On Nov. 18, the Food and Drug Administration (FDA) announced that an oversight policy regulating laboratory developed tests (LDTs) will be put on hold. The agency will reconsider this guidance in discussions with the new administration, Congress and stakeholders.
This is good news for those expecting a widely accepted regulatory framework that protects patient safety and test efficacy. It is also good news for those expecting to protect the development of innovative laboratory tests.
The healthcare sector and the laboratory test industry have been expecting this guidance for over five years and this decision has significant consequences for all stakeholders.
What is an LDT?
All laboratory tests in the U.S. are regulated through the Clinical Laboratory Improvement Amendments (CLIA) statute, passed by Congress in 1988. CLIA certifies the quality of all laboratories using commercially available FDA-approved tests as well as non-FDA-approved tests. An LDT is defined by the FDA as a laboratory test that is manufactured by and used within a single CLIA-certified laboratory, such as a hospital or biotech laboratory.
Reasons for favoring the FDA guidance on LDTs
Like drugs, all laboratory tests must demonstrate safety and effectiveness, independent of the manufacturing origin. To protect patients, the regulatory oversight of LDTs is a necessary requirement. The question is the degree of oversight and the agency that should be responsible. Currently, the FDA is exercising “enforcement discretion,” leaving the regulation of LDTs under CLIA dependent on the Centers for Medicare and Medicaid Services.
In the draft guidance, the agency has proposed to implement a risk-based classification of LDTs. Laboratory tests can be high-, moderate- or low-risk. A high-risk laboratory result can be critical for physician decision-making, such as the identification of a bacteria strain requiring the appropriate antibiotic. An inaccurate test result would cause serious harm, or death, to the patient. A moderate-risk test result would cause a non-life-threatening injury to the patient. A low-risk test result could cause minimal or no harm, for example, assessing the blood level of sodium, generally interpreted by the physician in the context of other clinical data, including a patient’s current situation and medical history.
The regulated in vitro diagnostics industry contends that moderate- to high-risk laboratory tests with the same diagnostic function should be regulated similarly to ensure accurate results. These manufacturers are usually large diagnostics companies, such as Abbott, Roche or Siemens, providing laboratories with standardized and high-quality test kits and instruments. These tests require a rigorous development process and must be approved by the FDA.
Reasons for opposing the FDA guidance on LDTs
LDTs are the cornerstone of personalized medicine, depending on sufficient flexibility for research, development and clinical adoption that may not be possible under the existing FDA framework. Among those critical of the FDA draft guidance on LDTs are biotech companies, research institutions and societies representing them.
The guidance implies that moderate- to high-risk tests will be required to follow the same regulatory pathway as test kits and instruments developed by large manufacturers. Smaller companies and institutions may not be able to fulfill these stringent and expensive requirements, which could cause halting or slowing down of research and development efforts. Flexibility on this guidance is critical for highly dynamic spaces, such as clinical genomics. Furthermore, these requirements may lead to the discontinuation of a significant proportion of over 60,000 LDTs currently available.
In sum, patients would not be able to access many existing and future innovative tests.
Will the FDA be able to reconcile these views?
Yes, the agency can and should exercise regulatory flexibility when developing this guidance. Key stakeholders should sit at the table and start finding common ground focusing on the patient and physician decision making process. Medical care is complex and nuanced, but at the core it relies on the experience and judgement of the physician. We need to protect the patient from safety risks and unnecessary costs from ineffective tests. We need to continue innovating and allowing flexibility for the development of life-saving tests, such as the genomic tests that are driving personalized cancer therapy.
Our increasing understanding of the role genetics plays in diseases such as cancer has significantly revitalized research in laboratory diagnostic technology. This research is leading to the development of molecular tests that are revolutionizing the way medicine is practiced, opening up the era of personalized medicine. Large and small companies and all other players of this revolutionary progress should be heard when regulating the future of medicine.
All sides in this discussion have raised valid arguments that should be thoroughly considered and integrated into the FDA guidance. Holding the legislative process temporarily shouldn’t mean inaction. As Meister Eckhart states “The price of inaction is far greater than the cost of making a mistake.”
Oscar Segurado, MD, Ph.D., director of Medic Affairs Consulting LLC, has extensive global experience covering oncology, immunology and molecular biology in academia and industry settings.
The views expressed by contributors are their own and not the views of The Hill.