Proposed Precertification Approach on In Vitro Clinical Tests Raises Questions

Comments submitted to Congress on a recent discussion draft for a new risk-based approach to the regulation of in vitro clinical tests (IVCTs) raised questions and concerns around the IVCT precertification framework.

The IVCT draft legislation would provide regulatory standardization for FDA-reviewed tests and laboratory developed tests (LDTs)—most of which do not meet the same standards in analytical and clinical validation—whereas IVCT precertification would enable exempted or streamlined FDA premarket reviews on certain tests.

Those that submitted comments on the December 2018 discussion draft of the Verifying Accurate Leading-edge IVCT Development Act of 2018 (Valid Act) earlier this month include industry associations AdvaMedDx, the American Clinical Laboratory Association (ACLA) and the Association for Molecular Pathology (AMC). The Pew Charitable Trusts and the Precision Medicine Coalition (PMC) submitted comment letters as well. They generally commended the draft legislation as the culmination of years in policy work to address a gap in regulations on IVCTs, particularly on LDTs.

Areas of concern among commenters ranged from a limited scope to the potential for duplicate work regarding new IVCT requirements and revised policies under the Clinical Laboratory Improvement Amendments of 1988. But criteria within the IVCT precertification framework was a shared area of concern.

AdvaMedDx said that it “supports the concept of precertification for diagnostics as part of a diagnostics reform framework.” But the division added that it believes the framework can be “further improved upon by thoughtfully expanding its scope to ensure it is not overly rigid and will withstand the test of time as technologies continue to evolve and our understanding of innovative test types and how they can be used effectively matures.” PMC and ACLA also had scope-related concerns.

Pew supported a narrow scope, at least initially, citing concerns on protocols, policies and a test developer’s experience for precertification eligibility. Pew’s health care product project director Elizabeth Richardson noted in an interview with Focus that precertification is not an entirely new concept for FDA. She pointed to the framework underway at FDA’s Center for Devices and Radiological Health—in collaboration with nine companies selected in 2017—for digital health precertification. Pew and AMP requested FDA provide clarity on the distinction between both precertification frameworks.

Still, Richardson argued that IVCT precertification would seek to provide additional regulatory-related relief for developers that would stem from actions FDA previously implemented. The agency exempted direct-to-consumer genetic health risk tests from 510(k) premarket notification under a final order issued last June based on its experience working with 23andMe, Richardson noted as an example.  

The IVCT precertification framework was initially proposed as part of the agency’s technical assistance (TA) in August 2018 in the Diagnostic Accuracy and Innovation Act (DAIA). The Valid Act incorporates DAIA but draws heavily from FDA’s TA, Richardson said. With the approach still under development, the new comments seek to aid in preventing unintended consequences and addressing areas lacking clarity.   

In addition to the scope some saw as too narrow, the commenters also took issue with subjecting test modifications to new premarket reviews, policies on grandfathered tests, the draft proposal to require a precertification status renewal after every two years and the test risk classification framework, among other criteria.