Premises, Facilities, and Utilities
This domain tests facility design, segregation, air handling, cleanroom classification, water and gas systems, and the maintenance regimes that keep them in control. It rewards candidates who can read a floor plan in words and identify where contamination or cross-contamination could occur.
Design and segregation
- 211.42(a) requires premises of suitable size and construction that facilitate cleaning, maintenance and proper operations.
- 211.42(b) requires separate or defined areas of adequate size for receipt, identification, storage, quarantine, release and rejection; for in-process materials; for components and containers; for packaging and labelling; for production and packaging operations; for QC laboratories; and for stability or reserve samples.
- 211.42(c) adds aseptic processing requirements: separate areas, airlocks, filtered air supply, cleanable surfaces, temperature and humidity control, and a validated cleaning and disinfection system.
- Dedicated facilities are required for penicillin (211.42(d)) and, under EU GMP, for beta-lactams, certain hormones and cytotoxics. Air handling for penicillin must be separate.
Cleanroom classification
- EU Annex 1 grades map to ISO 14644-1 classes: Grade A is ISO 5 at the critical zone; Grade B is ISO 7 at rest and ISO 5 in operation; Grade C is ISO 7 at rest and ISO 8 in operation; Grade D is ISO 8 at rest.
- At rest means installed with no operations and no personnel; in operation means with operations and typical staffing. Examiners test the distinction.
- Positive pressure cascades from cleaner to less clean areas, typically at least 10 Pa differential, with alarms and monitoring; airflow must be visualised in critical zones.
Utilities
- 211.46 requires adequate ventilation, air pressure control, and control of dust, humidity, temperature and filtration; recirculated air requires adequate filtration.
- 211.48 requires plumbing of adequate size, with drains sized and vented to prevent backflow or siphonage; 211.44 lighting, 211.50 sewage and refuse, 211.52 washing and sanitation, 211.58 maintenance.
- Purified water and water for injection must be validated, continuously circulated or stored under validated conditions, monitored for conductivity, TOC and microbial counts, and sanitised on a schedule with defined sampling points.
- Compressed air and process gases contacting product or surfaces must be oil-free where required, dried, filtered, and monitored for particles, moisture and bioburden.
Worked example
A new oral solid dosage suite is proposed. The correct design separates personnel and material flows, places airlocks at each grade boundary, cascades pressure from the highest-risk room outward to the warehouse, provides a dedicated dispensing booth with dust extraction, and confirms performance by installation, operational and performance qualification including air change rates, recovery time, pressure differentials, particle and microbial counts. A wrong answer treats the HVAC qualification as a single particle count.
Traps that cost marks
- Mixing up at-rest and in-operation limits, especially the Grade B in-operation ISO 5 requirement.
- Forgetting airflow visualisation, recovery testing and air change rates in HVAC qualification.
- Ignoring drain design, dead legs and sanitisation when asked about water systems.
- Placing penicillin or beta-lactam production in a shared air handling system.