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FDA Tells Congress it is Mulling Strategies to Regulate DTC Genetic Tests as Medical Devices

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Originally published July 23.

By Turna Ray

WASHINGTON, DC – At a congressional hearing on direct-to-consumer genomic testing this week, the US Food and Drug Administration stated unequivocally for the first time that it considers the tests marketed by these firms to be medical devices requiring the agency's clearance or approval. Furthermore, a high-ranking FDA official acknowledged that the agency has waited too long to take action against this rapidly growing industry.

The House Committee on Energy and Commerce was prompted to send letters to several DTC genomics firms in May requesting information about their services after one such firm, Pathway Genomics, announced plans to expand marketing of saliva sample collection kits for its genetic tests from the Web to retail pharmacies (PGx Reporter 05/26/10).

However, it seems the committee and its Subcommittee on Oversight and Investigations has been scrutinizing the consumer genomics industry since at least March 2009, when they asked the Government Accountability Office to investigate the nascent field due to worries that these companies' marketing practices could potentially harm consumers.

At the meeting this week, the GAO released findings from a year-long investigation into 15 DTC genetics firms — which included purchasing tests from 23andMe, Pathway, Navigenics, and Decode — and reported that the results were "misleading and of little or no practical use."

While Congress has been looking into DTC marketing of genetic tests, the FDA has been working to expand its oversight of laboratory-developed tests, which it believes are being increasingly marketed like in vitro diagnostics. Ahead of the congressional hearing, the agency held a two-day meeting on its stated intent to regulate LDTs, previously under the regulatory purview of the Centers for Medicare and Medicaid Services. At this meeting, stakeholders discussed how DTC firms might fit into FDA's overall regulatory framework (PGx Reporter 07/21/10).

DTC genomics firms Pathway, Navigenics, and 23andMe, asked to testify at the congressional hearing, invited federal regulators to standardize certain aspects of their business — particularly clinical validation of gene markers that are used in genetic analyses — but argued that regulation shouldn't be so restrictive as to bar consumer access to personal genomic information from a research and educational standpoint.

At the hearing, Jeff Shuren, director of FDA's Center for Devices and Radiological Health, acknowledged that regulation for this industry has been a long time coming. "If there is any issue with the FDA, and I'll say it here … it was why didn't we act sooner, and we should have acted sooner," Shuren admitted to the committee.

After Pathway's attempt to move from online sales to store shelves, FDA sent letters to Pathway, 23andMe, Decode, Navigenics, Knome, and Illumina, inviting them to discuss their services with the agency. In those letters, the agency informed some of the firms that their gene scans appeared to be medical devices requiring FDA clearance or approval (PGx Reporter 06/16/10). This week the agency again sent similar letters to 14 genetic testing firms.

During the hearing, committee members — several of them former physicians or currently practicing doctors — expressed alarm at the findings of the GAO report, which showed that not only were the genetic interpretations between DTC firms markedly different, but also that the companies' customer representatives provided GAO's fictitious customers with incorrect information about their risk profiles and advice that violated company privacy policies.

Donna Christensen, a Democratic congresswoman representing the Virgin Islands — where she served as an emergency room physician and then rose to the position of Acting Commissioner of Health for the territory — found it alarming that although many of the SNPs used for genetic interpretations by these companies aren't relevant to non-Caucasian ethnic populations, the firms did not display this information prominently on their websites, and still charged minorities for services without telling them that the risk interpretations may not be relevant to them.

Phil Gingrey, a Republican congressman from Georgia and a former obstetrician/gynecologist, worried that the marketing practices of DTC firms could have harmful effects on the public. "You've got a lot of hypochondriacs out there and we're going to make maniacs out of them," Gingrey said. Based on these genetic test results, "people may make the wrong decision … or a snap decision." Speaking to this concern, representatives from DTC genomics firms countered that there was no evidence to suggest that consumers would make rash decisions based on genomic data.

Republican Congressman from Texas Michael Burgess, also a physician for 30 years, urged FDA to keep up with the science. "This science has evolved so rapidly … is the FDA ready for what's coming?" he asked, noting the need for an infusion of money in the FDA's budget to regulate the influx of genetic tests.

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Out-of-the-Box Approach

The FDA had been in discussions with several DTC companies years before the agency took any action against them. For example, 23andMe Counsel Ashley Gould told the committee that 23andMe's first contact with the FDA was in 2007, a year before the company launched its service. After the company began operations in 2008, 23andMe employees met with then FDA Commissioner Andrew von Eschenbach, and "he encouraged us to proceed," Gould said.

According to Shuren, although the FDA observed these companies making increasingly risky claims to consumers, regulatory action was delayed as the agency tried to figure out whether consumer genomics firms fell under its practice of "enforcement discretion."

Additionally, President Obama's election brought in a new administration and new appointees to government agencies, among them HHS. Over the past two years, the FDA has undergone significant changes in personnel and policies, which has further delayed the agency's move to complete certain regulatory initiatives it has been working on for several years, particularly the regulation of LDTs.

Currently a two-pronged regulatory pathway exists for genetic tests. LDTs are commonly licensed under CMS' Clinical Laboratory Improvement Amendment. The FDA reviews and clears genetic test kits and some high-risk LDTs, but practices enforcement discretion over the majority of low-risk LDTs. The agency indicated for some time that it intended to regulate certain high-risk LDTs, but now with the exponential growth of genetic testing, the agency instead decided to lift its three-decade long practice of "enforcement discretion" over this subset of tests.

As a result, the agency's entire regulatory approach is in flux as it considers a number of options amid limited resources. At FDA's meeting on its oversight of LDTs this week, the agency presented several ideas for a new regulatory paradigm encompassing IVDs, LDTs, and genetic tests marketed directly to consumers.

