Executive Summary
The American Clinical Laboratory Association (ACLA) split with other stakeholder groups in criticizing US FDA’s proposals for a new diagnostics regulatory regime. ACLA asked Congress to stay closer to Reps. Diana DeGette’s and Larry Bucshon’s original Diagnostics Accuracy and Innovation Act draft bill language.
Makers of test kits, represented by AdvaMedDx, and at least two health research groups this week spoke in favor of US FDA’s newly-recommended approach to regulating in vitro clinical tests, but laboratories, represented by ACLA, questioned the agency’s suggested changes to the Diagnostics Accuracy and Innovation Act, a key diagnostics reform bill.
FDA had submitted its recommendations on the DAIA discussion draft to Congress earlier this month in a technical assessment (TA) document. (Also see “Pre-Certs, Test Groups And More: US FDA Outlines Possible New Dx Paradigm” – Medtech Insight, 16 Aug, 2018.) Stakeholders pushing for reforms, including ACLA, generally endorsed FDA’s effort in an Aug. 8 letter to leaders of the House Energy and Commerce Committee and Senate HELP Committee.
The groups wrote that FDA input was “an important part and necessary next step” in the legislation-creating process.
“A number of the agency’s proposals on the Diagnostics Accuracy and Innovation Act create general concern,” wrote ACLA President Julie Khani.
That letter and a prior one from an array of groups suggested a growing alignment between kit-makers and laboratories on an issue where there has been discord, with FDA-regulated kit-makers pushing for a more level regulatory playing field, while labs resisted FDA oversight. However, more comprehensive comments on DAIA sent by ACLA to bill authors Bucshon and DeGette, and to Sens. Orrin Hatch, R-Utah, and Michael Bennet, D-Colo., on Tuesday, suggests more work is needed to reach consensus.
“The diagnostic community, including clinical laboratories, have put in great effort to move the debate over reforming diagnostic oversight as far as it has come,” said ACLA President Julie Khani. “The FDA TA is another significant step in this process,” she added, “but a number of the agency’s proposals create general concern.”
Diagnostics Are Not Devices, ACLA Says
Among FDA’s proposals that raise “regulatory concerns and questions,” Khani said, was the issue that has long been a debate between the agency and the lab community – FDA’s assertions that it “retains” jurisdiction over laboratory developed test (LDTs) services, which the agency still considers devices.
ACLA also argued that any new framework for regulating IVCTs must ensure continued innovation and patient access to reliable clinical diagnostic services. Among the core principles ACLA said it wants retained in DAIA are:
- Reform that recognizes diagnostics as distinct services rather than being incorporated into existing regulatory frameworks;
- Grandfathering and transition policies that will not disrupt patient access to currently-available clinical laboratory services; and
- “Appropriate” balance between innovation, and assurances of accuracy and reliability through notice-and-comment regulation, rather than through guidance documents.
ACLA Wants Separate FDA Center, No Redundant Regulation Of Labs by FDA
ACLA also continued to endorse creation of a separate diagnostics center at FDA, a detailed provision included in the original DAIA discussion draft, but unmentioned in FDA’s technical assessment of the proposed legislation. (Also see “Lab Professionals Oppose Draft Dx Reform Bill; Lab, IVD Industry Ready To Work With Congress” – Medtech Insight, 13 Apr, 2017.)
As the lab group wrote in its comments, “ACLA objects to the FDA TA’s approach that inappropriately sets forth a framework where device regulations are the starting point for IVCT oversight. For example, under the FDA TA, the device quality system regulations (QSRs) apply to IVCTs until the Secretary amends the applicable regulations [but] there is no deadline by which such regulations must be amended.”
ACLA said FDA takes a similar approach to regulating diagnostics as it takes for devices, regarding labels, adverse event reporting, corrections and removals, and investigational use IVCTs. “It could be years or even decades before FDA amends regulations to specifically apply to diagnostics,” ACLA wrote. “As such, we believe it is inappropriate to shoe-horn oversight of IVCTs into a device framework.”
For these reasons and others, ACLA stated, “A diagnostic-specific center at FDA is a critical component any framework to regulate IVCTs.”
ACLA also charges FDA with ignoring the role the Centers for Medicare and Medicaid Services (CMS) plays in regulation of laboratory operations, under the Clinical Laboratory Improvement Amendments (CLIA), by “contemplating an overlapping system, where labs would be subjected to redundant regulation by both FDA and CMS.” Because the agency’s TA does not set clear boundaries for FDA and CMS in non-programmatic areas, it “leaves discretion to FDA to regulate laboratory operations.”
AdvaMedDx, ACLA Endorse Pre-Certification Program
ACLA does not object to all elements of FDA’s proposal. It did offer support to FDA’s proposed pre-certification approach to regulating certain diagnostics, in which labs and companies can be pre-vetted as a means to qualifying for reduced pre-market requirements. And that is one area where ACLA and AdvaMedDx are aligned.
