The U.S. Food and Drug Administration (FDA or Agency) recently announced a renewed attempt to regulate laboratory-developed tests (LDTs) as medical devices. FDA considers a LDT to be “a type of in vitro diagnostic test that is designed, manufactured and used within a single laboratory.”1 (emphasis added). FDA takes the position that it has authority over LDTs but that it is exercising enforcement discretion over most LDTs.2 FDA’s position has been disputed, and there have been unsuccessful legislative proposals, such as the Verifying Accurate, Leading-Edge IVCT Development Act, or VALID Act, to clarify FDA’s authority.
One step the Agency is taking is rulemaking to make “explicit” that LDTs are FDA-regulated medical devices.3 As another step, FDA announced the launch of a new pilot program, and corresponding guidance, for certain oncology drug products used with in vitro diagnostic tests (e.g., LDTs) to assist clinicians in selecting appropriate cancer treatments for patients.4 FDA considers the guidance and pilot program to be “important steps towards addressing safety risks posed by the use of poorly performing laboratory developed tests”, and “[t]he pilot aims to help by making transparent performance recommendations for diagnostic tests used to select certain oncology drug treatments.”5 The guidance has been implemented without prior public comment but remains subject to comment.6
LDT Proposed Rule
According to the Unified Agenda, published by the Office of Management and Budget (OMB), FDA intends to issue a proposed rule “to amend the Food and Drug Administration’s regulations to make explicit that laboratory developed tests (LDTs) are devices under the Federal Food, Drug, and Cosmetic Act.”7 The Unified Agenda also indicates that the notice of proposed rulemaking (NPRM) is expected to be published in the Federal Register in August.
FDA’s actions are consistent with comments made earlier this year that the Agency was considering LDT rulemaking following Congress’s repeated inability to pass the VALID Act last year, which would have explicitly extended FDA’s statutory authority to include LDTs.8 In the past, FDA also has faced challenges to its attempts to regulate LDTs through guidance. Enduring questions remain about how FDA intends to regulate LDTs under the existing device statutory framework. Given stakeholder interest, there will likely be a large number of public comments in the NPRM docket.
LDT Pilot Program and Guidance
FDA also recently announced a voluntary pilot program “intended to improve oncology patient care by providing transparency regarding minimum performance necessary for in vitro diagnostic tests used with oncology drug products enrolled into the pilot program.”9 Currently, in certain limited scenarios, FDA may approve a therapeutic product even if the corresponding diagnostic test does not receive marketing authorization when the product is approved.10 In these circumstances, LDTs, which are used under enforcement discretion and not generally reviewed by the Agency for safety or effectiveness, have been used for patient treatment decisions. The Agency has “become increasingly concerned that some tests made by laboratories and not authorized by the FDA may not provide accurate and reliable test results or perform as well as FDA authorized tests” and “may negatively impact treatment decisions.”11
FDA’s Guidance “Oncology Drug Products Used with Certain In Vitro Diagnostic Tests: Pilot Program” outlines the voluntary pilot program. FDA will first request performance information from oncology drug sponsors about in vitro diagnostic tests used to enroll patients in clinical trials that support drug approval. After an assessment of that information, if FDA concludes the drug meets approval standards, FDA will post to the FDA website “the minimum performance characteristics recommended for similar tests that may be used to select patients for treatment with the approved drug.”12 This information can help laboratories develop LDTs to identify specific biomarkers for selecting cancer treatment and facilitate more consistent performance of such tests.13 Some highlights of the pilot program:
- The pilot program began on June 20, 2023, and is scheduled to last a year.
- For the initial phase, FDA will evaluate no more than nine drug sponsors who meet the criteria described in the Guidance (e.g., Center for Drug Evaluation and Research–regulated drug product within the pilot program’s scope; drug sponsors that agree to discuss clinical test validation test data with FDA prior to clinical trial enrollment).14
- FDA will evaluate the pilot program periodically with review documents submitted to the docket and plans to hold a public meeting within three years.15
- To be considered for the pilot program, interested drug sponsors should submit correspondence entitled “A Statement of Interest in Participation in the Oncology Drug Products Used with Certain In Vitro Diagnostic Tests: Pilot Program” with their Investigational New Drug applications, New Drug Applications, or Biologic License Applications.16
- FDA will provide written feedback for action or rejection into the pilot program.17
- For drug sponsors that have submitted a statement of interest, FDA has provided a list of templates that can be used to provide diagnostic test performance characteristic and validation information when requested by FDA.18
Participating in this pilot program may provide sponsors with the opportunity to more directly shape FDA’s oversight of these types of diagnostic tests and to help set the relevant performance characteristics for similar tests. Additionally, it may provide greater assurance to healthcare professionals and patients that these tests have received FDA review.
Laboratories and companies that develop and market LDTs should take note that FDA is prioritizing oversight over LDTs, especially LDTs that it considers to be higher risk. Companies should track these developments closely and consider their existing and developing validation and verification data.
The status of FDA’s regulation of LDTs has been opaque in recent years, and FDA’s new approach is likely to be met with pushback in light of enduring questions about whether FDA’s authorities extend to LDTs.
6“Given the public health importance of such in vitro diagnostic tests for determining a patient’s cancer treatment, this guidance is being implemented without prior public comment because FDA has determined that prior public participation for this guidance is not feasible or appropriate (see section 701(h)(1)(C) of the FD&C Act).” See Pilot Guidance at 2.
9See Pilot Guidance at 4.
10“[W]hen the therapeutic product is intended to treat a serious or life-threatening condition for which no satisfactory alternative treatment exists and the benefits from the use of the therapeutic product are so pronounced as to outweigh the risks from the lack of an in vitro companion diagnostic with marketing authorization.” See Pilot Guidance at 2.
13Pilot Guidance at 4.
14Id.; see also Pilot Guidance at 4-5.
15See Pilot Guidance at 5.
16Id. at 5.
17Id. at 6.