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Lab Industry Queries FDA About Concerns Over VALID Act

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WASHINGTON, DC (GenomeWeb) – At a lab industry meeting on Tuesday, a US Food and Drug Administration official addressed concerns over a draft bill that contains its proposals for a new regulatory framework for diagnostic tests. 

In December, members of the House Energy & Commerce Committee and the Senate Committee on Health, Education, Labor, and Pensions circulated a draft of the Verifying Accurate, Leading-edge IVCT Development (VALID) Act, which contained proposals for regulating devices and lab-developed tests (LDTs)  under a single oversight framework. The ideas in VALID came from the FDA, which provided technical assistance to legislators on a previous iteration of a draft bill penned by lab and device makers, dubbed the Diagnostic Accuracy and Innovation Act (DAIA). The FDA's version ended up largely supplanting DAIA, except for maintaining the concept of in vitro clinical tests, or IVCTs, as a new category comprising test kits and LDTs.

"We tried to a take a balanced approach where we don't think we need to review every single test," said Lauren Silvis, chief of staff for FDA Commissioner Scott Gottlieb, at the American Clinical Laboratory Association's annual meeting. "In order to appropriately promote innovation and balance it with patient safety, we think there are ways of doing [product] reviews that are different than what we do now."

FDA's proposed regulatory framework would balance public safety with promoting innovation by using mechanisms like grandfathering and exemptions to ensure that already marketed tests or assays that are low risk or for rare diseases wouldn't have to seek premarket approval. Only around 10 percent of high-risk tests would require premarket approval, Gottlieb has estimated, while between 40 percent and 50 percent of tests would qualify for precertification, a program which is the centerpiece of the agency's proposals.

While the agency would use one set of levers to try to reduce the regulatory burden on industry, it would also retain the authority to take problematic tests off the market and request data and submissions from sponsors in the post-market setting. "Innovation can happen within guard rails that protect patient safety," said Silvis.

These ideas, however innovative, revive longstanding tensions between the FDA and the lab industry. Historically, tests developed by labs have been regulated by CMS under federal standards, the Clinical Laboratory Improvement Amendments, and the FDA has exercised enforcement discretion. But from time to time over two decades, the agency has also felt that LDTs are increasing in complexity and should come under its oversight, which the lab industry has thwarted, arguing that the agency lacks statutory authority to regulate lab processes and its oversight would quash innovation and test access.

However, Gottlieb had championed the idea of resolving this controversy through legislation, and during his tenure some leaders in the lab industry became more open to the idea that the FDA would have some role in test regulation. However, it is clear from the lab industry's feedback on VALID and comments stakeholders made at ACLA's annual meeting, that there is still concern about how much authority the agency would have over labs under the proposed framework and how this would impact labs' resources.

At the meeting, industry players queried Silvis about how the agency planned to ensure that its proposals related to precertification didn't burden them; how the agency would ensure that labs wouldn't have to meet duplicative requirements for FDA review and under CLIA; and why the agency decided to propose a whole new plan that departed so significantly from the industry-backed framework in DAIA.

DAIA would have spread regulation of IVCTs across FDA, CMS, and the states, with the FDA overseeing test development and validation, CMS remaining in charge of traditional lab activities necessary to perform testing, and states maintaining oversight of interpreting test results. This proposal was in line with the lab industry's stance that the FDA doesn't have statutory authority to regulate lab operations. In contrast, VALID creates a single regulatory pathway for all IVCTs, whether it is an LDT or a kit.

In formal comments on VALID, for example, ACLA raised the need for regulation to distinguish between IVDs and lab test protocols. The association also pointed out that while the draft bill states that FDA requirements shouldn't overlap with CLIA, it also allows the agency to issue redundant regulations if it is necessary to protect the public health. ACLA further noted that FDA's current quality system regulations overlap with many commitments labs have to meet under existing standards.

"Additional FDA regulation of already-regulated services and activities would be unnecessarily burdensome for labs and could hamper both innovation and ongoing performance of current testing services," ACLA wrote to legislators regarding VALID. "VALID should clearly state that FDA's authority to regulate IVCTs does not apply to laboratory operations. This approach would help ensure consistent availability and accessibility of testing services while granting FDA appropriate authority to oversee a new framework for diagnostic tests."

Silvis said that the FDA has worked with CMS to ensure that a new regulatory framework would leverage aspects of CLIA and not duplicate requirements labs are already subject to. "That's a huge piece of our thinking and a huge evolution of where FDA has come in this whole discussion about LDTs," she said. "It's certainly not where FDA started."

