FDA Commissioner Calls for More Active FDA Regulation of Laboratory-Developed Tests, and ACLA Promptly Responds with a Petition Opposing FDA

By Jeffrey N. Gibbs, Jamie K. Wolszon & Jessica A. Ritsick –

For many years, FDA has wrestled with how to regulate Laboratory-Developed Tests (“LDTs”).  FDA Commissioner Margaret A. Hamburg is now renewing FDA’s call for more active FDA regulation of LDTs and touting the Agency’s risk-based framework for regulating LDTs that is “under development.”  LDTs are diagnostic tests developed and performed by a laboratory.  They are widely used; among other tests, this category includes genetic tests, tests for rare conditions, and companion diagnostics.  Thousands of different LDTs are currently available.

Dr. Hamburg discussed LDTs as a part of broader remarks at the American Society of Clinical Oncology (“ASCO”) meeting on June 2, 2013.  She noted that LDTs do not undergo premarket review, and asserted “that can be a problem.”

Dr. Hamburg commented that FDA historically exercised enforcement discretion for LDTs “because they were relatively simple, low-risk tests performed on a few patients being evaluated by physicians at the same facility as the lab.”  Today’s LDTs, by contrast, according to Dr. Hamburg, are “more sophisticated and complex.  Results from these tests are rapidly becoming a staple of medical decision-making, particularly for cancer.  And some people with a family history of cancer are using these tests to decide whether to take preventive action.” 

Echoing prior statements by FDA officials, she asserted that “the Agency is working to make sure that the accuracy and clinical validity of high-risk tests are established before they come to market.  The risk-based framework we have under development will ensure that diagnostics used in cancer treatment will provide medical professionals with a critical baseline for confidence in the tests they order for their patients.” 

Dr. Hamburg did not provide details as to what the risk-based framework would entail or when it would be issued.

FDA announced in June 2010 that it was revisiting its years-long policy of exercising enforcement discretion over LDTs and was holding a public workshop to discuss the issue in July 2010.  FDA officials subsequently indicated that it was developing a plan to more actively regulate LDTs under a risk-based framework, to be issued for comment as guidance.  Members of the laboratory community have expressed deep concerns about the particulars of such a framework.  We previously reported on the agency’s plans to adopt a risk-based framework for LDTs here, here, and here. 

The Food and Drug Administration Safety and Innovation Act (“FDASIA”), enacted last summer, requires FDA to notify Congress at least 60 days prior to issuing a draft or final guidance on the regulation of LDTs.  The notice must include anticipated details of the action.

FDA has, in the past, made similar comments to the ones Dr. Hamburg made in her June 2013 remarks about LDTs.  Many of Dr. Hamburg’s statements mirror prior statements by Center for Devices and Radiological Health ("CDRH") officials.  For instance, the June 2010 Federal Register notice announcing the July 2010 meeting contained virtually identical language characterizing the agency’s perception that LDTs have moved from simple tests to high-complexity, high-risk tests.  The Federal Register notice states: “Initially, laboratories manufactured LDTs that were generally relatively simple, well-understood pathology tests or that diagnosed rare diseases and conditions that were intended to be used by physicians and pathologists within a single institution in which both were actively part of patient care.”  In contrast to LDTs in the past, the notice stated, today’s LDTs “are often used to assess high-risk but relatively common diseases and conditions and to inform critical treatment decisions and are often performed in geographically distant commercial laboratories instead of within the patient's health care setting under the supervision of a patient's pathologist and treating physician, or may be marketed directly to consumers.”

Whether Dr. Hamburg’s comments indicate that FDA is about to unveil a new proposal for regulating LDTs remains to be seen. 

Only two days after Dr. Hamburg’s comments, the American Clinical Laboratory Association (“ACLA”) submitted a Citizen Petition expressly requesting that FDA refrain from issuing draft or final guidance, or a proposed or final rule, regarding the Agency’s regulation of LDTs, and also asks FDA to respond to its Citizen Petition by explicitly confirming that LDTs are not devices under the Federal Food, Drug, and Cosmetic Act (“FDCA”).

