Guest Blogger Visiting Assistant Professor Valerie Gutmann Koch - FDA Announces Plans to Regulate LDTs (But What About DTC Genetic Tests?)

Oversight of direct-to-consumer (DTC) genetic tests and laboratory developed tests (LDTs) in general has garnered increasing attention in the media. Most recently, on July 31, pursuant to the 2012 Food and Drug Administration Safety and Innovation Act (FDASIA), the FDA notified Congress that it intends to issue draft guidance for the oversight of LDTs – diagnostic tests (including genetic tests and tests for rare conditions) developed and performed by a single laboratory.  The FDASIA requires the FDA to provide at least 60 days’ notice before publishing any draft guidance on the regulation of LDTs. 

FDA’s decision to exercise its jurisdiction over LDTs as medical devices has been discussed and even expected for almost a decade. In June 2013 FDA Commissioner Margaret Hamburg called for more active FDA regulation of LDTs, stating that the Agency’s risk-based framework for regulating such tests was under development. Hamburg noted that the FDA has discretion in overseeing certain LDTs as devices. Although historically “they were relatively simple, low-risk tests performed on a few patients being evaluated by physicians at the same facility as the lab,” she explained that they now warrant oversight because they have become “more sophisticated and complex.” 

Speculation about the possibly imminent release of a risk-based oversight framework for LDTs increased after the agency’s November 2013 Warning Letter to the personal genomic testing service 23andMe. The letter demanded an immediate halt to testing “until such time as [23andMe] receives FDA marketing authorization for the device.” The agency claimed that 23andMe hadn’t proven that its tests are clinically valid, thereby leading to possible harm due to the “potential health consequences that could result from false positive or false negative assessments for high-risk indications.” Based on 23andMe’s advertising campaign and its focus on health rather than simply information, the FDA’s letter stated that it considered the personal genome service a Class III device (the agency’s highest-risk classification) under the Medical Device Amendments, requiring the most stringent level of regulation. The letter led to a number of generally thoughtful responses and questions (some of which have been posted here) regarding whether DTC genetic tests are devices subject to FDA oversight (much less Class III devices) and the effects such regulation might have on patient access, innovation, and research. 

In the July 31^st press release issued concurrently with the letter to Congress, the FDA expresses concerns about the use of high-risk LDTs similar to those enunciated in the November 2013 Warning Letter to 23andMe. In particular, it focuses on the concern that “[i]naccurate test results could cause patients to seek unnecessary treatment or delay and sometimes forgo treatment altogether.” The notification to Congress provides certain anticipated details of the forthcoming draft guidance, with an emphasis on its risk-based framework for regulating LDTs. It states the agency’s intention to issue draft guidance to describe what it considers generally to be Class I, II, or III devices. In particular, it clarifies the needs for premarket review for higher-risk LDTs (“those that have the same intended use as FDA-approved or cleared companion diagnostics currently on the market”). The FDA will continue to exercise enforcement discretion over low-risk (Class I) LDTs, “Traditional LDTs” (those that reflect the types of LDT available when FDA began its policy of generally exercising enforcement discretion over LDTs in 1976), LDTs for rare diseases, and some LDTs for which there is no FDA-approved or cleared test (“LDTs for Unmet Needs”). After all LDT manufacturers notify the FDA of their tests (not to be confused with registration and listing the LDT with the FDA), the agency will phase in enforcement of premarket review requirements for relevant LDTs over time. Current LDT manufacturers needn’t take their products off the market during FDA review. 

With regard to DTC genetic tests like 23andMe’s product, notably, the agency’s press release claims that “the FDA already oversees direct-to-consumer tests regardless of whether they are LDTs or traditional diagnostics.” This seems not only to contradict history (one warning letter does not a system of oversight make), but also its later statement that the FDA has “generally not enforced applicable regulatory requirements” for LDTs. Importantly, however, the agency explains (in a footnote) that it will continue “not to exercise enforcement discretion” (never mind the seeming double-negative) for DTC tests regardless of whether they meet the definition of an LDT provided in the guidance, and therefore the enforcement policies described in the guidance do not apply to DTC tests. These statements may require further explication and additional efforts to provide consistency and guidance.

-Visiting Assistant Professor Valerie Gutmann Koch