FDA Quality Management System Regulation (QMSR)
In February 2022, FDA released proposals for aligning their Quality System Regulation (QSR) with the commonly used ISO 13485 Medical devices – Quality management systems[1] – Requirements for regulatory purposes. This had been long awaited and was rumoured to be coming for many years prior to this point. As many manufacturers of medical devices and in vitro diagnostics (IVD) were already complying with this standard due to other regulation requirements, it made sense for the FDA to align with this industry ISO standard.
There was an initial commenting period from February through May 2022 and then the FDA went away to work on all the feedback.
The initial timeline stated that the final rule and publication of the finalized QMSR, as it is to be known, would occur in December 2023[2]. That timeline passed but FDA updated[3] the industry that the amendments have been reviewed as of 6th December 2023 by the Office of Information and Regulatory Affairs within the White House[4]. The final rule was then rescheduled to be released on 2nd February 2024 and is now available in its finalized version.
This will trigger the need for companies who currently market medical devices and IVD in the US to review their QMS for the amendments. The initial proposal still included FDA specific accommodations, so even those who already hold ISO 13485 certification will need to make adjustments. The final rule gives 2 years to implement required changes.
Laboratory Developed Tests (LDTs)
Back in the fall of 2023, the FDA announced their intentions with regards to LDTs causing much uproar in the industry[5]. They did this in the form of a proposed rule which would place LDTs under the same expectations as IVDs unless they meet certain Clinical Laboratory Improvement Amendments (CLIA) requirements.
“Through increased FDA oversight, the public, including patients and health care professionals, should have confidence that the tests they rely on are accurate,” said Jeff Shuren, M.D., J.D., director of the FDA’s Center for Devices and Radiological Health.
This would replace an enforcement discretion policy from the 1970s and marks a significant change in direction. During a press release they noted that:
“Laboratory-developed tests play a central role in US healthcare, and many are similar to [diagnostics] that do come into the FDA for review,” the [FDA Commissioner Robert Califf] added. “This approach no longer makes sense and puts US patients at risk.”[6]
This rule overlaps with the proposed Verifying Accurate, Leading-edge IVCT Development (VALID) act[7] which would change how IVDs are regulated. At this time the VALID act is not being progressed, hence the FDA changed their approach.
Industry was given until 2nd December 2023 to comment on the proposed rule. Considering the significance and scale of the changes being proposed, this led to campaigners requesting extensions which were denied by FDA[8].
Even after the commenting period closed there were still many concerns about the proposed rule and expectations that further lobbying would be needed to align with industry wishes[9]. The FDA responded with a joint statement[10] on 18th January 2024 from Jeff Shuren, Director of FDA’s Center for Devices and Radiological Health (CDRH), and Dora Hughes, Acting Chief Medical Officer and Acting Director of the Center for Clinical Standards and Quality at CMS, asserting the need to “reconsider” the agencies’ longstanding approach to regulating LDTs and championing FDA’s proposed rule to enhance its enforcement oversight of LDTs.
These discussions are expected to rumble on in 2024.
FDA guidances planned for 2024
Each year, the FDA publishes their plans for guidances to be developed and released in the following year[11]. These are categorized into the A list of prioritized device guidance documents the FDA intends to publish during following year and the B list of device guidance documents the FDA intends to publish as resources permit during the following year.
In 2023 the key guidances of interest were the software submission content guidance and the cybersecurity guidance. For 2024 the A list consists of the following guidances which they intended to make final
- Remanufacturing of Medical Devices
- Medical Device Shortages – Implementation of Section 506J of the Federal Food, Drug, and Cosmetic Act
- Marketing Submission Recommendations for A Predetermined Change Control Plan for Artificial Intelligence/Machine Learning (AI/ML)-Enabled Device Software Functions
The final item will be the one of most interesting. It takes the next step in regulating AI/ML devices building on the Good Machine Learning Practice for Medical Device Development: Guiding Principles[12] which was published by the FDA in 2021 in conjunction with Health Canada and the Medicines & Healthcare Products Regulatory Agency (MHRA) of the UK, which was the last document seen on this topic. AI/ML development has progressed significantly in the last few years and it will be good to see the regulators catch up with this. The list of approved devices with AI/ML now numbers 692 on the FDA’s website[13]as more and more products are being approved including this technology.
This will be supported by other guidances listed as planned to be released as a draft in 2024:
- Artificial Intelligence/Machine Learning (AI/ML)-enabled Device Software Functions: Lifecycle Management Considerations and Premarket Submission Recommendations
- Predetermined Change Control Plans for Medical Devices
Timelines in the EU for MDR and IVDR
Currently 43 notified bodies are qualified to approve medical device CE marks against the MDR[14], and 12 for the IVDR[15], yet there are still struggles and concerns with delays in the EU.
In September 2023, the guidance MDCG 2020-3[16] “Guidance on significant changes regarding the transitional provision under Article 120 of the MDR with regard to devices covered by certificates according to MDD or AIMDD” was updated to give further extensions on the MDR.
But the Medical Devices Coordination Group (MDCG) were concerned enough in November 2023, to publish an additional position paper[17] stating that not enough products were gaining approvals to avoid shortages in the market[18].
A public dashboard is now available showing the number of applications in progress with notified bodies and their status[19] for both the MDR and IVDR. This indicates the median time for approval is currently sitting around 13-18 months. This dashboard includes data from surveys of notified bodies in March and June 2023. Hopefully it will be regularly updated with current data.
In 2024, thoughts are looking towards IVDR deadlines, and discussions are starting as to whether it should be similarly extended[20].
[1] ISO 13485 Medical devices – Quality management systems
[3] OIRA Conclusion of EO 12866 Regulatory Review (reginfo.gov)
[4] Information and Regulatory Affairs | OMB | The White House
[5] Federal Register :: Medical Devices; Laboratory Developed Tests
[6] FDA proposes long-awaited LDT enforcement rule | RAPS
[7] Stakeholders continue push for VALID Act in wake of FDA’s proposed LDT rule | RAPS
[8] FDA won’t extend LDT rule comment period | RAPS
[9] Experts expect opponents of LDT rule to ramp up Congressional lobbying | RAPS
[10] FDA and CMS: Americans Deserve Accurate and Reliable Diagnostic Tests, Wherever They Are Made | FDA
[11] CDRH Proposed Guidances for Fiscal Year 2024(FY2024) | FDA
[12] Good Machine Learning Practice for Medical Device Development: Guiding Principles | FDA
[13] Artificial Intelligence and Machine Learning (AI/ML)-Enabled Medical Devices | FDA
[14] EUROPA – European Commission – Growth – Regulatory policy – SMCS
[15] EUROPA – European Commission – Growth – Regulatory policy – SMCS
[17] Final Draft revision of MDCG 2022-11 – Notice to manufacturers and notified bodies to ensure timely compliance with MDR and IVDR requirements (europa.eu)
[18] MDCG raises alarm over lack of MDR, IVDR applications | RAPS
[20] Commission proposes to extend IVDR transition, accelerate EUDAMED adoption | RAPS
Helen Simons is a Director of QA/RA at StarFish Medical. Helen’s education is in Mechanical engineering, with a background of product development and QMS development across multiple industries with consumer and industrial products to medical devices, IVD and combination devices.
