What is PIC/S
PIC/S is the abbreviation of The Pharmaceutical Inspection Convention and Co-operation Scheme (The Pharmaceutical Inspection Convention and Co-operation Scheme). It was initiated by the European Union (EU) in 1970 and is composed of the inspection authorities for good manufacturing practices (GMP) in various countries. So far, the PIC/S international organization has 37 members and has expanded to five continents in the world including Europe, America, Australia, Asia, and Africa.
For the manufacture of sterile drugs, the clean area is divided into four levels A, B, C, and D according to the environmental characteristics of the demand, and the relevant air conditioning system verification is performed (dynamic and static, and the particle size of floating particles is 5 μm). The description and standards for floating particles are as follows:
| Level area description | |
| Partial area of A-level high-risk operations | Local areas of high-risk operations, such as filling areas, rubber stopper tanks, open ampoules and vials, perform aseptic connections. This condition is usually provided by laminar flow workstations/tables. In working locations where an open clean room application is used, the laminar air flow system should provide a uniform air flow rate of 0.36 to 0.54 meters per second (guide value). The maintenance of laminarity should be demonstrated (uni-directional air flow) and lower speeds should be used in closed isolation devices and glove boxes. |
| Class B | For aseptic preparation and filling, it is the background environment of Class A area. |
| Class C and Class D | In the manufacture of aseptic products, a clean area that performs a less critical stage. |
| level | per cubic meter The maximum allowable amount of particles equal to or greater than the following particle size | |||
| static | dynamic | |||
| 0.5 µm | 5 µm | 0.5 µm | 5 µm | |
| A | 3,500 | 1 | 3,500 | 1 |
| B | 3,500 | 1 | 350,000 | 2,000 |
| C | 350,000 | 2,000 | 3,500,000 | 20,000 |
| D | 3,500,000 | 20,000 | Undefined | Undefined |
Recommended limits for microbiological monitoring in dynamic clean areas
| Recommended average limit of microbial contamination | ||||
| level | Air samples cfu/m³ | Filling culture dish (90mm in diameter), cfu/4hr | Contact the petri dish (Diameter 55mm), cfu/culture dish | Gloves Fingerprint Print 5 fingers/gloves cfu/Gloves |
| A | <1 | <1 | <1 | <1 |
| B | 10 | 5 | 5 | 5 |
| C | 100 | 50 | 25 | — |
| D | 200 | 100 | 50 | — |
EU GMP standard
At present, the global pharmaceutical industry most often refers to the cleanliness standard EU GMP established by the European Union, and the cleanliness of its clean rooms adopts ISO standards:
EN/ISO 14644-1 also defines the minimum number of sampling points and sample size for each level, considering the largest particle size and the estimation method of the collected data, as the basis for each classification.
| static< /td> | dynamic< /td> | |||
| Level | 0.5μm | 5μm | 0.5μm | 5μm |
| A | 3,520 | 20 | 3,520 | 20 |
| B | 3,520 | 29 | 352,000 | 2,900 |
| C | 352,000 | 2,900 | 3,520,000 | 29,000 |
| D | 3,520,000 | 29,000 | undefined | undefined |
- For level A verification, the minimum sample volume for each sampling point is 1 cubic meter. .
- For class B (static), the floating particles are classified as ISO 5, considering two particle sizes.
- For Class C (static and dynamic), the floating particle classification is ISO 7 and ISO 8.
- For class D (static), the floating particle classification is ISO 8.
Different levels of work
| level | terminally sterilized products |
| A | When the filling of the product is at risk of abnormality. |
| C | When the preparation of the solution is at risk of abnormality, the product is filled. |
| D | For subsequent filling solution preparation and component preparation. |
| level | Aseptic preparation operations |
| A | Aseptic preparation and filling. |
| C | Preparation of the solution to be filtered. |
| Preparation of the solution to be filtered. | |
| D | Disposal of components after washing. |