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Seeking Broader Support, House Committee Moves Dx Regulatory Proposal into Draft Legislation

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NEW YORK (GenomeWeb) – A US House of Representatives committee has incorporated regulatory proposals from a small group of labs and test manufacturers into draft legislation and asked key industry groups to provide input on the document as a potential alternative to US Food and Drug Administration oversight of lab-developed tests (LDTs).

A few months ago, several large players in the clinical lab space came together as the Diagnostic Test Working Group (DTWG) and conceived a regulatory framework for so-called in vitro clinical tests (IVCTs) that spread oversight responsibilities across the FDA, Centers for Medicare & Medicaid Services, and the states. Their proposal placed IVCTs in their own regulatory category, separate from devices and drugs, and defined them as a "finished product or laboratory test protocol" used to analyze human biological samples for medical purposes.

Both LDTs and test kits could be an IVCT, but the proposal would establish FDA's authority over test development and validation, keep CMS in charge of traditional lab activities necessary to perform tests, and maintain state oversight of interpreting test results. Since the FDA issued its controversial draft guidance last year to bring all LDTs under its aegis, the DTWG's ideas have been a welcome compromise for some industry players who say the proposal recognizes the complex environment in which their tests are developed and used.

The DTWG involves Becton Dickinson, Roche, Mayo Clinic, LabCorp, and ARUP Labs. Abbott is also reportedly part of the group, but did not confirm its involvement to GenomeWeb before press time. Representatives from a number of these firms declined to comment for this piece. According to several sources knowledgeable of the goings on in Washington, the working group drafted the proposal hoping it would get incorporated into legislation. But these sources — who declined to be identified given the evolving nature of ongoing discussions — also said that the DTWG's proposal doesn't yet have public backing from key players in the life sciences field.

DTWG had previously presented its proposal to the US Senate Committee on Health, Education, Labor, & Pensions (HELP), as well as to the House Energy & Commerce (E&C) Committee staff. However, the House 21st Century Cures Act — a tome of provisions for improving nearly every conceivable aspect of biomedical research in the US — recently sailed through the committee without any mention of LDT regulation.

The House E&C entertained the idea of addressing LDT regulation in the 21st Century Cures bill, saying it would consider all ideas, and the DTWG sent in its white paper in March. However, the group's ideas weren't incorporated into draft legislative language until after the 21st Century Cures bill passed out of the E&C committee.

Some sources speculated that this happened because regulation of lab tests was too divisive an issue for incorporation into 21st Century Cures, a bill that congressional members like to uphold as one of their few bi-partisan successes. Other experts GenomeWeb spoke to said congressional staff needed to put more work into translating the ideas in the white paper into legislative language.

"21st Century Cures was moving at a very fast pace. Nailing down the specifics of a regulatory fix for LDTs couldn't move at that speed," Amy Miller, executive VP at the Personalized Medicine Coalition, told GenomeWeb. "However, the Senate [HELP committee] might be considering a fix for their companion bill," known as "Innovation for Healthier Americans."

The draft legislation that the House E&C Committee is now shopping around for comment tracks closely with the language and spirit of the DTWG's white paper. The legislation seeks to create a new center under the FDA in charge of regulating IVCTs. It outlines how the intended use of tests map to high-, moderate-, and low-risk classifications; the requirements labs and test manufacturers would have to meet in order to market tests in a particular risk class; when and what types of adverse events to report to the FDA center; and when post-marketing data might be necessary.

The legislation would allow labs and diagnostic developers to submit published data on the clinical and analytical validity of already well-established tests, a somewhat easier evidence bar than the trials that the FDA may ask for. The FDA can request clinical studies, but only with scientific justification, and can ask for a randomized trial as a last resort if the data can't be garnered any other way. There are concessions and exemptions for investigational and research-use tests, as well as diagnostics for rare diseases and unmet needs.

In line with the DTWG's paper, the legislation distinguishes regulation of lab activities from the IVCTs in critical ways. For example, the legislation differentiates lab errors while performing an IVCT (overseen by CMS) from IVCT errors that result in serious patient injuries or death and would have to be reported to the FDA. Although finished test products will require unique identifiers that regulators can use to track how they are used, lab protocols won't need them. And labs' payments to certify their facilities with CMS would be subtracted from user fees to the FDA for reviewing IVCTs.

Nobody has really presented evidence that there is a systemic problem with laboratory testing in the US.

Although the draft legislation would keep CMS overseeing laboratory operations, labs developing and marketing IVCTs would have to contend with FDA regulations under this plan, and according to sources, this may not sit well with certain factions in the testing space that don't want any FDA oversight for LDTs. Public health labs, some smaller academic labs, and pathologists are still holding out for a plan that would keep LDT regulation entirely in the hands of the CMS, under the Clinical Laboratory Improvement Amendments (CLIA), where it has traditionally resided.

The American Medical Association in January provided feedback to the E&C Subcommittee on Health stating that they'd like to see legislation that nullifies FDA's draft LDT guidance; improves LDT regulation through changes to CLIA; reins in FDA's "overreaching" and slow regulation of in vitro diagnostic kits; and allows the agency "limited authority" to regulate direct-to-consumer genetic tests or tests with methodologies that aren't transparent. The AMA did not comment on the DTWG proposal.

Similarly, Roger Klein on behalf of the Association for Molecular Pathology wouldn't comment on the DTWG proposal, but said the organization remains focused on modernizing the 23-year-old CLIA regulations so they can ensure the accuracy of current lab testing methods and services.

