June Monthly Topic:

MammaPrint is the First Gene Expression MicroArray Cleared by FDA under Controversial Draft Policy

In the latest development surrounding the Food and Drug Administration’s (“FDA”) regulation of genetic tests, the agency has granted a 510(k) clearance to Agendia’s MammaPrint as an aid in the prognosis of previously diagnosed breast cancer.  Following clearance of the MammaPrint, FDA has recently released the Special Controls Guidance document for Gene Expression Profiling Test Systems for Breast Cancer Prognosis.(1.)  FDA clearance of the MammaPrint was particularly significant in that it represents the first time the agency has cleared a diagnostic test that profiles gene activity, or expression patterns, of multiple genes.  While existing genetic tests either look at the activity of one gene or simultaneously assess the presence of multiple gene mutations, the MammaPrint is an in vitro multivariate index assay (“IVDMIAs”) which profiles expression patterns of over 70 different genes.  The genes of interest are arrayed on a chip and, using fluorescent labeling, tested against the genetic material from a patient’s breast tumor.  The patterns are then analyzed with software, resulting in a overall risk score.  Despite the novelty of this device with respect to in vitro diagnostic devices (“IVDs”) already on the market, which automatically rendered the MammaPrint a Class III device requiring PMA approval, FDA determined it was appropriate to downclassify the MammaPrint to Class II subject to the less demanding 510(k) regulatory pathway.  Notably, MammaPrint is not available in kit form in the United States.  Samples must be sent to Agendia’s laboratories, which are in the Netherlands. 

FDA’s clearance of the MammaPrint as a Class II device was the first clearance of an IVDMIA under the agency’s controversial draft policy for laboratory-developed multivariate index assays.(2.)  The 2006 draft FDA guidance document asserts regulatory jurisdiction over the MammaPrint and similar types of genetic tests even when developed for use in a single laboratory.(3.)  Traditionally, such laboratory-developed tests, also known as “home-brew” tests, are regulated under the Center for Medicare and Medicaid Services’ (“CMS”) Clinical Laboratory Improvement Amendments (“CLIA”).  However, FDA has begun asserting premarket regulatory jurisdiction over such tests due to their complexity.  Specifically, IVDMIAs such as MammaPrint, rely on clinical data from one or more assays on which a proprietary algorithm is based.  This algorithm results in a score that cannot be interpreted by a clinician without information about the clinical performance and effectiveness of the test. 

Industry has voiced concern since the release of the draft guidance that this agency policy will hinder innovation as the regulatory requirements will be overly burdensome for small companies.  In addition, the diagnostic industry is concerned with the ambiguity of the draft guidance in terms of exactly what tests constitute IVDMIAs and will thus be subject to FDA premarket review.  Whether FDA decides to pursue formal rule-making to assert jurisdiction over laboratory-developed tests, as industry has requested, or continues working to improve on the existing non-binding guidance document, the impact of FDA regulation on physician access to laboratory-developed tests remains to be seen.