FDA’s Global Harmonization Efforts in Medical Device
Welcome back! For medical device groups, the Food and Drug Administration (FDA) integrating Quality Management System (QMS) elements of the International Organization for Standardization (ISO) 13485:2016 is a milestone, especially for those wanting to market and distribute their devices internationally. What does this mean?
In the United States (U.S.), Quality Management Systems (a.k.a. Quality Program) are built with specific requirements for Current Good Manufacturing Practice (CGMP). CGMP requires manufacturers ensure their products are safe and compliant to regulatory requirements, as well as to ensure specifications meet their customers’ needs. These regulations are under the Food, Drug, and Cosmetic Act (FDA&C) (21 U.S.C 360j(f)), and under the medical device side (43 FR 31508) for Title 21 Part 820.
In 1996, the FDA revised Part 820 which established the Quality System Regulation (QSR). The QSR included requirements related to methods used in, and the facilities and controls used for, designing, manufacturing, packaging, labeling, storing, installing, and servicing of devices intended for human use. These requirements have been effective in providing assurance that devices are safe and effective and otherwise in compliance with the FD&C Act. FDA has not undertaken a significant revision of part 820 since the 1996 Final Rule [1] .
Also in 1996, ISO issued the first version of ISO 13485, “Quality Systems—Medical Devices—Particular Requirements for the Application of ISO 9001,” as a voluntary consensus standard to specify, in conjunction with the application of ISO 9001, the QMS requirements for the design and development and, when relevant, installation and servicing of medical devices. Over time, ISO 13485 has evolved into a stand-alone standard outlining QMS requirements for devices. With each revision, the requirements in ISO 13485 have become more closely aligned with, and similar to, the requirements set forth in FDA’s QS regulation. This alignment and similarity are particularly true for the 2016 version of ISO 13485 [1] .
FDA has embraced global harmonization and actively participated in the development of internationally harmonized documents and standards on risk management through the International Medical Device Regulators Forum (IMDRF). The IMDRF (who replaced the Global Harmonization Task Force – GHTF), is a voluntary group of medical device regulators from around the world who have come together to build on this work to accelerate international medical device regulatory harmonization and convergence. IMDRF was established in October 2011 with medical device regulatory authorities from Australia, Brazil, Canada, China, European Union, Japan, the U.S., and the World Health Organization [2] .
IMDRF developed the Medical Device Single Audit Program (MDSAP) in 2012 where audits performed by third parties are conducted based on core ISO 13485 requirements with additional country-specific requirements, many other countries and FDA participate in this. FDA conducted a thorough review and comparison of ISO 13485 and the QSR and concluded that very few FDA-specific requirements needed to be added to the MDSAP model due to the similarities between the two, and because of the comprehensive and effective QMS approach by ISO 13485. This has allowed FDA to participate in MDSAP and accept certain MDSAP audits as a substitute for its own routine surveillance of device quality systems. Harmonizing differing regulations removes unnecessary redundancy regulatory requirements (decreases inefficiencies) and increases patient access.
In March of 2022, the Device Good Manufacturing Practice (DGMP) Advisory Committee met with FDA and stakeholders who proposed the harmonization to use global standards to help increase overall compliance with regulatory requirements from both medical device and combination products (those products that have parts made from drugs, devices, biological product constituent parts that comprise them). A comment period was opened and brought many questions for the FDA around the scope and requirements.
On January 31, 2024, the FDA issued a final rule amending the device current good manufacturing practice (CGMP) requirements of the Quality System (QS) Regulation under 21 CFR 820 to align more closely with the international consensus standard for Quality Management Systems for medical devices used by many other regulatory authorities around the world.
This rule amends 21 CFR 820 by incorporating by reference the quality management system requirements of the international standard specific for medical device quality management systems set by ISO, ISO 13485:2016. The FDA has determined that the requirements in ISO 13485 are, when taken in totality, substantially similar to the requirements of the QS regulation, providing 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).
The FDA will begin to enforce the QMSR requirements upon the effective date, February 2, 2026.
To mitigate inconsistencies between ISO 13485 and FDA, FDA added provisions with more significant revisions, additions, and removals to the codified sections [1] :
Revise § 4.2 terms to replace “QMSR for devices” with “QMSR.”
Revise § 4.4(b)(1) to replace the term “QMSR requirements” with “QMSR.”
Revise § 4.4(b)(1)(i) to revise the term “management responsibility” by adding the phrase “general requirements” and adding § 820.10 to the section.
Revise § 4.4(b)(1)(ii) to add the requirement that “[t]he organization shall document one or more processes for risk management in product realization. Records of risk management activities shall be maintained.”
Revise § 4.4(b)(1)(iv) to revise the term “improvement” by adding the phrase “analysis of data” and “complaint handling” and adding Clause 8.2.2 and § 820.35(a) to the section.
Revise § 820.1(c) to align with statutory language in sections 501 and 801 (21 U.S.C. 381) of the FD&C Act.
Revise § 820.3(a) to clarify use of definitions from ISO 13485 and ISO 9000 in this rulemaking.
Remove from § 820.3(a) definitions for the terms “customer,” “design validation,” “nonconformity,” “process agent,” “process validation,” “rework,” “top management,” and “verification.”
Revise § 820.3(b) to clarify use of definitions from ISO 13485 and ISO 9000 in this rulemaking.
Remove from § 820.3(b) the definition for the term “product” and add to § 820.3(b) the definition for the term “rework.”
Incorporate certain portions of proposed § 820.15, Clarification of Concepts, into § 820.3(b), not including § 820.15(c), “validation of processes.” Delete proposed § 820.15.
Revise clarification of term “safety and performance” in § 820.3(b) to apply only to Clause 0.1 of ISO 13485.
Add to § 820.3(b) clarification of term “implantable medical device.”
Remove from § 820.35 the requirement that a manufacturer must “obtain the signature for each individual who approved or re-approved the record, and the date of such approval, on that record.”
Revise § 820.35(a) to clarify expectations for record keeping related to complaint handling.
Revise § 820.35(a)(6) to add “correction.”
Revise § 820.45 to replace the term “establish” with the term “document,” and replace the term “where appropriate” with the term “as appropriate.”
Revise § 820.45(c) to remove the term “immediately” with respect to inspection of labeling and packaging.
For Frequently Asked Questions to FDA on this, check out the link here [3] .
Keep checking back as we’ll continue following and updating as we have more information!
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