Polsinelli Shughart PC Life Sciences e-Alert

The world of FDA regulation of diagnostic tests is likely to dramatically change, and soon!

With the coming of personalized medicine, multiplexing and other innovations in the area of diagnostic testing, the FDA is reevaluating its position regarding regulatory oversight of both commercially distributed diagnostic tests (CDTs), which currently are regulated by the FDA as medical devices, and laboratory developed tests (LDTs), which until recently the FDA has elected not to regulate based on an exercise of “enforcement discretion.”

In an article dated June 15, 2010, published in The New England Journal of Medicine, Dr. Margaret Hamberg, Commissioner of the FDA, and Dr. Francis Collins, Director of the NIH, announced: “Through a process that includes public input, the FDA will work to ensure the quality of key diagnostic tests, helping to protect patients and giving clinicians confidence that personalized medicine will lead to real health improvements.”
The FDA has recently sent enforcement letters to many companies offering diagnostic tests “direct to consumers.”
In a symposium in Kansas City on July 6, 2010, Commissioner Hamberg reconfirmed that the FDA would focus much attention on developing a new regulatory scheme for diagnostic tests and that recent draft regulations on in vitro diagnostic multivariate index assays (IVD-MIAs), a complex type of diagnostic test, were “out the window.”
On July 19 and 20, 2010, the FDA hosted a Public Meeting seeking input on the oversight of LDTs. At this meeting, representatives of more than 70 interested public and private parties offered their views and FDA representatives, including Principal Deputy Commissioner of the FDA Dr. Joshua Sharfstein discussed the background of and certain issues related to the FDA regulation of diagnostic tests.

Following are key observations from these FDA pronouncements and the Public Meetings:

Increased FDA regulation of ALL diagnostic tests (both CDTs and LDTs) are highly likely in the near future. According to the FDA representatives at the public meeting: “The FDA has decided to exercise regulatory authority over LDTs. It has not decided how to exercise this authority.”
The new regulatory scheme is likely to regulate all diagnostic tests and avoid the “piecemeal” approach evidenced by the previous Analyte Specific Reagent and draft IVD-MIA regulatory schemes.
Small volume LDTs developed and used in hospital laboratories for diagnosis or monitoring of rare diseases may well have little additional regulatory burden.
New diagnostic tests without a prior predicate that have low “risk” profiles (see below) may actually be “downgraded” and face less regulatory hurdles in the future.
Many commentators at the Public Meeting emphasized the need for any regulatory scheme to be transparent, clear, and consistent, and create a “level playing field” between CDTs and LDTs, a line of demarcation that has been substantially blurred in the commercial market in recent years.
The key element to any regulatory scheme will be a “Risk Based” analysis, in which the regulators will focus on the risk of lack of prompt treatment that may result from false negatives; the risk of unnecessary therapies that may result from false positives; and the risk that the science behind the test is not valid.
FDA views tests posing the highest risks as (1) tests predicting the likelihood of disease, (2) tests leading to decisions about companion therapeutics that may have potential high-risk consequences, (3) tests that have high rates of false negatives, and (4) tests that have high rates of false positives. Other “risk” indicators include tests with complex analytical software and those that involve complex analytical models based on multiple variables.
However, many participants commented that these risks must be balanced against the benefits of any testing paradigm, including the benefit of any test (regardless of its level of certainty) when only less certain alternatives are available, the benefit of earlier diagnoses, and the benefit of tests that have fewer downside implications. The need to continue to incentivize innovation and to avoid unnecessary interruptives in current patient care regimens was emphasized.
Physician prescribed and interpreted tests will likely receive a lower level of regulatory scrutiny than “direct to consumer” tests in which the patient does not receive any professional counseling or assistance in interpreting the test results or in determining what therapeutic steps to take in light of the test results.
The FDA views the CLIA regulatory scheme as complimentary to, but not a replacement for, an FDA regulatory scheme that will focus on the analytical validity, clinical validity, labeling, and risk profiles of the tests.
The FDA indicated its intent to continue to gather public comment to help guide it in developing an oversight structure that balances the many competing interests. However, the FDA representatives at the open meeting firmly stated that because the FDA already has the authority to regulate diagnostic tests, it does not intend to follow a rulemaking “notice and comment” procedure that would be used if new rules were being promulgated. Many commentators expressed concern about this procedure and, at a minimum, urged the FDA to appoint an expert Advisory Committee to assist it in this process.

What might all of this mean to you? First, if your laboratory has in the past relied on the belief that LDTs are not regulated by the FDA, this is highly likely to change in the near future. Second, if your diagnostic test falls into one of the higher “risk” categories noted above, then you should start preparing NOW for a regulatory regime that is likely to require much more data regarding the analytical and clinical validity of the test. Third, any new regulatory paradigm will focus on evaluation of the risks posed by known and unknown consequences of the increasing array of complex information that the new generations of diagnostic tests can produce and how that information is communicated to and used by physicians and patients.

If you have questions or need further comment, please contact Kevin Sweeney, chair of the Polsinelli Shughart Life Sciences group at (816) 572-4638 or KRSweeney@polsinelli.com; or Jason Sapsin, head of the FDA practice of the Life Sciences group, at (303) 572-9300 or jsapsin@polsinelli.com.