FDA to Regulate Laboratory-Developed Tests

The US Food and Drug Administration (FDA) recently took initial steps toward regulating laboratory-developed tests (LDTs). Used to select appropriate treatment for individual patients, LDTs are designed, made, and used within a single laboratory,1 and include genetic tests and tests used by clinicians to guide their patients’ treatment.

On July 31, 2014, the FDA announced it would take “impor­tant steps to ensure that certain tests used by healthcare professionals to help diagnose and treat patients provide accurate, consistent, and reliable results” by developing a framework for regulation of LDTs.2 Until now, the FDA has opted to “exercise enforcement discretion.”3 LDTs differ from tests sold to users such as hospitals and doctors’ offices; the latter are regulated as medical devices. There are approximately 2000 laboratories that produce LDTs in the United States.

The only standards that laboratories using LDTs have had to comply with are generally accepted standards for good laboratory practices under the Clinical Laboratory Improvement Amendments,3 and also state laws and accreditation requirements by relevant authorities. However, with its announcement in mid-July, the FDA indicated it will publish a proposed risk-based oversight framework for LDTs.4

The framework was written, in part, because “the agency has serious concerns regarding the lack of independent review of the evidence of clinical validity of LDTs. Clinical validity is the ability of a diagnostic device to measure or detect the clinical condition for which the device is intended. LDTs that have not been properly clinically validated for their intended use and are used to make critical clinical decisions potentially put patients at risk of missed or incorrect diagnosis, failure to administer appropriate treatment, or administration of potentially harmful treatment with no benefit.”3

The FDA will phase in the requirements over 9 years, beginning with high-risk tests—including those used in the decisions of which therapy is best for individual patients or to screen for serious conditions such as malignant cancer3—that have the same intended use as an FDA-approved or cleared companion diagnostic test that is already on the market.3 The FDA will continue to exercise enforcement discretion for low-risk tests; these are tests with very few or no possible deleterious consequences of inaccurate results to patients; those aimed at diagnosing rare diseases; those that have no FDA-approved or cleared alternative; or those that are made for laboratories that are within healthcare facilities in which the patients who are being tested are also being treated.3

“Phasing in the requirements is a way not only to give the labs time to come into compliance, but [also so that] we can then adjust, based upon our resources, to provide the appropriate level of oversight,” said Jeffrey Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological Health, in a media teleconference on the day of the midsummer announcement.3

A few days earlier, a group of 23 pathologists and heads of diagnostic laboratories wrote to the head of the Office of Management and Budget.5 They urged that the FDA “refrain from issuing any draft, proposed, or final guidance document or rule that would purport to regulate LDTs as medical devices.” They expressed concern that, among other points, “FDA regulation of LDTs would stifle innovation, [and] be contrary to public health” due in part to the probable slowdown of test approval “under the rigid, inflexible, and duplicative [proposed] FDA regulatory scheme.”

Richard L. Schilsky, MD, chief medical officer, American Society of Clinical Oncology (ASCO), said the society supports the FDA’s approach, particularly with respect to genomic tests used to guide cancer treatment.

“Failure of such tests to perform as intended can lead to patients receiving an inappropriate and potentially harmful treatment or, alternatively, not receiving a treatment that has the potential to benefit them,” Dr Schilsky wrote in an e-mail. “In contemporary oncology practice, a patient’s treatment options are increasingly driven by detection of molecular abnormalities in the tumor that drive treatment selection. ASCO believes that tests used to detect those abnormalities must be of the highest quality and thoroughly validated before being offered to doctors and patients. Our patients depend on high-quality tests as much as they depend on carefully studied, safe, and effective drugs to achieve the best possible outcomes.”

On July 31, the FDA also provided to Congress with a draft proposal on its LDT regulation. It also intends to publish a draft version of the LDT guidance this fall,1 and then to gather public comments for 90 days.1 Meanwhile, it has also produced a final guidance on the development, review, and approval or clearance of companion diagnostics, which are all types of tests used to identify patients who will benefit or be harmed by treatment with a particular drug.2


  1. US Food and Drug Administration. Laboratory developed tests. www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/InVitroDiagnostics/ucm407296.htm. Accessed September 11, 2014.
  2. US Food and Drug Administration. FDA takes steps to help ensure the reliability of certain diagnostic tests. News release. July 31, 2014.
  3. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm40732.htm. Accessed September 11, 2014.
  4. US Food and Drug Administration. Framework for regulatory oversight of laboratory developed tests (LDTs). July 31, 2014. www.fda.gov/downloads/MedicalDevices/ProductsandMedicalProcedures/InVitroDiagnostics/UCM407409.pdf. Accessed September 11, 2014.
  5. US Food and Drug Administration. Transcript of media briefing on companion diagnostic final guidance and proposed risk-based oversight framework for laboratory developed tests. www.fda.gov/downloads/NewsEvents/Newsroom/MediaTranscripts/UCM408370.pdf. Accessed September 11, 2014.
  6. American Clinical Laboratory Association. July 16, 2014. www.acla.com/wp-content/uploads/2014/07/Letter-to-OMB-from-Lab-Leaders.pdf. Accessed September 11, 2014.

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