She noted that some of FDA's quality system requirements will be things labs aren't currently doing. The FDA is taking "a targeted approach," Silvis explained, by identifying areas that FDA regulation can address that's not being addressed by CLIA. "We're open to identifying other areas," she said. The agency also wants to make use of third parties, such as the College of American Pathologists and New York State Department of Health, to help reduce duplicative requirements and streamline regulations.

The agency has already tried this out under its current authorities, with its authorization of Memorial Sloan Kettering Cancer Center's MSK-IMPACT next-generation sequencing tumor profiling assay. With that authorization, the FDA accredited the NYSDOH as a third-party reviewer of certain IVDs so that cancer panels similar to MSK-IMPACT can become eligible for the 510(k) clearance process either by applying to the FDA or going through NYSDOH. 

One of the persistent concerns about FDA oversight of LDTs has been that it would burden labs by having to make a new submission to the agency every time they tweaked or made adjustments to a test. In comments to legislators on VALID, for example, the Personalized Medicine Coalition pointed out that the draft bill contains new categorical test definitions, such as a "first-of-a-kind" IVCT, and it is not clear how modifications to such tests would be treated.

"The VALID Act also details several common modifications that would potentially trigger the need for premarket submission to the FDA," the PMC wrote. "This broad view of modifications subject to premarket submission would undermine a test's grandfather status and in some cases it may disrupt patient access to currently available laboratory tests and service."

VALID does list a number of modifications that would trigger additional reporting or submissions, for example, if a change affects the test's performance characteristics or safety profile. At the meeting, Silvis highlighted that VALID would also allow sponsors to submit a prospective protocol that describes anticipated changes, and if labs make modifications in accordance with that plan, they won't have to make additional submissions.

With the precertification pathway, the agency also aims to reduce regulatory burdens on labs. For this reason, the precertification program for diagnostics has sparked a lot of interest among industry players, and it has raised questions and concerns about new test categories and regulatory definitions. Diagnostics industry association AdvaMedDx, for example, pointed out the need to clarify definitions of new terms that relate to the precertification program, such as, "test group." 

The precertification pathway for diagnostics is drawn from a pilot effort FDA is running in digital health. The idea is that a sponsor would pick one test representing a group of tests using the same technology and of the same subspecialty (such as a disease indication) and take that through premarket review. Once approved, tests in that group or category wouldn't be subject to premarket review. Some categories, such as a first-of-a-kind test, high-risk tests, assays cross-labeled with other medical products, CLIA-waived tests, or over-the-counter tests wouldn't be eligible for precertification, but as FDA gains a better understanding of diagnostics in the high-risk category, the agency has said they could become eligible for precertification over time.

One concern raised at the meeting was that restricting precertification test groups to a technology and subspecialty would be too burdensome for labs that market tests in multiple subspecialities using different technologies. "We've heard that the medical specialty is a concern in terms of it being to narrow," Silvis said. "We're planning to address that and have a broader approach."

Some meeting attendees noted that under the digital health precertification program, participating sponsors have to meet significant submission requirements and wondered if this is a fair reflection of the burden that labs would face by undertaking this pathway. Silvis explained that the digital health precert pilot is different because it is being conducted within the existing regulatory framework, but VALID would create a new statutory authority and an entirely different pathway. "I do think it would be very different for diagnostics in the laboratory setting," she said.

Lastly, some at the meeting wondered why VALID differed so significantly from the industry-backed DAIA. "It was an evolution in thinking," said Silvis, noting that while pre-certification wasn't an idea in DAIA, it was something FDA had been discussing and testing out in the digital health space. "Sometimes you see a sponsor come in with a great idea and it shows you a way to do things differently. We always have to keep pace with innovation."

"I think you can gauge from the types of questions you've received that this is a priority issue for ACLA and its members," ACLA President Julie Khani told Silvis at the meeting. "We want to work with you on getting it right."

Despite the industry's interest in VALID, it's not clear how much support there is in Congress for advancing the draft bill in the current political climate, and now that Gottlieb has announced his resignation. However, Silvis indicated that the commissioner will continue to express his support for comprehensive regulatory reform for diagnostics during his last days in public service.

She acknowledged that Gottlieb has had calls with lawmakers discussing a comprehensive reform plan for diagnostics regulation that he believes would be good for patients and innovation, and said he'll continue to impress this upon legislators as he testifies before Congress this week and next week.