Although FDA’s fiscal year begins October 1st every year, now in 2024 significant FDA initiatives are set to reshape the landscape for medical device and IVD manufacturers. We're closely tracking the pending Quality System Regulation Amendments, the proposed Laboratory Developed Tests rule, the Diversity Action Plan for clinical trials, and the 2024 New Guidance Agenda. Read more below as Qserve's expert teams provide insights and assistance for navigating these regulatory changes.
1. QSR Amendments
FDA's Quality System Regulation Amendments final rule is pending review at the White House Office of Management and Budget (OMB). Although not published as of the date of this blog, it is coming any day now! The resulting regulation will be referred to as the Quality Management System Regulation (QMSR).
Regulatory expectations for a Quality Management System (QMS) have evolved since the current part 820 was implemented over 20 years ago. By proposing to incorporate ISO 13485 by reference, FDA is seeking to explicitly require current internationally recognized regulatory expectations for QMS for devices subject to FDA's jurisdiction. FDA intends to converge its requirements with quality management system requirements used by other regulatory authorities. This will be accomplished primarily by incorporating by reference ISO 13485:2016 Medical devices—Quality management systems—Requirements for regulatory purposes, Third Edition 2016–03–01 (ISO 13485). FDA also proposes conforming edits to 21 CFR part 4 to clarify the device QMS requirements for combination products. The revisions are intended to promote the use of more modern risk management principles and reduce regulatory burdens on device manufacturers and importers.
21 CFR 820 will be amended with additional definitions, clarifying concepts, and additional requirements, all of which would require compliance within a manufacturer's QMS in addition to ISO 13485. A high-level summary of alignment between ISO 13485 and the proposed QMSR is in the proposed rule.
FDA proposes a one-year transition period from the date that the final rule is published in the Federal Register. So, assuming it is published in January 2024, it will be effective Jan 2025 giving manufacturers a year to update their QMS to incorporate the QMSR terminology and references.
Qserve’s Quality Management Team is watching this closely and will post another blog once the final regulation is published and will be ready to assist you with your transition to compliance.
2. Proposed Rule of Laboratory Developed Tests (LDTs)
The comment period for the proposed rule “Medical Devices; Laboratory Developed Tests” closed on Dec 4, 2023. According to FDA’s unified agenda, the final rule publication date is in April 2024.
The proposed rule would alter the way that LDTs are regulated, effectively bringing these products under FDA purview to be regulated as medical devices with very limited exemptions. Along with this amendment, the FDA proposes a policy under which FDA intends to phase out its general enforcement discretion approach for most laboratory developed tests (LDTs). This rule will amend 21 CFR 809.3(a) by adding the phrase "including when the manufacturer of these products is a laboratory” in the definition of “in vitro diagnostic products.” Ten words added to the definition of an in vitro diagnostic product could not have a more significant and staggering impact to the industry particularly the clinical laboratory industry. This change has a dramatic knock-on effect to the pharmaceutical industry that has a vested interest in using IVDs, mostly LDTs for biomarker identification for targeted drug therapy known as companion diagnostics (CDx).
Years of enforcement discretion by the FDA of LDTs has allowed the LDT market to flourish financially with the number of clinical laboratories being established. Without FDA establishment registration requirements of clinical laboratories engaged in LDT manufacturing, no one really knows the number of laboratories impacted nor the number of LDTs! The number is likely staggering.
Clinical laboratories have traditionally not had to interact with FDA so the regulations, processes, and expectations will be completely foreign to them. With this expectation as well as the sheer volume, FDA’s proposal has a 5-stage transition period:
- 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 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 809) 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, or De Novo requests if there is no legally marketed device upon which to base a determination of substantial equivalence and for which the laboratory seeks classification into Class I or Class II.
Qserve’s IVD Team is watching this space closely and working with our existing clients to develop transition plans.
3. Diversity Action Plan
FDA plans to revise their approach to race and ethnicity diversity plans for clinical trials that will be laid out in guidance documents. FDA expects to release the final guidance in early 2024.
