In the field of medical devices, it is particularly important to have a clear concept of quality in order to apply it to a system or as a standard for products. But what is quality? In simple terms, it is the best possible version of an object. This version is defined by established standards. This is why FDA provides the Code of Federal Regulation and defines quality in Section 820.3 as “the set of characteristics and properties that affect a product’s ability to meet fitness for use, including safety and performance.”
In general, as a manufacturer, it is important to implement and follow a quality system. Such a system ensures that products meet applicable requirements and specifications. Within the FDA-regulated area, the quality system is (also) known as current Good Manufacturing Practice. In 21 CFR Part 820 – Quality System Regulation (QSR), the FDA imposes cGMP requirements on medical devices.
Because the QSR must apply to a variety of different types of medical devices, it does not regulate in extensive detail exactly how a particular medical device must be manufactured. This would also likely go beyond the scope of the regulation. Instead, it provides all manufacturers with the basic conditions they must follow. Therefore, the QSR requires manufacturers to develop and follow procedures to ensure high quality for the product they manufacture, using appropriate details and state-of-the-art knowledge. It is important to note that Title 21 is revised once a year and then always published on April 1. This ensures that the law is state of the art.
The quality system regulations are divided into 14 subsections. Each section regulates a single aspect of the overall quality system and is a separate entity. The following paragraph lists all subsections and briefly explains what the most important aspect of each is.
Furthermore, it is now obvious that the FDA was heavily involved in the revision of ISO 13485:2016, as QSR and ISO 13485 have become very similar. Thus, many familiar elements of ISO 13485 can now be found in the QSR and vice versa.
1. general provisions
The general provisions ensure that a finished product is safe and effective. In addition, the provisions must apply to all medical device manufacturers. Here, a finished device refers to any medical device or accessory for devices that are suitable for use or are functional, whether or not they are packaged, labeled, sterile. Each important term for the implementation of the QSR is defined in subsection A.
This section corresponds to Chapter 4 of ISO 13485.
2. requirements for the quality system
There are certain requirements that must be part of the quality system such as: Quality Policy, Organizational Structure, Responsibility and Authority, Resources, Management Representatives, Management Evaluation, Quality Planning, Quality System Procedures, also the establishment of procedures for quality audits and the conduct of such audits. Personnel are also a part of the QA, as they must have the appropriate education and background, training, and experience.
This section corresponds to chapters 4, 5 and 6 of ISO 13485.
3 Design Controls
Controls the entire design and development process, consisting of
Design and Development Planning (corresponds to chapter 7.3.2 of ISO 13485)
Design input (corresponds to chapter 7.3.3.3 of ISO 13485)
Development result / Design Output (corresponds to chapter 7.3.4 of ISO 13485)
Development Evaluation / Design Review (corresponds to chapter 7.3.5 of ISO 13485)
Design Verification (corresponds to chapter 7.3.6 of ISO 13485)
Development Validation / Design Validation (corresponds to chapter 7.3.7 of ISO 13485)
Transfer of development / Design Transfer (corresponds to chapter 7.3.8 of ISO 13485)
Control of development changes / Design Changes (corresponds to chapter 7.3.9 of ISO 13485)
As a result of the design controls, the so-called Design History File (DHF) and the Device Master Record (DMR) are created. For more information, please refer to our article on “Design Controls”.
4. documentation requirements
This part describes the requirements for approval and distribution of documents as well as document changes. A record must be kept of when (date) a document was approved and by whom (signature). This is to ensure that obsolete documents are removed and that there is a traceable overview of all important documents created during the process. The same procedure applies to changes to documents. In addition, changes should be communicated to the appropriate personnel in a timely manner.
This section corresponds to chapter 4.2 of ISO 13485.
5. procurement
Management (identification, evaluation and qualification) of suppliers, contractors and consultants based on their ability to meet specific requirements. Arrangements for suppliers, contractors and consultants to inform the manufacturer of changes to the product or service are very important.
This section corresponds to chapter 7.4 of ISO 13485.
6 Identification and traceability
To avoid confusion, each manufacturer must establish and maintain procedures to identify a product at all stages of receipt, manufacture, distribution, and installation. Each product requires a control number to ensure traceability at each stage.
This section corresponds to chapters 7.5.8 and 7.5.9 of ISO 13485.
7. control of production, monitoring and measuring equipment
Develop, implement, control, and monitor production processes to ensure that a product meets its specifications. Procedures for changes to a specification or method, process, or procedure must also be established and maintained. Changes must be verified or validated. Control environmental conditions that could adversely affect product quality. In addition, a process should be established and maintained for requirements for personnel health, cleanliness, personal habits, and professional attire. Procedures to prevent contamination of equipment or products by substances expected to adversely affect product quality. Other processes must be established and maintained related to building, equipment, customization, manufacturing materials, automated processes, inspection, measurement and test equipment, and process validation. It is necessary to avoid negative effects on the entire process and to ensure quality.
This section corresponds to chapters 7.5 and 7.6 of ISO 13485.
8. product realization
Acceptance of receiving, in-process and finished devices. These activities must be documented and are part of the Device History Record. Activities to identify the acceptance status of a product to indicate compliance or noncompliance of products with acceptance criteria.
