While the Food and Drug Administration’s proposed framework for regulating laboratory developed tests (LDTs) remains to be finalized, other stakeholders are proposing alternative oversight models. On August 4, the Association for Molecular Pathology (AMP; Bethesda, Md.) 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.” “While we maintain that there is no evidence of systemic problems with laboratory testing or LDPs that would necessitate an increase in what is already rigorous oversight, the CLIA statute and regulations are over twenty years old. Given the advances in technology and laboratory science, these regulations can be modernized to better fit with contemporary practice,” says AMP Professional Relations Chair Roger D. Klein, M.D., J.D., in a press release announcing the proposal. “Our proposal is a streamlined, cost-effective approach that enhances transparency, ensures quality, and preserves innovation.”
Identifying specific sections of CLIA regulations for updating, the proposal describes a tiered, risk-based model, that defines each risk level based on the purpose for the test, associated morbidity or mortality or threat to public health of the disease for which the LDP is used or the consequences of incorrect results, the test methodology employed, and the ability to perform inter-laboratory comparisons or proficiency testing. 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.
While the AMP’s proposal seeks to avoid duplicative regulation it does include a role for the FDA, requiring that multianalyte assays with algorithmic analyses (MAAAs) with proprietary algorithms be submitted to FDA unless the laboratory reveals its proprietary algorithm to third party review and inspection.
The proposal defines an LDP as a “testing procedure or service that encompasses and integrates, in a single CLIA-certified laboratory, the design, development, validation, verification, and quality systems used in laboratory testing and interpretative reporting in the context of clinical care or public health services.” It 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.