21 CFR Part 820

21 CFR Part 820, commonly known as the Quality System Regulation (QSR), is the FDA regulation that establishes the current Good Manufacturing Practice (cGMP) requirements for medical device manufacturers operating in the United States. First issued in 1978 and significantly revised in 1996, this regulation ensures that medical devices are consistently manufactured to meet their specifications and quality standards.

Scope and applicability:

21 CFR Part 820 applies to all finished medical device manufacturers in the United States, whether domestic or foreign. The regulation covers all aspects of device design, production, distribution, and servicing. While most Class I devices are exempt from certain QSR requirements, Class II and Class III device manufacturers must fully comply with all provisions.

Key requirements of 21 CFR Part 820:

Management Responsibility (820.20)
- Establish and maintain quality policy
- Define organizational structure and responsibilities
- Provide adequate resources
- Conduct management reviews of the quality system

Design Controls (820.30)
- Design and development planning
- Design input and output documentation
- Design verification and validation
- Design transfer procedures
- Design changes and design history files

Document Controls (820.40)
- Document approval and distribution procedures
- Document changes and revisions
- Master record maintenance
- Obsolete document control

Purchasing Controls (820.50)
- Supplier evaluation and selection
- Purchasing data requirements
- Supplier quality agreements
- Receiving, in-process, and finished device acceptance

Production and Process Controls (820.70)
- Manufacturing procedures and work instructions
- Process validation and monitoring
- Environmental controls for manufacturing
- Equipment maintenance and calibration
- Inspection, measuring, and test equipment control

Corrective and Preventive Action (CAPA) (820.100)
- Investigation of quality problems
- Root cause analysis procedures
- Implementation of corrective actions
- Verification of corrective action effectiveness
- Preventive action to eliminate potential nonconformances

Records and Documentation (820.180-820.198)
- Device Master Record (DMR)
- Device History Record (DHR)
- Quality System Record (QSR)
- Complaint files
- Record retention requirements (typically 2 years, or device lifetime for implants)

Statistical Techniques (820.250)
- Procedures for identifying statistical methods
- Use of statistical techniques for process monitoring
- Validation of statistical methods used

Comparison with ISO 13485:

While 21 CFR Part 820 and ISO 13485 share similar objectives, there are important differences. The FDA's proposed QMSR (Quality Management System Regulation) aims to harmonize these requirements, making it easier for manufacturers to comply with both US and international standards.

FDA inspections and enforcement:

The FDA conducts routine inspections of device manufacturers to verify compliance with 21 CFR Part 820. Inspections may be triggered by new device applications, post-market surveillance, or in response to complaints or adverse events. Common inspection findings include:
- Inadequate CAPA procedures
- Insufficient design controls
- Incomplete documentation
- Inadequate supplier controls
- Deficient complaint handling

Penalties for non-compliance:
- Warning letters
- Import detentions
- Consent decrees
- Civil monetary penalties
- Criminal prosecution in severe cases
- Market withdrawal orders

Best practices for compliance:
1. Establish a robust quality management system
2. Conduct regular internal audits
3. Maintain comprehensive documentation
4. Implement effective CAPA processes
5. Provide ongoing employee training
6. Engage qualified consultants for gap analysis
7. Monitor regulatory updates and guidance documents