Most laboratory-developed tests have no predicates, said Elizabeth Mansfield, director of personalized medicine in CDRH’s diagnostics office, hinting that many may require pre-market submissions that go beyond 510(k) review standards once the agency initiates plans for active oversight of the category.

“There is nothing that has ever been regulated that is like them,” Mansfield told industry Oct. 20 at the group’s AdvaMed 2010 meeting in Washington, D.C.

Mansfield provided a peek at what FDA’s forthcoming guidance on lab-developed tests might look like.

“A lot of the tests offered, these laboratory tests, have no predicate. There is nothing that has ever been regulated that is like them” – Elizabeth Mansfield, CDRH

She noted that agency staff “worry a lot” about lab-developed tests, because “they have potential to bring a significant risk if the test results are incorrect.”

Following a long period of enforcement discretion under which certain laboratories could develop assays in house to offer as a lab service to physicians without direct FDA involvement, the agency held a heavily attended two-day public meeting on lab-developed tests in Hyattsville, Md., last July, to gather input on developing a framework for oversight. (See “ Also see "FDA Gathers Feedback To Guide Oversight Of Lab-Developed Testing" - Medtech Insight, 26 July, 2010. ” – “The Gray Sheet” July 26, 2010.)

FDA is now reviewing the 115 comments received on the public docket opened on the matter. (See “ Also see "FDA Resists Push For Longer Rulemaking Route On Lab-Developed Tests" - Medtech Insight, 27 September, 2010. ” – “The Gray Sheet”- Sept. 27, 2010.)

Registration Of Tests To Be First Step

As part of its framework to implement oversight of lab-developed tests, FDA will is expected to try to first register the tests, then classify them.

The agency wants to register them because “we don’t know what’s out there, or what they are offering.”

Although the National Institutes of Health already has announced plans for a genetic test registry, Mansfield noted that the NIH registry “does not exist” yet, and neither FDA nor NIH knows what will be in it. (See " Also see "NIH Gene Test Registry Aims To Shed Light Where Oversight Has Been Patchy" - Medtech Insight, 22 March, 2010. " – "The Gray Sheet" March 22, 2010.)

She also said that registration listing of devices “is a general control, part of FDA medical device regulations, so it already exists.”

However, FDA is keeping NIH's registry plans in mind and is trying to implement a mechanism where device makers can register in one place or the other, and the two databases would be interactive. “We are not interested in having people enter the same information in a hundred different places,” Mansfield said.

Classification Of Lab-Developed Tests Planned

FDA also plans to classify the lab-developed tests, most likely into high, moderate and low-risk categories, according to Mansfield. While classification may be difficult because many of the tests have no predicate, the agency hopes that by classifying lab-developed tests up front, “we don’t have to do a lot of de novo classification.”

Tests likely to fall into the highest risk category would include companion diagnostics, cancer tests, tests that direct or very strongly influence patient management of a serious disease, and tests for serious or fatal communicable diseases, Mansfield told participants at the public meeting in July.

In contrast, moderate-risk tests might be those for which an undetected wrong result would lead to a non-serious injury, where false results are relatively easy to detect and where adjunctive tests are available.

Mansfield also indicated that FDA has adopted an idea vetted by test manufacturers at the July meeting: that a “classification panel” be convened to determine where to place tests, based on their risk, clinical use, novelty of analyte being tested, novelty of the testing technology and experience of test users.

“Loophole” Impression Drives Regs

According to Mansfield, recent technological advances have pushed the agency to up its regulatory game.

“What we saw was that our practice of enforcement discretion became a loophole, a way to avoid FDA regulations,” Mansfield said.

Until recently, she said, FDA was content to allow qualifying laboratories to develop home brews without its involvement, but then researchers “had to go and sequence the damned human genome,” resulting in more increasingly complex molecular-based tests being offered with insufficient oversight, in the agency's view.

“What we saw was that our practice of enforcement discretion became a loophole, a way to avoid FDA regulations,” Mansfield said.

Ultimately, many of the tests became especially dependent on and marketed by, “unknown entities,” rather than conventional clinical laboratories, creating an un-level playing field for manufacturers of diagnostic test kits, she noted.

The agency plans to release its guidance on how laboratory-developed tests will be regulated, “as soon as we can get it out,” Mansfield said.

She speculated that the lab-developed test guidance could take longer because it is the type of guidance that “a lot of people within the agency have to look at,” and “everybody wants to make changes.”

By Sue Darcey

FDA Official Gives Policy Update On Lab-Developed Tests

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