AMP Offers Proposal for Regulation of Laboratory Developed Tests

Last month in Compliance Perspectives, we highlighted the current status of the Food and Drug Administration's proposed regulation of laboratory-developed tests (LDTs). While the FDA's proposed framework remains to be finalized, other stakeholders are proposing alternative oversight models. This month, the Association for Molecular Pathology issued a proposal for modernizing CLIA regulations. The proposal reiterates AMP's position that FDA regulations are not appropriate for professional services and refers to the testing as laboratory developed testing procedures or LDPs. Representatives from AMP presented the recommendations to the Senate Health, Education, Labor, and Pensions (HELP) Committee, which is now drafting legislation that would provide opportunities for enhanced support for medical innovation and patient access to new medicines and technologies. The proposal's stated objectives include ensuring "[r]egulatory oversight does not slow innovation, constrain flexibility and adaptability, or limit a test's sustainability as a result of being unduly burdensome and beyond the fiscal capacity for the laboratory to reasonably perform or the health care system to financially support."

Explaining the need to update the CLIA regulations, the proposal highlights the growth and evolution of molecular diagnostics and distinguishes LDPs from medical devices asserting that one set of regulations "can never address both adequately."

Identifying specific sections of the CLIA regulations for updating, the proposal describes a tiered, risk-based model. The review process for each risk category is as follows:

• Low-risk: validated by the laboratory, put into service, and subject to inspection in the normal course of laboratory inspection.
• Moderate-risk: information submitted for third party review at least 30 days before the test is offered to the public with a time limit on the review process and grandfathering provision for previously introduced LDPs.
• High-risk: information submitted for third party review at least 90 days before the test is offered to the public, with a time limit on the review process.

Multianalyte assays with algorithmic analyses (MAAAs) with proprietary algorithms would be submitted to FDA unless the laboratory reveals its proprietary algorithm to third party review and inspection.

The proposal also includes publication requirements geared to providing transparency for providers, patients and regulatory agencies, and allowing comparisons between LDPs by giving access to information about "accuracy, precision, and known clinical significance of an LDP." Addressing concerns raised by many in the debate about FDA regulation in this area, the proposal also: 1) calls for development of a minimum level of standards and time frames for submitting information about a new laboratory developed procedure prior to offering the test to the public and imposes presumptive approval if the reviewing party doesn't make a determination in the required time period; 2) addresses types of evidence for demonstrating clinical validity; and 3) discusses when modifications to an LDP or to an FDA cleared or approved IVD require notice or a new review. Finally, to fund the oversight functions, the proposal allows for an annual fee linked to a laboratory's number of LDPs and "limited to cost recovery."

Takeaway: The debate concerning oversight of laboratory developed testing continues with detailed alternatives to the FDA framework being recommended to legislators.