Recently there have been several US and OUS IVD-focused new or proposed regulatory requirements with the potential to impact IVD and LDT manufacturers’ quality management systems (QMS). The implications of these evolving pre- and post-market requirements are wide-ranging and require a clear understanding to inform a strategic yet pragmatic approach for implementation. An overview of these recent regulatory requirements and proposals follows:
QSR to ISO 13485:2016
On January 31, 2024, the FDA issued the Quality Management System Regulation (QMSR) Final Rule, amending the device good manufacturing practice (CGMP) requirements of the Quality System (QS) Regulation under 21 CFR 820 to align most closely with the international consensus standard for Quality System Systems, ISO 13485:2016. Substantively, there is no change to the scope of FDA expectations for a comprehensive quality management system.
The FDA refers to the revised 820 as the “Quality Management System Regulation” (QMSR) and uses the terms “Quality System (QS) Regulation” or “QS regulation” when referring to the unrevised 820.
Incorporation by reference[1] of the QMS requirements of ISO 13485:2016 and Clause 3 of ISO 9000:2015, will provides a similar level of assurance in a firm’s quality management system and ability to consistently manufacture devices that are safe and effective and otherwise in compliance with the Federal Food, Drug, and Cosmetic Act (FD&C Act). However, this amendment makes the integration of risk management into quality systems much more explicit, with changes to terminology that aligns with ISO 13485 – such as the elimination of design history file and device history record.
The FDA extended the proposed transition period from one to two years. FDA will enforce the QMSR requirements beginning February 2, 2026. The changes introduced in the amendment will require a comprehensive gap analysis to gain a clearer understanding of how to align your QMS with the new QMSR. This potentially presents a large scope of work for all manufacturers, especially for those that have previously only conducted business domestically and have less experience with the ISO standard.
Our specialized experience can support your efforts to ensure compliance with the following services:
• QMS design and implementation
• Process and documentation review
• Gap assessment & remediation
• SOP development
• Auditing
• Inspection Readiness
• Training
Laboratory Developed Tests (LTDs)
Historically, FDA has generally exercised enforcement discretion over most Laboratory-Developed Tests (LDTs). When the Medical Device Amendments of 1976 were introduced, LDTs were often lower-risk IVDs developed and used in a single laboratory. LDTS were often developed to address an unmet medical need, e.g., targeting rare diseases for which there were no commercial tests available because the tests would be used so infrequently as to be deemed unprofitable by most companies. Today’s LDTs are developed, manufactured, and used more in-line with those cleared or approved by the FDA; they are often complex, instrument-based assays manufactured in high volume and used to test patient samples shipped in from across the United States.
Due to the impact that the use of diagnostics, including LDTs, is having on patient care, as well as concerns about safety and accuracy of LDTs, FDA has proposed phasing out the general enforcement discretion approach they have taken with most types of LDTs, to make explicit that “in vitro diagnostic products” as defined in 21 CFR 809.3 include those devices manufactured by a laboratory.
Manufacturers of certain types of LDTs will need to be prepared for increased FDA scrutiny during the four-year phaseout period and be fully in compliance with requirements for IVDs by the conclusion of the phaseout program.
With the rule under review by the Office of Information and Regulatory Affairs (OIRA) within the Office of Management and Budget (OMB) since early March, the FDA’s goal of finalizing the rule by Q2 of 2024 appears to be within reach.
Our team can assess and support the impact on your new and existing product development with:
• Classification assessments
• QMS design and support
• LDT verification and validation
• FDA Inspection readiness
• Pre- and post-market submission support
Read more details in our blog here: https://beaufortcro.com/blog/fdas-proposed-rule-for-ldts/
IVDR
To mitigate the risk of shortages for certain high-risk IVDs, on January 23, 2024, the European Commission posted a proposal aimed at further extending the transition period for Regulation (EU) 2017/746 (IVDR). As part of the proposal, the transition period for class D devices, those with high individual and public health risks, would extend until December 2027. Class C devices would have a transition period until December 2028, and class B and class A sterile devices would follow, with a transition period ending December 2029. This extension will only apply to CE-marked IVDs that are already on market and comes with additional conditions.
Manufacturers of all classes of IVDs must have IVDR-compliant quality management systems in place by 26 May 2025, which means that class C or class B and class A sterile devices may be working with less time to align their quality management systems than had previously been anticipated. The manufacturer must also submit an application to the notified body indicating the intent to transition to the IVDR in order to qualify for the extended transition. The deadline for these applications is May 2025 for class D devices, May 2026 for class C devices, and May 2027 for class B and class A sterile devices. In a press release dated February 21, 2024, the European Council stated they have endorsed the updates to Regulation (EU) 2017/746; publication in the Official Journal of the EU could occur as early as April 2024.
Beaufort can help translate all of the complexities to understandable requirements and support all aspects of your implementation with the following:
• Legacy and new device support
• Conformity assessments
• IVDR-compliant QMS assessments and implementation
• Technical documentation preparation and review
• Clinical evidence strategies
• Performance Study Documentation preparation
• Responses to Competent Authority / EC Review questions
• Labeling and UDI compliance
• Distance sale (“LDT”) requirements
Read more here: https://beaufortcro.com/blog/the-potential-impact-of-the-eu-commissions-proposal-to-delay-ivdr-implementation/
Learn More About How Beaufort Can Help
At Beaufort, we specialize in guiding manufacturers through the intricacies of the latest regulatory proposals and updates with expertise in global regulatory affairs and quality consulting, clinical trial services, and data sciences.
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1Incorporation by reference (IBR) allows Federal agencies to comply with the requirement to publish rules in the Federal Register and the Code of Federal Regulations (CFR) by referring to material already published elsewhere. The legal effect of IBR is that the material is treated as if it were published in the Federal Register and CFR. This material, like any other properly issued rule, has the force and effect of law. (https://www.archives.gov/federal-register/write/ibr#:~:text=Incorporation%20by%20reference%20(IBR)%20allows,to%20material%20already%20published%20elsewhere. Accessed March 13, 2024 and https://www.ecfr.gov/incorporation-by-reference Accessed March 13, 2024)