FDA's Proposed Rule to Regulate LDTs: 22 Questions Labs Should Start Asking Themselves Now
In September, the FDA proposed a rule that would end its enforcement discretion of LDTs by treating them as IVDs. Here are the questions impacted labs need to start considering.
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On September 29, 2023, the FDA proposed a rule to end the enforcement discretion policy for laboratory-developed tests (LDTs) by treating them as In Vitro Diagnostics (IVDs) subject to regulatory requirements as medical devices.
If you need a more thorough primer on the proposed rule, read our deep-dive first:
The rule would add ten words to the definition of "in vitro diagnostic products" in 21 CFR Part 809.3(a), stating that IVDs are considered devices under the FDCA, even if a laboratory is the manufacturer (revisions bolded):
“In vitro diagnostic products are those reagents, instruments, and systems intended for use in the diagnosis of disease or other conditions, including a determination of the state of health, in order to cure, mitigate, treat, or prevent disease or its sequelae. Such products are intended for use in the collection, preparation, and examination of specimens taken from the human body. These products are devices as defined in section 201(h)(1) of the Federal Food, Drug, and Cosmetic Act (the act), and may also be biological products subject to section 351 of the Public Health Service Act, including when the manufacturer of these products is a laboratory.”
The rule proposes a phased approach, with LDT manufacturers required to comply with regulatory requirements in stages:
Stage 1 (one year after issuance of the final rule): Begin filing medical device reports (MDR) under 21 C.F.R. Part 803 and notices of correction and removal under 21 C.F.R. Part 806.
Stage 2 (two years after issuance of the final rule): Register with the FDA as a device establishment and list LDTs performed, pursuant to 21 C.F.R. Part 807. Labs must also begin complying with device labeling requirements (21 C.F.R. Part 801) and investigational device exemption requirements (21 C.F.R. Part 812).
Stage 3 (three years after issuance of the final rule): Comply with the Quality System Regulation (QSR) (21 C.F.R. Part 820).
Stage 4 (three and a half years after issuance of the final rule): Laboratories offering high‑risk LDTs (i.e., Class III) would be required to submit an application for premarket approval (PMA) to FDA.
Stage 5 (four years after issuance of the final rule): Laboratories offering low and moderate‑risk LDTs (i.e., Class I or II) would be required to submit a 510(k) premarket notification unless eligible for exemption.
Compliance would begin one to four years after the final LDT rule is published. The final policy will be included in the rule's preamble. It does not intend to "grandfather" any LDTs currently available in the market.
It is currently unclear when the regulatory requirements would become effective. The proposed rule has received thousands of comments, and industry groups will certainly challenge it.
This 60-page comment on behalf of the Coalition to Preserve LDT Access and Innovation indicates the energy and resources being invested in killing the rule.
For now, labs are in a holding pattern, waiting to see what happens between now and the issuance of a final rule. We’ve been speaking with a number of consultants, some of whom are ex-FDA, who seem confident that this rulemaking will go forward, even if the final rule looks different in parts.
One of the most notable aspects of the proposed rule is its wildly ambitious timeline. It states that Stage 4 and Stage 5 would not begin before October 1, 2027, and April 1, 2028, respectively, to enable labs to participate in negotiations preceding user fee reauthorization in 2027 (taking effect in FY2028, which begins on October 1, 2027).
However, meeting this timeline would require the FDA to issue a final rule within approximately six months of the proposed rule’s publication date—that’s April 2024.
While it remains to be seen if the FDA can hit this date, we thought it’s worth presenting the preliminary questions impacted labs will need to consider if they have only a year to hit the Stage 1 requirements once that final rule is issued: Begin filing medical device reports (MDR) under 21 C.F.R. Part 803 and notices of correction and removal under 21 C.F.R. Part 806.
To conduct a high-level gap analysis and understand the work projects involved in hitting this milestone, we’ve identified 22 questions labs will need to consider.
21 C.F.R. Part 803:
Reporting Mechanisms (Medical Device Reporting - 21 C.F.R. Part 803)
Do we have a system in place for identifying and reporting adverse events and product problems?
Per 21 CFR 803.17, labs must develop, maintain, and implement written MDR procedures for the timely and effective identification, communication, and evaluation of events that may be subject to medical device reporting requirements.
Labs will need a structured process or system, ideally integrated with the QMS, that flags potential adverse events and product problems.
How effective is our current method of capturing data that could indicate a reportable event?
The requirement for effective event capture is implicit in the need to comply with the reporting obligations laid out in 21 CFR 803.50, which stipulates the criteria for reportable events.
Evaluate whether current data-capturing methods are consistently identifying potential reportable events. We suggest reviewing historical data to see if any reportable incidents were missed and analyzing the sensitivity and specificity of those detection methods.
Event Categorization (Medical Device Reporting - 21 C.F.R. Part 803)
Are we correctly identifying what constitutes a reportable event under FDA guidelines?
21 CFR 803.50 outlines what constitutes a reportable event, detailing the criteria for reporting deaths, serious injuries, and malfunctions.
Create and keep updated a reference guide or decision tree that outlines what constitutes a reportable event based on these guidelines.
Do we have clear criteria to distinguish reportable from non-reportable events?
This is based on the definitions and criteria provided in 21 CFR 803.50.
Develop clear, written criteria and examples to help staff differentiate between reportable and non-reportable events. Implement a review process for borderline cases, potentially involving a compliance officer or regulatory expert.
Staff Awareness and Training (Medical Device Reporting - 21 C.F.R. Part 803)
How will we ensure relevant staff members are aware of the FDA's requirements for medical device reporting?
While specific training requirements are not detailed in 21 CFR Part 803, the effective implementation of these regulations implicitly requires staff awareness and understanding. Regulators will be looking for a training program.
How will we ensure staff members have been adequately trained on how to identify and report adverse events?
This is an extension of the procedural requirements in 21 CFR 803.17. Make sure your training programs include real-world examples and simulations.