Nearly one year after the US Food and Drug Administration slammed Exact Sciences for misbranding a genetic colorectal cancer screening assay it was developing with the Laboratory Corporation of America as a laboratory-developed test, LabCorp is facing regulatory action from the agency for the same violation with regard to an ovarian cancer detection test it developed with Yale University.
The FDA issued a warning letter to LabCorp on Sept. 29 stating that its OvaSure test is “not within the scope of laboratory-developed tests over which the agency has traditionally exercised enforcement discretion.”
The warning letter follows an Aug. 7 letter, in which the FDA's Office of In Vitro Device Evaluation and Safety requested to meet with LabCorp to discuss the utility of OvaSure, developed at Yale University and launched in June, after it learned that the test's performance characteristics were based on results of a study that does not represent the intended treatment population [see PGx Reporter 09-03-2008].
Based on information collected by the FDA and data provided by the company at a Sept. 5 meeting, OIVD said it has determined that OvaSure is a test “designed, developed, and validated by investigators at Yale University and not LabCorp.”
Particularly, the FDA’s investigation has found that the instructions for use and the performance characteristics for the test were developed by Yale investigators. Furthermore, the agency found that certain materials associated with the tests were manufactured by another entity. The specific test parts and the manufacturer’s identity have been stricken from the publicly posted warning letter.
In clinical studies, Yale investigators used protein arrays to identify six candidate biomarkers to assess early-stage ovarian cancer in high-risk women, including leptin, prolactin, osteopontin, insulin-like growth factor II, macrophage inhibitory factory, and CA-125. These biomarkers were incorporated into a multiplex immunoassay.
In its warning letter, the FDA identifies OvaSure as a device under section 201(h) of the Food, Drug, and Cosmetic Act intended for diagnosing or treating disease, and therefore requiring marketing clearance or approval from the agency. “Because you do not have marketing clearance or approval from the FDA, marketing OvaSure in violation of the law,” the agency determined, calling the device “adulterated” and “misbranded” as a result.
While LabCorp is “disappointed about receiving the warning letter,” discussions are ongoing over possible next steps, Lindblom said.
Eric Lindblom, LabCorp’s senior VP of investor and media relations, told Pharmacogenomics Reporter this week that while the company is “disappointed about receiving the warning letter,” discussions are ongoing over possible next steps.
“LabCorp shares the FDA's determination to help assure that patients are protected,” Lindblom stated.
However, he would not comment when asked whether the company felt any part of FDA’s regulatory guidelines regarding LDTs were confusing, particularly since this is the second time the company has been involved in a situation where a test being developed with a partner has been deemed by the agency as “misbranded.”
The FDA’s Oct. 11 warning letter to Exact Sciences similarly found its PreGen-Plus assay “adulterated” and “misbranded,” after the company failed to appropriately characterize the product it was developing with LabCorp [see PGx Reporter 01-23-2008].
The FDA’s action against Exact came after an inspection by the Centers for Medicare and Medicaid of LabCorp’s facilities revealed that PreGen-Plus was “designed, developed, validated, and marketed by Exact rather than a test that was developed and validated by LabCorp.” As a result, the FDA found that Exact’s test is not a laboratory-developed test that traditionally falls under the regulatory purview of CMS, but a medical device requiring premarket approval or clearance from the agency.
Last year, the FDA released a draft guidance explaining that in vitro diagnostic multivariate index assays are medical devices. Before this guidance, laboratory-developed tests such as the OvaSure were considered homebrews and overseen by the Centers for Medicare and Medicaid's less stringent CLIA rules.
Industry observers have pointed out that FDA’s actions against LabCorp regarding OvaSure may further confound its regulatory stance on IVDMIAs, particularly since the agency has yet to issue a final guidance on the matter.
The agency’s first letter to LabCorp regarding OvaSure came during “a period of uncertainty about FDA’s regulatory intentions with respect to LDTs,” wrote Gail Javitt, law and policy director at Johns Hopkins University’s Genetics and Public Policy Center, in a September GPPC newsletter.
“The agency long has asserted it has jurisdiction to regulate all LDTs, but that in general it will exercise ‘enforcement discretion.’ FDA has further indicated, through a draft guidance document, that it intends to regulate a subset of LDTs that the agency has termed IVDMIAs. While the literature on OvaSure indicates it bears certain features of an IVDMIA, the letter makes no reference to the IVDMIA draft guidance.”
Similarly, FDA’s September 29 warning letter makes no reference to IVDMIAs.
LabCorp has 15 working days from receipt of the warning letter to present to the FDA its plan to correct the violations identified by the agency.
In Exact’s case, although the company had announced plans to submit a second version of the PreGen Plus test to the agency for 510(k) clearance, the company suspended the validation study for the submission after facing potential delisting of its shares from the Nasdaq exchange [see PGx Reporter 07-23-2008].
Meanwhile, LabCorp in July launched ColoSure, a homebrew stool-based colon cancer test that uses PCR to detect the methylation of the Vimentin DNA marker. ColoSure is based on technology LabCorp licensed from Exact Sciences.