Laboratory Developed Tests
Although many IVDs take the form of kits that go through the FDA review process, many other diagnostic tests enter the market as laboratory developed tests (LDTs). This is particularly true for genetic tests. To date, FDA has cleared only a handful of the more than 1,300 genetic tests now offered in the U.S.
This is because historically, FDA has not regulated LDTs. In 1992, however, the agency asserted that it did have the authority to regulate all LDTs. This was challenged via a citizen petition, which FDA denied (Gibbs, JN, Bump, CP. Developments in the Law: Questions over FDA’s Authority to Regulate Laboratory Developed Tests. Hyman, Phelps & McNamara website. www.hpm.com/devitem.cfm?RID=74.0. Accessed January 16, 2008). Until very recently, however, the agency did not try to invoke this power. Then, FDA began to invite some laboratories to come to the agency to discuss the regulatory status of their LDTs.
On September 7, 2006, FDA issued the “Draft Guidance for Industry, Clinical Laboratories, and FDA Staff on In Vitro Diagnostic Multivariate Index Assays (IVDMIAs)” (Federal Register—2006; 71:52800-52801). In this document, for the first time, FDA declared its intention to regulate LDTs that involved the testing of multiple markers and used an algorithm that could not readily be understood by physicians.
This proposal generated significant opposition. The Washington Legal Foundation filed a petition challenging FDA’s legal authority to regulate LDTs (CaseDetail: Petition to Stop FDA Regulation of Clinical Labs. www.wlf.org/Litigating/casedetail.asp?detail=451). Others criticized the agency’s failure to go through notice-and-comment rulemaking. Even those who supported the concept expressed concerns regarding unclear language in the draft guidance document.
On July 26, 2007, FDA issued a revised draft guidance document (Draft Guidance for Industry and Food and Drug Administration Staff; In Vitro Diagnostic Multivariate Index Assays; Federal Register—2007; 72:41081-41083), reiterating that LDTs are considered devices but modifying the definition and including a transition period. FDA said that IVDMIAs are expected to be a niche area, which was also disputed. Many diagnostic tests that will affect drug therapy decisions will fall outside this category. Pharmacogenomic or proteomic LDTs that use multiple markers and algorithms, however, may fall into the IVDMIA classification.
Thus, drug companies expecting that multiple-marker diagnostics could quickly enter the market through the LDT route may—depending on the outcome of the IVDMIA debate—need to reassess this strategy. Moreover, given FDA’s repeated statements that all LDTs are subject to FDA regulation, pharmaceutical companies should be careful about attaching their regulatory fate to an LDT.
FDA’s approach toward how it exercises enforcement discretion could shift again. In addition, the agency might try to regulate an LDT if a manufacturer provided significant support to the laboratory (Gutman SI, MD, Director, OIVD, CDRH. Letter to Luber JR, President, EXACT Sciences Corporation. October 11, 2007. www.fda.gov/foi/warning_letters/s6568c.pdf. Accessed January 16, 2008).
FDA also regulates laboratory tests by asserting jurisdiction over software. With increasing frequency, laboratories are acquiring data and then using a computer to analyze the data and generate a test report. FDA has stated that this software is a device subject to FDA jurisdiction (Gutman SI, MD, Director, OIVD, CDRH. Letter to Levine PJ, President and CEO, Correlogic Systems, Inc. July 12, 2004. http://www.fda.gov/cdrh/oivd/letters/071204-correlogic.html. Accessed January 16, 2008). FDA has long asserted authority to regulate software that plays a role in diagnostic testing, and has reviewed and cleared numerous software-based products.