was a savvy politician as well, and had served in Congress as an advisor to the Senate's Committee on Labor and Human Resources. Dr. Kessler had the support of Senators Orrin Hatch (R, Utah) and Ted Kennedy (D, Mass); thus, a bipartisan speedy approval of his nomination to the post ensued. The new Commissioner's first acts included shoring up FDA's enforcement visibility with highly publicized raids on a producer of "fresh" orange juice (for "misleading" labeling) and hiring a cadre of criminal investigators. Dr. Kessler was a strongly activist FDA Commissioner who supported the rapid review and approval of new drugs to combat human immunodeficiency virus, but who also ultimately made the regulation of nicotine an FDA goal. Many FDA resources were targeted at the tobacco effort at the expense of other FDA activities, such as product approvals. One of Kessler's early gifts to the medical device industry was to establish an internal review committee to examine the Center for Devices and Radiological Health's (CDRH) medical device review practices, specifically the examination of the quality of science in the review and approval of medical devices.

The Committee for Clinical Review, headed by a Center for Drug Evaluation and Research (CDER) director named Dr. Robert Temple and comprised of CDER physicians and statisticians, looked at a total of 29 completed or pending premarket approval (PMA) applications, 510(k) notifications, and investigational device exemption (IDE) applications for an array of medical devices. In March 1993, the so-called Temple Report was issued, and its conclusion articulated the deficiencies the committee found in the clinical data used to support these applications. (1) Table 1 lists those clinical research design problems. In addition, the committee found deficiencies in study reporting and analysis.

The report recommended early and greater interaction between sponsors and CDRH reviewers, including biostatisticians and other study design experts, when studies were being planned; better integration of biostatisticians into the review process; the development of guidance for industry and reviewers on study design and analysis; and better use of advisory committees to help improve the quality of data submitted to CDRH in device applications.

The thrust of the report, as interpreted by members of regulated industry, was that medical device clinical trials should be more like drug clinical trials, and thus was ushered a transition at CDRH from engineering and bench science to a drug study model, including randomized, controlled clinical trials. Such trials even would be applied on many occasions to low-risk medical devices cleared by FDA through the 510(k) notification process.

"Less Than the Sum of Its Parts"

This was both the title of a report on a Congressional investigation of medical devices and a characterization of CDRH that was issued by a Democrat-controlled Congress in May 1993. (2) The purpose of the investigation was to ascertain FDA's progress since 1983 in implementing the requirements of the 1976 medical device amendments. The report was a blunt condemnation of the inability of CDRH to manage the review and approval of medical devices, and it confirmed the plight medical device manufacturers were experiencing. The report stated that CDRH was "unable to either protect adequately the public from unsafe devices or to approve useful and safe devices in a reasonable period of time." The report identified CDRH weaknesses that "included inadequate attention to warnings of likely problems, excessive delays and disorganization in the review and approval process, poor communication …