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A House Subcommittee plans to take up draft legislation at a hearing next month that brings together test kits and lab-developed tests into a new regulatory category. The proposal offers many ways for tests to avoid a “high-risk” classification. “The Gray Sheet” compares the provisions to recent proposals vetted in the Senate.


The House Energy and Commerce Health Subcommittee will consider a legislative discussion draft to establish new regulated medical product category of in vitro clinical tests to counter FDA’s proposed laboratory developed test (LDT) framework at a Nov. 17 hearing.


The draft contains provisions intended to limit the number of tests, including test kits, that are labeled as “high risk." It also proposes that FDA establish a separate center to regulate IVCTs.


The draft looks like a more fully-developed proposal set out by a coalition of test kit makers and laboratories called the Diagnostic Test Working Group earlier this year. The IVCT proposal is intended to address the concerns of laboratories, which say FDA’s proposed LDT framework is an overreach, while also responding to calls by diagnostic test-kit manufacturers for a level regulatory playing field for all assays sold to and developed by labs.


Although legislation is being considered, Senate and House staffers signaled last month that Congress is willing to wait for FDA’s final guidance on LDTs, before making any changes. (See (Also see "Congress Will Not Tinker With FDA LDT Guidance Before Final, Staffers Indicate" - Medtech Insight, 10 Sep, 2015.).) FDA officials affirmed this week at the Regulatory Affairs Professionals Society annual meeting in Baltimore that the agency plans to finalize its guidance documents establishing an oversight framework for LDTs in 2016. (See (Also see "FDA Plan To Regulate LDTs Includes Long Phase-In, Unmet-Need Exceptions" - Medtech Insight, 31 Jul, 2014.).)


It's not yet clear if diagnostics reform legislation as proposed in the latest discussion draft, might be included in some version of the previously passed House 21st Century Cures legislation after it is aligned with a Senate medical innovation bill that could come out by next year.


Draft legislative language providing alternative plans for regulation of diagnostics and laboratory operations, with shared roles for FDA, the Centers for Medicare and Medicaid Services, and state governments, are also being vetted by the Senate’s Health, Education, Labor and Pensions Committee in. One proposal circulating is the draft developed by the Diagnostic Test Working Group that would cover rules for both in vitro diagnostic kits and LDTs. (see (Also see "Senators Circulate Plan For Standalone FDA Diagnostics Center, ‘In Vitro Clinical Test’ Rules" - Medtech Insight, 16 Jun, 2015.)). A separate proposal is backed by the Association for Molecular Pathology. (See (Also see "Molecular Pathologists Propose Third-Party Review Of High-Risk Dx In Alternative To FDA LDT Plan" - Medtech Insight, 21 Aug, 2015.).)


Burden Of Proof On FDA For "High-Risk" Classification


The proposed House legislation provides several options for existing and new laboratory tests to avoid being classified as high risk products that would require tougher regulations than moderate-risk or low-risk tests. Under the proposal, moderate-risk tests could be cleared for marketing by an accredited third-party reviewer that the lab selects and pays for, rather than undergoing direct agency scrutiny. To gain moderate-risk status, a lab or test manufacturer could employ or point to risk-mitigation measures for its diagnostic, submit a request for reclassification into a lower class, or appeal a high-risk classification decision to an advisory panel, and the onus would be on FDA to prove that a high risk classification is warranted.


If, for example, a laboratory can provide a risk mitigation factor for what might otherwise be considered a “high-risk test”, such as that clinical use of the test is well characterized, or other tests are available to diagnose the target disease, it could be called a moderate-risk test.


If the IVCT has never been classified by FDA previously, a laboratory could submit a classification request to place it in a moderate- or low-risk class, and the agency would only have 60 days to make up its mind on classification. If the agency does not make a swift-enough decision to place it in a high-risk class, than it must publish an order rejecting, modifying or accepting the classification.


The draft sets a lower bar for FDA to accept a laboratory or lab-test manufacturer’s proposed low- or moderate-risk classification than if it wanted to modify or reject a reclassification request. If FDA wants to reject or modify a laboratory’s proposed moderate- or low-risk-classification, it would have to explain the reason for its objections, and say why the explanations provided by the laboratory do not support a lower classification.


Further, a laboratory would be able to request review of a recommended classification by an advisory panel within 180 days of FDA’s decision to reject or modify the lab’s proposed moderate- or low-risk classification request. Such advisory panels would have to include “a balanced representation of interested persons representing physicians, consumers and the in vitro clinical test manufacturing and laboratory industries.”


Also, if FDA failed to make a final determination about a test’s classification 90 days after the advisory panel’s recommendation, “it shall be presumed that the classification recommended by the advisory panel is the final classification” and the agency would have to post that decision as final, or “rebut such presumption using scientific evidence,” according to the draft. Such rebuttals would have to include “a public health justification demonstrating the need for upclassification,” the discussion draft says.


A section in the House discussion draft on “prevention of upclassification” instructs FDA how to add mitigation measures to a test to avoid a “high-risk” classification.


In separate sections of the discussion draft, labeled “prevention of upclassification” and “upclassification”, respectively, the draft lays out a process for FDA to add mitigation measures during a review to prevent an IVCT’s upclassification, and prevents any FDA employee or official except the chief scientific officer or other FDA IVCT Center senior manager from generating an upclassification order.


If FDA proposed a high-risk classification for an IVCT, the laboratory or manufacturer sponsoring it would rarely or never have to perform a clinical trial to provide valid scientific evidence to support its clearance or approval. Sponsors can claim that an FDA requirement for additional data collection would provide a negative “impact on innovation” – or use any other of 15 factors the discussion draft lists and sponsors can draw upon to limit their collection of data in support of a test approval application.


Comparison Shows Diagnostic Proposal Differences

Several legislative drafts are circulating to reform regulations of diagnostic in lieu of FDA's LDT proposal. In addition to the latest House discussion draft, two other proposals have been vetted by the Senate Health, Education and Labor Committee. Those include the Diagnostic Test Working Group (DTWG) IVCT proposal, detailed in a March 5 white paper endorsed by test kit makers Becton Dickinson & Co. and Roche, and laboratories including Mayo Clinic, Laboratory Corp. of America Holdings and ARUP Laboratories, and a proposal backed by the Association for Molecular Pathology (AMP).


The three packages are compared in "The Gray Sheet" analysis below.






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