LDTs, Genomic Research & FDA Regulation: A Question of Intent

By Jordan Paradise

Last month, Seton Hall University School of Law’s Center for Health & Pharmaceutical Law & Policy hosted Prof. Barbara Evans, Ph.D., J.D., LL.M, as a Visiting Scholar. Prof. Evans is the George Butler Research Professor at the University of Houston Law Center; Director of the Center for Biotechnology and Law; and is an affiliated member of the Center for Medical Ethics and Health Policy at Baylor College of Medicine.

Prof. Evans’ visit included a public lecture entitled FDA Regulation of Genomic Testing: Will Regulation Do More Harm Than Good? The lecture examined the changing legal environment for genomic testing driven by recent legislative, judicial, and executive branch activity. She discussed the restructuring of the genetic testing industry itself in the wake of the Supreme Court decisions in Association for Molecular Pathology v. Myriad Genetics (2013) and Mayo Collaborative Services v. Prometheus (2012). Health Reform Watch has covered aspects of both of these cases in the previous blog post here. She also assessed the effect of the Health Insurance Portability and Accountability Act of 1996 (HIPAA) and the Health Information Technology for Economic and Clinical Health Act of 2009 on data sales and pricing, as well as the emergence of individual access rights established in HIPAA, the Clinical Laboratory Improvement Amendments, and FDA research regulations.

Prof. Evans’ lecture specifically targeted the FDA’s recently-announced position on the oversight of laboratory developed tests, or LDTs. LDTs exist in the spectrum of products categorized by the FDA as medical devices subject to premarket review or clearance, and other substantive requirements. The FDA defines an LDT as “an in vitro diagnostic (IVD) that is intended for clinical use and designed, manufactured, and used in a single laboratory.” The FDA has historically not enforced premarket review and regulatory requirements for LDTs because they have been relatively simple laboratory tests available on a limited basis.

Following a July 2014 Notice of Intent to Congress, the FDA released its Framework for Regulatory Oversight of Laboratory Developed Tests (LDTs) in October 2014. Ending decades of enforcement discretion, the FDA highlights the inherent risk of certain LDTs as a means to subject products to medical device requirements. The FDA cites changed technological capabilities and the proliferation of advanced marketing and business models. “Some LDTs are now more complex, have a nation-wide reach and present higher risks, such as detection of risk for breast cancer and Alzheimer’s disease, which are similar to those of other IVDs that have undergone premarket review.” In addition, the FDA flagged problems with product claims unsupported with adequate evidence, lack of appropriate controls, and falsification of data pertaining to specific products.

The FDA hosted a public workshop in January 2015 to vet the framework with stakeholders. Detailed legal blog coverage of the FDA’s flurry of activity in the LDT realm can be found here and here. A short article on the topic was also published in the January/February edition of FDLI Update, available here. Opposing views were also published in JAMA, available here.

In March 2015, the Diagnostic Test Working Group (DTWG), an independent group of clinical laboratories and diagnostic manufacturers, publicly responded to the FDA’s position. The DTWG policy document is framed as an alternate proposal to the FDA guidance. Coverage from the FDA Law Blog describing the DTWG effort as “an intriguing start toward potential LDT compromise” can be found here.

Prof. Evans’ lecture focused on a piece of the larger debate involving LDTs: how the draft guidance will impact genomic research. She identified an implicit threat in the FDA draft guidance, in that the FDA seemed to be saying that many genomic tests never deserved enforcement discretion and thus do not comply with the federal Food, Drug, and Cosmetic Act.

Evans’ framed the real issue as a question of intent, and whether a genomic test is in fact an IVD that the FDA can regulate. She emphasized that FDA authority to regulate is triggered by intent for clinical use. The FDA regulations state:

In vitro diagnostic products are reagents, instruments, and systems intended for use in the diagnosis of disease or other conditions, including a determination of the state of health, in order to cure, mitigate, treat, or prevent disease or its sequelae. 21 C.F.R. §809.3

Clinical use is defined by FDA regulations in terms of objective intent of the person legally responsible for labeling the device and can be based on aspects such as labeling claims, advertising, oral and written statements by the person or representatives, and particular circumstances. Specifically, intent may be found if the device “is, with the knowledge of such persons or their representatives, offered or used for a purpose for which it is neither labeled nor advertised.” 21 C.F.R. §201.128

However, Evans pointed out that the regulations are more subtle than the FDA’s LDT draft guidance suggests. Ultimately, Evans’ view is that the LDT guidance incorrectly treats any return of genomic results as showing intent for clinical use and requires further nuancing. She argued that there are meaningful ethical and legal distinctions among the following in the context of genomic research: simple data-sharing, the return of results, clinical care, research uses that do not make clinical claims or create significant risk, statements about the test and statements about the gene variants the test detects, and statements made both before a test is administered to a patient and statements made afterward.

Evans’ forthcoming article in the Food & Drug Law Journal further addresses her concern with FDA regulation of LDTs utilized in genomic research. In this article, she argues that “intrusive” FDA regulation may “(1) slow the progress of genomic discovery; (2) interfere with scientific inquiry and suppress investigators’ and clinicians’ speech in ways incompatible with the First Amendment to the U.S. Constitution; and (3) upset longstanding Congressional and FDA policies on federalism that respect the primacy of States to regulate the practice of medicine.” The full article is available here.

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