FDA Synthesizes Feedback on LDTs in New Discussion Paper

Following up its decision not to issue final guidance in 2016 regarding oversight of laboratory developed tests (LDTs), the U.S. Food and Drug Administration released a discussion paper Friday, Jan. 13, 2017. The paper synthesizes the feedback it has received on its 2014 draft guidance and offers a possible alternative approach to regulating LDTs.

The FDA observes that the various proposals put forth by stakeholders in the wake of the FDA’s 2014 guidance all have some similar features, including:

• Risk-based approach
• Premarket review for some tests, with exemptions for certain categories
• Test approval based on analytical and clinical validity
• Adverse event reporting
• Quality systems
• “Grandfathering” for certain existing tests
• Transparency regarding test performance information

“Based on the feedback received, a prospective oversight framework that focuses on new and significantly modified high and moderate risk LDTs would best serve the public health and advance laboratory medicine,” the FDA concluded in its discussion paper. The agency also explained that because of the two years of “engagement” on the topic, the “positions of many groups, including the FDA, have evolved.” Key features of the FDA’s proposed alternative include:

• Phased in oversight program over four years rather than the originally proposed nine years
• Grandfathering for many LDTs already on the market
• More broad definition of LDTs for unmet needs
• Collaboration between FDA and third parties to use existing review standards and certification programs for evidence standards—such as the National Glycohemoglobin Standardization Program or the Cholesterol Reference Method Laboratory Network
• Potential use of existing review programs for third-party review, such as New York State’s Clinical Laboratory Evaluation Program and independent CLIA accreditation programs
• Clinical collaborations with stakeholders and health care professional organizations on standards for analytical and clinical validity
• Public availability of evidence of analytical and clinical validity
• Reliance on CLIA certification requirements plus three FDA quality systems requirements regarding test development processes—design controls, acceptance activities, and procedures for corrective and preventive action (CAPA)
• Postmarket surveillance requiring labs report serious adverse events for tests except for traditional LDTs, LDTs for public health surveillance, specific transplantation related LDTs, and forensic-use LDTs

The FDA expressly stated however that this discussion paper and the proposal included isn’t a final version of the 2014 guidance and “does not represent the formal position of the FDA, nor is it enforceable. We hope to simply advance the public discussion by providing a possible approach to spur further dialogue.”