“Race and Ethnicity Diversity Plan” will be required for medical device IDE studies. What to expect in the guidance will be information on enrollment targets based on the intended use of the device, strategies to enroll clinically relevant population, assessment of how race or ethnicity could have different safety or effectiveness profiles, and how those risks will be mitigated. This guidance specifically recommends enrolling representative numbers of participants from underrepresented racial and ethnic populations in the United States, such as Black or African American, Hispanic/Latino, Indigenous and Native American, Asian, Native Hawaiian and Other Pacific Islanders, and other persons of color, in clinical trials. In addition, FDA advises sponsors to seek diversity in clinical trial enrollment beyond populations defined by race and ethnicity, including other underrepresented populations defined by demographics such as sex, gender identity, age, socioeconomic status, disability, pregnancy status, lactation status, and co-morbidity. To discuss a proposed enrollment strategy before submitting the Plan to the IDE or for clinical studies not conducted under an IDE, a sponsor should follow the Q-submission process for obtaining feedback or requesting a meeting with FDA.
Qserve’s Medical Writing Team is monitoring the development of the DAP requirements and will be able to assist with analysis and writing DAPs for your clinical studies.
4. 2024 New Guidance Agenda
The Center for Devices and Radio Health (CDRH) posts two lists of guidance documents each year that it intends to publish during the fiscal year. The A-list is a list of prioritized device guidance documents that FDA intends to publish during FY2024. The B-list is a list of device guidance documents that FDA intends to publish as resources permit during FY2024.
Final Guidance Topics: Remanufacturing, Shortage reporting under 506J, Pre-Determined Change Control Plans (PCCPs) for AI/ML products
Draft Guidance Topics:
- Eighteen guidance total, indicating an ambitious policymaking cadence
- New guidance on: AI/ML lifecycle management, PCCPs for other devices, Emergency policies for diagnostic products, Chemical Analysis for biocompatibility assessments
- Revisions to existing guidance: Q-submissions, Cybersecurity, Patient Preference Information (PPI), 506J Disruption/shortage reporting, Evaluating sex- and gender-specific data, Accreditation Scheme for Conformity assessment (ASCA) policies, MDUFA fee small business qualification and certification, and Pulse Oximeters
- Guidance with a FDORA due date: Select updates on use of RWE, Third-party review of EUAs
- Final: Computer Software Assurance for Production and Quality System Software, Voluntary Malfunction Summary Reporting (VMSR)
- Draft: 3D Printing Medical Devices at the Point of Care
Qserve’s Medical Device and IVD Teams will be monitoring as new guidance is drafted and finalized.
Continuing Device Regulations
a. Pre-determined change Control Plans (PCCP) – initially released for artificial intelligence and machine learning software, expect to see these for some IVD devices for molecular testing to add specific genes to cleared or PMA devices.
b. eSTAR – the system works! eSTAR became mandatory for 510(k) submissions in October of last year. Q-submissions, de novo submissions and PMA are available on a voluntary basis. Please be sure to use the updated version when preparing a new submission if you intend to submit after the retirement date of the previous version. The previous version can be submitted until the retirement date.
Qserve’s Medical Device and IVD Teams have reviewed some PCCPs and have used the eSTAR system with success and are eager to assist our clients succeed with their Q-submissions, 510(k)s, de novo requests, and PMAs.
The FDA is a government body overseen by Congress and the FDA Commissioner appointed by the president. If Biden wins and thus the White House remains under a Democrat, expect status quo. Robert Califf will likely remain as the FDA Commissioner. FDA will be working furiously to implement everything on the Biden agenda to make it difficult to overturn should the presidency go to a Republican.
If Trump wins and thus the White House under Republican control, it is likely that Califf will be replaced by a Republican appointee that will have to be approved by the Senate. The Senate is expected to remain with a democrat majority and thus not a smooth republican nominee confirmation. Also expect reforms to Civil Service legislation that will have direct impact on FDA senior staffing allowing persons to be fired by the Executive Branch; HHS (Health and Human Services-agency under which FDA sits) will exert itself into FDA policymaking. All of this creating turmoil within FDA that could stall and impact manufacturers.
Qserve’s Medical Device and IVD Teams will be monitoring the impact of election outcomes to FDA and how they affect efficiency to our customers with 510(k) and PMA clearances/approvals and post market activities.