Manufacture of sterile pharmaceutical preparations, four grades of clean areas are distinguished as follows:
- Grade A: The local zone for high-risk operations, e.g. filling and making aseptic connections. Normally such conditions are achieved by using a unidirectional airflow workstation. Unidirectional air flow systems should provide a homogeneous air speed of 0.36–0.54 m/s (guidance value) at a defined test position 15–30 cm below the terminal filter or air distributor system. The velocity at working level should not be less than 0.36 m/s. The uniformity and effectiveness of the unidirectional air flow should be demonstrated by undertaking airflow visualization tests.
- Grade B: In aseptic preparation and filling, this is the background environment for the Grade A zone.
- Grades C and D: Clean areas for carrying out less critical stages in the manufacture of sterile products or carrying out activities during which the product is not directly exposed (i.e. aseptic connection with aseptic connectors and operations in a closed system).
Table: 1. Airborne particulate classification for manufacture of sterile pharmaceutical preparations
|
Grade
|
At rest
|
In operation
|
|||
|
Maximum number of particles permitted/m3
|
Maximum number of particles permitted.m3
|
||||
|
0.5m
|
5.0 m
|
0.5m
|
5.0 m
|
||
|
A
|
3520
|
20
|
3 520
|
20
|
|
|
B
|
3520
|
29
|
352 000
|
2 900
|
|
|
C
|
352 000
|
2 900
|
3 520 000
|
29 000
|
|
|
D
|
3 520 000
|
29 000
|
Not defined
|
Not defined
|
|
Table : 2 . Limits for microbiological contamination
|
Grade
|
Air sample
(CFU/m3)
|
Diameter 90mm( Settle plates)
(CFU/ 4hours)
|
Contact plates
(diameter 55mm) (CFU/plate)
|
Glove print (5 fingers) (CFU/glove)
|
|
A
|
<1
|
<1
|
<1
|
<1
|
|
B
|
10
|
5
|
5
|
5
|
|
C
|
100
|
50
|
25
|
–
|
|
D
|
200
|
100
|
50
|
–
|
Reference: World Health Organization Technical Report Series, No.921,2011
