A draft of FDA user fee reauthorization legislation released by the Senate Health, Education, Labor and Pensions (HELP) Committee includes provisions that committee members said would improve and modernize the regulation of diagnostic tests.

The proposed Food and Drug Administration Safety and Landmark Advancements (FDASLA) Act of 2022, S. 4348, released May 17 and introduced in the Senate May 26, revives proposals for regulating in vitro clinical tests (IVCT) previously introduced in Congress in March 2020 and June 2021.

Title VIII Subtitle C of the bill, the Verifying Accurate Leading-edge IVCT Development (VALID) Act of 2022, would create a risk-based approach to the FDA’s regulation of IVCTs, including in vitro diagnostics and laboratory-developed tests (LDTs).

In the past, device groups, including the Advanced Medical Technology Association (AdvaMed), have voiced support for such an approach, while the American Clinical Laboratory Association (ACLA) and other clinical testing groups have criticized details of the proposal.

The provisions of the VALID Act were not included in the version of FDA user fee legislation released by the House Energy and Commerce Committee on May 4.

Premarket Approval Provisions

Like previous iterations of the VALID Act, the version included in the proposed FDASLA Act would create a risk-based scheme for the FDA’s regulation of certain IVCTs. The legislation sets forth details for the premarket, abbreviated premarket, and supplemental application review and approval process for the tests.

Included is the information that would be required in premarket and supplemental submissions for IVCTs, which would be intended “to ensure the test meets the applicable analytical and clinical validity standard required.”

The bill also provides a pathway to market for test instruments. Abbreviated premarket approval would be the pathway for moderate-risk IVCTs, test instruments and specimen receptacles.

Exclusions from the IVCT premarket review process would be provided for low-risk IVCTs, humanitarian use IVCTs, custom and low-volume IVCTs, modified IVCTs and manual IVCTs.

The bill also specifies the types of modifications to IVCTs with premarket approval that could be made without additional FDA review — specifically, changes that do not affect the analytical or clinical validity of the test.

Technology Certification Pathway

S. 4348 also would establish a technology certification pathway that would permit developers of moderate-risk IVCTs to be certified to offer multiple tests using the same technology, thereby eliminating the need for premarket review by the FDA for each test individually.

A IVCT developer that holds a technology certification could continue innovating and offering IVCTs within the scope of a technology certification order issued by the agency. The developer would be required to submit a representative IVCT for FDA review to help the agency determine the scope of the technology certification order.

Regulatory Pathway Designation

The legislation would set up a process through which test developers could clarify the risk classification of a particular IVCT. The process could be initiated by either the developer or the agency.

Through the process, the FDA could determine whether mitigating measures to reduce or control the risk of a test would be appropriate to support a particular classification. The agency could redesignate an IVCT in response to new information that requires or allows for a change to a test’s risk classification.

The bill also would establish a process through which test developers could request and receive feedback from the FDA before submitting a marketing application for a test. The feedback could include information about the submission process, the appropriate regulatory pathway for a particular IVCT, and investigational plans for the test.

Grandfathering of IVCTs

Under the legislation, an IVCT that was developed by a laboratory with an existing high complexity certificate under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) and was available for use before enactment of S. 4348 would be able to continue to market the test in interstate commerce without meeting the bill’s premarket review, labeling, test design, and quality requirements.

The FDA would be able to request information from test developers about grandfathered IVCTs to ensure that the tests continue to be accurate and safe. If a grandfathered test is found to be no longer eligible for the exemption, the developer would be required to submit a premarket, abbreviated premarket or technology certification application for agency review of the test in accordance with the test’s risk classification.

Additional Provisions

Other elements of the FDA’s regulation of medical devices would be applied to the agency’s regulation of IVCTs through the legislation, including:

• breakthrough designation for IVCT technologies that do not have an alternative on the market or the availability of which would be in the best interest of patients or public health, which would provide for priority FDA review of tests using breakthrough technologies;
• registration and listing requirements;
• quality requirements for test design and manufacturing based on the type of test and the certification status of the developer;
• labeling requirements, including instructions for reporting adverse events, intended use, warnings and limitations;
• adverse event reporting requirements;
• correction and removal reporting requirements;
• authorization of the FDA to accredit qualified entities to review and make recommendations concerning IVCT applications for premarket approval or for technology certification;
• FDA recognition of national and international standards for IVCTs;
• investigational use application procedures for the development of IVCTs;
• circumstances under which an IVCT would be deemed to be adulterated or misbranded;
• provisions for requiring postmarket surveillance of an IVCT; and
• postmarket remedies, such as FDA requirements for developers to submit plans for notifying individuals of an IVCT’s risks, and FDA orders mandating that a developer repair, replace or provide refunds for an approved IVCT found to present an unreasonable risk of substantial harm to public health.

Transition

The VALID Act would become effective Oct. 1, 2027, and mitigating measures could be established before the effective date to ease the transition for test developers.

IVCTs marketed after the bill’s enactment but before the effective date would be deemed “transitional tests” that could continue to be marketed while undergoing premarket review, if a premarket review application for the test is submitted to the FDA within 90 days of the effective date.

IVCTs that were medical devices with existing FDA approval, licensure, clearance, humanitarian use exemption, investigational use exemption or breakthrough designation as of the effective date would be deemed IVCTs with those designations under the VALID Act.

The legislation also includes user fee, combination product, emergency use authorization, and preemption provisions.