Description
What is the certification of clean rooms for pharmaceutical production?
In accordance with the "Rules of organization of production and quality control of medicines", approved by the Order of the Ministry of Industry and Trade of Russia dated June 14, 2013 N 916, and GOST R 52249-2009, the production of medicines and pharmaceutical substances should be carried out in clean rooms.
In the production of medicines, the concept of "sterility", meaning "the absence of living microorganisms", is of particular importance. To ensure sterility in pharmaceutical production, technological operations in the production of drugs, both undergoing finishing sterilization and under aseptic conditions, must be carried out in clean rooms or clean areas.
Basic requirements for clean rooms in the pharmaceutical industry
The requirements for clean rooms for aseptic pharmaceutical production and the production of medicines that can be subjected to finishing sterilization are different. The filling / filling process (critical process) in the manufacture of drugs that are not subjected to final sterilization in packaging requires a clean zone "A" surrounded by a clean zone of class "B" to minimize the risk of contamination of the finished product with particles and microorganisms.
For pharmaceutical products that undergo final sterilization, the “Rules for organizing the production and quality control of medicines” set less stringent requirements, in particular, filling with products subject to finishing sterilization, can be carried out in a class C production environment, however, with an increased risk of contamination ( filling operations are slow or packages have a wide throat, or they need to be kept open for more than a few seconds before sealing), the filling should also oestriasis in a clean zone of class A (but with the environment, at least P).
Requirements for the equipped and maintained condition should be established for each clean room or complex of clean rooms.
Table 1. Examples of operations in clean areas for aseptic pharmaceutical production.
Aseptic production
Zone type Operations performed
BUT
Aseptic preparation and filling
Preparation of solutions that do not undergo further sterilizing filtration
Operations for processing and filling aseptic products
Transportation of partially closed primary packaging, for example, during freeze drying until closure is completed.
Preparation and filling of sterile ointments, creams, suspensions and emulsions, when the product is in the open form and is not subject to subsequent filtering
AT
Zones surrounding zone "A"
WITH
Preparation of Filtration Solutions
Automatic packaging lines using blowing-filling-sealing technology
D
Operations with materials after washing
Zones around the isolator
Table 2. Examples of operations in clean areas of pharmaceutical production with products subject to final sterilization.
Operations with products subject to finishing sterilization
Zone type Operations performed
BUT
Operations with the product when it can not be put at risk of contamination
AT
Zones surrounding zone "A"
C
Filling product
Preparation of solutions when they can not be put at risk of contamination
D
Preparation of solutions and preparation of primary packaging, materials, etc. for the subsequent filling
Automatic packaging lines using blowing-filling-sealing technology
Cleanroom classes in the pharmaceutical industry
GOST R 52249-2009 "Rules for the production and quality control of medicines" defines the types of clean zones (A, B, C, D) and the corresponding purity classes according to ISO (GOST R ISO 14644-1-2002) for various clean rooms of pharmaceutical production and separate technological processes.
Table 3. Classification of clean rooms and clean zones according to GOST R 52249-2009
Type of clean zone Maximum allowable number of particles in 1 m3 of air with a particle size equal to or greater
In the equipped state In the exploited state
0.5 micron 5.0 micron 0.5 micron 5.0 micron
A 3520 20 3520 20
3520 29 352000 2900
From 352000 2900 3520000 29000
D 3520000 29000 - -
How is the validation of clean rooms at the farm?
The main parameter of a clean room, requiring verification during certification in pharmaceutical production, is the ISO cleanliness class (type of clean zone).
For clean zones of class A (ISO 4.8 for particles with sizes> 5.0 μm and ISO 5 for particles with sizes> 0.5 μm), the allowable concentrations of particles are 20 and 3520 pcs / m3, respectively. To measure low concentrations of particles with sizes> 5 µm, at least 1 m3 of air is taken. In some cases, a sequential counting method can be used to speed up the analysis process without compromising the accuracy of the results. In particular, this method is used when checking laminar boxes.
Depending on the characteristics of a particular pharmaceutical
