Laboratory-Developed Test Oversight

1976 type tests have the following characteristics:

• They use manual techniques without automation performed by lab personnel with specialized expertise.
• They use components legally marketed for clinical use.
• They're designed, manufactured, and used in a single high complexity CLIA lab.

Tests with these three characteristics generally fall within the 1976-type enforcement discretion policy. FISH and IHC tests often have these three characteristics and in those cases would fall within the policy.

Tests using automation, including automated staining methods, automated plate readers, or automated interpretation would not have the first characteristic, because they would not be considered manual techniques without automation—and they would not be in the policy. Tests with components that are labeled Research Use Only (RUO) would not meet the second characteristic, because appropriately labeled RUO IVD products are not legally marketed for clinical use.

Some IVDs manufactured and first offered by laboratories after the date of issuance of the regulation (May 6, 2024) may fall within a targeted enforcement discretion policy described in the regulation. The FDA refers laboratories to the regulation for complete details, but the table above provides a high-level view of the different enforcement discretion policies. The phaseout policy details when compliance with the different requirements would be expected. For example, in phase one beginning May 6, 2025, the FDA expects compliance with medical device reporting requirements, correction and removal reporting requirements, and complaint files. In phase two, May 6, 2026. The FDA expects compliance with requirements that are not covered during the other stages of the phase out policy, including registration and listing, labeling, and investigational use requirements.

Stage three is in 2027 and the FDA expects compliance with quality system requirements. For LDTs specifically, the FDA expects compliance only with design controls, purchasing controls, acceptance activities, CAPA, and records requirements. And then premarket review would begin for high-risk tests in November 2027 and for moderate- and low-risk tests to which premarket review requirements apply in May 2028. The FDA does not intend to enforce premarket authorization requirements after a complete PMA, 510(k) or De Novo application has been submitted, if it's submitted on time according to this phaseout until the FDA completes its review of the submission. Given that such IVDs that are introduced during this transition period may already be on the market and available to patients when laboratories go to the FDA for review, the FDA does not intend to interrupt access at the point when a submission is made. IVDs for which a PMA, 510(k) or De Novo request is submitted prior to the applicable timeframe will remain under enforcement discretion for the pendency of the FDA review, whereas those that are submitted after the applicable timeframe detailed in the phaseout policy would not fall within the enforcement discretion policy and FDA clearance or authorization would be expected prior to such test being offered.

If an IVD was offered as an LDT prior to May 6, 2024, and is not modified in a way that changes its indications for use, alters the operating principle, includes significantly different technology, or adversely changes the performance or safety specs, then the FDA intends to exercise enforcement discretion and generally not enforce premarket review and most quality system requirements. This enforcement discretion policy is not limited to manual tests. Additionally, for tests that have certain characteristics that are common among LDTs offered in 1976, the FDA intends to exercise enforcement discretion with respect to all applicable requirements. The characteristics of tests under this enforcement discretion policy are that they use manual techniques without automation performed by lab personnel with specialized expertise. They use components legally marketed for clinical use, and they're designed, manufactured, and used in a single high-complexity CLIA laboratory.

If the same laboratory is offering the same LDT before and after publication of the final rule, the LDT generally would fall within the currently marketed IVD offered as an LDT policy, so long as the IVD is not modified, or modified in a way that does not change indications for use, alter the operating principle, include significantly different technology, or adversely change the performance or safety specs of the IVD.

TDM tests, including mass spec based TDMs, are IVDs. TDM tests manufactured by laboratories are covered by the final rule and the phaseout policy described in the regulation.

FDA premarket review timelines are negotiated with industry in connection with our medical device user fee reauthorization process. The FDA generally meet timeframes for MDUFA decisions that are negotiated with industry, including for IVD submissions outside of our experience in the pandemic. The FDA says this process aligns with the timeline for reauthorization discussions around our next user fee cycle, providing an opportunity for us to negotiate fees and goals for premarket reviews with our stakeholders.

The FDA intends to exercise enforcement discretion with respect to premarket review for LDTs that are approved, conditionally approved, or within an approved exemption from full technical documentation by New York CLEP. As described in the regulation, this policy applies to the version of the LDT approved by New York. Therefore, if a test is not approved by New York, it would not be in this policy.

