Design and Construction of Solid Preparation Clean Room

Requirements for Clean Rooms in Solid Preparation Facilities:

The layout of the workshop shall comply with the following principles: rational floor plan according to the process flow; strict division of clean areas; prevention of contamination and cross-contamination; facilitation of production operations.

Sampling of raw and auxiliary materials, as well as packaging materials that come into direct contact with pharmaceuticals, is one of the key aspects of product protection. Sampling should be conducted in a separate sampling area, where the air cleanliness level must match the production requirements. If sampling must be performed in the production area, a separate sampling room should be set up within the production area. This room should have direct exhaust ventilation, and the return air should not be recirculated.

When rooms with high dust generation are relatively concentrated, a central dust collection system can be established for centralized dust removal. For workshops producing multiple products with frequent batch changes, rooms generating large amounts of dust should not use recirculated air if no purification measures are in place.

The sampling environment for materials must match the cleanliness level of the production feeding area;

lSeparate setup for personnel and material flows to prevent cross-contamination;

Operating areas with high dust generation should maintain relative negative pressure. Exhaust air discharged outdoors must be purified and meet requirements, and the exhaust outlet should be far away from the air intakes of other air purification systems.

Process Flow Diagram and Environmental Zoning Schematic for Wet Granulation Tablet Production

Grade D Controlled Area

The air cleanliness level of clean rooms (areas) for oral solid preparations should be controlled with reference to GMP Annex 1 Grade D for sterile pharmaceuticals.

lProduction areas prone to generating dust, such as the batching, granulation, and tableting processes of oral solid preparations, should maintain relative negative air pressure compared to adjacent rooms. Rooms for highly allergenic drugs like penicillin should maintain positive pressure and relative negative pressure compared to adjacent rooms.

lAir purification should employ three-stage filtration with primary, medium, and high-efficiency filters. For Grade D air purification, sub-high-efficiency air filters may be used instead of high-efficiency filters.

Local exhaust systems in clean rooms should be set up separately under the following circumstances:

lClean rooms generating dust and harmful gases;

lThe toxicity of the discharged medium is very high;

lMixing of discharged media may exacerbate corrosion, increase toxicity, or cause combustion and hazards.

Air Conditioning System Requirements for Oral Solid Preparations

lDust-generating processes in multi-product production should not utilize return air. If return air is used, measures to prevent cross-contamination must be in place.

lDust-generating rooms or points should be equipped with dust removal facilities, such as in weighing, crushing, screening, tableting, capsule filling, drying and granulation, and mixing processes.

lThe operation of supply, return, and exhaust air systems should be interlocked. The system startup sequence should be: start the supply fan first, then the return and exhaust fans.

lNon-unidirectional airflow organization may be used in controlled areas for oral solid preparations. The air change rate should be determined based on the dust generation level of the room. For example, rooms for crushing and screening, as well as rooms with high temperature and humidity, should have correspondingly higher air change rates.

Relevant Standards:

"Good Manufacturing Practice for Pharmaceuticals" 2010

GB 50457-2019 Design Standard for Clean Rooms in Pharmaceutical Industry

GB 50073-2013 Design Code for Clean Rooms

GB 51110-2015 Code for Construction and Quality Acceptance of Clean Rooms

GB 50019-2015 Design Code for Heating, Ventilation, and Air Conditioning of Industrial Buildings

GB 50243-2016 Code for Construction Quality Acceptance of Ventilation and Air Conditioning Works

GB 50016—2014 (2018 Edition) Code for Fire Protection Design of Buildings