Group Suggests FDA, CMS Share Lab-Developed Test Oversight

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By John T. Aquino

Sept. 16 — The FDA and the CMS would share oversight of laboratory developed tests (LDTs) under a legislative proposal issued Sept. 15 by the College of American Pathologists.

CAP issued its plan to be part of the discussion as Congress considers the Food and Drug Administration's proposed regulatory framework under which it would exercise increased oversight of LDTs after years of “enforcement discretion”. Clinical laboratories that perform diagnostic procedures such as LDTs currently are overseen by the Centers for Medicare & Medicaid Services (CMS) under the Clinical Laboratory Improvement Amendments (CLIA).

The CAP proposal would modify CLIA and the Federal Food, Drug and Cosmetic Act to split oversight of LDTs between the FDA and the CMS. The FDA's increased regulatory participation would be targeted to tests that currently have the least transparency and the highest potential patient risk, while moderate- to low-risk LDTs would be regulated by the CMS.

The organization's three-tiered, risk-based stratified model also emphasizes the roles of analytic and clinical validation of LDT's.

The CAP proposal follows a separate alternative framework issued by the Association for Molecular Pathology (AMP) on Aug. 4.

CAP said its proposed framework is based on one it submitted to the FDA in 2009. 

Three-Tiered, Risk-Based Plan

CAP's regulatory framework for LDTs would provide the FDA with statutory authority under the FDCA to regulate high-risk LDTs, which are tests where an incorrect result or interpretation could pose moderate or high risk of serious harm or death. Such tests would be subject to existing FDA premarket and postmarket regulatory requirements.

The CAP proposal also would provide statutory authority to the CMS to regulate moderate- and low-risk LDTs under the CLIA provisions of the Public Health Service Act. A laboratory couldn't use a moderate-risk LDT until either the Department of Health and Human Services or an accredited body informed the lab that the LDT met the agency's moderate-risk standards.

For low-risk LDTs, the laboratory would perform analytical validation and determine the adequacy of clinical validation prior to offering the test for clinical use. The third-party accrediting body, during normally-scheduled inspections, would verify that the laboratory performed appropriate validation studies.

Analytical validity establishes that the LDT is a valid and reliable method of identifying or measuring the targeted analyte or substance. Clinical validity shows that the LDT consistently and accurately identifies, measures or predicts a disease or condition in an individual or characteristics related to an individual's clinical status.

Exemptions for Some LDTs

The CAP framework would exempt some tests from premarket review (but not premarket notification) unless the HHS considers it necessary after consultation with the CMS and the FDA. Tests that would qualify for this exemption are:

• LDTs for rare diseases or conditions;

• LDTs for unmet needs;

• low-volume LDTs;

• LDTs developed by public health laboratories; and

• traditional LDTs, which use techniques and components marketed for clinical use that are interpreted directly by qualified health care providers.


LDTs used to respond to public health and infectious disease emergencies and LDTs in use before April 23, 2003, would be completely exempt from the regulatory scheme.

Reporting would be required for any modification to a moderate- or low-risk LDT that results in a change to the intended use and has a meaningful clinical impact.

Enhanced CLIA Standards

Under the CAP proposal, the HHS would develop enhanced CLIA standards for moderate-risk and low-risk LDTs and a process for determining how laboratories meet those standards.

The HHS standards would include requirements for the laboratory to meet analytical and clinical validity for moderate-risk and low-risk LDTs. The HHS also would establish evidence-based standards for analytical and clinical validity.

In addition, the CAP proposal would require laboratories to report adverse events to the HHS or accrediting body, create a public and transparent process for classification and reclassification of LDTs into risk categories and promote transparency by making test information publicly available.

AMA Supports CAP Proposal

James L. Madara, chief executive officer and executive vice president of the American Medical Association, said in a statement released by CAP, “The framework for reforming the oversight of laboratories offering LDT services advanced by CAP strikes the right balance by raising standards to ensure quality testing without overburdening laboratories. The AMA supports CAP’s efforts to modernize and support innovation while safeguarding patient safety and access.”

On Feb. 2, the AMA submitted comments on the FDA's proposed framework and requested that it be withdrawn.

To contact the reporter on this story: John T. Aquino in Washington at

To contact the editor responsible for this story: Randy Kubetin at

The CAP proposed framework is at