A Medical Device Daily

The regulatory scheme for in vitro diagnostics has looked like something of a grey zone for some time, given that some such diagnostics are not subject to the kind of scrutiny that drugs, devices and biologics must withstand. In an attempt to nudge the agency into a more proactive stance, the Advanced Medical Technology Association (AdvaMed; Washington) has proposed a risk-based paradigm for the regulation of in vitro diagnostics that would eliminate any regulatory differences between the so-called "home-brewed" diagnostic and those that are packaged for commercial sale.

According to the March 27 letter by AdvaMed to Dan Schultz, MD, the director of the Center for Devices and Radiological Health, the proposal "sets forth a risk-based tier triage model" for diagnostics regulation, which the association says would be "based on the risk associated with use of a test" and which would eliminate the distinction between commercially sold diagnostics and those developed and used solely in a lab. AdvaMed is of the position that because "there are [more than] 1,000 genetic disorders where tests are developed in labs and are not subject" to regulation by FDA or by the Clinical Laboratory Improvement Amendments of 1998 (CLIA), "the regulatory system must ensure a risk-based approach to all diagnostic tests."

AdvaMed makes note of the citizen petition filed by Genentech (South San Francisco, California) this past December, which would also subject home-brewed diagnostics to the same standard as those made for sale. One of the driving forces behind the concern is the increasing drive toward personalized medicine, which some observers believe will foster a proportionally larger use of home-brewed diagnostics than is the case now, albeit without federal regulatory oversight. FDA has issued warning letters over the practice recently, including an October 2007 warning to Exact Sciences (Marlborough, Massachusetts) and a September 2008 warning letter to LabCorp (Burlington, North Carolina).

Predictably, however, opinions are divided on the subject. The Coalition for 21st Century Medicine (CCM; Washington) published a Dec. 30, 2008, statement in opposition to Genentech's letter, stating that the adoption of such a proposal "threatens innovation in laboratory tests, would harm patient care and rests on flawed scientific and legal premises."

The question of how the agency should regulate home-brewed diagnostics has popped up periodically over the years, and FDA published a guidance document for this set of diagnostics in January 2008 in an attempt to provide clarity (Medical Device Daily, Feb. 8, 2008). FDA mandated in that guidance that such a test require no operator action during analytical procedures and that the diagnostic be "a fully automated instrument or a unitized, self-contained test."

FDA also took the position in that guidance that while "reference methods may not be available for every device type," but nonetheless insisted that any such diagnostics "should be traceable to true reference methods of known accuracy when such methods are available."

The AdvaMed proposal contains a number of guiding elements, including that "FDA should regulate all diagnostics ... and in vitro diagnostic tests based on the risk associated with the use of the results in patient management." However, AdvaMed proposes that some tests be exempt because some lab-based tests "represent well-established technologies used to detect familiar biomarkers." However, the association's position is also that "higher-risk tests be cleared or approved through an approach that aligns data submission requirements and the intensity of review with [the diagnostic's] risks."

AdvaMed also addressed reimbursement. According to the association's proposal, "Medicare's reimbursement system is based on an outdated process and a fee schedule that dates back to the early 1980s, before the development of many of the new diagnostic technologies available today." AdvaMed also states that a study published by the Lewin Group (Washington) in 2005 concluded that "the current fee schedule is flawed, complex, lacks transparency and does not efficiently incorporate new technologies."

As for AdvaMed's triage system for risk-based review, a new technology dealing with a new biomarker or a new use of an existing biomarker would be subject to the PMA process or a de novo 510(k). AdvaMed proposes that any established diagnostic used to detect a new biomarker, or a new diagnostic used to detect an established biomarker, be subject to one strand or another of the 510(k) process. AdvaMed also suggested "a test driving approach" to the proposal in order to weed out problems, and urged FDA to conduct "regular classification meetings" to deal with any questions dealing with specific diagnostics or analytes.

CMS eyes outpatient infusion coverage

The Centers for Medicare & Medicaid Services has announced that it will accept public comments until April 24 on the subject of whether it should universally reimburse for outpatient infusion therapy of insulin for diabetic beneficiaries. According to the March 25 announcement, the idea was prompted in part by the fact that some clinical investigators see the "pulsatile nature" of insulin release as potentially important in how the substance affects glycemic control for patients with Type 2 diabetes. Insulin infusion as an adjunct to the typical insulin management regime, which not all Medicare contractors cover, is said to offer "improved glycemic control and blunted progression or reversal of diabetic complications."

The action is said to have been internally generated, and the agency expresses an interest in clinical studies relating to infusion therapy and metabolic measurements taken during therapeutic sessions. CMS notes that if the evidence is deemed inadequate to justify coverage, "we are especially interested in what types of studies are needed." The agency expects to issue a draft determination by Sept. 25 and a final decision on Dec. 24.

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