FDA Recommends Precertification Program to Legislators as They Consider Dx Regulatory Reform

NEW YORK (GenomeWeb) – The US Food and Drug Administration has pitched the idea of creating a precertification program for in vitro diagnostics and lab-developed tests to legislators interested in advancing a new regulatory framework.

The agency suggested the precertification program as part of its technical assistance on the Diagnostic Accuracy and Innovation Act (DAIA) that Representatives Larry Bucshon (R-IN) and Diana DeGette (D-CO) have been drafting and discussing with stakeholders for over a year. This bill seeks to settle the longstanding controversy over LDT regulation, and there appears to be growing support among stakeholders for its introduction this year. 

"Many of the concepts that DAIA proposes are important to include in any legislative framework, including, for example, a streamlined path to market," the FDA said in the technical assistance document obtained by GenomeWeb. "FDA also recommends further streamlining by including a precertification for many tests."

The recommendations in the technical assistance document represent the agency's high-level comments, but the FDA said it will also provide more detailed input to legislators and stakeholders as they work on refining DAIA. Generally, the agency said it is supportive of the goal of the draft bill as long as "it does not impose unreasonable barriers for FDA to take action to address problematic tests, or unnecessary costs or delays of implementation."

DAIA — publicly released for stakeholder input in March 2017 and fashioned closely after a framework developed by the Diagnostic Test Working Group in 2015 — lays out a plan to create a new, in vitro clinical test (IVCT) category, which comprises both test kits and LDTs. The FDA would be in charge of developing and validating an IVCT, while the Centers for Medicare & Medicaid Services would oversee the performance of the developed IVCT within CLIA-certified labs. The states will continue to have jurisdiction over the interpretation of IVCT results by a medical professional.

Meanwhile, FDA Commissioner Scott Gottlieb has publicly discussed crafting a precertification program for diagnostics based on the application of this framework in the digital health space. The FDA told Bucshon and DeGette that the precertification program would factor in the entity, technology, and clinical context to assess which tests are eligible for this pathway. Once an entity (a lab or test developer) has gained precertification for a category of tests, other tests in that category would not be subject to premarket review. 

DAIA defines high-, intermediate-, and low-risk test categories, and the regulatory requirements for IVCTs that confer such risks. The FDA envisions that low-risk IVCTs would be exempt from premarket review requirements and precertification. But "a significant proportion of IVCTs" would be eligible for precertification, which "would assure that test developers are capable of developing analytically and clinically valid tests for patients."

A smaller proportion of IVCTs — for example, tests that are first-of-a-kind, high-risk, cross-labeled with other medical products, CLIA waived, or over the counter — would not be eligible for precertification. However, as FDA gains a better understanding of tests in the high-risk category, they could become eligible for precertification over time. If tests don't qualify for precertification or labs choose not to take that pathway, the tests would go through a new premarket review and approval pathway.

The FDA also expressed a number of concerns with the DAIA draft that would make it harder to meet its obligation to protect the public health. For example, the agency noted that the draft bill would make it difficult for it to regulate grandfathered tests that aren't analytically or clinically valid. While the FDA could require pre- and post-market clinical trial data for high-risk IVCTs under this legislation, the agency felt the language in the bill restricts its ability to ask for raw data to further evaluate the analytical and clinical validity of these tests.

Other provisions in the draft bill that the FDA said would restrict its ability to ensure patient safety include one that will "automatically force regulatory decisions if FDA does not act before various deadlines" and another that would leave vaguely defined "platforms" without sufficient regulatory oversight. The FDA also didn't like the proposal to create a new center for IVCTs, which it said would be extremely costly and unnecessary.

While DAIA leaves oversight of IVCT development and validation to FDA and lab operations to CMS under CLIA, the FDA sees areas "where the same activity would be regulated by FDA if conducted by a conventional manufacturer or by CMS if conducted by a lab." The agency recommended getting further technical assistance from CMS, but noted that it could rely on CLIA to provide assurances around certain lab processes, while the FDA enforces certain quality systems requirements.

The FDA articulated this and other ideas earlier in a 2017 discussion paper, released a few months after it announced it would not finalize its controversial draft guidance on LDT regulation. For example, in the discussion paper, the agency suggested that test developers wouldn't have to make a premarket submission when they make modifications to tests, if those changes were described prospectively in initial submissions. The agency also described the use of third-party reviewers as part of the regulatory process. 

Both of these ideas show up in its technical assistance document to Bucshon and DeGette. Particularly, the agency highlighted that it recently accredited the NY State Department of Health as a third-party reviewer of certain IVDs. In authorizing Memorial Sloan Kettering Cancer Center's MSK-IMPACT next-generation sequencing tumor profiling assay last November, the agency also established a Class II regulatory pathway for similar cancer panels, allowing them to become eligible for the 510(k) clearance process either by applying to the FDA or going through NYSDOH.

It's unclear the extent to which stakeholders support FDA's precertification program idea. The agency said it doesn't comment on proposed legislation.

However, a growing number of organizations believe this is the year to enact a legislative solution for diagnostic regulation reform. American Clinical Laboratory Association President Julie Khani said the FDA's input helps advance that goal.

Myriad Genetics spokesperson Ron Rogers also agreed that FDA's technical assistance on the DAIA draft marks a major step forward for enacting legislation. He said the company is waiting for "more specifics from the agency on any new ideas like pre-certification that will ensure innovation continues and patient care improves."

The objections FDA raises about DAIA have been noted in the past by Gottlieb and other FDA staff, Khani said. "We ultimately need more detail to fully assess any of these ideas," Khani said.   

Lisa Schlager, VP of community affairs and public policy at the non-profit Facing Our Risk of Cancer Empowered, said that while the organization needs more time to review the draft bill and FDA's feedback, it has encouraged those involved in legislative discussions to reach out to other patient groups to gain their input on DAIA.

"We agree that there is a need for regulatory improvement and modernization to accommodate the rapidly changing diagnostic test landscape," Schlager said. "We are still reviewing the nuances of the documents so we don’t have a position at this time, but we are very supportive of FDA involvement and hope its suggestions will be seriously considered."

While support for enacting legislation on this issue this year may be growing among stakeholders, they may not all be on the same page about the nuances of the draft bill or of FDA's input. While there is broad consensus on the need for a legislative solution to regulating diagnostics, policy experts GenomeWeb spoke to indicated that some groups support DAIA in its current form, while others want to see revisions.

"There is a growing belief among stakeholders, ACLA included, that 2018 is the year to move comprehensive legislative reform of diagnostic oversight," Khani said. "We definitely believe there is appetite in both the House Energy & Commerce Committee and Senate HELP Committee to work on this reform effort this year."

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