ACLA’s Citizen Petition echoes and expands on the arguments made in HP&M’s 1992 Citizen Petition, advocating against FDA’s assertion of authority to regulate LDTs, as well as the Washington Legal Foundation’s ("WLF") 2006 Citizen Petition, also advocating against FDA regulation of LDTs.  FDA denied HPM’s Citizen Petition in 1998, stating that the “Commissioner of Food and Drugs may regulate assays developed by clinical reference laboratories strictly for in-house use as medical devices.”  FDA has yet to respond to WLF’s Petition.  In 2008, Genentech submitted its own Citizen Petition to FDA regarding the Agency’s authority to regulate LDTs, but unlike HPM, WLF, and ACLA, Genentech supports FDA’s assertion that it has authority to regulate LDTs.  Genentech requests that FDA “require all in vitro diagnostic tests intended for use in drug or biologic therapeutic decision making be held to the same scientific and regulatory standards,” regardless of whether the test is an LDT or a kit.  As with WLF, FDA has yet to respond to Genentech’s Petition.

ACLA’s Petition advances four main arguments:  (1) FDA lacks statutory authority and jurisdiction to regulate LDTs; (2) FDA’s regulation of LDTs would have an adverse impact on public health; (3) FDA’s regulation of LDTs would pose significant burdens on the laboratory industry; and (4) FDA’s regulation will complicate, rather than enhance, the existing regulatory framework, which Congress intended to be governed by one statute – the Clinical Laboratory Improvement Amendments of 1988 (“CLIA”).

In arguing against FDA’s authority and jurisdiction over LDTs, ACLA asserts that LDTs are services or know-how, not devices:  “LDTs are proprietary procedures for performing a diagnostic test using reagents and laboratory equipment.  They are essentially know-how, not articles” (emphasis added).  FDA rejected this argument in its 1998 denial of HPM’s Citizen Petition, and stated that “[a]ny in-house assay, test, or system which is a diagnostic test produced using an ASR [(Analyte Specific Reagent)] falls within the definition of device as delineated in the FDCA and its regulations.”  ACLA appears to have attempted to preemptively rebut FDA from making this argument again by citing the legislative history of the Medical Device Amendments.  ACLA asserts that “the legislative history clarifies that this amendment did not expand the device definition beyond its tie to tangible articles.”  Thus, ACLA argues, “[w]hen Congress added in vitro reagents to the device definition, [which FDA leans on for assertion of authority], the definition was still tied to an ‘article,’” and not a service, such as LDTs.

ACLA asserts two additional arguments against FDA’s assertion of jurisdiction over LDTs:  (1) Congress gave the Centers for Medicare and Medicaid Services, not FDA, authority to regulate LDTs under CLIA; and (2) LDTs are not commercially distributed, and commercial distribution is a prerequisite to FDA regulation.  As to number one, ACLA asserts that CLIA gave FDA “authority only over the laboratory equipment used in tests, not the tests themselves.”  As to number two, ACLA asserts that commercial distribution is a prerequisite to FDA enforcement jurisdiction.  See 21 U.S.C. §§ 360(k), 360c(f); 21 C.F.R. §§ 807.81(a), 814.1(c)(1).  In its 1998 denial of HPM’s Citizen Petition, FDA asserted jurisdiction to regulate LDTs under the Agency’s new (at that time) ASR rule.  FDA reasoned that because it had authority to regulate ASRs, and because LDTs contain ASRs, FDA could thus regulate LDTs “consistent with the [ASR] final rule.”  In denying the Petition, FDA, however, did not address HPM’s assertion (now echoed by ACLA) that commercial distribution is a prerequisite to FDA’s exercise of jurisdiction.  Rather, FDA asserted that if “ingredients of the ASR as well as the ASR itself” are transported in interstate commerce, there exists an “interstate commercial nexus,” supporting FDA’s regulatory jurisdiction.

ACLA also argues that FDA’s regulation of LDTs will impose unnecessary burdens on patients and industry alike.  Regulation of LDTs could increase costs on industry exponentially, according to ACLA, thus making development of LDTs cost prohibitive.  Further, if LDTs become too expensive and stop being developed, certain diseases and conditions for which the only testing available is an LDT may no longer have any testing available.  Or, if LDT manufacturers do not go out of business, FDA regulation may take these tests out of use until they are FDA approved or cleared, thus removing these tests from the market from some period of time, leaving a diagnostic gap.  Whether FDA would allow a grace period and, if so, for how long, is one of the many issues that FDA will need to address in any policy.  In responding to HP&M’s 1992 Citizen Petition addressing these issues, FDA cited its need to balance benefits and risks, and asserted that the risks of unpredictable test quality and results needed to be balanced against any benefits to patients from the use of such test.

So what does all of this mean?  FDA still wants to regulate LDTs, and the laboratory industry is still opposed.  How this will play out is uncertain.  One thing is for sure, however:  based on the recent statements by FDA and ACLA’s Petition, at least for the near future, the debate about how FDA should regulate LDTs—if at all—has flared up yet again.