This section corresponds to chapters 7 and 8 of ISO 13485.
9. control of non-conforming products
Control of nonconforming products: Establish and maintain procedures to control a product that does not conform to specified requirements. Nonconformity assessment and disposition: justification for the use of the “nonconforming” predicate. The product must be revised and should then conform to the current approved specifications.
This section corresponds to chapter 8.3 of ISO 13485.
10. labeling and packaging control
Label integrity states that the label must be printed and affixed to remain legible and attached to the product under normal conditions. It also requires ensuring that product packaging and shipping containers are designed and constructed to protect the product from alteration or damage.
This section corresponds to chapter 7.5 of ISO 13485.
11 Handling, Storage, Distribution and Installation
During handling of the product, there shall be no mix-ups, damage, wear, contamination or other adverse effects on the product. Control of storage areas and storage rooms is essential to avoid adverse effects. Only products approved for release may be distributed and purchase orders must be verified. Appropriate installation and inspection instructions must be included.
This section corresponds to chapter 7.5 of ISO 13485.
12. further documentation requirements
Documents should be made available to FDA for inspection and copying, and should be legible and retained to minimize attrition and prevent loss. Some documents may be marked as confidential by the manufacturer. The retention period for documents shall be a period consistent with the design and expected life of the product, but not less than two years from the date of release. Exceptions are management reviews, quality audits, and supplier audit reports. Other important documents and their regulations include the Device Master Record, Device History Record, Quality System Log, and Complaints. The DMR contains records of the procedures and specifications for a finished product, while the DHR deals with the production history of a finished product. The quality system log contains procedures and documentation of required activities. With complaints, all complaints are handled in a consistent and timely manner and must be evaluated to determine if an investigation is required.
This section corresponds to chapters 4.2, 7 and 8 of ISO 13485.
13. maintenance
Service reports must be analyzed using an appropriate statistical methodology.
This section corresponds to chapter 7.5.4 of ISO 13485.
14. statistical techniques
Procedures for identifying acceptable statistical techniques required for establishing, controlling, and verifying acceptance of process capability and product characteristics.
This section corresponds to all chapters of ISO 13485 related to data collection and processing.
Differences between the quality system regulations and ISO 13485
Although at first glance there is a great deal of correspondence between the two regulatory systems, certain differences should not be underestimated. The following table shows some of them:
QSR
ISO 13485
Documentation requirements
Specifically requires communication of document changes to affected personnel and communication with FDA.
Much more detailed documentation in general.
Requires the organization to establish a retention period for obsolete documents.
No equal naming of files. DHF corresponds to design and development files.
DMR is equivalent to medical device files.
DHR does not have exact equivalence, but such records are required in Chapter 7.5.1.
Customer Orientation
Less important
Considered in the Communication, Feedback, and Complaint Management sections.
Management Responsibility
Focus on communication
Focus on meeting customer needs and applicable regulatory requirements.
Management review
Summary for FDA inspection is required
–
Maintenance
Focus on establishing maintenance schedules, inspections, and adjustments to equipment and manufacturing materials.
Same intent, but not as detailed.
Control of production
Control of product used to prevent contamination of other product, the production environment, and personnel.
Same intent, but not as detailed.
Procurement
Agreement by the supplier to inform the organization of changes to the product or service -> Opportunity to evaluate the potential impact on the quality of the medical device.
The organization should ensure the adequacy of procurement requirements before communicating them to the supplier.
Other
More detailed statistical techniques
Complaints focus on customer complaints
Higher requirements for investigation of defective products
More detailed CAPA
How does the FDA conduct its inspections?
A company must carefully prepare for an FDA inspection. In doing so, the FDA may request copies of important documents such as the company’s quality policy, quality manual, or others.
The FDA inspector will be well prepared, especially in the areas of management controls, corrective and preventive actions (CAPA), design controls, and for production control processes.
Once everything is prepared, the FDA inspection follows a specific process. It starts with an opening session that can last up to two hours. The company is introduced, the inspector is authorized and the agenda is discussed. The inspector decides on the agenda and the aspects to be inspected. This is followed by the actual inspection, which can last between 5 and 8 hours per day. After the inspection, there is a summary of the results, the auditor explains the further procedure and officially closes the inspection.
If there are one or more nonconformities with the QSR, the company under investigation will receive an FDA Form 483 (“Inspectional Observations”) or a warning letter from FDA. These nonconformities may be a total failure to define, document, or implement a quality system or one of the subsystems; a significant deficiency in one or more elements of the subsystem; products that clearly do not meet the manufacturer’s specifications and/or the QSR; noncompliance with significant deficiencies from previous inspections; or an excessive number of minor nonconformities.
Major nonconformities are employees who have not been adequately trained in a specific system or other key procedures. Other nonconformities represent calibration procedures that do not include a limitation on accuracy and precision or where design validation results have not been documented and filed in the Design History File.
FDA quality system guidelines are quite complex, but with the right help, any company can successfully implement them. We, seleon gmbh, can provide you with all the necessary support and knowledge to help you implement the QSR!
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