In GMP EU factory, the production process of sterile preparations is subject to special requirements. This helps to reduce the risk of microbiological contamination and other airborne particles. So how many types of clean rooms are there and what are the principles of clean room classification according to GMP EU? Let’s find out in this article.
1. GMP EU factory cleanliness levels
For the production of sterile preparations, the space in the GMP EU factory will be divided into 4 different levels of cleanliness:
+ Level A: Areas for high-risk activities, e.g. filling, capping, vial closing, aseptic sealing areas.
+ Level B: Area for preparation of sterile vials and preparation, this is the background environment for a grade A zone.
+ Levels C and D: Clean areas where less important steps are involved in the production of sterile preparations.
2. GMP EU cleanroom air standards
Clean rooms and clean air equipment in GMP EU plants must be classified according to EN ISO 14644-1. The maximum allowable concentrations of airborne particles in GMP EU cleanrooms are illustrated in the following table:
| The maximum allowable number of particles with size greater than or equal to the size in the table per m3 | ||||
| At rest | Operation | |||
| Cleanliness grade | 0,5 mm | 5,0 mm | 0,5 mm | 5,0 mm |
| 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 | NA | NA |
For class A cleanliness, the minimum sample volume should be 1 m3 per sampling site. ISO 4.8 equivalent airborne particle classification according to limits for particles 5.0 µm.
For cleanliness class B, the airborne particle classification for two sizes 0.5 m and 5.0 m is equivalent to ISO 5.
For cleanliness class C, the airborne particle classification is equivalent to ISO 7 and ISO 8.
For cleanliness class D, which has the lowest cleanliness, the particulate classification in the air is equivalent to ISO 8.
Particle counters used should be portable with short sampling tubes because particles with sizes 5.0 m can settle in particle counters with long sampling tubes..
3. Microbiological limit in GMP EU cleanroom
After classifying clean rooms according to EU GMP standards, clean areas must be microbiologically monitored during operation. The recommended limits according to the EU GMP guidelines are presented as follows:
| Cleanliness Grade | Air sample (CFU/m3) | Agar plate (diagram 90mm) (CFU/4h)b | Contact late (diagram 55mm) (CFU/đĩa) | Contact glove (5 fingers) (CFU/glove) |
| A | <1 | <1 | <1 | <1 |
| B | 10 | 5 | 5 | 5 |
| C | 100 | 50 | 25 | – |
| D | 200 | 100 | 50 | – |
Table of limits of microbial contaminationa
a Average value
b Placing each agar plate separately can be for less than 4 hours.
For each different class of cleanliness, appropriate alarm and action limits for the monitored microbiological and particulate indices are required. If there are any abnormal signs, exceeding any limit, it is necessary to have procedures to handle and overcome in time, to avoid affecting the safety of employees and product quality
Depending on the requirements of the product, the GMP EU cleanroom classification factory corresponds to different areas. Compliance with clean room principles and standards is a prerequisite for the factory to ensure pharmaceutical quality.
INTECH always accompanies your business on the path of building a clean room that meets GMP EU standard.
Reference :
https://ec.europa.eu/health/sites/health/files/files/eudralex/vol-4/2008_11_25_gmp-an1_en.pdf