Full article reprinted from "The Gray Sheet" - October 27, 2008
Laboratory Corporation of America pulled its early-stage ovarian cancer test service from the market last week in response to FDA scrutiny, but the lab giant called the agency's actions leading up to the withdrawal "unprecedented."
In an Oct. 20 1letter to FDA, LabCorp defends its decision to launch OvaSure out of its nationwide lab network in June without FDA clearance or approval, but also announced plans to discontinue the product as of Oct. 24 to maintain "positive and responsible relationships with regulatory agencies." LabCorp is requesting a meeting with FDA's Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD).
The letter was sent by LabCorp in response to a Sept. 29 2warning letter charging the firm with marketing OvaSure without a 510(k) or PMA. The warning letter followed an Aug. 7 letter from FDA detailing concerns with the data supporting OvaSure's ability to detect early-stage ovarian cancer (3"The Gray Sheet' Aug. 25, 2008, p. 9).
The enforcement action is unusual since FDA typically does not exert authority over "home brew" tests used as a lab service. Instead, CMS regulates lab processes and protocols under the Clinical Laboratory Improvement Amendments.
In the warning letter, however, OIVD Director Steve Gutman notes that OvaSure was "designed, developed and validated by investigators at Yale University and not LabCorp." He suggests that due to this fact, "the device is not within the scope of laboratory-developed tests over which the agency has traditionally exercised enforcement discretion."
LabCorp General Counsel F. Samuel Eberts, III, counters that the firm's interactions with Yale scientists do not change OvaSure's status as a lab-developed assay that is not subject to FDA regulation.
Eberts explains that Yale's role in the development of OvaSure ended with the licensing of intellectual property. LabCorp did not purchase any products or materials from Yale, and the university "has no control, contractual or otherwise, to influence the development, methodology, validation, performance characteristics, use, distribution or any other aspects of LabCorp's testing service," he writes.
Furthermore, "many" tests offered by labs were initially developed by academic research centers, he says. "We are deeply concerned that the unprecedented position FDA has advanced in its warning letter will limit the dissemination of information and expertise, and will stifle the ability of [labs] to provide innovative diagnostic tests."
Supporting Data, Test Complexity May Be An Issue
OvaSure tests for six proteins and uses the results to calculate the likelihood that ovarian cancer is present with a specificity of 99.4% and a sensitivity of 95.3%, according to LabCorp. However, in July, the Society of Gynecologic Oncologists issued a statement on OvaSure calling for more research "to validate the test's effectiveness before offering it to women outside the context of a research study."
In its August letter, FDA questioned the Yale study that formed the basis of LabCorp's performance claims, pointing out that the women enrolled were either recently diagnosed with ovarian cancer or were in the healthy control group; but none were in the population targeted by the test - "high-risk women who might have ovarian cancer."
Aside from the data, OvaSure also may have attracted FDA scrutiny due the test's complexity. OvaSure's use of multiple markers that feed into an algorithm to calculate a diagnostic score appears to qualify it as what the agency terms an "in vitro diagnostic multivariate index assay."
FDA says IVDMIAs have a higher risk potential than most tests since they are more complex and rely on calculations that are not transparent to an ordering physician. Thus, FDA plans to subject IVDMIAs to pre-market and post-market requirements, whether or not they are lab-developed (4"The Gray Sheet" July 30, 2007, p. 14).
That policy, however, is still in the draft guidance stage. FDA has said that it would give labs up to 18 months of enforcement discretion following the publication of final guidance. Neither LabCorp nor FDA has confirmed that OvaSure is an IVDMIA.
- David Filmore
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