reported in November, the American Clinical Laboratory Association (ACLA) has hired some renowned legal advisors to respond to the FDA's proposed regulation of laboratory developed tests (LDTs) (See NIR
, Nov. 25, 2014, p.1). ACLA's legal team, former Solicitor General Paul D. Clement, now a partner with Bancroft PLLC, and Laurence H. Tribe, Professor of Constitutional Law at Harvard University, have hit the ground running and prepared a White Paper asserting that LDTs shouldn't be subject to FDA regulation. The White Paper argues FDA regulation of LDTs is not supported in the language of the Food, Drug & Cosmetic Act (FDCA), the proposed regulation interferes with the practice of medicine, and FDA guidance flouts administrative law requirements for rulemaking. ACLA released the white paper January 7, the day before a two-day FDA workshop that provided a forum for public comment on the issues. "FDA is attempting to saddle a dynamic and innovative industry with sweeping new regulatory burdens without any statutory basis," Clement and Tribe state in the Executive Summary to their white paper. Here are the highlights of the legal arguments Clement and Tribe raise. LDTs are Services Not Devices
Treating LDT services as medical devices is akin to forcing "a square peg into a round hole," Clement and Tribe assert. The white paper defines laboratory developed testing as a service: a "methodology or process-based on a laboratory's unique knowledge of the protocols, performance characteristics, and means of analysis." Indeed, throughout the paper, the authors use the phrase "laboratory-developed testing services." The FDA's guidance document, on the other hand, uses the acronym LDT for the phrase "laboratory developed test." This distinction in phrasing emphasizes just how pivotal definitions will become in this debate. The authors explain that the LDT is part of the practice of medicine because it "generates biochemical, genetic, molecular, or other forms of clinical information about a patient specimen that is provided to the treating physician." They assert an LDT is not a product made for use by others or commercially sold but rather "a proprietary methodology that is performed only by the developing laboratory." As many have already argued, the white paper explains that such methodology often fills a void that FDA-approved, in vitro diagnostic test kits do not fill-distinguishing mutational variants, testing biomarkers and analytes for which there are no approved tests , and addressing rare diseases and conditions for which it may not be commercially feasible to develop test kits. LDTs allow laboratories to nimbly adapt to scientific advances and patient care needs, providing a "purely informational service" utilizing "their unique knowledge of the protocols, the performance characteristics, and the means of analyzing each test, to generate clinical information about a specimen for the ultimate use of the treating physician." Thus, the authors contend this informational service is not a device subject to the Food, Drug and Cosmetic Act. FDA Doesn't Have Authority Under the FDCA
Clement and Tribe maintain that Congress decided laboratories should be regulated by CMS under CLIA and not by the FDA under the FDCA. They claim the language in the FDCA itself expressly makes this clear and they characterize as "remarkable" the FDA's claim that the 1976 Medical Device Amendments, which added reference to in vitro reagents to the FDCA, subject all LDT services to FDA regulation. The authors draw an analogy to radiology services, dependent on x-ray machines, to argue that LDT services are similarly a health care service that makes use of or relies upon medical devices but is not itself a medical device subject to FDA regulation. Pointing the Act's definition of devices which refers to "physical articles" and its use of the phrases "commercial distribution" and "introduction into interstate commerce," the authors emphasize that LDT services are not devices (as explained above), remain in house at the laboratory that has developed them and aren't distributed into commerce. Finally, the authors point to express language added in 1997 that states the Act doesn't "limit or interfere with the authority of a health care practitioner to prescribe or administer any legally marketed device to a patient." LDT services assist the physician in medical decision-making and thus differ, they claim, from drugs or devices that "yield a particular diagnosis or treatment" when applied to a patient. Highlighting the lack of FDA regulation of LDTs for decades, imposing premarket approval requirements now, Clement and Tribe declare "would have a breathtaking economic impact on traditional laboratory practices, on physicians who rely on laboratory medicine to facilitate their diagnosis and treatment decisions, and on the allocation of regulatory authority between FDA and CMS." The authors argue that enactment of the 1988 CLIA amendments "would be well-nigh inexplicable" and "utterly pointless" if the FDA was intended to have oversight over LDT services. They also point to legislative history that expressed the goal of CLIA was to replace the preexisting "patchwork" of laws and standards. FDA Guidance Violates Administrative Law
Lastly, the authors attack the FDA's release of guidance documents targeting LDT services as an effort to sidestep Administrative Procedure Act (APA) requirements for notice and comment periods for rulemaking. There is also no economic impact analysis provided in the FDA guidance document, as is required for rulemaking. Analysis of the financial impact FDA approval for laboratory developed tests is "essential" the authors claim. As discussed, such regulation impacts feasibility of developing tests to respond to rare conditions and emerging infectious diseases for which there are no marketed test kits available. The Battle Lines are Drawn
The gauntlet has arguably been thrown down. While this white paper reiterates many arguments already asserted in opposition to LDT regulation, it does so while providing extensive references to case law, legislative history and other legal resources. At times, it reads much like a legal brief. In fact, the authors assert that the FDA's efforts to exercise regulatory authority in this area could raise constitutional issues with regard to interference with the physician-patient relationship. While not referring directly to the white paper, Jeff Shuren, MD, JD, Director, Center for Devices and Biological Health opened the FDA Workshop on January 8, 2015, by indicating that the FDA is listening to all feedback and the proposed guidance is indeed merely a proposal. "All aspects are open for discussion," he said, before calling on all parties to work together. Takeaway: While not expressly threatening litigation to oppose FDA regulation, this white paper has provided a preview of potential legal arguments that might be raised against the FDA in court.
Source: Paul D. Clement & Laurence H. Tribe, Laboratory Testing Services, As the Practice of Medicine, Cannot Be Regulated As Medical Devices, American Clinical Laboratory Association (2015); http://www.acla.com/wp-content/uploads/2015/01/Tribe-Clement-White-Paper-1-6-15.pdf