From QSR to QMSR (Quality Management Regulation)
FDA intends to harmonize and modernize its quality system regulations for medical devices. This revision will replace existing requirements with the specifications of ISO 13485:2016, the international consensus standard for medical device manufacturing. The revision is intended to reduce the compliance and recordkeeping burden on device manufacturers by harmonizing domestic and international requirements. The revision also modernizes the regulation.
FDA is proposing amendments to align the current good manufacturing practice (cGMP) requirements of the 21 CFR Part 820 Quality System Regulations (QSR) more closely with the internationally recognized ISO 13485:2016 Medical devices – Quality management systems – Requirements for regulatory purposes. The proposed amendments also affect the regulation of 21 CFR Part 4 combination products The Medical Device Single Audit Program (MDSAP), developed in cooperation with five regulatory agencies, including FDA, further demonstrates the practicality of harmonizing CGMP requirements FDA is working with other regulators to develop the current regulatory framework in wants to coordinate to “promote consistency in device regulation and ensure the timely introduction of safe, effective, and high-quality devices for patients.”
The cGMP requirements for medical devices under 21 CFR Part 820 were first authorized by Section 520(f) of the Federal Food, Drug, and Cosmetic Act (FD&C) Under Section 520(f) of the FD&C Act, FDA issued cGMP requirements for medical devices. This became effective in 1978 and was codified in 21 CFR Part 820.
FDA revised the cGMP requirements in 1997, adding design controls authorized by the Safe Medical Devices Act (SMDA). FDA felt that it would be beneficial to the public and the medical device industry if cGMP regulations were consistent with the requirements of ISO 9001:1994 Quality Systems – Model for Quality Assurance in Design, Development, Production, Installation, and Servicing. There have been no major changes to 21 CFR Part 820 since 1997.
The first edition of ISO 13485 was released in 1996 and was titled ISO 13485:1996 Quality systems – Medical devices – Specific requirements for the application of ISO 9001. The first edition was the first transitional edition from the ISO 9001:1994 standard; the second edition of ISO 13485 was released in 2003 and was titled ISO 13485:2003 Medical devices – Quality management systems – Requirements for regulatory purposes. The current version, the third edition, is 13485:2016; with each release of ISO 13485, the requirements have become closer and more consistent with the cGMP requirements of 21 CFR Part 820.
FDA proposes to incorporate by reference ISO 13485:2016 Quality Management Systems – Requirements for Regulatory Purposes (current edition).Any revision or update to ISO 13485, as required by 1 CFR Part 51 Incorporation by Reference, before approval The impact of any revision or update to ISO 13485 should be evaluated to determine its impact prior to approval, as required by 1 CFR Part 51 Incorporation by Reference. If incorporated by reference, the resulting regulation would be referred to as the Quality Management System Rule (QMSR).
FDA believes that the requirements of 21 CFR Part 820 and ISO 13485:2016 are “substantially similar” and that the intent and purpose of the identified differences from ISO 13485:2016 are “generally consistent” with the requirements of 21 CFR Part 820. 21 CFR Part 820 and ISO 13485:2016 regulations, the FDA believes that they will provide the same level of safety and effectiveness for medical devices, including combination products.
FDA is in the process of streamlining 21 CFR Part 820 and will either accept the ISO 13485:2016 requirements without modification or propose requirements that supersede the corresponding ISO 13485:2016 requirements. Table 1 provides a rough summary of the differences and additions to the proposed rule in 21 CFR Part 820.
