By Steven J. Gonzalez & Lisa M. Baumhardt, Senior Medical Device Regulation Expert —
On August 22, 2024, FDA hosted a webinar to provide further guidance on the regulatory requirements it intends to apply to Laboratory Developed Test (LDT) developers in Stage 1 of the phaseout policy of the LDT Final Rule – during which FDA has said laboratories developing LDTs will need to comply with Medical Device Reporting (MDR) (21 CFR Part 803), Corrections and Removals (21 CFR Part 806), and Complaint Handling (21 CFR § 820.198) by May 6, 2025 unless the LDTs offered are those for which the Final Rule says FDA may provide enforcement discretion with respect to these specific requirements. See our prior blog post summarizing the different phaseout stages and categories of enforcement discretion.
The webinar largely consisted of summarizing the general requirements under Parts 803, 806 and 820.198, which we do not reproduce here (but see another of our prior blog posts discussing these requirements and their applicable to LDTs in greater detail; you can also find FDA’s slides from the webinar here). Instead, we focus here on the few notable statements that provide new or more detailed guidance than FDA has previously offered.
Complaints
FDA discussed how LDT developers should handle the transition from the current Quality System Regulation (QSR)(21 CFR Part 820) to the recently promulgated Quality Management System Regulation (QMSR) that is scheduled to take effect on February 2, 2026. The new QMSR incorporates the requirements of ISO 13485 by reference, including those related to complaint handling. FDA noted that because the scope of ISO 13485’s complaint handling requirements are “substantially similar to the QS Regulation for complaints”, FDA believes that laboratories that satisfy the current QSR complaint requirements “will meet the amended QS Regulation requirements” for complaints. Prior to February 2, 2026, FDA also said that it does not intend to enforce complaint requirements under 21 CFR 820.198 for developers that are already in compliance with the complaint requirements under ISO 13485.
MDR
FDA discussed a few preliminary steps that it says laboratories should take prepare for submitting MDRs as medical device manufacturers.
FDA indicated that, prior to submitting an MDR, laboratories will first need to request FEI Numbers from FDA, which are ordinarily provided as part of FDA’s establishment registration process (a requirement that FDA has said it does not intend to enforce for LDTs until Stage 2 of the phaseout policy). To request an FEI Number, laboratories will need to provide a long list of identifying information to FDA via email (feiportal@fda.hhs.gov) (see slide 23 of the FDA’s presentation for the complete list). Of note, laboratories will need to provide a comprehensive list of activities conducted at the laboratory site. There is no cost associated with obtaining an FEI Number.
Additionally, the Agency said that laboratories will need to identify a Product Code for each LDT that FDA says is subject to MDR requirements, and such Product Code will need to be identified in any future MDR reported to FDA. Product Codes are typically assigned to a device based on the regulatory classification of the device, found in 21 CFR Parts 862-892. Although a test developer can use one of these existing device-specific Product Codes if one is identified for the specific LDT, FDA has also issued 7 LDT-specific Product Codes that it says will need to be used in place of or in addition to the device-specific Product Codes. The LDT-specific Product Codes are as follows:
- SCE: IVD offered as LDT, first marketed before May 6, 2024, and not modified beyond scope described in preamble to LDT Final Rule.
- SCF: LDT, unmet need within an integrated healthcare system.
- SCG: Modified version of another manufacturer’s FDA-authorized test within scope described in preamble to LDT Final Rule.
- SCH: LDT, approved by NYS CLEP.
- SCI: IVD offered as LDT—not designed, manufactured, and used in a single lab—that is not under a targeted enforcement discretion policy described in the preamble to LDT Final Rule.
- SCJ: LDT—designed, manufactured, and used in a single lab—that is not under a targeted enforcement discretion policy described in preamble to LDT Final Rule.
- SCK: LDT, non-molecular antisera for RBC antigens when there is no alternative IVD.
There are no Product Codes for the categories of LDTs the Final Rule identifies as being subject to potential enforcement discretion for all regulatory requirements, including MDR requirements (i.e., 1976-type LDTs; Human Leukocyte Antigen LDTs for transplantation; Forensic Use LDTs; and LDTs performed within the Veterans Health Administration or Department of Defense).
The Agency also said that laboratories should set up an eMDR account, the online system used for submitting MDRs, before the lab needs to submit an MDR. This process includes requesting an ESG (electronic submission gateway) account, submitting a “test MDR submission”, and sending FDA a copy of the “pass” acknowledgement (AcK3) to the eMDR help desk to request approval for a production account, all of which can take some time before the laboratory is able to submit MDR electronically.
After a lab submits an MDR, FDA said that laboratories should save the electronic “Acknowledgement 3” (Ack3) generated after submitting an MDR in the MDR event files. This callout is notable as FDA recently issued its first Warning Letter citing a manufacturer for failing to save these electronic acknowledgements in MDR event files. It should be noted that 21 CFR 803.18(b)(1)(ii) requires manufacturers to keep copies of ALL electronic acknowledgments sent by FDA in response to electronic MDR, not just Ack3.
