Lawmakers in the Senate Health, Education, Labor, and Pensions Committee are circulating draft legislation to create a standalone center at FDA to regulate diagnostics as a distinct regulatory category from medical devices. The draft would establish a new framework for regulating ‘in vitro clinical tests’ (IVCTs), including in vitro diagnostic kits and lab-developed tests, if it becomes law, stakeholders say.

The concepts behind the legislation are contained in a March white paper, “A Proposed Regulatory Framework for In Vitro Clinical Tests,” developed by the Diagnostic Test Working Group, including in vitro diagnostic kit makers like Becton Dickinson & Co., and Roche and laboratories like Mayo Clinic, Laboratory Corp. of America Holdings(LabCorp), and ARUP Laboratories, according to an industry consultant and a public health group representative who have seen the Senate proposal.

IVD kit manufacturers and labs have typically been on opposite sides of the debate on whether lab-developed test services (LDTs) should be overseen under FDA's device regulation. Kit makers support FDA regulation of LDTs to establish a level playing field for all diagnostics, while clinical labs generally argue against FDA oversight, saying LDTs are different from kits and are already appropriately regulated under the Clinical Laboratory Improvement Amendments (CLIA) administered by CMS.

The draft bill envisions a regulatory landscape that brings IVDs and LDTs together into a new category, IVTCs, that is not subject to device regulations. Under the proposal, FDA would have jurisdiction over IVCT design, development, validation and preparation of reagents for use by a third party; CMS is in charge of preparation of reagents for use at a single laboratory and development of lab standard operating procedures; and states oversee interpretation and consultation about lab test results.

The draft bill has not been released to the public, but floated to key stakeholders including lab test kit manufacturers, clinical laboratory organizations, and public health communities for their input. Senators likely to sponsor such a proposal include Sen. Orrin Hatch, R-Utah, who previously worked on legislation calling for a separate FDA diagnostics center in 2011 (See Also see "Senate Bill Would Create New Diagnostics Center At FDA" - Medtech Insight, 4 April, 2011.), and Sen. Richard Burr, R-N.C., whose state hosts the headquarters for LabCorp, in Burlington, N.C., as well as large clinical laboratories at its universities.

“It is clear that the FDA, the IVD industry, all the laboratories, were at an impasse. So I think this is an effort to try to bring everybody into the fold, and distribute some statutory authority to the federal [government], and to the states," said Lakshman Ramamurthy, director of FDA Regulatory Policy at Avalere Health LLC. "Generally, it’s a compromise,” Ramamurthy, a former diagnostics reviewer at the agency, explained.

"We are still reviewing the details of the proposal but welcome the prospect of diagnostics regulatory reforms that recognize the unique nature of diagnostics, advance risk-based oversight, and appropriately balance the interests of all stakeholders. We look forward to working closely with the Committee, FDA, and stakeholders on these reforms,” an AdvaMedDx representative said in a statement.

FDA released a proposal last year to begin active oversight of LDTs under device regulations over a risk-based phase-in period after decades in which the agency says it has elected not to subject these lab services to premarket review or postmarket controls. (See Also see "FDA Releases LDT Regulatory Framework, Notification Draft Guidances" - Medtech Insight, 6 October, 2014.). The recent Diagnostic Test Working Group proposal comes amid general support for FDA's proposal by the IVD industry but strong opposition from some clinical laboratories. (See [A#01150119004].)

User fee funding would be limited to 25 percent of total resources for the new center, under the proposal.

But the Senate is contemplating much more significant changes, creating a special regulatory center under the FDA umbrella with staff dedicated only to reviewing new tests, or reclassifying older ones to fit a new regulatory standard. The draft Senate proposal would limit any user fee funding for the new diagnostics center to 25 percent of the total resources supporting it, according to sources who have viewed the draft.

The proposal would set up a detailed set of regulations for the IVCTs, and look somewhat similar to FDA’s LDT framework, but also allow some flexibility for CLIA lab performance standards under CMS regulations, according to Ramamurthy from Avalere.

