QMSR: FDA proposes QSR overhaul after years of delays

Four years after the US Food and Drug Administration (FDA) signaled its intent to align its Quality System Regulation (QSR) with the international standard ISO 13485:2016, the agency on Tuesday issued a proposed rule laying out its vision for the long-awaited regulatory overhaul.

The resulting regulation would be dubbed the Quality Management System Regulation (QMSR). According to FDA’s analysis, the regulation as written would result in a cost savings of $439-533 million over 10 years for medical device establishments that comply with both standards.

FDA is also proposing to give device makers one year from the publication of the final rule to adapt to the new regulatory requirements.

Since early 2018, FDA has said it is considering how to harmonize its regulatory requirements for medical device quality systems contained in 21 CFR part 820 with ISO 13485:2016, amid the international standard’s three-year transition period. (RELATED: New ISO 13485: Device companies have three years to transition, Regulatory Focus 1 March 2016; FDA considers shift on device quality system regulations, Regulatory Focus 27 February 2018)

In each of the agency’s biannual unified agendas since spring 2018, FDA has listed the QSR overhaul as one of its upcoming regulatory actions. With each passing year, the timeline for the mammoth undertaking slipped, including most recently in the Fall 2021 unified agenda, where the proposed rule was expected in December 2021.

The release of the proposed rule follows FDA’s announcement last week that it would convene its Device Good Manufacturing Practice Advisory Committee for the first time since 2013 to discuss the “feasibility and reasonableness” of the proposed rule.

With the publication of the proposed rule on Tuesday, FDA has finally revealed its plans to amend the QSR to allow for greater international harmonization for medical device quality management systems (QMS).

FDA is also taking the opportunity to amend other aspects of its regulations to better align with provisions of the Federal Food, Drug, and Cosmetic Act and to clarify good manufacturing practice (GMP) requirements for combination products.

“This action, if finalized, will continue our efforts to align our regulatory framework with that used by other regulatory authorities to promote consistency in the regulation of devices with that used by other regulatory authorities to promote consistency in the regulation of devices and provide timelier introduction of safe, effective, high-quality devices for patients,” FDA wrote in the 52-page Federal Register notice announcing the proposed rule.

FDA explains that at the same time it issued the current QSR in 1996, ISO released the first iteration of ISO 13485, establishing the first consensus standard specifically addressing medical device QMS requirements. “Over time, ISO 13485 has evolved into a stand-alone standard outlining QMS requirements for devices. With each revision, ISO 13485 has become more closely aligned with, and similar to, the requirements in part 820,” FDA said.

After years of review, FDA said it has “determined that the requirements in ISO 13485 are, when taken in totality, substantially similar to the requirements of the current part 820, 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 FD&C Act.”

FDA said it reached this conclusion in part based on its recent experience with ISO 13485 through its participation in the Medical Device Single Audit Program (MDSAP) and an earlier audit report pilot program in which the agency accepted manufacturers’ audit reports based on ISO 13485:2003.

Part of FDA’s reasoning for aligning its regulations with ISO 13485 is to reduce the regulatory burden for device makers by eliminating redundancies involved in complying with both the current QSR and ISO 13485.

Proposed approach and definitions

FDA’s chosen approach to aligning with ISO 13485:2016 involves incorporating references to the standard in its regulations. The overhaul would only apply to the 2016 version of the standard, and, “Any future revisions to this standard would need to be evaluated” before making their way into US regulations.

The agency also acknowledges that recognizing ISO 13485 “without clarification or modification would create inconsistencies with FDA’s statutory and regulatory framework.” As such, the agency is proposing a suite of additional definitions, clarifying concepts and other requirements that would be required as part of a manufacturer’s QMS in addition to ISO 13485.

In a table provided in the proposed rule, FDA lays out how different chapters of ISO 13485 would be mapped to the current subparts of the QSR, and whether the proposed rule is substantially similar or different. Where there are differences, FDA provides a reference to the subpart where those differences are addressed. For instance, the differences between the current part 820 subpart K – Labeling and Packaging Control and ISO 13485:2016 Chapter 7. Product Realization are detailed in part 820.45 of the proposed rule.