Corrections and Removals
Under 21 CFR Part 806, manufacturers generally need to communicate corrections and removals (i.e., recalls) to consignees of the product, i.e., the customers to whom a device was distributed. During the webinar, FDA described two examples of recalls: one where the consignee (presumably a patient) is in possession of a specimen collection device associated with an LDT that the laboratory instructs the consignee to dispose of, and a second where the consignee is a healthcare provider that is notified not to use false test results and use a different test instead. However, even after the webinar, it is not entirely clear who the “consignee” is in the case of an LDT that does not leave the laboratory (i.e., is it the lab itself, the healthcare provider, or the patient?).
With respect to FDA’s example of a sample collection kit that has been distributed outside the laboratory, it is unclear why this activity would be considered a recall of the LDT, since use of the collection device in and of itself it not likely to cause adverse health consequences. In the preamble to the Final Rule, FDA explicitly stated that collection devices are not LDTs and expressed its expectation that collection devices are already in compliance with applicable medical device regulations. The removal of the collection device from its point of use or instructing the patient to destroy the collection devices would be separate from any actions taken with respect to the LDT that would be subject to a correction or removal.
It also occurs to us that FDA has not provided any guidance regarding the use of risk management files in connection with recalls. In practice, traditional medical device companies establish risk management files during the design phase of a device, which are then used to inform the severity of harm and probability of occurrence in health hazard evaluations and, in turn, help determine whether a recall is necessary. Because most LDT developers will not implement risk management files until design controls are required (in Stage 3), they may have to conduct more ad hoc risk analysis when evaluating complaints that may necessitate recalls prior to Stage 3.
LDT Case Studies
FDA provided two “case studies” with mock situations involving LDTs, walking through how each situation should be handled as an MDR or recall (see slides 41-42). Although neither addresses the questions we raise about the difficulty in assessing recalls without risk management files or determining who the consignee is, these examples may be helpful to laboratories looking for straightforward examples of what it looks like to receive a complaint and process it as either an MDR or recall.
Previously Submitted Questions
FDA then proceeded to answer questions that were submitted to the agency before the webinar. We are not reproducing the questions that were simple recitations of regulatory definitions or FDA’s arguments in the Final Rule. Below are a few of the more interesting Q&As (paraphrased, as FDA did not provide these in the slides):
- Q: How do recall requirements apply if LDT materials and equipment never leave the laboratory?
- A: FDA explained that recalls are actions taken by a manufacturer to remove or correct a device that FDA considers in violation and against which FDA would take action. While a removal requires physical removal from the point of use, a correction does not. Therefore, FDA asserted that an action may constitute a recall whether or not a device is physically removed from its point of use. Even if LDT materials never leave a lab, they can be recalled. [HPM Note: This suggests that the vast majority of LDT recalls will be corrections, as LDTs typically do not have materials that leave the laboratory unless FDA is now considering the collection device to be part of the LDT which we noted above is different from the FDA’s position in the preamble to the LDT rule.]
- Q: The Final Rule states that LDTs falling within its potential enforcement discretion policies for currently marketed LDTs or LDTs to meet unmet needs are expected to comply with 21 CFR Part 820, Subpart M (Records), but these regulations cite to other sections of Part 820 for which these categories of LDTs are subject to enforcement discretion (e.g., 21 CFR 820.20 and .40) – so what requirements are expected for these LDTs under this subpart of the regulation
- A: As the Final Rule states, FDA recognizes that part 820, subpart M (records) includes cross-references to sections 820.20, 820.22, 820.40, and 820.50, for which FDA does not expect compliance for these categories of LDTs. FDA indicated that it does not expect labs will comply with these regulations simply because they are referenced in Subpart M.
- Q: What are the differences between CMS/CLIA and FD&C Act requirements for complaint records?
- A: FDA asserted that CLIA’s complaint requirements relate to lab operations/processes (e.g., specimen handling errors, lab personnel qualification issues, record falsification) and are not specific to identifying test-specific problems, whereas FDA’s complaint handing requirements focus on investigation of test-specific problems (e.g., issues with the design, manufacturing, and components of the device). FDA explained that all test-related complaints that a lab receives should be evaluated for FDA MDRs and noted that to address test-related complaint handling requirements outlined in 21 CFR 820.198, a lab may decide to expand its current complaint handling procedures, which meet CLIA requirements.
- Q: When a lab modifies another manufacturer’s cleared or approved test, is the laboratory considered a manufacturer responsible for meeting MDR requirements?
- A: According to the Agency, the lab would be considered a manufacturer of the new, modified test and must follow applicable regulatory requirements, including MDR requirements.
What Now?
Stage 1 is scheduled to take effect on May 6, 2025. According to FDA, by this date, laboratories should have established procedures and trained employees on requirements for complaints, MDR, and corrections and removals. As noted above, this will also entail setting up eMDR, requesting an FEI Number from FDA, and evaluating currently used LDTs to determine which product code(s) apply to each procedure. FDA is unlikely to provide significantly more guidance on these topics before they are implemented, although laboratories can consider reaching out to the agency with specific questions as they arise during implementation (e.g., reaching out to FDA’s Division of Industry and Consumer Education – DICE@fda.hhs.gov).
FDA plans to hold its next webinar on September 24, 2024, which will cover the labeling requirements that go into effect in Stage 2.
