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The FDA’s final rule regulates LDTs ​​as medical devices

On May 6, 2024, the U.S. Food and Drug Administration published its anticipated final rule on laboratory testing (LDT) surveillance. The final rule (i) reaffirms FDA’s position that in vitro diagnostic (IVD) products are devices under the Federal Food, Drug, and Cosmetic Act (FDCA), including when the manufacturer of the IVD is a laboratory; (ii) establishes a phased policy to phase out FDA enforcement discretion for LDTs; (iii) applies “targeted” enforcement discretion to certain categories of LDTs; and (iv) reiterates that certain other categories of LDTs ​​that have either full enforcement discretion or no enforcement authority at all are not subject to the phase-out policy. Concurrent with the publication of the final rule, FDA also issued two draft guidance documents: (i) Consideration of Test Enforcement Policies for a Section 564 Emergency Declaration and (ii) Enforcement Policies for Certain In Vitro Diagnostic Devices for Immediate Response in the field of public health in the absence of a declaration in accordance with Art. 564.

The FDA defines an LDT as a subset of IVD devices designed, manufactured, and used in a single laboratory certified under the Clinical Laboratory Improvement Amendments (CLIA) to perform high-complexity tests. The FDA has stated that increased oversight of LDTs ​​is necessary to protect patients and ensure the accuracy of diagnostic tests. According to the FDA, many modern LDTs ​​rely on increasingly technologically advanced instruments or software and are often used to make key decisions, but scientific data collected over the years indicates that IVDs offered as LDTs ​​do not always provide accurate and reliable results. Therefore, the FDA believes that LDTs ​​should meet FDA requirements for medical devices to ensure patient safety.

LDT Law Enforcement Termination Policy

Under the final rule, FDA will phase out its enforcement authority for LDTs ​​in five phases over the next four years. Each stage includes a deadline for compliance with specific regulatory requirements, so that by the deadline in Stage 5, all regulated LDTs ​​must be fully compliant with the medical device requirements of the FDCA. All LDTs ​​must comply with Medical Device Reporting, Correction and Disposal Reporting, Registration and Listing Requirements, and Recall Policy Labeling Requirements unless specifically excluded.

*Provided a premarket notification is received by this date, FDA states that it will continue to exercise enforcement discretion with respect to LDTs ​​pending resolution.

Targeted enforcement freedom

Specifically, the final rule applies “targeted” enforcement discretion to the following categories of LDTs ​​under the phaseout policy. According to FDA, these limited exceptions were added to the LDT final rule in response to public comments on the proposed LDT rule.

  • LDTs currently on the market that were first placed on the market before the issuance of the final regulations on May 6, 2024, they are not required to undergo pre-market review or to meet most QMSR requirements (except for provisions) if there are no significant modifications to the indications for use, principles of operation, technologies, performance specifications or safety specifications. All other withdrawal policies apply. If LDTs ​​are modified (e.g., indications for use or modifications to principles of operation, modifications involving significantly different technology, or modifications that adversely affect performance or safety specifications), they will be required to meet premarket review and quality requirements.
  • LDT approved by the New York City Department of Health Clinical Laboratory Evaluation Program (CLEP) do not need to undergo premarket review if they are designed, manufactured, and used in a single, high-complexity, CLIA-certified laboratory. This category includes LDTs ​​introduced to the market after the issuance of the final rule (May 6, 2024), which are high-risk LDTs ​​that will undergo full technical review and approval by CLEP, and moderate-risk LDTs ​​that will receive conditional approval if approval is not will then be withdrawn by CLEP after a full technical review. All other withdrawal policies apply.
  • 510(k)-approved or de novo-approved LDT modified by a CLIA-certified high-complexity laboratory are not required to undergo pre-market review, even if authorized under Art. 510(k) or de novo authorization is held by another manufacturer if the modification is such that the manufacturer will not require the submission of a new authorization under s. 510(k). All other withdrawal policies apply.
  • LDTs that address the “unmet needs” of patients in the healthcare system with which the laboratory is integrated are not required to undergo premarket review or meet most QMSR requirements (except for documentation), provided either there is no FDA-approved IVD for the specific disease or condition covered by this LDT, or such an IVD exists but which IVD does not is available to the patient or is not indicated for use in the patient. FDA intends to provide additional guidance to clarify remaining uncertainty regarding the definition of the term “unmet need.” It is worth noting that this exclusion does not apply to tests used at an affiliated hospital whose owner is different from the hospital that developed the test. All other withdrawal policies apply.
  • Non-molecular LDT antisera for rare red blood cell antigens do not have to undergo premarket review or meet most QMSR requirements (except documentation) if the LDTs ​​are manufactured and performed by blood services facilities (e.g., transfusion facilities and immunohematology laboratories) and when no alternative IVD is available to meet the patient’s need for transfusion blood. All other withdrawal policies apply.

