On April 29, 2024, the U.S. Food and Drug Administration (FDA) announced a final rule amending the regulations for in vitro diagnostics (IVDs) to include laboratory-developed tests (LDTs) explicitly. Effective July 5, 2024, this amendment initiates a phased approach to enforcing regulations for LDTs, ensuring they meet the same standards as other IVDs.

Background

LDTs, initially developed in the 1970s, were excluded from certain regulatory frameworks due to their limited use in diagnosing rare diseases and serving local patient populations. Over time, the landscape has changed significantly, with LDTs now playing a crucial role in clinical diagnostics, utilizing advanced technologies, and addressing broader healthcare needs. This shift necessitates stricter regulatory oversight to ensure the safety, effectiveness, and reliability of these tests, many of which are now critical in diagnosing and treating serious conditions such as cancer and heart disease.

Enforcement Discretion Phase-Out

The FDA’s final rule outlines a structured, five-stage, four-year phaseout of the general enforcement discretion previously applied to LDTs:

1. Stage 1 (July 5, 2025): Compliance with Medical Device Reporting (MDR) requirements, correction, and removal reporting, and quality system (QS) requirements for complaint files.
2. Stage 2 (July 5, 2026): Compliance with additional requirements including registration, listing, labeling, and investigational use.
3. Stage 3 (July 5, 2027): Compliance with full QS requirements.
4. Stage 4 (January 5, 2028): Premarket review requirements for high-risk IVDs unless a premarket submission is pending.
5. Stage 5 (July 5, 2028): Premarket review requirements for moderate- and low-risk IVDs unless a premarket submission is pending.

Out of Scope

The enforcement discretion phase-out will not apply to:

• Devices covered under the 1976 Medical Device Amendments.
• Forensic tests used by law enforcement.
• LDTs developed by the Department of Defense and the Veterans Health Administration.
• “Grandfathered” devices established before the final rule.
• Human Leukocyte Antigen (HLA) tests.
• LDTs within integrated healthcare systems meeting unmet patient needs where no FDA-authorized IVD is available.
• Non-molecular antisera LDTs for rare red blood cell antigens manufactured by blood establishments.

What Does This Mean for Industry?

The new regulations aim to create a level playing field, enhancing the safety and effectiveness of LDTs. Laboratories must now adhere to stringent FDA requirements, which include:

• Premarket review.
• Compliance with QS and labeling standards.
• Adverse event reporting.
• Establishment registration and device listing.

These changes are expected to enhance public confidence in IVDs and improve overall public health outcomes.

How Can I Be Prepared?

To comply with the upcoming regulations, laboratories should:

1. Review the Final Rule: Understand the specific requirements and timelines.
2. Conduct a Gap Analysis: Identify current practices versus new regulatory expectations.
3. Implement Quality Systems: Ensure all processes meet FDA’s QS requirements.
4. Prepare for Premarket Review: Gather necessary data and documentation for high-risk IVDs first, followed by moderate- and low-risk IVDs.
5. Train Staff: Educate laboratory personnel on new compliance obligations.
6. Engage with the FDA: Consider early engagement with the FDA for guidance and clarification.

By taking proactive steps, laboratories can navigate the transition smoothly and ensure continued compliance, ultimately benefiting patient care and public health. For personalized guidance and support in meeting these new regulatory requirements, we encourage impacted parties to reach out to dicentra. Our team of experts is ready to assist you in ensuring a seamless transition and maintaining compliance with FDA regulations.