The FDA’s Quality System Regulation (QSR) for medical device manufacturers is commonly known as FDA 21 CFR Part 820. Here’s a run-down of what’s inside.
What is it all about?
Under US federal regulations, all medical device manufacturers operating or selling products into the United States market are required to establish and maintain a quality system. This Quality Management System (QMS) is the set of policies and procedures intended to ensure quality and safety throughout the design and manufacturing process. The definitive description of these requirements can be found in FDA 21 CFR Part 820
21 CFR Part 820 - What’s inside?
1. General Provisions
This section outlines the scope, definitions, terms and applicability of Part 820 to medical device manufacturers.
“Current Good Manufacturing Practice (cGMP) requirements are set forth in this quality system regulation. The requirements in this part govern the methods used in, and the facilities and controls used for, the design, manufacture, packaging, labeling, storage, installation, and servicing of all finished devices intended for human use.”
It contains important information about who the regulation applies to, the specific meaning of key terms, and details of potential exemptions.
2. Quality System Requirements
This section lists requirements for the quality management system, it contains details of required contents, including:
- Quality policy
- Organisation structure
- Responsibility and authority
- Details of quality representative
- Management representative, reporting and review provisions
- Quality planning details
- Quality system procedures
- Procedures for quality audits
Requirements for personnel are also a part of the Quality System regime. This section outlines requirements for workers to have appropriate education, training and experience - and how these all need to be documented.
3. Design Controls
This section outlines required controls for the whole design and development process, consisting of:
- Design and development planning
- Design input
- Design output
- Design review
- Design verification
- Design validation
- Design transfer to production
- Design changes
The correct implementation of the specified design controls will facilitate the generation of the necessary Design History File (DHF) and Device Master Record (DMR).
4. Document Controls
This section describes requirements for document approval, distribution as well as document changes.
The QSR states manufacturers must designate someone to review and approve all documentation generated by the quality system - and that those approvals must be dated and signed. For details of the compliant use of e-signatures within a digital QMS see this blog post on FDA 21 CFR Part 11.
The QSR also states that any documents produced need to be ‘available at all locations for which they are designated, used or otherwise necessary’ and that obsolete documents should be removed from use immediately.
The same procedure must be applied for changes in quality documentation, with records that contain:
“The description of the change, identification of the affected documents, the signature of the approving individual(s), the approval date, and when the change becomes effective.”
5. Purchasing Control
“Each manufacturer shall establish and maintain procedures to ensure that all purchased or otherwise received product and services conform to specified requirements.”
This includes the evaluation of all suppliers, contractors and consultants on the basis of their ability to meet all requirements ‘including quality requirements’. This process and the results of the evaluation must be documented.
Purchasing data must also be recorded and maintained:
“Each manufacturer shall establish and maintain data that clearly describe or reference the specified requirements, including quality requirements, for purchased or otherwise received product and services”
6. Identification and Traceability
To prevent mistakes being made and replicated across the product lifecycle, each manufacturer shall establish and maintain procedures for identifying a product during every stage of its journey to the consumer.
Each device (unit, batch or lot) needs a control number to ensure traceability through every phase of manufacture.
7. Production and Process Controls
"Each manufacturer shall develop, conduct, control, and monitor production processes to ensure that a device conforms to its specifications”
There must be control over environmental conditions that could have an adverse effect on product quality.
There must be a process for requirements for the health of the personnel, cleanliness, personal practices and clothing.
There must be procedures to prevent contamination of equipment or product by substances that could be expected to have an adverse effect on product quality.
Other processes need to be established and maintained around:
- Manufacturing material
- Automated processes
- Inspection, measuring and test equipment
- Process validation
- Label integrity
- Labeling inspection
- Labeling storage
- Labeling operations
- Device packaging and shipping containers
Manufacturers shall also establish and maintain procedures for changes to specification, method, process or procedure. Any changes need to be verified or validated.
8. Acceptance Activities
These activities need to be documented and form part of the Device History Record (DHR)
Manufacturers must establish and maintain activities to identify the approval status of a product (finished and in-process) - as well as incoming materials - in order to indicate its conformance or non-conformance with acceptance criteria.
“The identification of acceptance status shall be maintained throughout manufacturing, packaging, labeling, installation, and servicing of the product to ensure that only product which has passed the required acceptance activities is distributed, used, or installed.”
9. Nonconforming Product
“Each manufacturer shall establish and maintain procedures to control product that does not conform to specified requirements.”
This section of the QSR intends to ensure that non-conformities in products are detected, investigated and acted upon throughout the lifecycle of the product. It should be noted this includes materials and parts, not just finished products.
There is emphasis given to the importance of documenting these activities for accountability and traceability purposes. The QSR specifies that any rework and reevaluation activities undertaken need to be recorded in the DHR.
“Each manufacturer shall establish and maintain procedures for rework, to include retesting and reevaluation of the nonconforming product after rework, to ensure that the product meets its current approved specifications.”
10. Corrective And Preventive Action
“Each manufacturer shall establish and maintain procedures for implementing corrective and preventive action.”
The procedures must include the requirements for:
- Identifying the actions needed to correct and prevent recurrence
- Verifying and validating the corrective and preventive action
- Implementing and recording resulting changes in methods and procedures
- Ensuring that information is disseminated to those responsible for quality in the organisation
- Submitting relevant information for management review
- Documenting all the above activity.
11. Labeling and Packaging Control
Establishing and maintaining a labeling and packaging control procedure controls the risk of product mix up and inappropriate storage and transportation.
The QSR specifies requirements for
12. Handling, Storage, Distribution and Installation
Manufacturers must have procedures in place to ensure no mix-ups, damage, deterioration, contamination or other adverse effects can occur to the product.
The control of stock rooms and storage areas is also listed as fundamental to prevent adverse effects in end products.
There must be procedures in place to ensure only those devices approved for release can be distributed, and that purchase orders are reviewed to ensure that ambiguities and errors are resolved before devices are released for distribution.
Adequate installation and inspection instructions need to be provided with every device.
The QSR specifies the way records shall be made available for review by FDA.
They should be legible and stored to minimize deterioration and to prevent loss.
In addition, there are strict rules about their retention:
“All records required by this part shall be retained for a period of time equivalent to the design and expected life of the device, but in no case less than 2 years from the date of release for commercial distribution by the manufacturer.”
The QSR also specifies the requirements for important records and their associated regulations, namely:
Device Master Record (DMR)
The DMR should contain records on the procedures and specifications for a finished device
Device History Record (DHR)
The DHR is about the production history of a finished device. This is documentary evidence to demonstrate that the device has been manufactured in accordance with the DMR. Advice about compiling your DHR can be found here.
Quality System Record (QSR) and complaint files
The Quality System Record includes procedures and documentation of required activities. These are not specific to any particular type of device but relate to company-wide activities and business processes.
The complaint file should document how complaints are dealt with in a uniform and timely manner, and how they are evaluated to determine if an investigation is necessary. The QSR includes details about what needs to be included in the records of investigations.
The QSR documents the requirement to analyze service reports with appropriate statistical methodology.
15. Statistical Techniques
Procedures for identifying valid statistical techniques are required to establish, control and verify the acceptability of process capability and product characteristics.
So, that’s a brief look at the QSR enshrined in 21 CFR Part 820. It’s important to note that the regulation does not specify in exhaustive detail how a medical device must be produced. Instead, it is a framework for device manufacturers to develop a comprehensive and fail safe QMS. The QMS is there to help you define, document and implement current best practice, delivering traceability and accountability across your business. Its objective should be to prevent product failure and ensure the ultimate safety of the people who will use it.