December 2008: Volume 34, Number 12
LabCorp Withdraws Ovarian Cancer Test
Warning Letter Ads New Twist to FDA’s Approach to LDTs
By Bill Malone
In response to a September FDA warning letter, LabCorp recently cut the OvaSure test for ovarian cancer from the company’s menu. The warning letter came after the agency asked to discuss the test’s performance characteristics with LabCorp. FDA ultimately determined that the test could not be marketed under the rubric of lab-developed tests (LDT), pushing regulation of LDTs back into the spotlight for another reason.
In the warning letter, FDA asserts that because Yale researchers developed the test, it doesn’t count as the type of in-house test that FDA allows to skip premarket review or 510(k) clearance. The letter states that OvaSure was “designed, developed, and validated” by Yale researchers, and so is “not within the scope of laboratory-developed devices over which the agency has traditionally exercised enforcement discretion.”
In reply to the warning letter, LabCorp made the case that OvaSure is no different from other tests based on know-how from academic researchers. In an SEC filing that officially announced the withdrawal of OvaSure from the market, LabCorp states that OvaSure was “rigorously validated pursuant to CLIA requirements” and that it disagrees with FDA that its interactions with Yale “provide FDA any basis for exercising jurisdiction over the test. LabCorp licensed intellectual property from Yale University; we did not purchase any products or materials from Yale.” The letter goes on to argue that labs frequently offer tests which originate in academic research centers, a practice that can “permit this research to be translated into innovative diagnostic test services.”
The Fine Print: All LDTs are Devices
While FDA has maintained for over a decade that LDTs are devices subject to FDA jurisdiction, the agency has generally declined to regulate them (CLN, November 2006). Instead, the agency regulates the building blocks of LDTs—analyte-specific reagents (ASR), which encompass the anti-bodies, nucleic acid sequences, and other reagents that are the primary ingredients.
FDA laid out its view on LDTs in its final rule on ASRs published in 1997. This rule classified low-risk ASRs as class I devices exempt from premarket 510(k) requirements, and moderate and high-risk ASRs as class II and III devices, respectively. The purpose was to regulate all ASRs in a consistent way.
Some stakeholders had asked for a more strict approach, arguing that even labs that are qualified to perform high-complexity testing don’t necessary have expertise in developing tests themselves. Another argument for stricter oversight of ASRs was that CLIA regulation of labs does not require LDTs—which are made up of ASRs—to be validated in rigorously controlled clinical trials to establish expected values and performance characteristics. Such clinical trials are only required under FDA-cleared products. However, in the final rule, FDA stated that it “recognizes that the use of in-house developed tests has contributed to enhanced standards of care in many circumstances and that significant regulatory changes in this area could have negative effects on the public health.” Even at that time, FDA made its view clear that LDTs are still devices under its purview: “FDA believes that clinical laboratories that develop such tests are acting as manufacturers of medical devices and are subject to FDA jurisdiction.” But the agency asserted that its oversight, as explained in the ASR final rule, was sufficient to assure quality of LDTs.
Ironically, LabCorp’s OvaSure seems to have been fated to run into the same problems as a similarly named test that also worried FDA—Correlogic’s OvaCheck test, which also identifies early-stage ovarian cancer. In Correlogic’s case, FDA took issue in 2004 with the test’s sophisticated interpretation software, a new element in test interpretation. Two years later, FDA released its controversial IVDMIA draft guidance that deals with software that interprets data from multiple analytes.