Navigating FDA’s LDT Final Rule: Key Terminology Every Clinical Lab Should Know

The FDA published its LDT final rule in May of this year, and we’re nearing the halfway point of the first implementation milestone. 

One of the key challenges for clinical laboratories is understanding FDA terminology and expectations. Here are some key terms for the first two milestones that laboratorians should familiarize themselves with:

Milestone 1

Medical Device Reporting (MDR) (Part 803)

An MDR is required when a laboratory becomes aware that an event¹ has occurred that reasonably suggests² that their LDT may have caused or contributed³ to the death or serious injury⁴ of a patient. 

1. This includes any information that suggests a reportable event has occurred, e.g., a complaint, a request for repeat testing, etc. Note, this does not only include bench staff—a complaint to any employee of the entity could be considered “made aware.” This timepoint is critical as an MDR must be submitted within 30 days of becoming aware of reportable event.
2. This includes observations or opinions in addition to factual information.
3. This includes a test failure or malfunction, a problem with the design of the test, or user error.
4. This is defined as an error that is life-threatening, requires intervention to prevent, and/or causes permanent damage to the patient.

Complaint File (820.198)

Laboratories must create procedures for receiving¹, reviewing², investigating³, and reporting⁴ complaints. 

1. Complaints include verbal or written concerns about an LDT, and the laboratory must formally designate a team responsible for the complaint process. Complaints should be captured in a standardized manner for consistency.
2. The first step is determining if further investigation is required, e.g., if the complaint is not about an LDT but is instead an unrelated matter such as a complaint about missing specimens. If further investigation is not pursued, the rationale must be documented.
3. Complaint investigation documentation should include the name, address, and phone number of the person making the complaint, a detailed description of the situation or incident, dates of investigation and their conclusions, corrective action, and any response to the complainant. 
4. The laboratory must determine if a complaint is reportable through the MDR process, e.g., if it is due to the LDT failing to meet specifications, such as an inaccurate test result. 

Milestone 2

Registration (Part 807)

Any laboratory¹ offering non-exempt LDTs² must register³ annually with the FDA.

1. It is not yet clear how the FDA expects laboratories to register; at one extreme, laboratories may be allowed to register as a corporate entity encompassing multiple geographic locations, at the other, each individual CLIA certificate location may have to register if that location tests LDTs. More information from the FDA is needed.
2. Laboratories offering LDTs under a targeted enforcement discretion category will still need to register. This includes “IVDs previously offered as LDTs” (LDTs that were offered prior to May 6, 2024) and LDTs that are modified commercial kits.
3. Registration information includes the name and address of the laboratory, website address (if applicable), contact information for the owner, and contact information for an official correspondent. There is an annual fee for registering as a medical device manufacturer, which is USD$9,280 for FY 2025.

Listing (Part 807)

Any laboratory offering LDTs must list¹ each test² in a specified, public FDA database.

1. Listing for most medical devices may include labeling information, package inserts, and/or advertisements. LDTs are not physical objects, so the concept of a label for an LDT is challenging. The FDA interprets labeling for an LDT as including “performance information and a summary of supporting validation, as applicable.” Laboratories should expect the need to submit accuracy, precision, etc., along with supporting data to the FDA, even if an LDT qualifies for an enforcement discretion category.
2. A “test” is a combination of intended use, analyte(s), and methodology, and potentially other factors; for example, a flow cytometry LDT using 12 specific markers to diagnose lymphoma. A laboratory may have multiple order codes for a single test, e.g., separate order codes to test for fentanyl in serum or urine may be a single test for the purpose of an FDA submission.  

What laboratories should be doing now

The primary focus should be on milestone 1, which is only about seven months away. Most laboratories will already have at least rudimentary systems and processes for identifying, investigating, and documenting nonconformances or adverse events. 

Staff should perform a gap assessment against the MDR and complaint handling requirements to determine the necessary steps to enhance those processes. Once processes and procedures are updated, all affected staff must be trained to ensure nonconformances and complaints are identified and triaged appropriately. 

MDR must be reported electronically through the FDA’s Electronic Submissions Gateway (ESG), which requires a user account. This account can be set up at any time, and it is recommended that laboratories set up an account well in advance of needing to submit an MDR. 

Laboratory staff should also be thinking ahead about LDT listing requirements. The FDA may require a significant amount of information for listing, even with IVDs previously offered as LDTs. Staff will need to know where validation summaries and supporting documentation are stored for all LDTs and ideally have a process developed to efficiently collate this information. This activity may become a significant clerical exercise for institutions with large LDT test menus with hundreds or thousands of tests. 

Planning ahead is key.