Medical Device Link.

AdvaMed (Washington, DC) submitted a proposal to FDA at the end of March for modernizing premarket oversight of IVDs. The proposal, titled “Risk-Based Regulation of Diagnostics,” sets forth a risk-based “tier triage” model for regulating all diagnostic tests, regardless of origin.

The proposal was developed over the course of roughly two years, said Khatera Calleja, associate vice president, technology and regulatory affairs for AdvaMed. Its intent, as stated in its Overview section, is to “build on the strengths of the current system and infrastructure, avoid duplicative regulation, and promote transparency to the process by identifying objective, scientific, and regulatory criteria to help triage diagnostics, from well-established to new emerging diagnostic tests, into the appropriate level of regulatory scrutiny.”

AdvaMed, believing the risk-benefit profile for patients to be unaffected by test origin, supports FDA oversight of the safety and effectiveness of diagnostic tests developed by both manufacturers and labs. “There’s a whole universe of new technology that FDA hasn’t looked at yet: lab-developed genetic tests and other lab-developed assays,” said Richard Naples, vice president of corporate regulatory affairs for BD (Franklin Lakes, NJ) and an active participant in the development of the proposal. “There are now over 1000 tests for genetic disorders that labs offer. These tests are not regulated by FDA today. Labs argue that they are regulated under CLIA 88,” he said. But CLIA does not perform any premarket regulation. “AdvaMed is suggesting that FDA oversight be extended to lab-developed tests, but that FDA use its device-classification process to exempt low-risk lab-developed tests,” he explained.

AdvaMed also wants FDA to focus its oversight primarily on high-risk technologies and make exempt those technologies that are well established and carry low risk. “FDA did an exemptions effort about 11 years ago,” Calleja said. “At that time there were a number of Class I and Class II diagnostics exempted from premarket notification. We feel that there are a number of additional IVDs that would be appropriate for exemption.” This belief is supported by FDA’s qualitative goal commitment to facilitate IVD innovation following passage of the FDA Amendments Act in 2007.

Added Naples, “FDA still reviews a number of tests that are very low risk. The safety profiles of these tests are well standardized. There are very few adverse events associated with them. There are very clear standards for the technology performance, and additional safeguards in the laboratory.” FDA is still looking at old technologies, he said, and that “makes it more difficult for them to focus on the novel technologies and devote the resources needed to handle the newest, most-important tests that are coming to market.”

Under AdvaMed’s updated system, to determine the level of regulatory oversight required for a diagnostic test, the agency would examine the risk associated with the test’s clinical use, the degree of novelty of the test’s analyte, the degree of novelty of the technology involved, and the site of service or level of training of the test’s operator. In assessing risk, FDA would consider various risk-mitigation factors—scientific evidence, general and special controls for medical devices, laboratory process controls, and user experience.

Naples said that AdvaMed’s approach would use information from FDA’s own adverse-events databases to help determine whether a test is a candidate for exemption. The “beauty of this proposal,” he explained, “is that the risk-stratification model is already used to a great extent by FDA. Our proposal just formalizes all the good things they’ve been doing and adopts the standards of ISO 14971:2007. We think FDA could put both the exemption proposal and the tier-triage proposal into place using its existing authorities.”

Calleja added, “We’re trying to improve the current review process. We’re not trying to do some sort of overhaul.”

Both Naples and Calleja said that FDA response has been positive so far. The agency is “always interested in hearing from stakeholders about what we can all do to work together to make the process better,” according to Naples.

AdvaMed’s proposal does not directly address the dicey subject of reimbursement, which has been and still is a big issue for AdvaMed members. “Payers and FDA should make sure the systems are aligned and that the important tests can be reimbursed in a timely fashion. Today it takes forever to get a coverage decision,” Naples said. “Both sides of the equation—the FDA side and the payment side—have to work in tandem, seamlessly, to ensure timely patient access to important diagnostics that can improve outcomes—and today that’s not happening. That isn’t anybody’s fault, it’s just the way the system was set up over the years. Something the association is working on is to come up with a proposal to reform the process for payment.”