Forget 2014: New Discussion Paper Outlines FDA’s Current Thinking on LDT Regulation

In December, the U.S. Food and Drug Administration ended two years of anticipation or dread, depending on your point of view, by announcing that it would not finalize the guidance on agency oversight of laboratory developed tests (LDTs) that it proposed back in 2014—at least not yet. Instead, the FDA said it would work with the new administration and Congress "to get our approach right."

With that in mind, on Jan. 13, 2017, the agency issued a discussion paper summarizing the public feedback it has received on the 2014 draft guidance and outlining the key features of a possible alternative approach to FDA regulation of LDTs. Here is an overview of the key points from the new discussion paper.

Analysis of the Feedback
As part of the feedback process, the FDA asked stakeholders to suggest how they think the agency should regulate LDTs. According to the discussion paper, the various proposals shared 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; and

• 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 new discussion paper concludes.

The FDA Alternative Model
The FDA also sets out how its own thinking on LDT regulation has developed since 2014. Over the two years of "engagement," "positions of many groups, including the FDA, have evolved." The paper sets out key features that may be incorporated in an alternative to the framework the FDA proposed back in 2014, including:

• Phased-in oversight program over four years rather than the originally proposed nine years;

• Grandfathering for many LDTs already on the market;

• Broader definition of LDTs for unmet needs;

• Collaboration between FDA and third parties to use existing review standards and certification programs—such as the National Glycohemoglobin Standardization Program or the Cholesterol Reference Method Laboratory Network—for evidence standards;

• 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 collaboration 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); and

• 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.

What It Means
The FDA expressly states that its discussion paper and the proposal it outlines is not 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."

Takeaway: LDTs remain very much a work in progress, one that has evolved since 2014, and you need to stay tuned for further developments.