The FDA’s Final Rule on LDT Oversight – What Does it Mean for Labs?

On April 29, 2024, the U.S. Food and Drug Administration (FDA) announced a final rule that classifies in vitro diagnostic (IVD) products as devices that fall under the jurisdiction of the Federal Food, Drug, and Cosmetic Act (FD&C Act) including when the manufacturer of the IVD is a laboratory.

Under the new policy, the FDA will provide greater oversight of IVDs offered as LDTs. It will phase out its general enforcement discretion approach for LDTs over the next four years. The phased approach is intended to help avoid unnecessary disruption to patient care.

Defining LDTs

LDTs are lab tests that are developed, evaluated, and validated within one laboratory. They are used within that laboratory, and not distributed or sold to other labs. Often, a lab will develop a LDT because a commercial test is not available for a specific testing need within their patient population. Many IVDs are designed by one manufacturer and used by many different laboratories; however, LDTs are designed, manufactured, and analyzed within a single laboratory.

Examples of LDTs include, “panels to monitor immunosuppressant concentrations after organ transplantation, large PCR-based panels to diagnose urinary tract infections and identify antibiotic resistance markers, comprehensive toxicology panels to identify acute drug exposure and monitor pharmacological treatment compliance, newborn screening for early diagnosis of serious but treatable conditions, and genetic testing to detect mutations associated with cancer.”¹

History of LDT Oversight

The FDA has had the authority to regulate LDTs since the 1970s but has used “general enforcement discretion” and has not taken an authoritative stance on LDT oversight. In 1976, the Medical Device Amendments to the Federal Food, Drug, and Cosmetic (FD&C) Act gave the FDA the authority to regulate medical devices, including IVDs (which include LDTs). However, because there were few LDTs at that time, the FDA did not use its authority to regulate those tests. Prior to the ruling released in April 2024, the FDA regulated medical devices, including other IVDs, and the Centers for Medicare & Medicaid Services (CMS) regulated labs via the Clinical Laboratory Improvement Amendments of 1988 (CLIA), which included oversight of LDTs as part of high complexity laboratory regulations. This means that for most LDTs, the FDA generally has not enforced requirements.

“The FDA has generally considered an LDT to be an IVD that is intended for clinical use and that is designed, manufactured, and used within a single laboratory that is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) and meets the regulatory requirements under CLIA to perform high complexity testing.”²

Since the 1970s, diagnostic testing complexity and availability has grown rapidly, which has caused concerns about LDT accuracy and oversight. Today, many LDTs require complex instrumentation and software for results and clinical interpretations. This change in the LDT landscape is part of the reason behind the FDA’s LDT ruling.

What Does FDA LDT Oversight Mean for Labs?

There is much concern within the laboratory industry about meeting FDA regulatory requirements for LDTs and the effect that this ruling may have on patient care. For example, “ARUP believes the FDA does not have statutory authority over LDTs and maintains that the rule will limit access to essential testing services, stifle innovation, and increase healthcare costs.”³

The new rules require labs that use LDTs to comply with device requirements under the FD&C Act, which include premarket review, quality system (QS) requirements, adverse event reporting, establishment registration and device listing, labeling requirements, and investigational use requirements.⁴

The FDA’s Phaseout Policy

The policy goes into effect on May 6, 2024. For the following four years, a portion of the requirements are added each year. This is a “phaseout” of their general enforcement discretion approach. The phaseout policy contains five stages.

Year 1 – Medical Device Reporting, Correction and Removal

The first stage of the phaseout requires laboratories performing LDTs to maintain documentation of complaint files and subsequent investigation results. The documentation must include the following:

• Whether the device failed to meet specifications
• Whether the device was being used for treatment or diagnosis
• The relationship, if any, of the device to the reported incident or adverse event

The record of investigation must include:

• Device name
• Date the complaint was received
• Any unique device identifier (UDI) or universal product code (UPC), and any other device identification(s) and control number(s) used
• Complainant name, address, and phone number
• Nature and details of the complaint
• Dates and results of the investigation
• Any corrective action taken
• Any reply to the complainant⁶

Exemptions – Enforcement Discretion

As discussed in the phaseout policy, following the four-year period, IVDs offered as LDTs will be expected to meet requirements. However, there are certain scenarios with targeted enforcement discretion policies.

“The FDA intends to exercise enforcement discretion with regard to premarket review and most quality system requirements for certain categories of IVDs, including but not limited to:

• Currently marketed IVDs offered as LDTs that were first marketed prior to the date of issuance of the final rule.
• LDTs manufactured and performed by a laboratory integrated within a health care system to meet an unmet need of patients receiving care within the same health care system when an FDA-authorized test is not available.”⁴

Resources

To guide this change, the FDA is planning to:

• Host educational webinars
• Provide guidance documents and templates
• Participate in conferences

Orchard Software is actively working alongside its customers to fully understand the implications and phases of FDA oversight of LDTs. We intend to leverage and advance our technology to support our customers through this change in every area we can. 

References

1. Budelier, M. and Hubbard, J. The regulatory landscape of laboratory developed tests: Past, present, and a perspective on the future. J Mass Spectrom Adv Clin Lab. 2023 Apr; 28: 67–69. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9985058.
2. Food and Drug Administration. Medical Devices; Laboratory Developed Tests. FDA.gov. https://www.federalregister.gov/public-inspection/2024-08935/medical-devices-laboratory-developed-tests. Published 06 May 2024.
3. ARUP Statement on FDA Final Rule to Regulate Laboratory-Developed Tests as Medical Devices. ARUP Laboratories. https://www.aruplab.com/news/04-29-2024/arup-statement-fda-final-rule-regulate-ldt. Published 29 April 2024.
4. Food and Drug Administration. FDA takes action aimed at helping to ensure the safety and effectiveness of laboratory developed tests. FDA.gov. https://www.fda.gov/news-events/press-announcements/fda-takes-action-aimed-helping-ensure-safety-and-effectiveness-laboratory-developed-tests. Published 29 April 2024.
5. Food and Drug Administration. Laboratory Developed Tests. FDA.gov. https://www.fda.gov/medical-devices/in-vitro-diagnostics/laboratory-developed-tests. Published 29 April 2024.
6. Food and Drug Administration. CFR – Code of federal regulations title 21. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?fr=820.198. Published 22 Dec 2023.
7. Food and Drug Administration. Laboratory Developed Tests: Frequently Asked Questions. FDA.gov. https://www.fda.gov/medical-devices/laboratory-developed-tests/laboratory-developed-tests-frequently-asked-questions#resources. Published 29 April 2024.