FDA Proposes Rule to Regulate Lab-Developed Tests

New rule would specify that all IVDs are devices under the Federal Food, Drug, and Cosmetic Act, including when the manufacturer is a laboratory

On Sept. 29, the Food and Drug Administration announced a proposed rule for laboratory developed tests (LDTs), with the stated goal of "helping to ensure the safety and effectiveness of these tests, which are used in a growing number of health care decisions and for which concerns have been raised for many years."

If the rule is implemented, FDA will no longer use enforcement discretion for LDTs. Instead, laboratories with LDTs will be required to comply with the same regulations as manufacturers who make other in vitro diagnostics (IVDs), which would be a major change for many laboratories.

Don't miss FDA's webinar on Oct. 31 for more information on the proposed LDTs rule. Participants must submit questions by Oct. 23 to be considered for the Q&A. Registration is not necessary. 

Learn more and view details on how to join the webinar.

What is FDA proposing for laboratory developed tests and in vitro diagnostics?

The proposed rule seeks to amend FDA's regulations to make explicit that IVD products are devices under the Federal Food, Drug, and Cosmetic Act, including when the manufacturer of the IVD is a laboratory (i.e., LDTs). Along with this amendment, FDA is proposing a policy that will imply greater oversight of LDTs through a phaseout of its current general enforcement discretion approach.

Ending a bifurcated system of regulatory compliance for in vitro diagnostics

FDA regulates some IVD products like other medical devices, subject to premarket and postmarket controls. Once approved, this means an IVD product can be manufactured and distributed in the same manner as a medical device. In contrast, LDTs offer an alternative to FDA-approved IVD products. LDTs have historically been manufactured by and used within a single laboratory that is Clinical Laboratory Improvement Amendments (CLIA) compliant under the authority of the Centers for Medicare & Medicaid Services.

FDA has indicated this bifurcated system presents public health risks and needs to be corrected by bringing LDTs under its general IVD regulatory framework.

Concerns over the performance of laboratory developed tests

"A growing number of clinical diagnostic tests are being offered as laboratory developed tests without assurance that they work," said FDA Commissioner Robert M. Califf, M.D., in the agency's announcement for the proposed rule. "The stakes are getting higher as these tests are increasingly being used to drive treatment decisions. According to the Centers for Disease Control and Prevention, 70% of today's medical decisions depend on laboratory test results. Given the role these tests play in modern medical care, their accuracy and validity have a significant impact on public health."

FDA cites several pieces of evidence to support their assertion that the current oversight of LDTs is insufficient and poses a risk to public health, including multiple published studies documenting high variability in performance among LDTs; FDA's experience reviewing COVID-19 diagnostics from laboratories seeking emergency use authorization for their LDTs; and complaints, adverse event reports, and other allegations identifying problems with LDTs.

New requirements for laboratory developed tests to be phased in over four years

FDA is proposing a five-stage approach to be completed four years from the publication date of the final phaseout policy, but not before April 1, 2028. The first three stages would each take one year, and the last two stages would each take six months.

• Stage 1 would end enforcement discretion for medical device reporting and correction and removal reporting requirements.
• Stage 2 would end enforcement discretion for registration and listing, labeling, and investigational use requirements.
• Stage 3 would end enforcement discretion for quality systems requirements and impose quality management requirements, such as Current Good Manufacturing Practice (CGMP), design controls, purchasing controls, acceptance activities, corrective and preventative actions (CAPA), and records requirements. FDA may allow for some latitude in compliance with full quality system requirements for some LDTs.
• Stage 4 would end enforcement discretion for premarket review requirements for high-risk (Class III) IVDs, i.e., those requiring a premarket approval application (PMA).
• Stage 5 would end enforcement discretion for all other IVDs.

Implications and recommendations for clinical laboratories and healthcare providers

Today, thousands of LDTs are offered in the U.S. for a variety of clinical applications, from consumer health testing to cancer screening. The implementation of a regulatory framework and phasing out of LDT enforcement discretion would have major impacts on a range of stakeholders — including clinical laboratories, healthcare providers, and patients. At a minimum, the proposed rule would require a significant number of new submissions to FDA to obtain marketing authorization, but it may also result in loss of access for certain patient populations and potential shortages of certain tests.

Exponent recommends that those potentially affected by the proposed rule provide comments to FDA. Specifically, FDA is seeking public comments on:

• Potential unintended consequences to certain patient populations and steps that could mitigate those consequences
• Implications of continued enforcement discretion for LDTs used for law enforcement
• Implications for academic medical centers that are integrated with direct patient care
• The potential to leverage certain outside oversight programs
• Data supporting the points of view of stakeholders who oppose the proposed rule

Additional information, including how to submit comments, can be found here. The Regulations.gov electronic system will accept comments until 11:59 p.m. EST, Dec. 4.