Currently marketed IVDs offered as LDTs, the ones that are marketed prior to May 6, 2024 the FDA intends to exercise enforcement discretion with respect to both premarket review and most quality system requirements. Now, for new IVDs offered as LDTs that weren't marketed prior to May 6, 2024, the FDA expects compliance with applicable requirements, premarket review, quality system, etc, consistent with the stages in the preamble. However, if such a new IVD falls within an enforcement discretion policy described in the preamble, we intend to exercise enforcement discretion as described in that policy. The New York policy relates to general enforcement discretion with respect to premarket review requirements.

The FDA is using its existing risk classification to determine the risk categorization for LDTs. This existing framework established classifications for approximately 1,700 different generic types of devices and grouped them into 16 medical specialties referred to as panels. Each of these generic types of devices is assigned to one of three regulatory classes based on the level of control necessary to assure the safety and effectiveness of the device.

CLIA risk categorization is different from the FDA’s as all LDTs are considered high-complexity tests under CLIA while the FDA may classify LDTs from low-, moderate-, and high-risk tests.

Since 2009, the CAP has advocated for a regulatory framework that enhances patient safety, maintains quality laboratory testing, and promotes innovation without creating significant regulatory burdens on pathologists. LDTs have become more complex and unique presenting greater risk to patients that a tiered classification system could provide a balance streamlined approach and focus federal oversight on the highest risk LDTs.

No, the CAP will not update the CAP Accreditation checklists in 2025 with information on the FDA LDT regulation. Checklists will be updated to reflect recent changes in CLIA. We will reevaluate any needed updates to the checklist for 2026, but currently no updates are planned with regards to the FDA regulation.

At the federal level, the government does not define the practice of medicine; the practice of medicine is defined at the state level. As some laboratory-developed tests are created and developed by nonphysicians in the laboratory, the CAP does not believe creation of an LDT solely translates to, or constitutes, the practice of medicine.

Quality system requirements are outlined by the FDA in its regulation. The CAP has advocated for the FDA to recognize that most of the requirements are similar to those overseen by the laboratory director and that the individual be considered as the CEO of the laboratory.

The FDA action is independent of payment policy decisions. We don’t believe there will be a related effort to revise CPT coding.

The CAP will provide resources and education for each phase to assist CAP members and laboratories compliance with the rule (see the information above).

The CAP is now reviewing the final regulation and determining our next steps. We will continue to keep our members and laboratories updated on this and other concerns regarding the FDA oversight of LDTs as new information becomes available.

The FDA is using its existing authority to regulate LDTs. The CAP and CLIA auditors are not approved by the FDA to conduct inspections currently. The CAP will continue to engage the FDA to ensure clinical laboratories have the least burdensome approach for compliance the final rule.

Since 2009, the CAP has advocated for a regulatory framework that enhances patient safety, maintains quality laboratory testing, and promotes innovation without creating significant regulatory burdens on pathologists. LDTs have become more complex and unique presenting greater risk to patients that a tiered classification system could provide a balance streamlined approach and focus federal oversight on the highest risk LDTs.

CLIA regulations defined test complexity for clinical laboratory testing. The CMS CLIA program states modifying waived or moderate complexity test (including modifications in its intended use) is considered uncategorized for CLIA purposes and therefore becomes a high complexity test.

As a deemed accreditor, CAP must be equivalent or more stringent to the CLIA regulations to maintain its deemed status.

No, medical device adverse event reporting is required for deaths, serious injuries and malfunctions. Proficiency testing (PT) is the testing of unknown samples sent to a laboratory by an HHS-approved PT program. Most sets of PT samples are sent to participating laboratories on a scheduled basis (usually three times per year). After testing, the laboratory reports its sample results back to their PT program. The program grades the results using the CLIA grading criteria and sends the laboratory their scores. The CMS and accreditation organizations routinely monitor their laboratories’ performance.

Publications produced by the CAP are driven by its members and leaders who volunteer on various councils and committees. At present, the CAP does not distinguish between LDTs and IVDs in most of its programs – thus, it would be difficult to compose a publication addressing the topic suggested in the question.