The FDA Takes Steps Toward Regulating Laboratory-Developed Tests

By Rachel Sachs

On Thursday, the FDA finally began to take an action that it had been publicly contemplating for over four years: the regulation of laboratory-developed tests (LDTs). In the FDA’s words, LDTs are diagnostic tests which are “designed, manufactured and used within a single laboratory.” There are thousands of LDTs, including very high-profile ones, such as Myriad Genetics’ test for assessing breast cancer risk. Although these diagnostic tests fall under the Federal Food, Drug, and Cosmetic Act’s (FDCA) definition of “medical device,” the FDA has for decades stated it was exercising its enforcement discretion in declining to regulate LDTs. (The FDA has exercised its regulatory powers over diagnostic tests that are designed and manufactured by one laboratory and sold to another for use.)  Although the official draft guidelines have not yet been released, the FDA’s report regarding their anticipated contents suggests that regulation of LDTs will follow a risk-based framework similar to the one in place now for other medical devices.

Much (though not all) of the relevant industry opposes the FDA’s actions here, and it’s easy to see why. Many of these LDTs would now be subject to premarket review, or at the very least additional reporting requirements, which make the development of these tests both riskier and more expensive.  Some firms argue that the FDA lacks jurisdiction to regulate LDTs, but they also argue that their LDTs are already sufficiently regulated by the Clinical Laboratory Improvement Amendments (CLIA), under the auspices of the Centers for Medicare and Medicaid Services. But here’s the problem: CLIA and the FDCA regulate different aspects of LDTs. And it can be detrimental to patient health to leave the FDCA aspects of LDTs unregulated.

I’ve written previously about this issue in the context of the interaction between patent law and the lack of LDT regulations (the paper is here, for those who are interested). Essentially, CLIA does certify laboratory testing processes for their analytical validity: in layman’s terms, “does the diagnostic test predict the presence or absence of the biological marker it’s testing for.” To use Myriad’s test as an example, under CLIA regulation their BRCA test might do a terrific job of minimizing false positives and false negatives, for the specific BRCA mutations the test is designed to test for. But CLIA does not test for clinical validity: essentially, “how does the biological marker the test is looking for relate to the specific disease in question.” That is, without FDCA regulation, the question of how accurately Myriad’s test is able to predict a woman’s risk for cancer is unknown. Several scientists have argued that earlier versions of Myriad’s test didn’t look for up to 10-20% of relevant BRCA mutations, potentially leaving many women with false expectations from erroneously negative test results or at the very least with no way to detect their harmful mutations, as long as Myriad was the exclusive testing provider.  The FDA’s proposed system, if designed and implemented correctly, has the potential to ameliorate such consequences.

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