The agency also discusses differences in the terms and definitions used in part 820 and ISO 13485 and explains its decision to retain or revise certain definitions.

Table 1. Terms that do not appear in ISO 13485 that will be retained
“Act”	Retained but expanded to “more precisely reflect” the term’s reference to the FD&C Act.
“Management with executive responsibility”	Replaced with “top management” as per ISO 13485, though the definition in the current part 820 will be retained. “This will maintain the principle and requirement that the most senior employees of a manufacturer are responsible for establishing and making chances to the quality policy and ensuring the manufacturer follows the policy.
“Rework”	The definition is retained with the removal of the term “device master record (DMR)” as the concept “is adequately covered under the requirements for a medical device file under Clause 4.2.3 of ISO 13485.
“Process validation”	FDA is retaining the definition while clarifying that the term is synonymous with “validation of processes” as used in ISO 13485.
“Customer”	FDA is proposing to include the definition of this term, “as it is important to the interpretation of the proposed rule. FDA notes that it has not historically used the term but finds it useful to “encompass many types of individuals and organizations throughout the device manufacturing process, such as component manufacturers, contract manufacturers, and end users.” FDA further explained that it expects manufacturers to comply with the customer property provisions in Clause 7.5.10 of ISO 13485 “to the extent necessary to assure the safety and effectiveness of the devices being manufactured.” However, FDA notes that it does not intend to enforce any customer property provisions that go beyond the safety and effectiveness of the devices being manufactured.
“Component”	Retained without change
“Finished device’	Retained without change
“Human cell, tissue, or cellular or tissue-based product (HCT/P) regulated as a device”	Retained without change
“Design validation”	Retained without change
“Remanufacturer”	Retained without change
“Nonconformity”	Retained without change
“Verification”	Retained without change

FDA explains that there are also a number of terms and definitions in ISO 13485 that “would create inconsistencies with the FD&C Act and its implementing regulations,” and thus will be superseded by its own definitions for those terms.

“In particular, the definitions of ‘device’ and ‘labeling’ … supersede the correlating definitions for ‘medical device’ and ‘labelling’ in ISO 13485,” FDA proclaims. Additionally, FDA said it will retain its definition of “manufacturer” and retain with modifications its definition of “product,” as the ISO 13485 definitions for those terms “do not align with the established range of these terms by FDA.”

The proposed rule also contains clarifications for three concepts: “organization,” “safety and performance” and “validation of processes.”

Other differences and changes

One of the primary differences between the current part 820 and ISO 13485 is the international standard’s “greater emphasis on risk management activities and risk-based decision making.” While the current part 820 only “explicitly” addresses risk management activities in its section on risk analysis within design validation, FDA clarifies that it has expected manufacturers to “integrate risk management activities throughout their QMS and across the total product lifecycle.”

The proposed rule would also clarify that Clause 7.3 of ISO 13485 on Design and Development only applies to manufacturers of certain listed class I devices, in addition to manufacturers of class II and III devices.

Notably, FDA would extend the traceability requirements in Clause 7.5.9.2 for implantable medical devices to instead cover devices that support or sustain life. Such products are currently subject to traceability requirements in § 820.65 but are not subject to traceability requirements in ISO 13485.

Additionally, the proposed rule contains supplementary provisions for control of records and controls for device labeling and package.

Inspections

While the proposed rule does not impact FDA’s authority to conduct inspections, FDA said it intends to replace its current approach -- Quality System Inspection Technique (QSIT) – with a new approach consistent with the amended part 820.

“Similar to the current QSIT inspection approach, these inspections would involve the collection of information to support observations noted during the inspection and those included on a Form FDA 483, as appropriate and necessary. FDA inspections will not result in the issuance of certificates of conformance to ISO 13485, nor is FDA developing a certification program for ISO 13485. In addition, manufacturers with a certificate of conformance to ISO 13485 are not exempt from FDA inspections,” FDA said.

Federal Register Notice

QMSR: FDA proposes QSR overhaul after years of delays

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