Four years after the U.S. Food and Drug Administration (FDA) announced plans to align its Quality System Regulations (QSR) with international standard ISO 13485:2016, the agency on Tuesday released a proposed rule setting out its vision for the long-awaited regulatory overhaul.
The resulting regulation would be dubbed the Quality Management System Regulation (QMSR). According to the FDA’s analysis, the regulations as written would result in cost savings of $439 million to $533 million over 10 years for medical device establishments that comply with both standards.
The FDA is also proposing to give device makers a year from the publication of the final rule to adapt to the new regulatory requirements.
Since early 2018, the FDA said it was considering how to harmonize its regulatory requirements for medical device quality systems contained in 21 CFR part 820 with ISO 13485:2016, amid the three-year transition period of the international standard. (RELATED: New ISO 13485 standard: device manufacturers have three years to make the transition, Regulatory guidance March 1, 2016; FDA considering change in device quality system regulations, Regulatory guidance February 27, 2018)
In each of the agency’s semi-annual unified agendas since the spring of 2018, the FDA has listed the QSR overhaul as one of its next regulatory actions. With each passing year, the mammoth company’s schedule has slipped, including most recently in the Fall 2021 Unified Schedule, where the proposed rule was expected in December 2021.
The release of the proposed rule follows the FDA’s announcement last week that it would convene its Device Good Manufacturing Practices Advisory Committee for the first time since 2013 to discuss “feasibility and reasonableness.” of the proposed rule.
With the publication of the proposed rule on Tuesday, the FDA finally revealed its intention to modify the QSR to allow for greater international harmonization of medical device quality management systems (QMS).
The FDA is also taking the opportunity to modify other aspects of its regulations to better align with the provisions of the Federal Food, Drug and Cosmetic Act and to clarify Good Manufacturing Practices (GMP) requirements for combination products.
“This action, if completed, will continue our efforts to align our regulatory framework with that used by other regulatory authorities to promote consistency in device regulation with that used by other regulatory authorities to promote consistency in device regulation. device regulation and provide faster introduction. safe, effective, and high-quality devices for patients,” the FDA wrote on page 52 Federal Register notice announcing the proposed rule.
The FDA explains that at the same time that it published the current QSR in 1996, ISO published the first iteration of ISO 13485, establishing the first consensus standard specifically addressing QMS requirements for medical devices. “Over time, ISO 13485 has evolved into a standalone standard outlining QMS requirements for devices. With each revision, ISO 13485 has become more closely aligned and similar to Part 820 requirements,” the FDA said.
After years of review, the FDA said it had “determined that the requirements of ISO 13485 are, when taken as a whole, substantially similar to the requirements of current Part 820, providing a similar level assurance in a company’s quality management system and its ability to consistently manufacture safe, effective and FD&C compliant devices. »
The 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 a pilot reporting program. previous audit in which the agency accepted manufacturers’ audit reports based on ISO 13485:2003.
Part of the FDA’s reasoning for aligning its regulations with ISO 13485 is to reduce the regulatory burden on device manufacturers by eliminating the redundancies involved in complying with both the current QSR and ISO 13485.
Proposed approach and definitions
The FDA’s approach to aligning with ISO 13485:2016 is to incorporate 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 will 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 the FDA statutory and regulatory framework.” As such, the agency offers a series 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, the FDA explains how the various chapters of ISO 13485 would map to the current QSR subparts, and whether the proposed rule is substantially similar or different. If there are differences, the FDA provides a reference to the subpart where those differences are addressed. For example, 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 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 accurately reflect” the term’s reference to the FD&C Act. |
| “Management with executive responsibility” | Replaced by “top management” according to ISO 13485, although the current part 820 definition is retained. “This will maintain the principle and requirement that a manufacturer’s most senior employees are responsible for establishing and implementing the quality policy and ensuring that the manufacturer adheres to the policy. |
| “Rework” | The definition is retained with the deletion of the term “device master record (DMR)” as the concept “is adequately covered by the requirements for a medical device record under clause 4.2.3 of ISO 13485 . |
| “Process Validation” | The FDA retains the definition while clarifying that the term is synonymous with “process validation” as used in ISO 13485. |
| “Customer” | The FDA suggests including the definition of this term, “because it is important to the interpretation of the proposed rule. The FDA notes that it has not used the term in the past, but finds it useful for “encompassing many types of individuals and organizations throughout the manufacturing process of the device, such as component manufacturers, subcontractors and end users”. The FDA further explained that it expects manufacturers to comply with the customer ownership provisions of clause 7.5.10 of ISO 13485 “to the extent necessary to ensure the safety and efficiency of the manufactured devices”. However, the FDA notes that it does not intend to enforce customer ownership provisions that go beyond the safety and effectiveness of manufactured devices. |
| “Making up” | Kept unchanged |
| “Finished device” | Kept unchanged |
| “Human Cell, Tissue or Cellular or Tissue Product (HCT/P) Regulated as a Device” | Kept unchanged |
| “Design Validation” | Kept unchanged |
| “Reproduction” | Kept unchanged |
| “Noncompliance” | Kept unchanged |
| “Verification” | Kept unchanged |
The 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 regulations”, and will therefore be superseded by its own definitions for those terms.
“In particular, the definitions of ‘device’ and ‘labeling’… supersede the corresponding definitions of ‘medical device’ and ‘labelling’ in ISO 13485,” the FDA proclaims. Additionally, the FDA said it would retain its definition of “manufacturer” and retain with modifications its definition of “product” because the ISO 13485 definitions for these terms “do not meet the established range of these terms by the FDA. FDA”.
The proposed rule also contains clarifications for three concepts: “organization”, “security and performance” and “process validation”.
Other Differences and Changes
One of the key differences between the current Part 820 and the ISO 13485 standard is the international standard’s “emphasis on risk management activities and risk-based decision making”. While the current Part 820 “explicitly” addresses risk management activities only in its section on risk analysis as part of design validation, the FDA clarifies that it expects manufacturers “integrate risk management activities throughout their quality management system and throughout the entire product life cycle”.
The proposed rule would also clarify that section 7.3 of the ISO 13485 design and development standard only applies to manufacturers of certain Class I listed devices, in addition to manufacturers of Class II and III devices.
Notably, the FDA would expand the traceability requirements of clause 7.5.9.2 for implantable medical devices to instead cover devices that support or sustain life. These products are currently subject to the traceability requirements of § 820.65 but are not subject to the traceability requirements of ISO 13485.
In addition, the proposed rule contains additional provisions for control of registrations and controls for labeling and packaging of devices.
Controls
Although the proposed rule does not affect FDA’s authority to conduct inspections, the FDA said it intends to replace its current approach – Quality System Inspection Technique (QSIT) – with a new approach that complies with amended Part 820.
“Similar to the current QSIT inspection approach, these inspections would involve collecting information to support observations noted during the inspection and those included in an FDA Form 483, if applicable and necessary. FDA inspections will not result in the issuance of certificates of compliance with ISO 13485, nor does the FDA develop a certification program for ISO 13485. compliance with ISO 13485 are not exempt from FDA inspections,” the FDA said.
Federal Register Notice
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