By Turna Ray
HYATTSVILLE, Md. (GenomeWeb Daily News) – During the first day of a two-day meeting held here this week to discuss the US Food and Drug Administration's regulatory strategy for laboratory-developed tests, agency officials said that all options are on the table and "nothing is set in stone."
However, comments from one high-ranking agency official provided a glimpse of the ideas in play with regard to its risk-based regulation of LDTs.
According to Elizabeth Mansfield, director for personalized medicine at the Office of In Vitro Diagnostic Device Evaluation and Safety at FDA's Center for Devices and Radiological Health, the agency is considering downgrading in risk classification certain regulated tests as a way to manage its limited resources; phasing in regulation of LDTs that aren't currently regulated; collaborating with the National Institutes of Health to develop a test registry that could serve FDA's purposes for keeping an eye on all test developers; and possibly enlisting the help of third-party inspectors to help the agency with its increasing regulatory burden.
FDA's decision to oversee all LDTs comes shortly after the agency sent letters to firms selling genetic tests directly to consumers as laboratory-developed tests. Although the agency had noted for some time that the use, marketing, and complexity of LDTs had evolved to a risk level that caused it to lift its three-decade-long "enforcement discretion" over LDTs, the agency formally announced its decision to regulate this subset of tests after DTC firm Pathway Genomics attempted to sell saliva sample collection kits for its online genetic risk assessments through retail pharmacy stores Walgreens and CVS.
Traditionally, the laboratories that develop and perform LDTs have been overseen by the Centers for Medicare & Medicaid Services, but the clinical validity of these so-called "homebrew" tests are not regulated by FDA or CMS. Meanwhile, the FDA has restricted its oversight to medical device kits developed by test manufacturers, certain high-risk LDTs, and analyte-specific reagents.
But now, "we are in a new era of molecular diagnostics and personalized medicine," Mansfield said, suggesting a new regulatory paradigm is needed to facilitate access and manage risks of medical devices based on advanced technologies. While in the past LDTs were low-risk tests developed by a laboratory for a limited population in a hospital setting, FDA officials presented a snapshot of the current landscape in which many LDTs are not really developed by a single laboratory, are launched commercially before the tests are fully validated clinically, and are aggressively marketed to a broad consumer market.
"LDTs have become a lot more like IVDs," Mansfield said. "So the logical basis for a bifurcated regulatory pathway has also faded."
The focus of FDA's meeting on the first day was to gather input on the patient and clinical issues that need to be considered in light of LDT regulation. During the first part of the day presentations addressed a wide range of regulatory concerns, and during the afternoon FDA convened a panel of experts for a focused discussion on how the agency's regulation will impact patients.
Among the panel was Steven Gutman, former FDA director of the Office of In Vitro Diagnostic Device Safety and Evaluation and currently associate director of the Technical Evaluation Center with Blue Cross Blue Shield; Paul Radensky, a partner in the law firm McDermott Will & Emery and counsel to the Coalition of 21st Century Medicine; Alan Magill, director of the Division of Experimental Therapeutics at Walter Reed Army Institute of Research; and Cara Tenenbaum, VP of policy and external affairs of the Ovarian Cancer National Alliance.
In setting the stage for the meeting, FDA officials acknowledged that the agency will need to ensure its regulatory approach is flexible to accommodate rapid access to LDTs for rare diseases or in an emergency public health crisis.
IVD developers feel that their innovation is stifled if labs rush to market with genetic tests, Mansfield pointed out, noting that the CLIA pathway for LDTs is "being used as a loophole" to offer tests with limited validation, inappropriate software, and a lack of formalized design controls.
Meanwhile, LDT developers pointed to the misaligned development timelines and regulatory pathways for drugs and diagnostic test kits to note that without the CLIA pathway, many companion diagnostics wouldn't come to market quickly enough to meet patient needs and in line with advancing science.
It appears from Mansfield's presentation that although FDA may exercise its regulatory authority over all LDTs, there will still be a role for CMS in ensuring the quality of laboratories. Specifically, FDA said it will make sure that its regulatory requirements for LDTs will not conflict with or duplicate CMS' requirements. And particularly when it comes to laboratory inspections, FDA is considering using CMS inspectors for CLIA certification.
"FDA regulates tests, not labs," Mansfield said. "That's CLIA's job."
Within FDA's evolving regulatory framework, areas still need to be ironed out with regard to which tests the agency would still keep under enforcement discretion, if any; whether the FDA should convene expert advisory panels to provide regulatory advice; and what the costs, timelines, and inspection requirements will be for labs coming into compliance with FDA regulation.
In the meantime, the agency advised test manufacturers — whether laboratories or diagnostic companies — to consult FDA's guidance documents, request face-to-face meetings, and attend the agency's informational sessions if they have questions about how to proceed with a formal submission for a particular test.
Following this two-day meeting, stakeholders will have until Aug. 15 to submit comments to the agency about its oversight of LDTs. After that, FDA may issue new guidance on the topic, but there will not be opportunity for the public to provide further comment.
OIVD Director Alberto Gutierrez noted that in deciding to lift its enforcement discretion over LDTs, the FDA is exercising its existing regulatory authority, which would not constitute new regulation. Thus, there will be no new rules issued in this regard, though there would be the possibility for guidance in the future.
This is an abridged version of an article appearing in this week's Pharmacogenomics Reporter.The complete article is available here.