ACLA “particularly recognizes FDA’s inclusion of a comprehensive test information system and proposed pre-certification program in the TA. ACLA believes that, if properly designed and originally rolled out through a pilot program, pre-certification could become a potentially valuable pathway to provide streamlined and efficient regulatory oversight of IVCTs.”
Similarly, AdvaMedDx Director Susan Van Meter told Medtech Insight Aug. 20 that the group likes FDA’s proposed pre-certification approach to regulating diagnostics. AdvaMedDx amplified their endorsement of pre-certification for diagnostics in the group’s Aug. 20 comments to Congress on the FDA TA on DAIA.
“AdvaMedDx strongly supports the concept of pre-certification for diagnostics and is pleased with FDA’s prioritization of such a pathway,” the group’s director Susan Van Meter says.
“AdvaMedDx strongly supports the concept of pre-certification for diagnostics and is pleased with FDA’s prioritization of such a pathway for all interested diagnostic developers to help promote excellence in quality and ensure patient benefit from a regulatory apparatus that keeps pace with scientific advancement,” the group wrote.
AdvaMedDx Supports FDA Inclusion Of Priority Review Process
AdvaMedDx was otherwise supportive of FDA’s proposed approach to diagnostic regulation in its TA, saying it appreciated FDA’s inclusion of a priority-review process, as well as “use of a pre-approved protocol to allow for certain updates that otherwise would be part of a pre-market submission, to support diagnostic innovation.”
On this point, AdvaMedDx added: “We are pleased with FDA implementation of use of change protocols in recent flexible, efficient reviews (e.g., next generation sequencing, tumor profiling)” saying it supports diagnostic innovation.
However, AdvaMedDx also wanted clarification and disagreed somewhat on several points that FDA raised in its TA, including:
- Diagnostic Instruments – AdvaMedDx said that because platforms themselves do not carry the risk, that “platforms should continue to be exempted as low risk.”
- Treatment of accessories – While parts and components should be grouped together and assessed under quality systems developers create, “accessories, on the other hand, are finished goods and should be classified independently based on their own risks.”
- Point of Care Diagnostics – AdvaMedDx wrote, “CLIA-waived tests (i.e. physician offices, clinics) play a vital role to support public health … We are unclear how FDA intends to address point of care technologies.”
- Grandfathering – The group said there should be some form of grandfathering of LDTs, and “we also agree no new tests introduced after 90 days prior to legislative enactment should be grandfathered.”
- Risk-Based Classification – AdvaMedDx said, “We will need to better understand the two-tier classification approach (for high-risk and low-risk tests), how it might work, and its potential impact … for moderate risk tests.”
Research Groups Support FDA Stance
Pew Charitable Trusts, which does public health research and advocates on some policy issues, praised FDA’s technical assessment of the DAIA bill, saying it “contains many important elements essential to protecting patients and consumers.”
Among the elements it highlighted were FDA calling for regulatory requirements that would enable physicians and patients to “trust the results of tests, no matter where assembled or performed,” outlining a process to assure a test’s analytical and clinical validity and tailoring regulatory oversight to risk.
“If the consequences of an inaccurate test are potentially serious, there should be a correspondingly greater burden on developers to demonstrate a test’s analytical and clinical validity. Thus, regulatory requirements should correspond to the consequences that flow from an inaccurate test result,” Pew wrote.
And Friends of Cancer Research (FOCR) CEO Jeff Allen told Medtech Insight Aug. 16 that the FDA TA document “represents a positive step forward in these discussions [around the DAIA bill] and we remain hopeful that a new regulatory paradigm for these critical tests can be achieved.”
Allen noted that the TA provides a great deal of flexibility and discretion to FDA, and that “the flexibility proposed in the TA does allow FDA to be able to respond to emerging science and look to establish a framework that balances patient protections and innovative development.” Such an approach is important for oncologists, Allen said, because “oncology science is evolving so quickly and we have seen rapid development of new diagnostic technologies, of increasing importance to cancer patient care.”
FOCR also supported elements in FDA’s proposal on adverse-event reporting, the need for the agency to request evidence to ensure validity of tests and programs such as priority review.
Groups Continue To Offer Congress Assistance On Diagnostic Reforms
Several of the groups commenting on FDA’s TA on the DAIA bill said they would have further input and look forward to assisting as House and Senate committees consider the bill this legislative session. “ACLA respectfully urges Congress to take up diagnostic reform and work with all stakeholders to achieve our mutual goals,” the clinical lab group stated.
AdvaMedDx wrote, “We applaud congressional efforts to support critical reform to modernize the regulatory framework for all diagnostics. We urge Congress to continue this forward momentum and move swiftly to advance diagnostic reform legislation so it may be enacted in 2018.”
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