The cleanroom is an important and necessary environment in the drug production process. The cleanroom limits the contaminating factors for components, equipment, and products during the production process. So what levels of cleanroom are there and what are their requirements? Let’s learn about cleanroom classification according to EU GMP standards in the article below:
1.Cleanroom classification
Cleanroom classification according to EU GMP standards used in the production of sterile drugs is divided into 4 grades A, B, C, D with different requirements..
1.1. Requirements for the number of particles
Clean room classification according to EU GMP based on ISO14644-1 are developed mainly in the two states of the cleanroom, “at rest” and “in operation”.
– “At rest” state is the condition when the factory has completed the construction and installation of production equipment and is operating to meet the requirements, but the operator is not present.
– “In operation” state is the condition when the machine is operating in a defined mode of operation and the presence of a specified number of employees.
By using a particle counter, each different level of cleanroom requires a maximum number of particles that are clearly specified in the table below:
For Grade A the airborne particle classification is ISO 4.8 dictated by the limit for particles ≥ 5.0µm.
For Grade B (at rest) the airborne particle classification is ISO 5 for both considered particle sizes.
For Grade C (at rest & in operation) the airborne particle classification is ISO 7 and ISO 8 respectively.
For Grade D (at rest) the airborne particle classification is ISO 8.
1.2. Limits for microbial contamination
To ensure the quality of products, clean rooms need to be regularly controlled to limit the occurrence of risk factors such as live microorganisms. The airborne particle control system may include stand-alone particle counters; a network of sequential sampling points connected by a manifold to a particle counter; or a combination of both. The system selected should be suitable for the particle size to be controlled.
The recommended limits for microbiological control during operation in Cleanroom classification according to EU GM are specified in the following table:
(a) These are average values.
(b) Individual settle plates may be exposed for less than 4 hours
2. Application of various types of clean rooms
Grade A: The local zone for high-risk operations, e.g. filling zone, stopper bowls, open ampoules, and vials, making aseptic connections. Normally such conditions are provided by a laminar airflow work station. Laminar airflow systems should provide a homogeneous airspeed in a range of 0.36 – 0.54 m/s (guidance value) at the working position in open cleanroom applications.
Grade B: For aseptic preparation and filling, this is the background environment for the grade A zone.
Grade C and D: Clean areas for carrying out less critical stages in the manufacture of sterile products
| Clean grade | Examples of activities in the production of end-stage sterilized products |
| A | Close the bottle of the product, when there is rarely a risk |
| C | Prepare solutions when there is little risk involved. Close the product bottle |
| D | Dispensing solutions and other ingredients for continuous vials |
| Clean grade | Examples of production operations under sterile conditions |
| A | Prepare and close sterile vials. |
| C | Prepare solutions to be filtered. |
| D | Handling ingredients after rinsing |
Strict requirements in the Cleanroom classification according to EU GMP are a condition to ensure the quality of drug production, but it is also an obstacle to the construction of factories of pharmaceutical enterprises. Today, the support of cleanroom classification consulting has become easier due to the support of professional businesses in this field.
INTECH always stands with your business to build clean rooms that meet EU GMP standards.
*Tài liệu tham khảo:
https://ec.europa.eu/health/sites/default/files/files/eudralex/vol-4/2008_11_25_gmp-an1_en.pdf