On September 29th, FDA announced a proposed rule regarding Laboratory Developed Tests (LDTs). LDTs are IVDs that are designed, developed, and used within a single laboratory. This new rule aims to improve the safety and effectiveness of these tests by superseding the previously exercised enforcement discretion. It details proposed amendments to existing policies and a phaseout of the regulation in stages to minimize market disruption.
Since LDTs were introduced in the 1970s, there have been growing concerns over their regulation. Today, the U.S. heavily relies on diagnostic testing to make healthcare decisions. If LDTs produce inaccurate test results, users could undergo costly and unnecessary treatments. The COVID-19 pandemic introduced new issues when at-home tests were rapidly manufactured and distributed on a large-scale. Ultimately, products experienced performance problems and were poorly validated due to the lack of LDT specific regulation and delayed FDA reviews.
The Agency outlines evidence further detailing why the current general enforcement discretion approach for LDT regulation is inadequate due to rapid technological and market growth. This proposed rule seeks to amend the definition of an in vitro diagnostic (IVD) to include LDTs within FDA jurisdiction under the Federal Food, Drug & Cosmetics Act (FD&C Act). The current definition of IVD considers the location where the IVD was manufactured, however, this definition excludes LDTs since they are manufactured in a laboratory. The revised definition of IVD will not consider where the test system was manufactured, thus including LDTs within the scope.
As mentioned, the phaseout would consist of five stages implemented over four years. The goal of this phaseout program is to assess LDTs to ensure patients are not exposed to excessive risk without disrupting the LDT market. The current general enforcement discretion approach is used by FDA which gives LDT manufacturers flexibility in terms of regulatory requirements. At the end of the phaseout program, LDTs will be generally regulated under the same strict requirements as IVDs, unless they fall in specific categories outlined in the proposed rule. In addition, this phaseout program allows FDA to monitor existing and future problems with LDTs. The suggested phaseout program is intended to be published in the preamble of the final rule.
The first stage would focus on ending the general enforcement discretion approach previously used by FDA in relation to medical device reports (MDRs), correction, and removal report requirements. Due to the risk posed to patients, and since MDRs are the foundation for corrections and removals, FDA prioritizes this category. FDA suggests the fulfilment of this stage one year after the proposed rule is published, since laboratories should have protocols and procedures already in place to detect problems with IVDs.
Stage 2 would aim to end the general enforcement discretion approach practiced by FDA regarding requirements other than those mentioned in Stage 1, QS (quality systems), and premarket review. Such requirements would include registration and listing, labeling, and investigational use. This stage would allow laboratories to gain compliance without determining the risk category of their IVD. FDA proposes this stage to be completed 2 years after the publishing of the final rule.
The third stage would seek to end the general enforcement discretion approach with QS. FDA proposes that laboratories should have quality systems compliant with requirements that IVDs follow, including purchasing controls, acceptance activities, corrective and preventative actions, and record requirements. In the best interest of the public, FDA suggests this phase be completed no later than 3 years after the final rule is published.
Stage 4 focuses on ending the general enforcement discretion approach regarding premarket review requirements for high-risk IVDs. This would include IVDs that may be considered Class III. FDA expects this to be accomplished in three and a half years after the publication of the new rule, but no earlier than October 1, 2027.
The final stage would end the general enforcement discretion approach regarding premarket review requirements for moderate and low-risk IVDs requiring premarket submissions. These IVDs would include those that may be considered class I or class II and include 510k and De Novo submissions. Ideally, FDA envisions this being finished 6 months after Stage 4, but no earlier than April 1, 2028, to allow FDA time to deal with IVDs with more serious consequences.
Additional Quality Management System Regulatory Requirements
As mentioned in Stage 3, this proposed rule would hold LDT manufacturers to comply with requirements in effect at the time for IVDs regarding QS found in Code of Federal Regulations (CFR) part 820. Additionally, in February of 2022 FDA proposed changes to the current QS regulation, published back in 1996, that would align more with ISO (International Organization for Standardization) 13485:2016. More specifically, the proposed rule states that ISO13485:2016 will be incorporated by reference, along with outlining additional FDA definitions, concepts and requirements for manufacturers. That proposed rule is supposed to be finalized and published by the end of 2023. Therefore, LDT manufacturers, above current Good Laboratory Practices, would now also be required to comply with QMS requirements relating to design controls, purchasing controls, acceptance activities, Corrective and Preventive Actions, additional document and records requirements, etc. This allows feasible convergence and consistency between international standards and FDA regulations for both LDT and IVD manufacturers. [The proposed Quality Management System regulation can be found on the Federal Register:
The entire LDT proposed rule is available to read on the Federal Register and FDA is accepting public questions, comments, and concerns until December 4th. Once FDA has time to read and respond accordingly to comments, a final rule will be released and all LDT regulations it describes will become effective 60 days after the date it is published in the Federal Register. To access and comment on the full proposed rule, click the link below.
Call to Action
Unsure if your device is an LDT that will be subjected to more regulatory oversight in the future? MEDIcept is here to help you prepare for all stages of the phaseout plan. Contact us today at email@example.com.
Medical Devices; Laboratory Developed Tests, 88 FR 68006 (proposed September 29, 2023) (to be codified at 21 CFR pt. 809).
Medical Devices; Quality System Regulation Amendments, 87 FR 10119 (proposed February 23,2023) (to be codified at 21 CFR pt. 4 and 21 CFR pt. 820).
Office of the Commissioner. (2023, September 29). FDA Proposes Rule Aimed at Helping to Ensure Safety and Effectiveness of Laboratory Developed Tests. U.S. Food and Drug Administration. https://www.fda.gov/news-events/press-announcements/fda-proposes-rule-aimed-helping-ensure-safety-and-effectiveness-laboratory-developed-tests
Shuren, J., & Stenzel, T. (2020). Covid-19 Molecular Diagnostic Testing — Lessons Learned. New England Journal of Medicine, 383(17). https://doi.org/10.1056/nejmp2023830
Sarah Boynton, Emily Sawtell, Elizabeth Smith – Associate Medical Device Consultants