On October 3rd, 2023, the U.S. Food and Drug Administration (FDA) issued a proposed rule to amend its enforcement approach to Laboratory Developed tests (LDTs). If implemented, this rule would result in LDTs generally falling under similar enforcement regulations as other in vitro diagnostic (IVD) products, a significant change from existing policy.
Many in the IVD community continue to view congress' failure to pass the Verifying Accurate Leading-edge IVCT Development or VALID act last year as a missed opportunity to provide a needed regulatory framework for the oversight of LDTs. In an alternative but similar endeavor, FDA is proposing the implementation of this rule that would explicitly define LDTs as IVDs that are subject to FDA’s existing regulations for medical devices.
Critical Gaps in LDT Regulation Under CLIA Authority
FDA has always contended that LDTs are IVDs under the 1976 Medical Device Amendments to the Food, Drug, and Cosmetic Act. However, the agency has previously exercised enforcement discretion with regards to LDTs instead permitting oversight of the tests via the Clinical Laboratories Improvement Amendments (CLIA). CLIA oversight addresses how clinical laboratories perform testing but lacks the review and enforcement of key processes that could better ensure the safety and efficacy of LDTs.
FDA has identified three critical gaps in LDT regulation exist under CLIA authority:
- Premarket assessments of test validation and clinical validity: CLIA does not require LDT manufacturers to submit their tests for premarket review by FDA. This means that FDA does not have an opportunity to assess the safety and efficacy of LDTs before they are marketed.
- Adverse event reporting and correction or removal of unsafe tests from the market: CLIA does not require LDT manufacturers to report adverse events to FDA, meaning that FDA may not be aware of unsafe LDTs until after they have been marketed and used by patients.
- Assessment of manufacturing quality: CLIA does not require LDT manufacturers to meet certain manufacturing quality standards. This means that there is no guarantee that LDTs are manufactured in a way that ensures their safety and accuracy.
The proposed rule would end FDA’s enforcement discretion for LDTs by amending the definition of IVD products under 21 CFR §809.3 clarifying that all IVDs are considered medical devices, "including when the manufacturer of these products is a laboratory." LDT manufacturers would be required to submit their tests for premarket review by FDA, report adverse events to FDA, and meet certain manufacturing quality standards.
What is the Timeline for Phaseout of LDT Enforcement?
As with the VALID act, the current proposed rule change has prompted concern over how the phaseout of LDT enforcement discretion will affect, among other things, resourcing for the review and approval of pre-market submissions for all IVDs. FDA has pointed to a gradual implementation approach to take place over at least four years, combined with opportunities to renegotiate Medical Device User Fees to support increased resourcing, as key measures to mitigate risks of slowing the review pipeline. The agency would start by phasing out enforcement discretion over adverse event, correction, and removal reporting within the first year of the rule change as stage 1 of the current plan.
Ron Freeze, ProPharma’s Global Head of Medical Technology, was recently quoted (paywalled) suggesting that a sampling-based approach to review (as used by the European Union's In Vitro Diagnostics Regulation) could be another effective way to avoid significant delays and backlogs.
FDA Requests Feedback and Comments for the Proposed LDT Rule
This is the second time in a decade that FDA has expressed intent to move away from the policy of enforcement discretion applied to LDTs. The FDA produced two draft guidance documents in 2014 that were never finalized: "Framework for Regulatory Oversight of Laboratory Developed Tests (LDTs)," and "FDA Notification and Medical Device Reporting for Laboratory Developed Tests (LDTs)." FDA’s current posture indicates it is likely to move forward with the rule change that is currently under consideration, and is holding fast to a 60-day comment period that will end on December 4th of this year.
In an educational webinar regarding the proposed rule delivered to industry professionals, FDA presented a list of topics on which it is specifically interested in receiving comments. Impacted members of the industry are strongly encouraged to provide feedback on these topics, most of which address the finer points around the scope of applicability of the proposed phaseout of enforcement discretion. These details, however, could prove critical for current LDT manufacturers.
Get Help with Your LDT Regulation Compliance
In response, LDT manufacturers should take a forward-thinking approach, starting with an assessment of their current procedures and processes to existing medical device regulations. Next, develop a detailed plan to address any gaps to meet the required implementation timeline of the proposed rule.
As the close of the public comment period approaches and the proposed rule moves closer to adoption, if you are interested in learning more about the potential impact to your organization, ProPharma can help. Our team of experts can help you assess your situation and develop a plan to comply with the proposed rule change. Contact us to speak with one of our medical device regulatory experts.
