Considerations for Cleanliness Classification in Pharmaceutical Workshops

1. Application of (Grade B + A) Environment

Filling (or filling and sealing), aliquoting, stoppering, and capping of non-terminally sterilized products (in an unsealed state).

Preparation of drug solutions or products that cannot be sterilized by filtration before filling for non-terminally sterilized products.

Assembly of packaging materials and containers in direct contact with drugs after sterilization for non-terminally sterilized products (including sterile APIs), as well as transfer and storage in an unsealed state. 

Exposed operations such as refining, crystallization, and drying before drying of sterile APIs for non-terminally sterilized products where the drug solution cannot be sterilized by filtration.

2. Application of Grade B Environment

Transfer of unsealed non-terminally sterilized products placed within fully sealed containers.

Transfer of packaging materials and containers in direct contact with drugs for non-terminally sterilized products, after sterilization and placed within fully sealed containers.

3. Application of Grade C Environment

Preparation of drug solutions or products that can be sterilized by filtration before filling for non-terminally sterilized products.

Filling and sealing of terminally sterilized products with low contamination risk.

Preparation and filtration of terminally sterilized products with high contamination risk.

Preparation, filling, and sealing of terminally sterilized ophthalmic preparations, sterile ointments, and sterile suspensions.

Handling of packaging materials and containers in direct contact with drugs for terminally sterilized products after final cleaning.

4. Application of Grade D Environment

Final cleaning, assembly, packaging, and sterilization of packaging materials and containers in direct contact with drugs for non-terminally sterilized products.

Capping of terminally sterilized products.

Material preparation (weighing, aliquoting, etc.) before filling for terminally sterilized products.

Concentrated preparation or preparation and filtration in a closed state for terminally sterilized products.

Final cleaning of packaging materials and containers in direct contact with drugs for terminally sterilized products.

The exposed environment for production operations such as refining, drying, crushing, and packaging of non-sterile APIs shall be set up according to Grade D clean area requirements.

Pooling of raw plasma for biological products, fractionation, pre-filling pasteurization, closed system environment for fermentation culture of oral preparations, and preparation, filling, drying, and inner packaging of in-vitro immunological reagents such as ELISA reagents require Grade D.

Processes such as bag breaking, pooling, separation, extraction, and pre-filling pasteurization inactivation of raw plasma for blood products shall be carried out at least in a Grade D clean area. Open operations for TCM extraction, concentration, and paste receiving should correspond to the cleanliness level of the preparation area.

The refining process before concentrated preparation of TCM injections shall be completed at least in a Grade D clean area.