Did FDA Create a Way Forward for Lab-Developed Tests?

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By Jeannie Baumann

Recent FDA authorization of a test to screen for tumors using sophisticated genetic sequencing techniques may provide critical insight on how the agency will treat laboratory-developed tests.

The Food and Drug Administration approved Nov. 15 an in vitro diagnostic test developed in a Memorial Sloan Kettering Cancer Center laboratory that uses next-generation sequencing (NGS) technology to screen hundreds of genes for cancer tumors in an unprecedented way. As part of this authorization, the FDA also announced a new approval pathway for these types of tests. FDA Commissioner Scott Gottlieb said the new pathway will reduce the burden on test developers and modernize the authorization of laboratory tests from developers who voluntarily seek 510(k) clearance, which is how the FDA determines whether a device is equivalent to one that’s already on the market.

The new regulatory framework for NGS tests for tumor profiling is in line with steps the FDA has taken in digital health and regenerative medicine to adapt to rapidly evolving technologies. But questions remain whether these new approaches resolve the debate over if and how the agency should exert its authority over lab-developed tests—in vitro diagnostic tests that are designed, manufactured, and used within a single laboratory. The LDT issue has been a regulatory tug of war between the device makers who want more oversight and clinical lab groups that eschew it.

“This is really a clever sleight-of-hand in a way,” Carol Pratt, an FDA regulatory attorney based in Portland, Ore., with Lee & Hayes PLLC, told Bloomberg Law in a Nov. 16 email. “It appears that the FDA is announcing a new, low-burden regulatory pathway for IVD devices, when it is really about a voluntary ‘authorization’ process for LDTs.” The word “voluntary” in Gottlieb’s statement is critical, she said, because it acknowledges that 510(k)s aren’t required for LDTs. The FDA clears devices through the 510(k) process or approves them through the premarket approval process, but it doesn’t “authorize” them, said Pratt, a member of Bloomberg Law’s health-care advisory board.

Lab Test Implications

Jennifer Dickey, director of regulatory and quality for Personal Genome Diagnostics, said the FDA is taking the next step in addressing a key category of the many uses of NGS in the clinic. Because the test is an LDT, “FDA appears to be establishing a pathway to encourage developers of NGS-based LDTs serving oncology patients to submit their tests to be cleared for marketing.”

Gail H. Javitt, an attorney with Epstein Becker Green in Washington who has published several scholarly articles on the regulation of NGS, said it remains unclear how the announcement fits into a broader framework of regulating the use of genomics and clinical care. She also said it raises questions about what this means for LDTs.

“FDA is currently exercising enforcement discretion over laboratory-developed tests. And yet FDA just cleared a laboratory-developed test for cancer,” Javitt said in a Nov. 16 interview.

The FDA reviewed the Memorial Sloan Kettering diagnostic called IMPACT as a de novo product, an approval mechanism for some low- to moderate-risk devices that are novel and for which there is no legally marketed device, she noted. It’s unclear whether the FDA’s decision on IMPACT will pressure other health systems to go through the IMPACT pathway, or what the incentive would be to use this pathway when the FDA isn’t regulating LDTs now. “FDA clearly is trying to figure out their role in this new universe.”

Joyce E. Gresko, a health-care attorney with Alston & Bird LLP in Washington whose clients include clinical laboratories, said the announcement doesn’t change the agency’s thinking about standards for NGS-based tests, but it may provide another way for a test developer that wants a test to be cleared to demonstrate that it has met those standards.

Lab Test Oversight Plan Withdrawn

About a month before President Donald Trump took office, the FDA withdrew its plan to regulate LDTs in anticipation of the new administration, while making clear in a subsequent paper it believed some oversight was necessary. At issue is whether advances in LDTs raise safety and efficacy issues that mean oversight is needed under the FDA’s device regulations, or if new oversight constitutes double regulation of laboratories, which already are overseen by the Centers for Medicare & Medicaid Services under the Clinical Laboratory Improvement Amendments.

“We are really just at the beginning of understanding how to integrate next gen sequencing and whole genome sequencing into clinical practice,” Javitt said.

Mark E. Brager, a spokesman for the Advanced Medical Technology Association, said the FDA created a more efficient and timely authorization pathway for a subset of next-generation sequencing tests. “AdvaMed has long supported broader application of risk-based approaches to the regulation of all diagnostic tests,” he told Bloomberg Law in a Nov. 16 email.

The American Clinical Laboratory Association, which hailed the FDA’s withdrawal of its LDT enforcement plan, “has consistently maintained that LDTs are not medical devices and cannot be regulated as such,” the association said Nov. 17. The lab group supports legislative reform on diagnostics under a set of association principles.

No Effect on Draft Guidances

While the IMPACT authorization may have implications for LDTs, it shouldn’t affect the two draft guidances the FDA released in July 2016 to regulate NGS tests. The one-test, one-disease model under the regulations aren’t equipped to handle NGS tests that can examine millions of DNA variants at one time, Robert M. Califf, who was FDA commissioner at the time, said then.

FDA spokeswoman Tara Rabin told Bloomberg Law in a Nov. 16 email the FDA’s authorization for the IMPACT test is distinct from its work on the NGS draft guidances. But the draft guidance on analytical validation of NGS tests for suspected hereditary diseases also proposed using the de novo pathway to make tests with this intended use class II, the same risk level as the IMPACT device. “It is possible that in the future, tests of this type could be available for 510(k) clearance through an accredited third party.”

The FDA is reviewing and addressing stakeholder feedback on the two draft guidances, which remain on the device center’s list of priority guidances, Rabin said. The FDA wants to release them as soon as possible but won’t speculate on a date.

To contact the reporter on this story: Jeannie Baumann in Washington at jbaumann@bna.com

To contact the editor responsible for this story: Randy Kubetin at RKubetin@bna.com

For More Information

The FDA announcement on the IMPACT test is available at https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm585347.htm.

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