General Principles of Cleanroom Design
The main purpose of a cleanroom is to protect the product from contamination. According to EU-GMP or ISO 14644 standards, the classification of rooms is defined by the maximum number of particles and microorganisms in suspension.
Air quality parameters (temperature, humidity, pressure) are maintained by specialized engineering constructions and dedicated HVAC systems.
Specific Requirements for Upstream Processes
In the upstream, where cell culture and fermentation take place, the following should be considered:
- Biological containment: use of Class II A2 biological safety cabinets (BSC) with HEPA filters.
- Prevention of cross contamination: segregated areas or dedicated lines for different products.
- Flexibility: multiple bioreactors and skids adaptable to different crops.
- CIP/SIP systems: optimized for cleaning and sterilization in place, minimizing time between batches.
- Air quality control: unidirectional (laminar) flow in critical areas and pressure gradients.
Specific Requirements for Downstream Processes
Downstream purification, which includes filtration, centrifugation and chromatography, is key:
- Room classification: Grade A/B in aseptic filling stages.
- Material flow: intermediate storage tanks to stop processes if necessary.
- Versatility of equipment: skids and reprogrammable chromatography columns.
- CIP/SIP systems and filtration: dedicated circuits to avoid cross contamination.
- Aseptic transfer: use of isolators or RABS for transfer to filling.
Critical Ancillary Services
In addition to the process areas, clean rooms require:
- Pharmaceutical water: WFI for injectables and purified water for previous stages.
- Clean steam: for equipment SIP.
- Specialized HVAC: particle, pressure, temperature and humidity control.
- Technical gases: nitrogen and compressed air according to process.
- Biological waste treatment: thermal and chemical inactivation tanks.
- Personnel and material locks: changing room sequences and SAS with VHP.
Additional Design Considerations
In the conceptual phase, specific processes, regulations and complexities are defined. It is essential to choose smooth, non-porous materials and to plan personnel and material flows to optimize efficiency. Finally, everything must undergo GMP qualification and validation processes.
