In Public Comments, Lab Lobbies Want FDA to Back Off on LDT Regs

The primary lobbying groups for the laboratory sector have submitted their comments to the U.S. Food and Drug Administration (FDA) regarding its proposal to regulate lab-developed tests, or LDTs. The consensus is that major changes need to be made by the FDA to the proposed regulations—or even have the agency withdraw them completely—before the sector will consider them acceptable. The FDA issued the draft regulations last year out of concern that the complexity of some LDTs may wind up placing patients in danger if improperly used or interpreted. It proposed classifying tests in three different risk designations and requiring labs to obtain premarket approval for the riskiest assays. The new regulations would be phased in over the better part of a decade. The lobbies expressed significant concern in their comments that many of their constituents would not be able to commit the resources to get their tests to pass FDA regulatory muster. As a result, they fear that the hundreds, if not thousands, of LDTs that are created every year could diminish in both volume and clinical value. “If the guidance is finalized as written, (the) FDA would require laboratories, as medical device manufacturers, to submit applications for pre-market review for thousands of laboratory-developed testing services,” the Association for Molecular Pathology said in a statement. “AMP members will likely be unable to continue offering these tests; therefore, FDA will have in effect significantly diminished or eliminated patient and physician access to these services.”

FDA’s Legal Authority Challenged

The American Clinical Laboratory Association went so far as to raise specific legal issues regarding the FDA’s ability to regulate LDTs at all. “The clinical laboratory industry emphatically maintains that the FDA lacks the statutory authority to regulate laboratory developed testing services and likens its attempt to define a lab test as a medical device to trying to fit a round peg into a square hole,” said ACLA President Alan Mertz in a press release regarding the Association’s submitted comments. “FDA’s attempted expansion of its authority is inconsistent with the statutory text and would raise serious constitutional questions that Congress itself sought to avoid when crafting the current regulatory framework for LDTs.” The ACLA has been the most aggressive of the lobbying groups in challenging the FDA. It has gone so far as to retain two of the nation’s leading federal appellate attorneys, Laurence H. Tribe and Paul Clement, strongly suggesting it would litigate the matter in the federal courts. Most of the comments submitted suggest that the current CLIA regulations will suffice for regulating LDTs. Along with its comments, the College of American Pathologists submitted a 41-page graph demonstrating where the FDA’s proposed regulations “crosswalk” with CLIA’s. The CAP asked the agency to refrain from requiring each LDT to have a unique device identifier; remove the requirement that a change of specimen type in a test results in an LDT; and relax its guidelines for assessing the patient risk stemming from an LDT. Currently, the FDA proposes that it use its existing classification system for medical devices, which the CAP objected to. “The existing FDA medical classifications categories will subject many well-established and validated LDTs to high- er-level regulatory requirements. These well-established LDTs already represent the standard of care with required proficiency testing and professional guidelines written for recommended performance and interpretation.” The CAP suggested that “LDTs should be classified based on patient risk, the laboratory’s claims for the test, and the potential for harm to patients in instances of an incorrect or misinterpreted test.” The CAP also wants the FDA to include multi-hospital health care systems under the definition of a single laboratory. “The laboratories in many of these systems continue to operate collectively as a single laboratory when developing an LDT. We believe the FDA’s definition would arbitrarily restrict these laboratories that have the same safeguards and controls as single laboratories from developing vital tests,” wrote the CAP in its comments, which were authored by President Gene Herbek, M.D. “Without these changes, the CAP believes the guidance would stifle medical innovation and cause significant hardship for laboratories and patients,” Herbek said. “The College’s comments to the FDA seek to address oversight of these tests in an inclusive, systematic way that is best for our patients.”

More Legal Brief Than Commentary

The ACLA’s comments were in the form of a nearly philosophical critique that reads like a legal brief, questioning whether the right exists at all for the FDA to regulate LDTs. Its conclusion: Not. “FDA has authority to regulate only manufacturers of commercially distributed medical ‘devices,’ including devices that perform standardized clinical tests (so-called ‘test kits’). But laboratory-developed testing services are processes and methodologies that are qualitatively and categorically different from the tangible goods that FDA may regulate as ‘devices,’” the ACLA claimed. “Statutory text, basic principles of interpretation, and common sense leave no doubt that laboratory-developed testing services are not medical ‘devices.’” The dense yet pointed 17-page document went on to question whether LDTs are placed into interstate commerce (no); whether the FDA not regulating LDTs for decades prior suggested that the tests were breaking federal laws (no); whether CLIA eclipsed the FDA’s regulatory authority (yes); whether FDA had the authority to establish regulations through “guidance documents” as opposed to the more onerous process of rulemaking and gathering comments (no); whether the FDA had considered the economic impact of the regulations (no). “In summary, FDA must withdraw the draft ‘guidances’ in their entirety,” concluded the comments, which were under Mertz’s signature but no doubt contained many of Tribe and Clement’s fingerprints. The AMP requested more clarity from the agency as to how it plans to classify LDTs by risk. It also objected to classifying the use of companion diagnostic tests into the higher risk categories and restricting the “off-label” use of tests— assigning them to assay issues for which they were not originally designed. Physicians are able to prescribe drugs for off-label uses with few restrictions. Like the CAP, the AMP also wants the proposed restrictions on multi-hospital system labs relaxed. And it also wants the FDA to restrict reporting of any adverse patient events connected to tests restricted to those where premarket approval has already been obtained. The laboratory sector has gained some allies in some unusual places. The Boston Globe recommended against the new regulations in a January editorial, saying it was “far from reassuring” that the FDA is involved. The newspaper warned that the proposed regulations are “overkill” and would stifle innovation in prenatal testing. The Boston area is home to a significant swath of biotechnology companies, including a number of labs that offer esoteric molecular testing. “Advocates for the labs recommend a wiser course: making a few changes to CLIA regulations that would address the questions raised by the FDA. Non-in- vasive prenatal screening has a valid place in the physician’s toolkit—so long as the results are properly understood,” the Globe concluded. The FDA is expected to issue final regulations sometime later this year. Takeaway: The laboratory sector is pushing back hard against the regulation of laboratory-developed tests.