Lab Groups’ LDT Comments Will Highlight Barriers To Test Accessibility
Executive Summary
Laboratory groups, who are facing the prospect of a new regulatory scheme in FDA’s proposed lab-developed test framework, intend to discuss barriers to test accessibility and clinical validation of LDTs.
Clinical laboratory groups plan to focus their comments on FDA’s proposed regulatory framework for laboratory developed tests on the barriers to test access they say the new scheme will create.
Representatives of some lab groups indicated recently that they have already started to address FDA’s concerns about the clinical validity of the tests.
The LDT framework would direct makers of the tests, which are developed and offered as services out of the same laboratory, to subject the services to FDA pre- and post-market requirements. These tests currently fall under the jurisdiction of CMS and laboratory accreditation rules established under the Clinical Laboratory Improvement Amendments. FDA in its framework said the CLIA rules only address lab processes, and not the tests developed by labs ( (Also see "FDA Plan To Regulate LDTs Includes Long Phase-In, Unmet-Need Exceptions" - Medtech Insight, 31 Jul, 2014.)).
The American Clinical Laboratory Association said that clinical labs have already started to work on clinical validation of its tests. “Labs are doing more [than just undergoing accreditation], and they do look at the clinical validity of tests, whether it’s by the College of American Pathologists, or other accrediting institutions,” ACLA President Alan Mertz said.
Mertz cited a proposal in a bill by Rep. Michael Burgess, R-Texas, introduced in October 2011 called “Modernizing Laboratory Test Standards for Patients Act” (H.R. 3207) that would amend CLIA “to require that all new laboratory-developed tests go through a clinical validation process under CLIA” (Also see "Flurries Of New Bills Advance Device Industry Interests In Congress" - Medtech Insight, 17 Oct, 2011.).
The bill would also require the establishment of a publicly accessible test registry of all LDTs and direct-to-consumer genetic tests, which would include information on the purpose of the test, and information on the analytical validity of each test. However, the bill died in the House when the last session ended in 2012, and no version of it was reintroduced in the current Congress.
Regulatory Framework Will Stifle Innovation, ARUP Labs’ Ashwood Says
By imposing the regulations required for diagnostics made by manufacturers to be applied to clinical lab-developed tests, FDA will slow the introduction of laboratory tests and the improvement of any lab-developed tests that already exists, Edward Ashwood, president and CEO of ARUP Laboratories, said in an interview.
He added that development of LDTs is an iterative process, in that laboratory directors are continually improving them, particularly as new indications are found for the diagnostics.
Editor’s note: The story first appeared in “The Gray Sheet,”
which provides in-depth coverage of the medical device and diagnostics sectors.
Similarly, the Association for Molecular Pathology said it fears FDA’s proposed framework’s will have a negative impact on test accessibility, and consequently, on patient care. “We are concerned with plans for regulation of companion diagnostics, mandating the use of FDA cleared or approved tests when available, and treatment of modifications to FDA cleared or approved tests,” AMP President Elaine Lyon said.
Lyon said her group would be willing to work with anyone in Congress to possibly amend FDA plans, “who fully appreciates the rigorous regulations and standards set forth with existing CMS/CLIA oversight, and [who] aims to create a framework that benefits patients and the molecular pathology community.” Her group would also be willing to work with FDA on a beneficial and effective framework on lab-developed tests, she said.
FDA’s current guidance on companion diagnostics generally requires that a diagnostic be approved before or concurrently with a new drug that relies on the diagnostic to be safe an effective. This precludes approval of a drug that relies on biomarker testing using a non-FDA-approved LDT, outside of some limited exceptions, such as when the drug is the only option to treat a life-threatening condition. The proposed LDT regulatory framework also would mean that many LDTs used as drug companion diagnostics would eventually have to be approved through the medical device program’s full 510(k) or premarket application review, unless they fit one of those limited exceptions in the companion guidance (Also see "Companion Diagnostics Guidance Finalized, But Lab Test Enforcement To Be Key" - Pink Sheet, 4 Aug, 2014.). The LDT framework is viewed as years away from implementation
Washington Legal Foundation: FDA Lacks Resources To Regulate LDTs
The Washington Legal Foundation argued in a recently-denied citizen’s petition to FDA that the agency does not have the authority to regulate LDTs (Also see "Would Expanded Lab-Test Regulation Overstep FDA’s Legal Limits?" - Medtech Insight, 16 Mar, 2009.). Rich Samp, chief counsel of WLF said his group will probably file comments on the framework arguing that “the kind of regulation that FDA is threatening to impose has the real potential to delay the development of important tests.”
Samp also argued that FDA does not have enough resources to start regulating LDTs. “FDA is an agency always complaining that it doesn’t have enough resources, and we haven’t identified any major health concerns that have been caused in this area. Yet it is proposing to expand its regulatory authority in this area,” he said.
Both FDA Commissioner Margaret Hamburg and Center for Devices and Radiological Health Director Jeff Shuren said July 31 that the tests present health concerns. Part of what spurred the agency to release the regulatory framework were reports the agency received of inaccurate and faulty diagnostics that were used under the CLIA authority, which led to unnecessary treatments, or in some cases, no treatments for patients that needed it, Hamburg and Shuren reported.
The Coalition for 21st Medicine plans to submit comments to FDA on their regulatory framework for LDTs, and “will seek additional opportunities to work with the agency to address critical questions that remain,” on how FDA will implement its requirements, said coalition spokeswoman Sheila Walcoff, CEO of consulting group Goldbug Strategies LLC. Among those questions: How will FDA labeling requirements apply in the absence of a distributed or tangible “box” on which to put a label, with LDTs? And how does FDA intend to apply its rules on test design and quality systems to labs, which must also comply with CLIA quality system requirements?
“There are potentially thousands of CLIA labs that perform at least one high complexity test that FDA intends to review as a device. FDA will require substantial resources to establish and implement a new regulatory framework,” for these tests, the coalition warns.