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Federal Regulators Discuss DTC Genetic Testing Oversight at AACC Online Meeting

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Two federal agencies — the US Food and Drug Administration and the Centers for Medicare & Medicaid Services — with oversight of genetic tests are looking into the regulation of direct-to-consumer genetic testing, agency officials said during an online meeting hosted by the American Association of Clinical Chemistry last week.

Judy Yost, CMS' laboratory divisions director, said during the AACC meeting that the agency is "monitoring" DTC labs offering genetic testing to ensure compliance where the Clinical Laboratory Improvement Amendments are applicable.

Meanwhile, while still not expressing any intent to regulate DTC genetic testing firms, FDA continues to keep an eye on the evolving field, according to Courtney Harper, associate director for toxicology at FDA's Office of In Vitro Diagnostic Device Evaluation and Safety.

Neither agency has been particularly forthcoming in the past about regulatory efforts with regard to DTC genetic testing. CMS has said it is in discussions with DTC genetic testing firms. FDA, in turn, has said nothing more than it is watching this nascent field "with interest."

Although no specific regulatory efforts were discussed during the meeting, it was apparent from the comments of agency officials that the issue is at least on the radar of both CMS and FDA.

CMS Is 'Monitoring'

"CMS has an ongoing effort to monitor all of the DTC laboratories that offer genetic testing, not only to ensure compliance but to ensure that they are enrolled and overseen [under CLIA] … as all of our enrolled labs," Yost said.

So far, CMS has identified 117 "entities" associated with genetic testing and this list is growing, according to Yost.

"That doesn't mean that every one of these is a laboratory necessarily," she added. "We have also identified those that only market, those that may collect specimens, those that may provide information to an individuation with regard to their genetic analyses, and so forth. All of these are identified and monitored on a regular basis. Where necessary we will coordinate both with the FDA and the [Federal Trade Commission]."

Yost did not elaborate how CMS is planning to differentiate DTC genomic firms, such as 23andMe, that outsource the genotyping aspects of their genetic screening business.

Despite claims by some DTC genomics companies that they should not be regulated as clinical laboratories because they provide educational information about genetic risk, the New York State Department of Health has decided to regulate such facilities as laboratories. Of the big three DTC genomic testing companies — 23andMe, Decode, and Navigenics — the NY State Department of Health has decided the latter two are subject to laboratory regulations. State health regulators are still in negotiations with 23andMe regarding the company's ability to operate in New York. [see PGx Reporter 03-18-2009].

CMS has future plans to include DTC laboratories on its laboratory certificate website, where such labs are currently not identified uniquely.

"We will continue to develop mechanisms to consistently identify new tests requiring CLIA oversight," Yost said. "As new tests are identified we hope to evaluate … whether or not [they] should fall under CLIA.

"Some tests which are more lifestyle related, that are not necessarily health assessment related, [would not] be covered by CLIA," she added.

FDA is Still Watching

"FDA is very active in the area of the DTC genetic testing," Harper, from FDA's OIVD, said during the meeting, though she did not elaborate on the agency's specific activities in this regard.

As an example, she noted that Steven Gutman, the former head of the FDA's diagnostics division, had participated in a few hearings on the Hill on DTC genetic testing. Gutman left the FDA at the end of last year to join the University of Central Florida as a professor of pathology.

"We're certainly keeping our eye on that area," Harper said.

During the meeting, Harper would not provide timelines for any of the agency's pending regulatory efforts around regulation of genetic testing, including finalization of the draft guidance for in vitro diagnostic multivariate index assays, or IVDMIAs, and the agency's response to Genentech's Citizen Petition that FDA regulate all predictive laboratory-developed tests [see PGx Reporter 02-14-2007; 12-17-2008].

Traditionally, the FDA has practiced "enforcement discretion" over most laboratory-developed tests, which are overseen by CMS under CLIA. However, FDA decided in 2007 it would regulate IVDMIAs, a more complex type of LDT.

Many LDT developers fear that FDA's regulatory strategy would be arbitrary and that it would hinder innovation. On the other hand, diagnostics firms and large pharmaceutical firms that have already spent money to garner FDA clearance for their diagnostic tests feel FDA's regulatory practices are inconsistent and unfair.

The HHS Secretary's Advisory Committee on Genetics, Health, and Society in February 2008 issued a report on the regulation of genetic tests, recommending that FDA "close the gaps in oversight related to clinical validity" of genetic tests by "address[ing] all laboratory tests, regardless of how they are produced (i.e., as a commercial test kit or laboratory-developed test), in a manner that takes advantage of its current experience" [see PGx Reporter 02-20-2008].

Harper said that if adopted, this recommendation "could have implications" for the agency, but did not elaborate.

LDT Regulation

Meanwhile, CMS' Yost acknowledged that "there is a gap in oversight" of laboratory-developed tests where the FDA is practicing "enforcement discretion" because CLIA doesn't ensure clinical validity of genetic tests.

CMS has established a workgroup of stakeholders to look at specific issues in genetic testing, such as improved monitoring, data collection analysis, and the evaluation of the performance of specific genetic testing laboratories.

The agency also plans to release a new guidance developed by the Centers for Disease Control and Prevention outlining how laboratories can achieve CLIA certification for genetic tests.

Another major regulatory issue at CMS is the evaluation of proficiency testing standards for all CLIA-certified laboratories. Despite the urging of several non-profits for CMS to create a genetic specialty that would make proficiency testing mandatory for all CLIA-certified labs, the agency decided two years ago instead to use existing quality control guidelines to ensure the safety and efficacy of labs under its purview [see PGx Reporter 09-07-2007].

In this regard, CMS intends "to publish as quickly as we can" a proposed notice for final proficiency testing regulations, Yost said. The Centers for Disease Control and Prevention workgroup responsible for this effort was scheduled to meet with CMS this summer, but that has been postponed due to the swine flu epidemic, she said. As a result, work on the proposed notice for final PT regulations will convene in the fall.

"One of the greatest concerns of the genetic testing folks is the fact that there are no genetic tests listed in the CLIA regulations where mandated [performance testing] is necessary," Yost said. She noted there "is an absolute need" to update the CLIA regulations for proficiency testing.

For the past year, CMS and CDC have been working with the Clinical Laboratory Improvement Advisory Committee to update the regulations for both the performance testing programs under CLIA, as well as for laboratories under CLIA. Specifically, the agency plans to "add some genetic tests where performance testing may be available and also to evaluate and support some alternative assessment mechanisms for tests for which there may not be performance testing materials available," Yost noted.

One of the recommendations of the SACGHS was for FDA and CMS to work together to identify areas of collaboration where regulation of genetic tests are concerned.

"CMS has worked collaboratively with the FDA on laboratory-developed test methods [and] analytic validation reviews for the last several years," Yost said. In the process, CMS has encountered new types of tests, and this interaction has been "very valuable for FDA and CMS to see what's out there."