FDA issues guidance for laboratory developed tests

Last week the Food and Drug Administration released draft guidance regarding its planned oversight of laboratory-developed diagnostic tests.

Currently, lab developed tests, or LDTs, that are designed, manufactured and used within a laboratory are not regulated by the FDA. However, the rise in the complexity of LDTs and the growth in personalized medicine has led the FDA to begin to regulate the space.

"The FDA is set on doing something. There have been rumblings on this for a while," says Danielle M. Sloane, an attorney with Bass Berry & Sims.

The FDA released two draft guidance documents. The first — "Framework for Regulatory Oversight of Laboratory Developed Tests" — provides an overview of the agency's approach to regulating LDTs.

The second, "FDA Notification and Medical Device Reporting for Laboratory Developed Tests," provides guidance on how the FDA will collect information on existing LDTs from labs. Any lab using an LDT will be required to provide basic information and begin adverse event reporting on the LDT within six months of the release of the final guidance. Labs may either either (a) register and list their LDTs, or (b) go through the newly created "notification" process.

"The FDA seems to be promoting the 'notification' avenue. As part of the notification, the laboratory will need to report to the FDA information about each LDT, including laboratory legal name, contact email address, test name, monthly test volume, a brief narrative describing the intended...clinical use of the test and more," explains Ms. Sloane. "The FDA will use the information gathered and work with industry experts to classify LDTs ."

Similar to the FDA's current classification system for medical devices, LDTs will be grouped into three classes, with Class III representing the devices with the highest risks.

Classification of the LDTs will be interesting to watch, as LDTs are, by nature, "not a single machine," explains Ms. Sloane. "They will need to approve the whole testing process, which may involve several analytical steps, often involving several medical devices — some of which may already be FDA approved and some of which may not be approved."

Class III and Class II LDTs will face greater scrutiny than the tests deemed lower risk and will be subject to registration and listing, adverse event reporting, premarket review and quality systems requirements. Class I LDTs will be subject to FDA registration and listing and adverse event reporting but the agency will not enforce premarket review.

Premarket review for the highest-risk of the Class III devices will be enforced 12 months after the final guidance is released, and enforcement will expand to lower risk Class III, then Class II devices after that. Currently, "there's not a lot of clarity on what and how much clinical and research support the FDA is going to require in order to approve LDTs, particularly ones that have been on the market for some time," says Ms. Sloane.

The FDA will, however, continue to exercise enforcement discretion (i.e., not regulate) with respect to premarket review requirements for certain LDTs, for example, LDTs used for rare diseases or for unmet clinical needs. The FDA plans to also continue using its discretion with respect to what it considers "traditional" LDTs, and while the FDA will look at various factors to determine what qualifies as a "traditional" LDT, practically it applies to tests developed and run by a single laboratory or facility for diagnosing or treating a patient at that same facility or within a health system.

Proponents of FDA's regulation of LDTs have argued that existing regulations, notably the Clinical Laboratory Improvement Amendments, fail to evaluate LDTs before they are in use and don't include adverse event reporting. Medical device manufacturers are supporting the FDA's regulation of LDTs, arguing such regulation would improve safety and efficacy and "level the playing field" for the device makers who have long been subject FDA regulation, says Ms. Sloane.

Opponents argue existing regulations are sufficient, and FDA regulation adds an unwarranted burden on the labs. Additionally, some have noted concern that the FDA released the regulatory framework as guidance rather than part of its formal rulemaking process. However, the guidance does allow 120 days of comment, which is longer than the traditional 60-day comment period for FDA draft guidance documents, says Ms. Sloane.

While the FDA guidance confirms the long-discussed and controversial regulation of LDTs may be coming soon, Ms. Sloane says “the guidance isn't overly helpful to laboratories trying to predict its impact and potential burden once FDA enforcement goes into effect.”

"I think a big take away is that it's really difficult to project the most immediate impact, because until you know the [classification] of your tests, it's hard to plan," says Ms. Sloane. "Labs all realized this may be coming, but until the FDA issues the classification, many laboratories cannot predict precisely how and when the FDA's regulation of LDTs will impact their testing."

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