Combination Product Groups Calls For New FDA Policy on IVDs, LDTs

The Food and Drug Administration (FDA) needs to take action and make a decision on whether it has the authority to regulate laboratory-developed tests (LDTs) as medical devices, a group representing manufacturers of combination products said in a recent letter to the agency. The Combination Products Coalition (CPC) May 15 told the FDA it needs to make a decision about regulating LDTs and in vitro diagnostics (IVDs). According to the letter, the FDA’s approach to lab-developed tests and the FDA’s approach to IVDs can’t both be correct. Either the federal government is dramatically overregulating IVDs or underregulating lab-developed tests, or both, the group said. The group called on the FDA to create a single regulatory system for both IVDs and LDTs. LDTs are in vitro assays that clinical laboratories develop as testing services according to their own procedures. These tests are often created in response to unmet clinical needs and are commonly used for early and precise diagnosis, monitoring, and guiding patient treatment. LDTs are regulated under the Clinical Laboratory Improvement Amendments by the Centers for Medicare and Medicaid Services. “FDA must act now because the ‘dual system’ of regulation for IVDs and LDTs does a disservice to patients. The IVD and LDT regulatory systems cannot both be right. There is no way that the two systems can provide equivalent benefits to the public health. If extensive FDA regulation is necessary to ensure the safety and effectiveness of IVDs, then FDA must regulate LDTs. On the other hand, if FDA regulation is unnecessary, the amount of waste caused by compliance with unnecessary FDA requirements is harming the public health by limiting resources for innovation,” the letter said. The FDA regulates diagnostic tests only if they are developed and sold by device manufacturers as diagnostic kits, regardless of whether they were developed by clinical laboratory companies for in-house testing or by manufacturers for use in kits. The lab tests that companies develop internally generally aren’t subject to FDA review. “FDA has not only the authority, but the obligation, to create a single regulatory framework for in vitro diagnostics, one where regulations depend on the risks and benefits of the test and not who makes them or where they are made,” the CPC letter said. ‘Frustration’ at Delay Bradley Merrill Thompson, an attorney with Epstein Becker & Green PC in Washington and general counsel to the CPC, says the group decided to act because it appeared that all IVD- and LDT-related efforts at the FDA “have ground to a halt.” Thompson said, “We’ve been waiting and waiting for a [final] guidance on companion diagnostics. Our understanding is that it’s being held up” at the White House Office of Management and Budget because of unresolved concerns about LDT regulation. The CPC letter calls on the guidance to be released and for other agencies to “step aside” if they are holding up its release. Sending a letter “was the best approach we could think of. It’s pure and simple frustration. I don’t see how this gets resolved without FDA being more bold” about making a decision, Thompson said. The CPC letter acknowledged the FDA isn’t alone in making LDT regulatory decisions. “Other agencies within the Executive Branch have been playing a significant role in the decision to maintain the status quo,” the letter said. “Therefore, we also ask that the rest of the Obama Administration—the Office of Management and Budget, the Centers for Medicare and Medicaid Services, the Department of Health and Human Services, and others—all offer their support for equal regulation either by endorsing this effort, or not standing in the way of addressing this problem. Unequal regulation has existed for far too long.” According to the letter, “there is an optimal system for regulation that balances oversight of IVD manufacturing with flexibility that allows for innovation. Striking the right balance is crucial to the public health.” According to the CPC, the current system doesn’t offer balance “but treats two indistinguishable products—LDTs and IVDs—completely differently, and imposes a number of extra requirements on IVDs beyond those for LDTs.” The CPC’s letter asks the FDA to respond to a citizen petition filed in June 2013 by the American Clinical Laboratory Association (ACLA) that challenged the FDA’s authority to regulate LDTs as medical devices. ACLA requested that the FDA refrain from issuing any guidance or rules (draft or final) that would regulate LDTs as devices. It also asked that the FDA confirm LDTs aren’t medical devices. According to the CPC, the FDA responded in November 2013 that it “has been unable to reach a decision on [the] petition because it raises issues requiring further review and analysis by agency officials” and to date hasn’t provided a “fulsome response” to the petition. Thompson said the CPC letter builds on the efforts of the citizen petition but is also different. According to the letter, ACLA’s petition asks the FDA to refrain from regulating LDTs. According to the CPC, the FDA has “unquestionable” authority to regulate LDTs as devices. ACLA’s request “misses the real issue, which is whether FDA should regulate LDTs and IVDs equally.” The combination products group in the letter said it is “understandable that laboratories would fight FDA regulation” because of the rising burden regulations have placed on manufacturers. None of the industry arguments, however, support dual regulatory systems, the letter said. Call for Action Thompson said nothing can be done about the regulations without Congress getting involved, but as a minimum first step, he said the agency needs to act and come out with a policy. “Then we can have a discussion with Congress, get everyone talking,” Thompson said. “I want to have a debate. I’m convinced that once the debate starts, we will get somewhere. It all starts with FDA. FDA can’t walk around wringing its hands. Doing nothing can’t be good for patients. There’s no way the current system puts patients first.” The CPC in the letter said it understands that the FDA has drafted three guidance documents describing how it would propose to regulate LDTs, “so releasing those is the best way to quickly move the discussion forward.” Takeaway: Groups representing clinical laboratories and IVD manufacturers are at odds over whether the Food and Drug Administration should regulate lab-developed tests the same as IVDs. While lab groups would like the FDA to refrain from regulating LDTs, IVD groups believe LDTs should be regulated the same as IVDs. FDA action on this front appears to have stalled.