ACMG Issues Primer on Regulation of Laboratory-Developed Tests

The new statement, co-authored by a Nationwide Children’s laboratory geneticist, outlines how lab-developed tests are regulated and offers patient-centered recommendations for modernizing oversight.

Laboratory-developed tests (LDTs) are validated testing protocols developed by certified clinical laboratories for patient care and play an essential role in diagnosing and guiding treatment for many conditions that affect pediatric patients. They are often developed to fill an unmet clinical need when commercial testing kits are not available. These tests may be run infrequently but are crucial for patient care. For instance, they are used in diagnosing rare genetic diseases and tumor types and delivering timely, individualized care. Following a wave of regulatory uncertainty, the American College of Medical Genetics and Genomics (ACMG) has released a new statement as an educational resource about the regulation of LDTs for medical geneticists and other clinicians as well as policymakers.

Marco Leung, PhD, clinical director at the Steve and Cindy Rasmussen Institute for Genomic Medicine at Nationwide Children’s Hospital and ACMG fellow and chair of the Advocacy and Government Affairs Committee, served as lead author on the statement, which was published in Genetics in Medicine. The document explains how LDTs are subject to rigorous oversight under the Centers for Medicare and Medicaid Services (CMS) Clinical Laboratory Improvement Amendments (CLIA) of 1988 and makes several recommendations to strengthen and modernize that framework.

“There has been some confusion about how LDTs are regulated — especially after the FDA attempted to assert new authority over them,” said Dr. Leung. “We wanted to show that a strong system already exists, and more importantly, that it can be improved without duplicative regulation, which would jeopardize access to these critical tests.”

In May 2024, the FDA issued a final rule that would have treated LDTs as medical devices, adding a new layer of regulatory requirements that most labs would not have the resources to meet, explains Dr. Leung. But in early 2025, a federal court vacated the rule, concluding that the FDA had overstepped its authority and that LDTs are professional medical services — not manufactured products or devices.

While the rule is no longer in effect, the concern it created in the medical community still lingers. “The goal now,” said Dr. Leung, “should be to improve the existing regulatory framework, not to impose redundant oversight that could delay care or limit access, particularly in pediatric and rare disease settings.”

LDTs are essential in many children’s hospitals, especially when no FDA-approved test exists or when a test originally created for adult patients is modified to ensure that they are appropriate for pediatric use. Unlike commercial tests, LDTs are designed, validated, and performed by board-certified lab professionals specifically for use in their patient population. For example, in January 2024, the Institute for Genomic Medicine at Nationwide Children’s validated and launched rapid genome sequencing to serve patients in the pediatric and neonatal intensive care units. It is used to confirm a suspected genetic disorder and offers preliminary results in three to five days. LDTs such as this enable these children, who are often in critical condition, to get faster diagnoses, potentially leading to improved patient care and outcomes.

The ACMG statement recommends practical updates to the CLIA framework, such as requiring inspections before new labs begin high-complexity testing, improving transparency with public reporting of test performance, and ensuring both analytical and clinical validity of tests.

“CLIA was established in 1988, and since then, laboratory testing has evolved, methodologies have changed, and the range of diseases that we have tests for have increased,” says Dr. Leung. “These reforms would support improved safety and quality, while still allowing labs to innovate and respond quickly to patients’ needs.”

As the national conversation about test oversight continues, the ACMG’s statement offers a patient-focused reflection of current regulations and recognizes the value of innovation and the importance of timely, personalized care.

Reference

Leung ML, Caylor RC, D’Annibale O, McClure M, Narumanchi T, Sack LM, South ST; ACMG Advocacy and Government Affairs Committee. A primer on regulation of laboratory-developed testing procedures: A points to consider statement of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2025 May 2:101391. doi: 10.1016/j.gim.2025.101391. Epub ahead of print. PMID: 40314626.

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