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FDA, Industry Willing to Collaborate on Dx Regulation via Legislation Despite Differences

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BOSTON – After clashing over diagnostics regulations for more than two decades, lab industry players and the US Food and Drug Administration seem willing to work toward a legislative solution to a longstanding controversy.

House Representatives Larry Bucshon (R-IN) and Diana DeGette (D-CO) have worked with diagnostics and lab industry stakeholders to draft legislation, called the Diagnostic Accuracy and Innovation Act (DAIA). The draft bill describes a regulatory framework for a new category of products, called in vitro clinical tests, where different aspects of oversight are shared between the FDA, the Centers for Medicare & Medicaid Services, and states.

Labs and testmakers, wanting to limit FDA oversight of their province, have embraced DAIA as a far more workable regulatory option than the draft guidance on lab-developed tests (LDTs) the FDA issued a few years ago. However, much to the industry's surprise, the agency recently weighed in on the draft bill and proposed ideas that reassert its authority to oversee the space. 

In August, the FDA provided technical assistance to legislators on DAIA, but instead of providing line edits to the bill's language as is typical, the agency presented legislators with what many experts said was an entirely new framework. The FDA's version of the bill includes provisions related to premarket approval, provisional approval, and a precertification program and makes explicit its authority to revoke approval, request raw data, and take corrective action against test developers in order to protect the public health.

At the Personalized Medicine Conference here this week, American Clinical Laboratory Association President Julie Khani indicated that the agency's move was unexpected, and while there were areas of concern, there were also favorable aspects to the proposal. The FDA framework would "really immediately place LDTs into that device framework," she said. Also, it "doesn't have a clear timeline for when that new system would be set forward," Khani noted.

At the same time, industry stakeholders appreciated the agency's proposal for precertification — a pathway through which diagnostic developers would have to garner premarket approval or clearance for one test representative of a group of tests using the same technology and that have other elements in common. Approval of that representative test would precertify other tests in the group and allow the lab to launch them without premarket review.

"That is something that's really captured the interest of laboratories and manufacturers alike, as well as academic medical centers and others, [as something] that might really help with streamlining and setting up efficient regulation," Khani said.

The lab industry has historically been opposed to FDA regulation of LDTs, which are currently overseen by CMS under the Clinical Laboratory Improvement Amendments, and has maintained that the agency lacks statutory authority to regulate LDTs as devices. DAIA attempts to solve this difficulty by keeping FDA in charge of overseeing the development and validation of a new category of tests, so-called in vitro clinical tests, while keeping CMS in charge of overseeing the performance of these tests within CLIA-certified labs.

"There have obviously been disagreements over the right way to regulate diagnostics," said David King, CEO of the Laboratory Corporation of America, at the meeting. He noted that the FDA has to quit trying to fit the regulatory framework for medical devices onto LDTs and expressed support for the industry-backed version of DAIA as the right approach, in which he said stakeholders have recognized the importance of diagnostic validity, accuracy, and reproducibility.

The lab industry favors DAIA as a starting point for discussions, according to Khani, because the bill would establish a specific center at the FDA for diagnostics, set up clear divisions between FDA and CMS oversight to avoid duplicative regulations, and establish strong grandfathering provisions to exempt a large portion of tests from onerous regulatory requirements. At the meeting, while industry representatives were clearly intrigued by FDA's proposed precertification provision, they still harbored worries that the agency's regulation could be overly burdensome and hinder innovation.

Genomic Health CEO Kim Popovits, for example, recalled the lab industry's backlash to the FDA's prior attempt to regulate in vitro diagnostic multivariate index assays — an older term the agency used to describe proprietary, algorithm-based assays like the company's gene expression-based Oncotype DX. "That's clearly not the way we felt things should be done," Popovits said at the meeting.

But now that there is agreement among stakeholders that the issue of diagnostic regulation should be solved via legislation, and lawmakers have multiple proposals to consider, Popovits said that labs needed to be thoughtful about what kinds of evidence will be required for premarket review, what the review timelines would be, what labs would have to submit when they made changes to tests, and the costs under any resulting framework. She noted that "folks are listening" to the lab industry's concerns on these fronts.

Lauren Silvis, chief of staff within FDA's Immediate Office of the Commissioner, assured attendees that the agency did weigh industry feedback in crafting the technical assistance document. "I hope people saw in the TA that FDA listened," she said.

In particular, the agency was concerned about providing patients timely access to innovative tests, while ensuring their safety. FDA's technical assistance to lawmakers includes a provision for tests with priority review status — for example, tests that use breakthrough technology or address an unmet need — where they can be provisionally approved by the agency. This would allow test developers to bring diagnostics to market in an expedited manner, which could remain on the market as long as the developers complete and submit post-market studies within the specified time frame.

"We wanted to make sure a breakthrough pathway was there for products that could make a significant difference to patients, so they could have timely access to those products," Silvis said. "That's why we talked about the standard of analytical validity, but also probable clinical validity, while we're still generating that evidence."

Recognizing the rapid development cycle for some of these tests, the FDA also included measures that would exempt a lot of tests from having to garner premarket review. "We hope that eventually, we can have a precertification-like program for a lot of the diagnostics," Silvis said. "And there would be a limited bucket for individual test review." She also noted that the agency tried to limit the circumstances when a lab would need to resubmit a test, so it could continue to innovate and improve it.

Overall, at the conference, industry players indicated their willingness to work with the FDA to arrive at a legislative solution that the agency and labs can live with. Khani said stakeholders appreciate how willing the agency has been to address their concerns and that it included the precertification provision as a way to ease regulatory burdens. "It's really up to Congress now to to take those two proposals and try to combine them into something that can move forward," Khani said.

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