As the US Food and Drug Administration continues considering how it wants to handle in vitro diagnostic multivariate index assays, two bills recently introduced in the US Senate could further muddy the waters.
Last month, Senators Barack Obama (D-Ill.) and Edward Kennedy (D-Mass.) introduced separate bills that, if enacted, would directly impact the FDA’s ability to regulate IVDMIAs.
While both could give the FDA greater regulatory oversight over such tests, which use algorithms to interpret gene and protein data, Obama’s, which was originally introduced last August, could also reduce the agency’s regulatory control over such tests by giving the US Health and Human Services Secretary the power to chose between the agency and the Centers for Medicare and Medicaid Services.
Kennedy’s bill, called the “Laboratory Test Improvement Act,” pertains to all laboratory-developed tests, while Obama’s proposal, the “Genomics and Personalized Medicine Act of 2007” would apply to DNA- and protein-based tests.
Both bills are currently in the Senate’s Health, Education, Labor, and Pensions committee and not yet scheduled for action.
A spokeswoman for the FDA declined to comment saying it was agency policy not to talk about pending legislation.
Of the two bills, Kennedy’s explicitly gives the FDA jurisdiction over IVDMIAs by deeming such tests medical devices, which have always been regulated by the FDA. At the moment, IVDMIAs are performed as homebrew tests under Clinical Laboratory Improvement Amendments.
Under Kennedy’s proposal, the FDA would be given the authority to regulate a laboratory-developed test with “a low, medium, or high degree of oversight depending on the particular test,” said Gail Javitt, the law and policy director at the Genetics and Public Policy Center at Johns Hopkins University, in an e-mail to ProteoMonitor this week.
While most IVDMIAs would be classified as Class II devices requiring 510(k) pre-market approval, some could be given Class I status. The manufacturers of those tests would, however, be required to provide the HHS with information about the analytical and clinical validity of the test.
Such information would to be compiled in a database and made publicly available on the FDA’s website.
If the HHS reviews the information for a test and determines that it does not adequately demonstrate the analytical or clinical validity of the test or of an equivalent test that has already received pre-market approval, or if it is a direct-to-consumer test, HHS would notify the manufacturer, which would be given time to make necessary corrections.
If the maker doesn’t make the proposed changes within a set amount of time, the test would then be subject to either Class II status, which would necessitate a 510(k) pre-market review, or Class III status, which would require full approval by the FDA.
In contrast, Obama’s bill gives the HHS Secretary sole discretion to determine whether the FDA or CMS, by way of the Clinical Laboratory Improvement Amendments regulations, would have jurisdiction over the IVDMIAs.
His proposal would call for the Institute of Medicine to conduct a study and report recommendations to the HHS Secretary “to improve Federal oversight and regulation of genetic tests,” including IVDMIAs.
That includes recommending how genetic tests should be classified; which category of test would require a review, and the level of review; and what agencies would oversee the review process.
When determining the level of review for a test, HHS would consider factors such as intended use of the test, the disease it is targeting, and its potential to help or harm a patient.
Furthermore, Obama’s bill calls for HHS to “specify which elements of the test constitute a device that may be regulated by the [FDA] and which elements comprise a service that may be regulated under CLIA.”
Johns Hopkins’ Javitt said Obama’s bill “leaves open the question of whether the FDA would have authority to regulate any genetic tests, including IVDMIAs.”
However, the senator’s office left open the possibility that FDA’s statutory authority over IVDMIAs could increase if it is passed into law.
In an e-mail, a spokesman in Obama’s office said that though the bill does not directly expand the role of the FDA to regulate genetic and protein-based tests, that would be a likely outcome for some tests.
Also unclear is the ability of CMS to regulate IVDMIAs. Under the Kennedy bill, CMS would be required to create a special category for genetic testing, a power CMS already has but has not used.
Obama’s bill “leaves open the question of whether the FDA would have authority to regulate any genetic tests, including IVDMIAs.”
The bill, however, also requires IVDMIA makers to comply with CLIA, which they currently do, a set up that may overlap or contradict some rules. The bill would leave it to the HHS Secretary to address such issues.
Indeed, the bill does not explicitly segregate the responsibilities of the FDA and CMS. In an e-mail, a Kennedy spokeswoman said his office is currently “assessing the proper roles for CMS and FDA.”
Similarly, Obama’s bill directs CMS to create a special category for genetic tests, but just as the FDA’s role in regulating IVDMIAs is unclear under his proposal, Javitt said the HHS Secretary could give CMS — not the FDA — greater authority to regulate such tests.
For now, industry response has been muted. Peter Levine, president of protein biomarker company Correlogic, said he believes Congress needs to become more involved in creating clearer guidelines. He had not reviewed either bill in detail and declined to comment on them.
The Coalition for 21st Century Medicine, formed in February in response to a draft guidance the FDA released last September that defined its intended role in regulating IVDMIAs, has thrown its support behind Obama’s bill but not Kennedy’s.
“We believe [Obama’s bill] strikes the right balance between thoughtful regulation and the importance of encouraging innovation,” said Joe Eyer, a spokesman for the coalition. However, on Kennedy’s bill, Eyer said “we support the important concept of public disclosure of laboratory-developed tests included [in the bill] and look forward to continuing to work with him on the regulatory requirements that would be imposed by the bill.”
In its draft guidance, the FDA said the proliferation of IVDMIAs on the market had raised concerns within the agency about their efficacy and safety. Most IVDMIAs on the market and in development are gene-based, but some are protein-based, including tests by Correlogic and Ciphergen.
Since the agency released the draft, the industry has rallied against it, saying FDA regulation of IVDMIAs would increase R&D costs and stunt innovation. Some have also questioned the agency’s legal authority to regulate such tests [See PM 02/15/07 and 09/14/06].