TRENDS & PERSPECTIVES
More than a year ago, FDA said in a nonbinding draft guidance that in vitro diagnostic multivariate index assays (IVDMIA) are medical devices and would be subject to the agency’s enforcement discretion.
A letter that FDA’s Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD) sent earlier this summer to Laboratory Corporation of America (LabCorp; Burlington, NC) may show what the agency means by that policy.
In an untitled letter, OIVD asked LabCorp CEO David King to meet to discuss its OvaSure Yale test, saying that the agency believes “you are offering a high-risk test that has not received adequate clinical validation and may harm the public health.”
LabCorp spokesman Eric Lindblom said that LabCorp is working with the agency to review the clinical data related to the test but believes that the research that supports its use is solid.
The OvaSure test was developed by Yale University School of Medicine researchers to discriminate between disease-free women and ovarian cancer patients. LabCorp launched the service for the test, a six-panel biomarker, commercially in late June and continues to offer it.
Steve Gutman, MD, director of OIVD, said that he “cannot discuss product-specific reviews or compliance interests.”
Glen Freiberg, president of RCQ Consulting (San Diego), believes that FDA is using the LabCorp OvaSure test to set an example of what it means by “enforcement discretion” for laboratory-developed tests (LDT), or home-brew tests, that could be subject to the draft IVDMIA guidance. LDTs are developed and performed in the company’s laboratory for in-house use as a test service.
“To make a point, OIVD is dipping its toe toward coercion through the publicity of an untitled, yet public letter,” he said.
Freiberg said that when he was an FDA investigator, the agency occasionally would supplement local authorities and conduct restaurant inspections. What OIVD is doing with LabCorp is the same strategy and that the application of enforcement discretion, while sending a message, is inconsistent and unfair.
The problem with enforcement discretion, Freiberg said, is that it is not uniform or predictable. “Unless FDA is going to be definitive and treat everyone the same way, why should enforcement discretion be representative of FDA policy?” he said.
To be fair, Freiberg said, “FDA needs to decide what it is going to regulate and promulgate regulations and not try to regulate by guidance document or draft guidance document. The job of a regulatory affairs professional is just about impossible in situations like this because you have little way of knowing when you are crossing any official line.”
Freiberg said that another example of OIVD’s enforcement discretion over LDTs is the letter it sent to Exact Sciences in November 2007 about its stool-based DNA test for colorectal cancer screening, PreGen-Plus. In the letter, FDA said it believed that the commercial PreGen-Plus assay is a medical device requiring premarket approval or clearance.
LabCorp had purchased the rights to this test and had been marketing PreGen-Plus but it no longer does, Lindblom said. The stoppage is not related to FDA’s letter, he said. However, LabCorp is offering its own test, ColoSure, which is also a single marker laboratory-developed, stool-based DNA test.
Gutman would not comment on whether OIVD’s recent letters were examples of its enforcement discretion under the draft guidance. “The letters represent OIVD queries and are not subject to public discussion,” he said. Yet, the letters were made public, and Gutman has maintained that industry must evaluate the risks.
However, Gutman also said that FDA “continues to apply enforcement discretion to laboratory-developed tests” while two policies are under review: FDA’s draft guidance on IVDMIAs and the Secretary’s Advisory Committee on Genetics, Health and Society (SACGHS) report, which recommends how to move forward with issues related to laboratory-developed tests, especially those related to genetics and genomics.
Freiberg believes LabCorp may challenge FDA on its position regarding its LDTs and could be successful because OIVD really cannot enforce a guidance or a draft guidance. “There has to be a regulatory basis for enforcement,” he said. “When you go to court, you have to show what the regulatory basis is for what you are doing and how you’re applying it uniformly, and I don’t know that FDA can do that.”
The situation is somewhat unfair to OIVD as well, Freiberg said. Congress has provided a laboratory regulation through the Clinical Laboratory Improvement Amendments (CLIA) and a manufacturing/marketing/distribution regulation through the Federal Food, Drug, and Cosmetic Act, he said. “Congress has not addressed in sufficient detail how the two agencies are to handle the blend when the lab becomes a manufacturer with marketing claims for innovative products.”
