Lab Industry Files Petition Against FDA Regulation of Laboratory-Developed Tests

After several years of threats by the Food and Drug Administration (FDA) that it intends to regulate laboratory-developed tests (LDTs), the lab industry has taken the matter into its own hands. The American Clinical Laboratory Association (ACLA) on June 4 filed a citizen petition under the Federal Food, Drug, and Cosmetic Act (FDCA) challenging FDA authority to regulate LDTs as “devices” under the FDCA. The ACLA petition notes that LDTs differ from in vitro diagnostic test kits, which are packaged and commercially distributed and are regulated by FDA as medical “devices.” LDTs, argues ALCA, are laboratory services, not products, and are not distributed, delivered, nor placed into market. They are “proprietary procedures for performing a diagnostic test using reagents and laboratory equipment . . . essentially know-how, not articles,” says the petition. According to the ACLA petition, FDA cannot and should not regulate LDTs as medical devices under the FDCA for several reasons:

• The FDA lacks the requisite authority since LDTs are not “devices” as defined in the act. In addition, FDA’s assertion of jurisdiction over LDTs is incompatible with the Clinical Laboratory Improvement Amendments (CLIA) and their legislative history.

• FDA regulation of LDTs would be contrary to public health. Numerous critical tests are available only as LDTs, including many “gold standard” DNA sequencing assays, newborn screening tests, and tests for rare diseases. If FDA were to require clearance or approval for LDTs, laboratories may be unable to continue offering them.

• FDA regulation of LDTs as devices would result in numerous unintended consequences with significant economic repercussions for the U.S. laboratory industry.

• To the extent that stakeholders have concerns about regulatory gaps under CLIA, the most logical and appropriate solution would be to amend CLIA and its regulations—not to impose an additional layer of regulation based on a different statute designed for products rather than laboratory testing.

Concern About LDTs Since 1988, laboratories performing LDTs have been regulated under CLIA. While the FDA has said for years that it has enforcement discretion to regulate LDTs, it made little attempt to exercise what it viewed as its authority. In 2010, however, the FDA said it planned to exercise its enforcement discretion over LDTs and would issue guidance detailing its oversight scheme. Since then, the lab industry has been awaiting the guidance. While the agency is required to give Congress 60 days’ notice before issuing such guidance, FDA Commissioner Margaret Hamburg recently made some unexpected comments about LDTs that raised industry eyebrows. During remarks made June 2 during the American Society of Clinical Oncology’s annual meeting in Chicago, Hamburg said that LDTs are marketed without evaluation through FDA’s premarket approval process to determine whether they are accurate and clinically valid. “That can be a problem,” she noted. Concern has been expressed about the potential effect increased regulatory oversight of LDTs would have on personalized medicine. At the 2013 Policy Meeting of the College of American Pathologists in Washington, D.C.,  Debra G.B. Leonard, M.D., Ph.D., professor and chair of pathology at the University of Vermont College of Medicine, noted that genetic testing by next-generation sequencing is an LDT. “We must promote rigorous laboratory interpretive standards for clinical genomic testing. And we must advocate that interpretation of genomic data is the practice of medicine and not under the regulatory purview of the FDA,” Leonard told a CAP meeting audience. While Hamburg noted that advanced diagnostics are the cornerstone of personalized medicine, she argued that “not all complex diagnostics used in cancer diagnosis or treatment have been developed to perform at the same demonstrated standards.” She recalled how in 2008, OvaSure, an early-stage ovarian cancer screening test, came onto the market. “For high-risk patients and their doctors, this simple blood test appeared to offer great promise for combating the disease and providing peace of mind. Although FDA did not consider OvaSure to be a laboratory-developed test, it was offered as an LDT and thus did not undergo adequate clinical validation before the test was used across the country. Thanks in large part to the involvement of the oncology community, together with FDA, this flawed test was eventually withdrawn from the market, some four months after it had been launched.” LDTs are being used with a family history of cancer to decide whether to take preventive action, Hamburg said. “FDA does not know how many women may have received erroneous results from the OvaSure test, or how many may have used that flawed information to make critical medical decisions. But relying on advanced diagnostics to make critical, life-altering treatment decisions exposes patients to obvious risks if these tests do not perform as expected. False results put patients at risk of a missed diagnosis or a wrong diagnosis that could result in either inappropriate treatment or no treatment at all.” The agency is working to make sure that the accuracy and clinical validity of high-risk tests are established before they come to market, Hamburg said, and the risk-based framework under development will ensure that diagnostics used in cancer treatment will provide medical professionals with a critical baseline for confidence in the tests they order for their patients. The ACLA petition is available on the association’s Web site at www.acla.com.