As FDA considers input from stakeholders, the agency is considering downgrading the risk classification of certain regulated tests; phasing in regulation of LDTs that aren't currently regulated; collaborating with the National Institutes of Health's genetic testing registry to take stock of all marketed tests; and enlisting the help of third-party inspectors.

While DTC firms at the congressional hearing seemed willing to participate in a genetic testing registry, most company representatives in attendance suggested that FDA's regulatory policies for IVDs and LDTs should not necessarily extend to DTC firms. They noted that their business models needed guidelines specific to the industry, otherwise over-regulation could put many of them out of business, stifling the potential of these services to advance the incorporation of genomic medicine into healthcare.

"We're at the dawn of an era of personalized medicine," Navigenics CEO Vance Vanier said. "We're all small businesses here … and venture capital-funded," he said, adding that Navigenics has lost money every year that it has been in operation. Vanier urged FDA to institute regulations to the industry with a "deft hand" that protects public health while promoting innovation.

Pathway Genomics' Chief Scientific Officer David Becker said that under FDA's current system, "getting approval for all these tests [offered at a single DTC firm] could take a very long time."

According to Shuren, FDA is considering guidelines that would address the unique features of the DTC genomics industry. "We need an out-of-the-box approach" for DTC genetic firms, Shuren told the committee.

He suggested that one way to reduce the time required for regulatory review of multiple markers would be to review a subset of markers that these companies test for. "If they can show that they're accurate for a subset of genes, then we'd trust them on the rest," and DTC firms wouldn't have to get approval for every gene, Shuren said.

Furthermore, he noted that FDA might tell some of these companies that they cannot market directly to consumers and would have to go through doctors. However, even if FDA decides to allow these firms to keep operating under the DTC model, the involvement of genetic counselors in advising and counseling customers would likely be mandatory.

Industry observers have suggested that DTC genomics firms will require not only a new body of standards with regard to clinical validity of markers, privacy protections, and marketing, but perhaps also a new set of risk classifications. Currently, a test can be a Class I low-risk device requiring no premarket review; a Class II moderate-risk test that requires 510(k) clearance; or a Class III high-risk device requiring premarket approval. Shuren told the committee that most tests marketed by DTC firms would be considered Class II or Class III devices.

Although everyone that testified agreed that DTC genomics firms need some form of regulation and guidance from federal authorities, there was recognition that the problems identified by the GAO weren't due to intentional malice on the part of these firms. Gregory Kutz, managing director of forensic audits and special investigations at the GAO, acknowledged that the four DTC firms the GAO investigated were not intentionally attempting to deceive the public. "I think they believe what they're doing is good," he said.

'Regulation Isn't Proscription'

Several committee members challenged industry representatives' assertion that regulation would automatically stifle innovation. James Evans, genetics professor at the University of North Carolina, Chapel Hill, said in his testimony to the committee that "regulation doesn't necessarily mean proscription" for the DTC genomics industry.

According to Evans, the GAO's finding that customers received conflicting disease risk estimates from four firms points to the need for the regulatory oversight of the clinical validity of DTC services. "The gap between claims and reality should be closed," Evans said, agreeing with the GAO report that the information garnered through these companies is "of little or no use."

"It is dangerous to allow the conflation of entertainment to medicine," Evans said.

Noting that "smart regulation can enable innovation," Shuren told the committee that the lack of oversight in the DTC space has given IVD manufacturers a "disincentive" to become players in the DTC space.

Congressman Bob Latta, a Republican from Ohio, expressed the view that if the DTC firms represented at the hearing were to disappear tomorrow, "then it wouldn't impact our ability to advance genomics."

However, the rapid growth of DTC genomics firms in the short time that they've been in existence – not just in terms of number of customers they have but also in the many research partnerships they've inked – suggests that if direct access to testing were summarily revoked by regulatory authorities, it might dampen the empowerment many customers feel in gaining access to their own genetic data and could cut off the potential of patient-guided research. It is worth noting that DTC firms have been successful at building large online consumer communities interested in becoming partners in genomic research efforts for serious illnesses.

For example, with a total of 50,000 customers, 23andMe has said that its internal pipeline runs hundreds of genome-wide association studies nightly to generate updated statistics. Furthermore, the company's research project on Parkinson's disease has around 4,000 participants.

Even the FDA has said that it is interested in using DTC genomics firm's genomic databases to conduct post-marketing surveillance for drugs. Lawrence Lesko, director of FDA’s Office of Clinical Pharmacology, said in 2008 that the agency was beginning to have preliminary discussions with some undisclosed personal genomics firms “to evaluate the feasibility” of forging such alliances (PGx Reporter 11/19/08).

In the end, committee members asked representatives from Pathway, Navigenics, and 23andMe whether the firms would cease marketing their services to consumers while the FDA figures out its regulatory strategy for the industry. While none of the industry officials thought that was such a good idea, at least two of the firms have at least distanced themselves from the DTC model during this period of intense scrutiny.

Pathway's Becker said it has stopped its DTC service after it received its letter from the FDA, but is marketing its service through wellness programs and doctors. The company's website now only offers customers the option to get a test kit through a physician.

Navigenics' website has also removed the option for customers to order test kits directly online. It now offers instructions to customers about how to order tests through doctors and wellness programs as well.

23andMe is still offering its service under the DTC model. According to Gould, while the company has requested that the FDA and the National Institutes of Health come up with standards for the industry, it doesn't feel that revoking the DTC model is the right strategy. Then, she reiterated the company's steadfast belief that "every person has a right to their genomic data."

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