Detailed Regulations Proposed

The IVCT legislative proposal “generally lays out a very nice, long development cycle for in vitro testing,” and uses the same pretesting standards for both LDTs and in vitro diagnostic tests, Ramamurthy said in June 12 interview with “The Gray Sheet.” As in FDA's LDT proposal, tests would be put into high, moderate and low risk categories, with special pathways and exceptions for diagnostics for rare diseases, emergency use and unmet needs. Additionally, it would strengthen CLIA standards, “and CMS and FDA have already formed a joint task force that talks about how they want to educate the CLIA review system, to ensure that CLIA looks at tests, with a certain amount of due diligence, just as FDA does,” he added. (See [A#01150420020].)

The legislative proposal would ensure that diagnostics are reviewed with a certain level of “due diligence” that is based on the FDA model, Avalere’s Ramamurthy said.

Also, under the proposal, all diagnostics “should be reviewed with a certain level of due diligence, and they actually use the FDA model, as the due diligence for that,” he added.

While the draft legislation does not rely upon FDA’s standard asking that diagnostic devices be “safe and effective,” before they are put on the market, it does retain the two key ingredients to determine safety and effectiveness for a diagnostic, analytical validity and clinical validity, according to Ramamurthy.

Analytical and clinical validity, under the draft, can be proven by the test sponsor with peer-reviewed literature, clinical guidelines, case studies or registry data, and perhaps, clinical trials, although clinical trials specifically would not be required.

Standards For High-Risk Tests Could Be Weakened, Public Citizen Warns

However, if drafters of the legislative proposal adhere closely to the white paper is it based on, the resulting law will “weaken regulations for high risk tests for serious diseases or conditions,” said Sarah Sorscher, a researcher and attorney with consumer advocacy group Public Citizen, in a separate June 12 interview. She agreed to provide feedback only to the provisions in the white paper upon which the draft legislation is based.

“A test can affect important treatment decisions," Sorscher said. "It can expose patients to risk if the result is wrong, or if they are led to believe that it means something, when it doesn’t. And the concern is that FDA will be letting these devices on the market without adequate testing.”

Because the concept behind the draft bill does not require testing of human subjects to prove the safety of diagnostics that fit the highest risk category, “the default will be no clinical testing, and the FDA will have a very hard time, if they want to request it,” Sorscher said.

“The key thing is approval would be automatic” if FDA could not make a [quick] decision” – Public Citizen’s Sarah Sorscher

Other concerns she expressed about the concepts behind the draft legislation:

some tests for very high risk diseases, such as Lyme Disease, would be put in a “moderate risk” category;
if FDA does not accept or reject a classification recommendation by an FDA advisory panel about test within six months, the panel’s recommendation of high, moderate or low risk would be binding;
and that the period of review – 60 days for moderate risk tests, and 90 days for high risk tests – would be too short for FDA to make a carefully-considered decision to approve or disapprove a diagnostic.

“But the key thing is … that approval would be automatic” if FDA could not make a decision within the 60 or 90 days that a high risk or moderate risk test would be approved or cleared, Sorscher said.

“So essentially, if the company decides it wants the product approved, and then if the FDA does nothing after that, [it] gets approved,” she said. “The concern is that if the agency becomes swamped with too much work, they won’t be able to adequately review” the tests."

Question Of Funding

Both Sorscher and Ramamurthy wondered where the funds would come from to support a standalone FDA Center for diagnostics, particularly if user fee funding is limited to 25 percent of the total resources allowed to carry the center’s workload.

“They [Congress] are already trying to limit the funding of FDA to balance the budget – so what are they trying to do here? I don’t know how the plan is going to handle that,” Ramamurthy remarked. “It would be a shame if such a proposal ultimately would not fly because it would require a new center.”

From Public Citizen's perspective, Sorscher said, "The concern is that Congress would pass this law, and then wouldn’t provide traditional funding, so that would be money that would be diverted from other important agency activities. And the Center for Devices and Radiological Health doesn’t seem to be terribly well-funded, in the first instance.”

When or if the legislation might be introduced is unknown. It fits into the Senate HELP Committee's efforts to identify reforms to accelerate the path to market for new drug and device discoveries, paralleling the House 21st Century Cures effort. (See [A#01150302002].) The Senate has yet to issue legislative language tied to its efforts. The House, meanwhile, is moving closer to a vote on its Cures bill, but that legislation does not currently include major in vitro diagnostic regulatory reforms.

Senators Circulate Plan For Standalone FDA Diagnostics Center, ‘In Vitro Clinical Test’ Rules

More from Legislation

More from Policy & Regulation