|Current part 820.1||ISO 13485 requirement item 1||draft of regulations|
|Subpart A – General Provisions||Scope of Application, Article 4: Quality Management System||Requirements are substantially similar.|
|Subpart B – Quality System Requirements||Article 4: Quality Management System; Article 5: Management’s Responsibility; Article 6: Operational Control of Resources; Article 8: Measurement, Analysis, and Improvement.||Requirements are substantially similar.|
|Subpart C – Design Management||Clause 7. Product Realization||Requirements are substantially similar.|
|Subpart D – Document Management||Article 4. Quality Management System||Differences addressed in 820.35.|
|Subpart E – Purchasing Management||Clause 7. Product Realization||Requirements are substantially similar.|
|Subpart F – Identification and Traceability||Clause 7. Product Realization||Requirements are substantially similar.|
|Subpart G – Manufacturing and Process Control||Clause 4. quality management system, Clause 6. operational management of resources, Clause 7. product realization||Requirements are substantially similar.|
|Subpart H – Acceptance Activities||Clause 7. product realization; Clause 8. measurement, analysis and improvement||Requirements are substantially similar.|
|Subpart I – Nonconforming Product||Article 8. Measurement, Analysis, and Improvement||Requirements are substantially similar.|
|Subpart J – Corrective and Preventive Actions||Article 8. Measurement, Analysis, and Improvement||Requirements are substantially similar.|
|Subpart K – Packaging and Labeling Management||Clause 7. Product Realization||Differences addressed in 820.45.|
|Subpart L – Handling, Storage, Distribution, and Installation||Clause 7. Product Realization||Requirements are substantially similar.|
|Subpart M-Record||Article 4. Quality Management System||Differences addressed in 820.35.|
|Subpart N – Ancillary Services||Clause 7. Product Realization||Differences addressed in 820.35.|
|Subpart O – Statistical Methods||Clause 7. Product Realization, Clause 8. Measurement, Analysis, and Improvement||Requirements are substantially similar.|
1 This table is not intended to be a requirement-by-requirement analysis, but rather a high-level mapping of the entire ISO 13485:2016 and 21 CFR Part 820 subparts and provisions for reference purposes only.
2 It is important to note that while there are differences specifically identified in Subpart D, documentation requirements exist in most subparts and provisions of ISO 13485:2016 and 21 CFR Part 820.
For a more detailed mapping, see AAMI Technical Information Report AAMI TIR102:2019 Mapping of U.S. FDA 21 CFR to ISO 13485:2016 “Quality Management Systems” to applicable regulatory requirements references. Note AAMI TIR102:2019 maps the current 21 CFR Part 820 to ISO 13485:2016 and does not consider the proposal to amend the Medical Device Quality System Regulation.
820.1 scope (of a document)
FDA is not proposing to change the establishments or products covered by 21 CFR Part 820. Although the requirements apply to manufacturers of finished products, FDA notes that statutory authority exists to cover manufacturers of components or parts of finished equipment, contract sterilizers, installers, relabelers, remanufacturers, repackagers, or specification developers, and first-time distributors of foreign companies The report notes the existence of legal authority for the first distributor of a foreign company.
Amendments to the scope of the requirements include clarifying that more specific and conflicting regulations are superseded only to the extent of the conflict.
Replacement from 21 CFR Part 820
- (n) Top management with executive responsibility for ISO 9000:2015 3.1.1.
Removed from 21 CFR Part 820
- (j) Device Master Record (DMR) means a compilation of records containing procedures and specifications for completed devices, using ISO 13485:2016 4.2.3 Medical Device File Requirements.
Will be taken over from 21 CFR Part 820
- (a) Act means the Federal Food, Drug, and Cosmetic Act (Secs. 201-903, 52 Stat. 1040, as amended (21 U.S.C. 321-394)), as amended. All definitions in Section 201 of said Act shall apply to the regulations in this Part.
- maintenance (b) Complaint means any written, electronic, or oral communication alleging defects in the identity, quality, durability, reliability, safety, effectiveness, or performance of a device after it has been released for distribution.
- (c) Component means any raw material, substance, part, component, software, firmware, labeling, or assembly intended to be included as part of finished, packaged, and labeled equipment.
- (l)Finished equipment means equipment or equipment accessories that are fit for use or capable of functioning, whether or not packaged, labeled or sterilized.
- (o)Manufacturer means any person who designs, manufactures, fabricates, processes, assembles, or treats finished equipment. Manufacturers include, but are not limited to, those who perform the functions of contract sterilization, installation, relabeling, remanufacturing, repackaging, or specification development, and first-time distributors of foreign entities that perform these functions.
- (q) Nonconformity means that a specific requirement is not met.
- (r) Product means components, manufacturing materials, devices in production, finished devices, and returned devices.
