Purpose of Clean Area Classification
Define Cleanliness Levels: Establish acceptable levels of particulate and microbial contamination.
Regulatory Compliance: Meet standards set by regulatory bodies for sterile manufacturing.
Classification Standards
ISO 14644-1: International standard for cleanrooms and associated controlled environments.
EU GMP (European Union Good Manufacturing Practice): Provides guidelines for manufacturing medicinal products.
FDA and USP Guidelines: US-specific regulations for sterile pharmaceutical production.
ISO Cleanroom Classifications
ISO Class 5 (Class 100): Maximum of 3,520 particles ≥0.5 μm per cubic meter.
ISO Class 7 (Class 10,000): Maximum of 352,000 particles ≥0.5 μm per cubic meter.
ISO Class 8 (Class 100,000): Maximum of 3,520,000 particles ≥0.5 μm per cubic meter.
GMP Cleanroom Grades
Grade A:
Highest level of cleanliness, for high-risk operations like filling and aseptic connections.
Grade B:
Background environment for Grade A activities, such as the background for aseptic preparation and filling.
Grade C:
Clean areas for less critical stages in sterile product manufacturing.
Grade D:
Clean areas for less critical processes, such as handling of components after final cleaning.
Microbial Limits
Non-Viable Particles: Limits set for airborne particles based on cleanroom classification.
Viable Microbial Counts:
Air Samples: Colony-forming units (CFUs) per cubic meter.
Surface Samples: CFUs per plate or swab area.
Monitoring and Compliance
Environmental Monitoring Program:
Regular Testing: Scheduled monitoring of air and surfaces.
Trend Analysis: Evaluate data over time to detect deviations.
Certification and Recertification:
Initial Qualification: Validate cleanroom performance upon setup.
Periodic Requalification: Regular re-testing to ensure ongoing compliance.
Cleanroom Design Considerations
Airflow Patterns: Design to prevent turbulence and recirculation of particles.
Room Pressurization: Positive pressure gradients from cleaner to less clean areas.
Material and Personnel Entry: Use airlocks and gowning rooms to maintain pressure differentials. (Clean Area Classification)