This article was updated on Oct. 17 to note that Rep. Burgess has introduced the bill and to indicate that the legislation has support from two large laboratories. Originally published Oct. 14.
By Turna Ray
Legislation seeking to keep regulation of laboratory-developed tests under the purview of the Centers for Medicare & Medicaid Services is taking shape under the leadership of Texas Congressman Michael Burgess and so far has the support of certain laboratory industry stakeholders.
Burgess's office recently introduced a bill, called the "Modernizing Laboratory Test Standards for Patients Act," which would amend the Public Health Service Act to establish a notification and review process for tests developed and used within a single laboratory. Specifically, HR 3207 would expand CMS's regulatory authority by granting it the ability to assess whether marketed LDTs are "clinically valid" in that they can accurately measure or predict disease. Currently, under the Clinical Laboratory Improvement Amendments, CMS can only certify that tests performed in a lab are "analytically valid," or can measure the analytes or substances that they were developed to measure.
In addition to placing LDTs fully under CMS' purview, the bill would also mandate that the agency oversee direct-to-consumer testing firms – such as Mountain View, Calif.-based 23andMe – that work with external labs to analyze customer saliva samples and deliver genetic test results to consumers without the involvement of a doctor.
The Burgess bill is in response to the US Food and Drug Administration's intention to lift its longstanding practice of "enforcement discretion" over LDTs, which for more than 30 years have been regulated under CMS' Clinical Laboratory Improvement Amendments. Noticing that LDTs were increasing in complexity, being developed at multiple diagnostic and lab partners as opposed to a single lab, and being broadly marketed, the FDA determined last year that such tests should have to meet its regulations commensurate with the risk they pose to the public health.
As far as consumer genetics firms are concerned, after Pathway Genomics last year tried to expand its online DTC genetic testing business into brick-and-mortar stores by selling saliva collection kits at Walgreens and CVS, the FDA sent letters to Pathway and several other firms with similar business models, asking them to discuss the regulatory status of their testing services with the agency (PGx Reporter 5/19/2010). The agency hasn't yet released any guidance on DTC marketing of genetic tests.
The FDA has said, however, that it is working on releasing a series of guidelines to lay out its regulatory plan for LDTs (PGx Reporter 9/7/2011). Meanwhile, lab groups such as the American Clinical Laboratory Association, concerned that the regulatory changes taking place at the FDA may hinder the industry's ability to contribute to healthcare advances, have launched a counter-effort seeking statutory changes from Congress that would keep LDTs under CMS oversight.
An ACLA official told PGx Reporter this week that the organization supports the Burgess bill.
The aim of the bill, according to Burgess, is to keep regulation of LDTs from "falling into the lap" of the FDA. Requiring FDA approval or clearance for LDTs "would make the process ever so much more complex, and would make it more difficult to get the approval of [such tests]," Burgess told PGx Reporter this week.
Before becoming the Republican congressman for Texas' 26th district in 2003, Burgess was a practicing OB/GYN for 30 years. "Speaking as someone who has spent years in clinical medicine, some of the things that are out there are truly fantastic and I welcome the day that they will be available. I worry that if we leave them to the tender mercies of the FDA that they will never be here," he said.
Burgess introduced the bill on Oct. 14., with a statement that the legislation seeks to "protect jobs and foster innovation for patients." HR 3207 has been referred to the House Committee on Energy and Commerce.
Currently, there are three Republican co-sponsors to HR 3207, Marsha Blackburn of Tennessee, Robert Latta of Ohio, and Erik Paulsen of Minnesota. Burgess told PGx Reporter he would like to secure bipartisan support for the bill, and is currently seeking a cosponsor from across the aisle.
Two of the largest LDT developers in the US, the Laboratory Corporation of America and Quest Diagnostics, issued statements of support for Burgess's bill, noting that passing the legislation would help modernize CMS oversight and foster innovation in the lab testing sector. LabCorp employs 2,500 employees in Texas, and Quest employs 860 people in the state.
Increasing CMS's Regulatory Muscle
Although FDA is working to craft regulation for LDTs through guidances, Burgess's bill seeks to render those efforts moot by amending the Food, Drug, and Cosmetic Act to exclude LDTs and DTC DNA tests from the agency's definition of "device."
"Bear in mind these are tests. These are not drugs, these are not devices. These are tests designed to guide diagnosis," Burgess said. This legal distinction separating tests performed at labs from devices overseen by the FDA is a move that ACLA particularly agrees with.
The lab industry advocacy organization disclosed earlier this year that it was working with Congress to seek statutory changes regarding LDT oversight (PGx Reporter 5/4/2011). The Burgess bill "is very consistent with the CLIA-centric approach and that's certainly something that we have been suggesting as a better approach than to have both FDA and CMS be responsible for the oversight of LDTs," David Mongillo, ACLA's vice president for policy and regulatory affairs, said this week.