"Nobody has really presented evidence that there is a systemic problem with laboratory testing in the US," Klein, a molecular pathologist at Cleveland Clinic, told GenomeWeb. "While we can look at the CLIA regulations and see ways it can be improved, from our standpoint as experts in molecular pathology, we haven't seen evidence to justify a new regulatory regime." An AMP working group is crafting a plan for enhancing CLIA that addresses gaps critics have noted — for example that regulations don't ensure clinical validity of LDTs — but Klein couldn't provide a timeline for when the pathologist group would release this proposal.

In contrast, the College of American Pathologists, which certifies labs and conducts proficiency testing to gauge how accurately labs test for specific analytes, may be open to a regulatory solution that involves the FDA. The organization has previously proposed an LDT oversight framework where the FDA would review high-risk tests and CMS or an accrediting body like CAP would ensure compliance by laboratories performing high-risk LDTs.

The Association of Public Health Laboratories — which includes as members state labs involved in pathogen testing, assessing communicable diseases, and screening newborns — has argued that FDA's LDT requirements would diminish its ability to react quickly to local health emergencies and tweak tests as needed. The group has asked that public health labs be exempted from certain requirements the agency is proposing in its LDT guidance. Sources said that the draft legislation will need to factor in the needs of public health labs.

Some people think that I've changed my opinion about this topic, and I really have not.

The American Clinical Laboratory Association, meanwhile, hasn't dialed down its longstanding opposition to FDA regulation of the industry. The group has even raised the stakes by hiring legal heavyweights, Paul Clement and Laurence Tribe, who have detailed why the agency lacks statutory authority to oversee LDTs. ACLA declined to comment on the DTWG white paper for this article, but sources pointed out the group hasn't publicly spoken in favor of or against the proposal since its lab industry members aren't likely to be of one opinion on the matter.

While not all stakeholders have backed the draft legislation or the DTWG's proposal, Miller sees provisions that could address the needs of many different groups. "People understand that LDT regulation is problematic for personalized medicine and want a solution that will benefit innovations in the field of diagnostics but won't halt the industry," she said.  

Sources say that the DTWG members are working overtime to garner support for the draft legislation. ARUP Labs CEO Edward Ashwood spent 30 hours last week on work related to the DTWG proposal. It's his primary focus, he said, because getting LDT regulation right is so important for the industry.

ARUP, one of the largest reference labs in the US and a vocal critic of FDA oversight of LDTs, joined DTWG in March. ARUP signed on after the white paper was already written, because within the DTWG, labs and test kit manufacturers were working together to find solutions to the LDT regulatory quagmire. "It seemed to us that this group had made quite significant progress," Ashwood told GenomeWeb. "And it's different than the trade association groups, with AdvaMedDx representing the manufacturers and ACLA representing the labs. This is the first time we've seen those two groups try to work together."

At the public meeting on FDA regulation held earlier this year, Ashwood voiced his "outrage" over the agency's oversight framework, calling it "naïve." He said he felt sick knowing that FDA's "dangerous [regulatory] overreach" would end up hindering patient care. He recounted how the agency appeared to have little knowledge or understanding of ARUP's presence in the medical diagnostics space as a national reference lab. "They thought we did tests only for patients at the University of Utah," Ashwood said at the meeting. "They were unaware that we did tests outside our own health system, which means that the FDA had no real concept of the industry they were proposing to regulate."

Ashwood's comments struck a chord with workshop attendees. He got thunderous applause from his industry colleagues and some gave him a standing ovation. He emphasized to GenomeWeb last week that by joining DTWG he hasn't abandoned his core beliefs that lab tests are not medical devices, that laboratories are not manufacturers, and what labs do is practice medicine, which is beyond FDA's regulatory reach. "AMA's position, like my ideal position, would still be to let CLIA do it," he said. "But I don't think Congress will allow a CLIA-only proposal to go through."

Given that ARUP estimates it would cost upwards of $300 million to comply with FDA's regulatory requirements outlined in the draft LDT guidance, a viable alternative is of the essence. "I think some people think that I've changed my opinion about this topic, and I really have not," he said. "I believe that under the current laws FDA doesn't have the authority to regulate clinical laboratories. I am working with a group that would hopefully change laws that would change that, but not in a way that would destroy the industry."

Ashwood couldn't discuss details, but said the FDA has been open and engaged with the DTWG and has spent time discussing the group's proposal. The FDA declined to comment for this story.

Although DTWG members are working on getting support from other groups in the life sciences field and the House E&C committee is shopping the draft legislation for input, it's anyone's guess how far the bill will progress on Capitol Hill in the near term. The bill language needs more finessing, according to Miller, to clarify details around implementation and outline the enhancements that need to be made to CLIA. She noted that there's still a chance that the draft legislation may be find its way into 21st Century Cures as an amendment. Alternatively, the House committee could introduce it as a standalone bill or the Senate HELP committee could incorporate it as part of the "Innovation for Healthier Americans" legislation.

Given the divisive nature of LDT regulation, some legislators may not want to tackle the issue on the heels of the 2016 presidential elections, and Miller acknowledged that this might hold back the draft bill. "But we need to remember that in two years' time Congress is going to have to pass legislation on prescription drug user fees and medical device user fees," she said. "Those are must-pass legislations to keep the FDA up and running and approving new products. So, we need to work out the details of this proposal now, and if we don't now, we're going to have to in two years."

But if Congress waits too long, it might give the FDA an opening to finalize its draft LDT guidance right before the Obama Administration leaves the White House. The FDA looked for a lull in Congress last year — right before the summer recess and ahead of mid-term elections — when releasing its draft LDT guidance. Then again, by moving to finalize the guidance, the agency would risk getting sued by the lab industry.

Ultimately, if there is no legislative action on the DTWG proposal in the coming months, sources say that the standoff between labs, manufacturers, and the FDA will likely continue for a few more years, and with it, so will the regulatory uncertainty in the market … until someone blinks.

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