- (w) A remanufacturer is any person who processes, adjusts, refurbishes, repackages, restores, or otherwise substantially alters the performance or safety specifications of a finished device or its intended use.
- Remanufacturer means any person who processes, adjusts, refurbishes, repackages, restores, or otherwise substantially alters the performance or safety specifications of the finished equipment or its intended use.
- (x) Rework is the action taken to meet specified DMR requirements prior to placing nonconforming product into circulation
- (z) (1) Process validation is the demonstration by objective evidence that a process consistently produces a result or product that meets a given specification.
- (z) (2) Design validation is the demonstration by objective evidence that the specifications of the equipment are compatible with the needs of the user and the intended use.
- (aa) Verification is the confirmation that specified requirements have been met by inspecting and providing objective evidence.
- (bb)Human cells, tissues, or products based on cells or tissues (HCT/P) regulated as devices means HCT/P as defined in 1271.3(d) of this chapter that does not meet the criteria in 1271.10(a) and is also regulated as a device.
Terminology changed from 21 CFR Part 820
- (p) The manufacturing material will now become a process agent.
New terms not in either 21 CFR Part 820 or ISO 13485:2016
- Customer means a person or organization, including a user, who may or may receive a product or service intended or needed by this person or organization. A customer may be internal or external to the organization.
It will not be adopted from ISO 13485:2016 because it conflicts with the FD&C law.
- 3.4 complaint
- 3.8 labeling
- 3.11 medical equipment
820.7 risk management
This requirement will place greater emphasis on risk management activities and risk-based decision making throughout the quality management system (QMS) process. For equipment manufacturers, risk management is the essential systematic practice of identifying, analyzing, evaluating, controlling, and monitoring risks throughout the product life cycle to ensure the safety and effectiveness of the equipment they manufacture.
820.10 quality control system
It requires manufacturers to establish and maintain a quality management system that complies with the requirements of ISO 13485.
Clause 7.3 Design and Development applies only to Class II and III equipment and certain Class I equipment.
Clause 22.214.171.124 on implantable medical devices applies to devices that sustain or support life or whose malfunction, when properly used in accordance with the instructions for use on the label, could reasonably be expected to result in serious injury.
820.15 Conceptual Clarification
FDA proposes to clarify that the term “organization” also includes the meaning of manufacturer 820.3(o).
FDA suggests that if ISO 13485:2016 uses safety and performance, the wording should mean the same as safety and effectiveness.
FDA proposes to clarify the term process validation as used in ISO 13485:2016 to mean process validation 820.3(z)(1)).
820.35 Records Management
FDA proposes to include signature and date requirements in the records subject to ISO 13485:2016 Clause 4.2.5 Records Management to clarify the information FDA needs to ensure the validity of records (paper and electronic).
FDA is proposing specific requirements to ensure that the information required by 21 CFR Part 803 Medical Device Reporting is included in certain records of complaint and service activities.
Companies are required to document in their records the Unique Device Identification (UDI) of each medical device or batch of medical devices in accordance with 21 CFR Part 830 Unique Device Identification.
Retention 21 CFR 820.180 General requirements (a) Confidentiality. Records deemed confidential by the manufacturer may be marked to assist FDA in determining whether the information may be disclosed under the disclosure regulations in part 20 of this chapter.
820.45 Device labeling and packaging
Strengthen the current ISO 13485:2016 requirements for labeling and packaging controls, including inspection requirements, to better ensure safe and effective equipment manufacturing.
Effective Date and Implementation Policy
FDA is proposing that the final rule under this proposal will become effective one year after the date of publication of the final rule in the Federal Register to allow time for manufacturers to properly analyze and update their QMS and for FDA to properly train its personnel.
If this proposal is adopted, FDA inspections will continue as usual; FDA inspections will not result in the issuance of a certificate of conformity to ISO 13485, nor will FDA develop an ISO 13485 certification program. Furthermore, manufacturers with a certificate of conformity to ISO 13485 are not exempt from FDA inspections.
If you have any questions about this proposed rule, send an email to Proposed-Device-QMSR-Rule@fda.hhs.gov.
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