The FDA has said that it will work with CMS to craft its LDT regulations and ensure that test developers don't have overlapping or conflicting commitments for the two agencies. But instead of requiring developers to appease two agencies, Burgess's bill attempts to keep regulation of LDTs where it has traditionally been — with CMS — but expand the agency's authority to address the changes in the industry.
To help keep track of new tests that come on the market, the bill would require LDT developers and DTC genetic testing firms to submit information to a registry about the analytical and clinical validity of their tests, as well as note whether the test has been reviewed by CMS. Following this listing, consumer genetic firms and labs must submit a premarket notification to CMS about the claimed use and the clinical validity of the test, and the agency will have 90 days to issue a decision.
After the initial review, if the evidence submitted about a test is deemed insufficient by the agency, then the sponsor may submit a supplemental application to fill in the missing data. If the data does not support the clinical validity claims, then the agency can order the sponsor to cease marketing the test.
It is worth noting that sponsors are allowed to market the test during this notification and review process, according to the bill's current language. Additionally, if the agency fails to meet its 90-day notification deadline, the test is automatically deemed to have marketing authorization from CMS.
Furthermore, sponsors can appeal a negative marketing authorization decision from CMS. The bill provides for a panel review process or adjudication by a judge to resolve such regulatory disagreements.
The bill also requires sponsors to keep records of and report to CMS adverse events that patients may experience as a result of test errors or limitations. CMS can impose sanctions on labs, or suspend or revoke their CLIA certificate for violating regulations. The agency can also hire third-party reviewers to conduct this review, and can promulgate rules for expedited reviews of LDTs for rare diseases or for emergency use of infectious disease tests.
Making Room For Companion LDTs
Burgess' bill would allow test developers to market LDTs as companion diagnostics tied to specific drugs, essentially unraveling the regulatory criteria and definitions that the FDA has been moving toward for such tests.
The bill would allow a test developer to claim that an LDT is a "companion diagnostic test" intended to be used for "specifying the use of a drug or biological product for therapeutic purposes." More specifically, an LDT companion diagnostic would be reviewed by CMS, and not by the FDA.
In its draft companion diagnostics guidance issued in July, the FDA defined an IVD companion test as a diagnostic device that "could be essential for the safe and effective use of a corresponding therapeutic product." The ideal situation described by the FDA in the draft guidance is one in which the drug and its companion test are simultaneously reviewed and approved by the agency's relevant centers, although the agency acknowledges that other scenarios may arise where an LDT may be used under CLIA (PGx Reporter 7/13/2011).
Putting its regulations to work, the agency simultaneously green-lighted drug/test combination products twice over the summer: Roche/Plexxikon's melanoma drug Zelboraf for BRAF-mutated patients and Roche's Cobas 4800 BRAF V600 Mutation Test were approved on Aug. 17 and Pfizer's Xalkori for non-small cell lung cancer drug patients with ALK mutations and Abbott Molecular's Vysis ALK Break Apart Fluorescence In Situ Hybridization Probe Kit were approved on Aug. 26.
There are plenty of labs offering ALK and BRAF mutation tests under CLIA, and as long as FDA is practicing enforcement discretion over LDTs, those types of LDTs can remain on the market alongside FDA-approved companion tests. However, the way FDA is currently enforcing its regulations, labs that wish to specifically market such tests as companion diagnostics tied to particular drugs must gain FDA's OK, which would require clinical validation of those tests in trials using samples from patients treated with the drugs.
Under the Burgess bill, if clinical validation requirements for companion LDTs become the responsibility of CMS, it is unclear how closely those regulations would track with FDA guidelines for establishing the validity of companion IVDs.
FDA regulation of companion diagnostics has to do primarily with the intended use of the test in relation to the drug, and not whether the tests are intended to be performed at a single lab or by multiple entities. Meanwhile, the Burgess bill would essentially establish a different regulatory path for LDT companion tests, which are developed and performed at a single lab or labs owned by one entity.
Drug developers have generally supported FDA approval for companion diagnostics, since this provides added assurance that the test can indeed pick put which patients should receive their drugs. In 2008, Genentech petitioned the FDA to regulate all predictive laboratory-developed tests, noting that the agency's “inconsistent” regulatory oversight encouraged the development of tests "that make unsubstantiated, and therefore possibly inaccurate or misleading claims intending to guide both the treatment and payment decisions made by healthcare providers and payors" (PGx Reporter 12/28/2008).
Many drug developers and diagnostics firms who had invested in gaining FDA approval for their test kits supported Genentech's petition, but whether drug developers would be in favor of CMS-regulated LDT companion tests is uncertain. The proposed legislation would likely add a layer of complexity to companion diagnostic development, since drugmakers would then have to coordinate approval of the drug with the FDA and marketing authorization of the test with CMS.
