The U.S. Food and Drug Administration (FDA) is adding yet another job to its already long list of responsibilities.

The overburdened agency has taken steps to end its “enforcement discretion” authority over some laboratory-developed tests (LDTs) so it can instead regulate them as medical devices. Despite its commitment, though, the FDA has not yet worked out many of the details surrounding its latest endeavor, including the regulatory scheme.

“One of our issues will clearly be resource management within the FDA,” Elizabeth Mansfield, director of personalized medicine at the Center for Devices and Radiological Health’s (CDRH) Office of In Vitro Diagnostics, said last month at a public meeting on LDTs.

Mary Pendergast, an industry consultant and former associate FDA commissioner, agreed with Mansfield. “CDRH needs to fully appreciate how few applications it is really going to be able to review,” she warned.

Application reviews are the least of FDA’s worries right now. Before it can review applications, it must first establish a framework for the regulation of LDTs that attempt to answer a myriad of policy, legal and public health questions. FDA officials said that framework should include risk categorization; a phase-in period for premarket review and quality system requirements for new LDTs; registration and listings; and lab inspections.

Establishing a regulatory scheme for LDTs will undoubtedly be a challenging task for the FDA. During its public meeting in Hyattsville, Md., representatives from the laboratory testing industry warned agency officials to proceed carefully in creating regulations because the directives could stifle innovation, delay the development of tests, result in fewer test improvements and limit patient access to tests. Some speakers at the two-day meeting expressed their concerns about the effect on tests that are developed in response to new and emerging threats, and tests for rare disorders. Others claimed patient care could suffer and advances to personalized medicine could slow if LDT regulation is not implemented in a balanced manner.

“Applying a strict paradigm based upon the regulation of ‘traditional’ medical devices and applied to all LDTs will have major consequences to clinical laboratories—whose businesses and facilities are set up for far different purposes and in far different ways than those of device manufacturers or even in vitro device manufacturers—and will place those laboratories in jeopardy of being unable to comply, and in many cases, unable to continue important work in the development of cutting-edge LDTs,” stated a three-page letter from the Washington, D.C.-based American Clinical Laboratory Association.

LDTs are defined as diagnostic tests developed and performed by a single laboratory. Traditionally, the laboratories that develop and perform LDTs have been overseen by the Centers for Medicare & Medicaid Services (CMS) but the clinical validity of “homebrew” tests is not regulated by either CMS or the FDA. Over the last 34 years, the FDA has restricted its oversight to medical device kits developed by test manufacturers, certain high-risk LDTs and analyte-specific reagents. LDTs also are regulated by states (notably, New York) and other agencies (the College of American Pathologists).

In its public notice for the LDT meeting, the FDA explains its rationale for wanting to regulate laboratory tests. LDTs initially were “relatively simple, well-understood” diagnostic tests used by doctors and pathologists who played an active part in patient care. Components of the test generally were regulated by the FDA, and tests were performed according to Clinical Laboratory Improvement Amendment standards.

Over the past two decades, however, some elements of LDTs have changed, according to the FDA. Currently, tests often are used to assess high-risk but relatively common diseases and make critical treatment decisions. They also are often performed in “geographically distant commercial laboratories instead of within the patient’s health care setting under the supervision of a patient’s pathologist and treating physician, or may be marketed directly to consumers.”

The FDA alleges that LDTs are being manufactured increasingly by “corporations rather than hospitals or public health laboratories, which represent a significant shift in the types of tests developed and the business model for developing them.” Authorities also claim that when FDA-approved tests are available for a disease or a condition, laboratories often continue to use LDTs that have not been reviewed by the agency.

The increased prominence of LDTs has increased the risks associated with tests that have not been properly validated for their intended use, the FDA claims. These risks include missed or wrong diagnoses and the failure to receive appropriate treatment. The FDA wants the public to be assured that tests “used in the provision of health care, whether developed by a laboratory or other manufacturer, are safe and effective.”