February 2015, Vol 4, No 1

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To Regulate or Not to Regulate Laboratory-Developed Tests, That Is the Question

Edward Abrahams, PhD

The Last Word

No issue in personalized medicine has drawn more attention during the past 10 years than how laboratory-developed tests (LDTs) should be regulated, nor has any other so divided proponents of personalized medicine more than competing opinions on how best to protect the public’s health while encouraging innovation in diagnostics. With the exception of a guidance to regulate companion diagnostics, little progress has been made to provide clarity for the field since the first guidance to regulate in vitro diagnostic multivariate assays, increasingly common molecular tests that produce a diagnostic or predictive index, was issued in 2005 and later withdrawn.

The divisions in the community were on full display at an FDA public workshop on January 8-9, 2015, regarding the agency’s proposed framework, which was issued late last year and is presently under review. Opposing sides made their arguments and outlined their concerns.

The opposing perspectives are summarized neatly in back-to-back opinion pieces JAMA published online on January 5, 2015. Arguing that the FDA should regulate LDTs, Joshua Sharfstein, MD, secretary of the Maryland Department of Health and Mental Hygiene and former health policy advisor to Congressman Henry Waxman, contends that the current state of affairs, in which laboratories are regulated but not the tests they produce, poses a flagrant risk to public health. He writes, “A patient travels by an ambulance that is regulated, to a hospital that is regulated, for care using medicines that are regulated. Yet today, that same patient’s life or death could hinge on whether a single, unregulated diagnostic test result is meaningful.”

Arguing that the proposed LDT guidelines threaten the “emergence of genomic medicine,” James P. Evans, MD, PhD, and Michael S. Watson, PhD, medical geneticists at the University of North Carolina and the American College of Medical Genetics and Genomics, respectively, argue that the FDA’s regulatory framework, despite its good intentions, “could result in the closure of many laboratories, undermine innovation, and potentially limit patient choice,” if for no other reason than the FDA does not have the capacity to carry out its plans to regulate the tests that would come under its purview.

The Personalized Medicine Coalition (PMC) was also invited to participate in the workshop and will have presented formal views to the FDA at the end of January. Because PMC does not represent a single interest group or particular business model, and because the coalition listens to all the points of view in the continuing conversation about regulating LDTs and has incorporated them into our recommendations, it has developed a position that we believe can help move the field forward.

As Amy Miller, PMC executive vice president, told the workshop, “While some of our members actively oppose FDA’s regulation of lab tests, stating that device regulation was not designed to fit laboratory medicine, and some of our members actively support it and want the framework implemented as quickly as possible, arguing that many important tests are now unregulated, the coalition is committed to improving this framework so that personalized medicine can advance and improve the quality of patient care, thus reaping system cost saving.”

Based on our extensive work with PMC members last year, PMC, she said, believes that FDA’s proposed new framework is a “good start,” but unfortunately omits 2 critical components: an outline of LDT risk classification and clarification on the harmonization between the current program for laboratory inspections administered by the Centers for Medicare & Medicaid Services under the Clinical Laboratory Improvement Amendments (CLIA) and FDA’s manufacturing regulations. In short, the proposed framework does not diminish the uncertainty in the field in a way that would enable it to move forward.

Miller also told the workshop that PMC recommends releasing the 2 guidances in draft before finalizing the framework, giving both the agency and the community time to fill in the blanks regarding the important issues of risk classification and FDA-CLIA harmonization before superimposing a new regulatory system on an emerging field.

Whereas we understand that the FDA is under pressure to finalize the LDT guidances and to assert its regulatory authority on the emergence of molecular medicine, PMC urges the agency “to take the time to get it right. Future investment in the field depends on clear, reasonable guidelines, which are in our power to develop now, not at some future date.”

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