FDA Oversight of Laboratory Developed Tests

The FDA is taking steps to clarify policies and better regulate Laboratory Development Tests (LDTs). These regulations are in addition to the current policies enforced by Centers for Medicare and Medicaid Services (CMS) under the Clinical Laboratory Improvement Amendments (CLIA). Read more here about LDTs and the future changes for LDT regulation.

Stakeholders and the New LDT Regulations

Industry stakeholders are seeking further clarification from the Food and Drug Administration (FDA) on exactly how the agency expects to measure the risk that a laboratory-developed test poses to consumers. In a public workshop held January 8-9, 2014 in Bethesda, Maryland. More than 80 stakeholders, comprised of IVD manufacturers, laboratories and trade groups, testified during the two-day workshop, with many opposing efforts by the FDA to regulate LDTs.

The biggest concern is, “How will the FDA determine which LDTs are riskiest and therefore be required to go through the time-consuming and expensive. A number of participants asked agency officials to do a better job of explaining its risk-classification categories and explain how the agency will coordinate its oversight with the Clinical Laboratory Improvement Amendments (CLIA). Even Andrew Fish, executive director of AdvaMed, which has largely supported FDA oversight of LDTs, said that the agency needs to publish a document laying out how it plans to assess risk.

FDA’s LTD Risk Classifications

On October 3, 2014, the FDA issued a draft framework for regulation of LDTs based on three risk classifications, with the highest-risk being a Class III, and the more moderate-risk Class II LDTs requiring premarket approval and reporting of adverse events. Class I low-risk tests would be subject to enforcement discretion. The draft framework would allow for a modest number of operational exemptions from the FDA’s plan to regulate LDTs based on their potential risk to patient safety. The FDA would not consider a test to be an LDT if:

  • An entity that owns several clinics creates a test that is then transferred to another lab within its network;
  • An academic institution develops a test that it then licenses to a private venture that owns a CLIA-certified laboratory, which then begins manufacturing and distributing the test; and
  • An entity that creates LDTs and medical devices will continue to follow the existing regulations for medical devices.

Why the FDA Plans to Implement LDT Regulation

The FDA maintains that while CLIA is essential for ensuring that labs and their personnel maintain standards of high quality, compliance with CLIA regulations alone does not ensure that LDTs themselves are safe and effective as required by the Food, Drug, and Cosmetic Act. Specifically, CLIA does not require that labs prove their LDTs are clinically valid and does not require the removal of unsafe tests from the market.

The FDA estimates that there are some 11,000 LDTs on the market that have been created by more than 2,000 different labs, but industry sources say that number is much higher, especially if you count lab tests that have been modified by labs for their own purposes. To get a handle on the actual number of LDTs, the agency has asked labs to report all the LDTs they provide, regardless of risk class.

The Stakeholder Concerns

Many of the comments presented during the workshop related to the fact that labs already have to comply with quality systems regulations (QSRs) under CLIA and would have to meet separate QSRs under the FDA proposal.

“In the draft LDT guidance, the FDA proposes to require a vast variety of laboratories to comply with QSRs but provides scarce details on how those QSRs will be applied to LDTs generally and to different laboratories more specifically,” said Sheila Walcoff, CEO of the consulting firm Goldbug Strategies. Walcoff spoke on behalf of the Coalition for 21st Century Medicine, which repre¬sents the interests of diagnostic companies and venture capital firms.

In the draft guidance, the FDA proposes to continue to exercise enforcement discretion with respect to QSR requirements until a manufacturer of a given LDT submits a premarket application or the FDA issues a 510(k) clearance order for the LDT. Under this enforcement policy, the lab manufacturing and using the LDT will be responsible for having a quality system in place that meets the minimum requirements.

Concerns Expressed by Stakeholders at the Public Workshop

During the workshop, presenters expressed concerns about whether labeling an LDT with an intended use would mean they would be responsible for ensuring physicians don’t use the test off-label. Speakers also sought clarification on when a lab would need to submit a premarket approval application for a test that has already been approved by the FDA but that has been modified by the lab in some way.

The American Society for Clinical Laboratory Science (ASCLS) recommended that the agency focus its efforts on those tests that truly are novel and that pose the greatest risk. “We believe that the most important concern that should be kept in mind when formulating guidance is the need to demonstrate the clinical validity and medical applicability of a highly complex/high-risk LDT,” said ASCLS President Susanne Zanto.

Does the FDA really need to add regulation to LDTs?

While some groups believe that some form of FDA oversight may be inevitable, others – including the American Clinical Laboratory Association (ACLA) – maintain that FDA should have no role in regulating LDTs and that the proposed guidance be withdrawn. In a white paper released the day before the workshop, legal experts retained by ACLA argue that LDTs are not medical devices subject to FDA oversight, that FDA regulation of LDTs will interfere with the practice of medicine, and that FDA’s use of guidance documents circumvents the requirements of the Administrative Procedures Act.

Find more information pertaining to LDT regulation changes coming from the FDA on our Colaborate blog.

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