On the other hand, if CMS' clinical validity standards for companion LDTs developed under the Burgess bill are viewed by pharma to be rigorous enough to provide sufficient assurance of their safety and efficacy, then there may be an upside for drug developers. Under that scenario, drugmakers would be able to gain access to validated tests, partner with labs with broad distribution channels, and could avoid the more costly FDA approval process for diagnostics.
Federal Regulation Without Taxpayer Funding
The changes to CMS' authority proposed by this bill would grow the agency's regulatory responsibilities, but the legislation doesn't include any provisions for increasing CMS' budget. Instead, the notification and review process, as well as the test registry activities and lab inspections, would be funded entirely with user fees from industry.
"The [lab] industry is very supportive of that approach," Burgess said.
Labs already pay some user fees to CMS and FDA's device reviews are funded in part by user fees and congressional appropriations. If FDA decides to lift enforcement discretion over LDTs, labs will have to pay user fees to both FDA and to CMS.
ACLA has indicated that its members would rather pay higher user fees to CMS than pay user fees to two government regulatory agencies. However, it's unclear whether CMS would be willing to take on the additional regulatory responsibilities the Burgess bill would place under its aegis.
A CMS spokesperson told PGx Reporter that the agency has not taken a position on Burgess's draft bill and has no comment at this time. CMS also hasn't objected openly to FDA's decision to regulate LDTs. This, to some industry observers, signals that CMS may not be too excited about a plan that would add to its workload but wouldn't increase its congressionally appropriated budget.
The agency has already seen an exponential growth in its responsibilities under the healthcare reform law. As a result, in its FY2012 budget request, CMS estimated budgetary requirements of $507 billion, an increase of $20 billion over the FY 2011 estimate.
On Sept. 20, a Senate subcommittee appropriated discretionary funds to certain HHS programs and agencies, including $4 billion for CMS operations, an increase from the 2011 level of $3.6 billion. "Additional funding is needed to continue implementation of the Patient Protection and Affordable Care Act and to accommodate an increase in the Medicare population," the Senate Committee on Appropriations said in a release.
Burgess maintained that the implementation of the provisions in his bill would not require any increases to CMS' budget, which may be viewed favorably by fiscal conservatives in Congress.
This fact may give the bill a better chance than other legislation that has been proposed to address the LDT issue, such as Republican Senator Orrin Hatch's "Better Evaluation and Treatment Through Essential Regulatory Reform for Patient Care Act," or BETTER, act, which seeks to create a single regulatory path under the FDA for IVDs and LDTs (PGx Reporter 7/6/2011). Legislative experts have predicted that BETTER has a slim chance of being introduced in the current Congress since it would be viewed as a "big government" bill.
In Burgess, lab industry stakeholders opposing FDA regulation have found the best kind of ally, a congressman who is not just a supporter of limited government but can back his policy leanings with his experience as a healthcare professional. Burgess is founder and chairman of the Congressional Healthcare Caucus, a group of Republican congressman who seek to "advance reforms that reduce costs, increase patient control, expand choice, promote cures."
The Texas congressman has been a supporter of limited federal spending and a vocal critic of the FDA. At a July hearing this year held by a House Energy and Commerce subcommittee to investigate whether FDA regulations were holding back medical device innovations, Burgess questioned Jeff Shuren, director of FDA's Center for Device and Radiological Health, as to whether the agency's policies were "causing the US to lose its competitive edge."
According to Burgess, one of the reasons the draft bill includes DTC genetic testing firms under CMS' regulatory purview is because he was convinced after a 2010 congressional hearing on the practices of consumer genomics firms that the FDA was unprepared to oversee this nascent but rapidly growing industry.
In May 2010 Burgess signed a letter — along with House Committee on Energy and Commerce Chairman Henry Waxman, ranking member Joe Barton, and subcommittee chairman Bart Stupak — asking 23andMe, Pathway Genomics, and Navigenics to provide data on the accuracy of the genetic tests they were marketing directly to consumers (PGx Reporter 5/26/2010).
At the hearing held two months later, Burgess urged FDA to keep up with scientific advances in the field (PGx Reporter 7/28/2010). "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 agency's budget to regulate the influx of genetic tests.
Characterizing DTC genomics firms as the "future of medicine," he told PGx Reporter this week that at least one consumer genetics firm had provided input on the bill. 23andMe could not answer questions regarding this bill before press time. Pathway Genomics, which has moved away from the DTC model since facing regulatory action last year, did not return a request for an interview.
"Going back to that hearing, and we were the minority at that time, clearly the FDA was not doing its job as intended and there were some problems that were occurring," he recalled. "So, let's leave the testing where it belongs and that's with [CMS'] CLIA, which already regulates clinical labs and they're the ones with the expertise."
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