LDTs excluded from recall policy

FDA intends to maintain full enforcement discretion with respect to certain categories of LDTs, which continue to be exempt from all premarket review and quality requirements for medical devices under the FDCA or facility registration as long as the LDTs ​​are designed, manufactured and used in a specific CLIA Certified High Complexity Laboratory:

  • Type 1976 LDTs ​​(i.e., LDTs ​​that use only manual techniques and components legally marketed for clinical use);
  • Human leukocyte antigen tests used in connection with organ, stem cell and tissue transplantation;
  • Tests manufactured and used by the United States Department of Defense or the Veterans Health Administration;
  • Tests intended solely for use by law enforcement agencies for forensic purposes; AND
  • Tests used solely for public health surveillance purposes.

LDTs are not subject to general executive discretion

The FDA also states that certain other categories of LDTs ​​must meet device requirements under the FDCA:

  • Direct-to-consumer testing;
  • Tests intended for use in a declared emergency;
  • Tests for donors of blood or human cells, tissues and cellular or tissue products; AND
  • Collection devices.

GT conclusions from the LDT final rule

While the recall policy and new targeted categories of enforcement discretion provide expanded options for affected LDT manufacturers, as FDA emphasizes in the final rule, any enforcement discretion policy is not law and may be changed by FDA at any time, without additional rulemaking, as long as the changes are “consistent with good guidance practice.” Namely, if the FDA is concerned about the safety and effectiveness of any LDT already on the market, it may still require the performing laboratory to respond to inquiries and/or obtain 510(k) clearance for the LDT. The FDA says it will specifically request labels for currently commercially available LDTs ​​so that they can be used in conjunction with other information submitted under the recall policy to identify LDTs ​​that are “of particular concern.” This review may also be initiated as a result of publicly available information or a complaint followed by an investigation by the FDA. Stakeholders should consider this uncertainty in their compliance planning efforts under the phase-out policy.

The final rule also leaves several issues open to interpretation, particularly regarding what types of modifications would trigger the need for premarket review and how label submission requirements apply to LDTs ​​for which FDA intends to maintain targeted enforcement discretion.

Finally, while submitting LDTs ​​for premarket review before initiating Phases 4 or 5 of the recall policy (as applicable) has the advantage of increasing enforcement latitude pending an FDA decision, entities submitting data earlier will need to use review pathways pre-market (e.g., 510(k), de novo), which may involve uncertainty regarding the availability of source devices due to general differences between IVD devices and IVD devices manufactured by laboratories.

Notes on laboratories

Laboratories must ensure that they understand all distinctions and nuances resulting from the final rule and comply with applicable regulations under this recall policy within the specified time frames. The two most pressing compliance requirements for LDT manufacturers, which must be fully implemented by May 6, 2025, are medical device reporting (21 CFR Part 803) and correction and deletion notifications (21 CFR Part 806). . Before this first deadline, laboratories may wish to amend all policies and procedures related to the development and use of LDTs ​​to ensure (i) adequate documentation of all tests, audits, reports, and corrective actions taken in response to any LDT-related incidents; and (ii) regular review and appropriate reporting of data related to adverse events, corrections and deletions.

Although the next deadline after May 6, 2025 is not until February 2, 2026, developing and implementing quality systems for complaint notifications is a multi-step process involving complex documentation and registration requirements that require the implementation of solid organizational planning. Therefore, while medical device notification and correction and disposal notifications should be a priority, laboratories should start preparing for QMSR compliance no later than early 2025.