Description
The need for cleanrooms in the manufacture of medical products, labeled "STERILE", is even more obvious than in the manufacture of medicines. Even if the manufacturing process uses finishing sterilization processes, which is not always possible, it is possible to ensure sufficient purity of the final product only when all production operations are carried out in controlled and identical conditions for all batches of products.
The international standard GOST R ISO 13408-1-2000 "Aseptic production of medical products. Part 1. General requirements", which establishes the basic requirements for aseptic production of medical products, regulates the conduct of various technological operations in clean zones of different purity classes, conditionally dividing all aseptic production facilities production at critical and other production areas.
Classification and requirements for clean rooms in the production of medical products
GOST R ISO 13408-1-2000 "Aseptic production of medical products. Part 1. General requirements" identifies three types of production premises - a critical production area, other production areas and auxiliary facilities outside the production area, defining for each of them different class requirements cleanliness of the room. The Russian standard GOST R ISO 13408-1-2000 is a translation of the text of the international standard ISO 13408-1-98, canceled and replaced by ISO 13408-1-2008. In particular, the text of the standard does not quite accurately describe the requirements for the maximum permissible concentration of particles corresponding to the ISO cleanliness classes, and it is not quite clear that the type of clean zone for the exploited and equipped cleanroom conditions is consistent. Classification and requirements for premises are given in accordance with the text of the current standard in Russia.
Table 1. Classification of premises in the manufacture of medical products
Group of rooms Maximum number of particles with dimensions> 0.5 µm, pcs / m3 Type of clean zone ISO purity class
Critical Manufacturing Zones 3 500 A ISO Class 5
Other production areas 350,000 B * (C) ISO Class 7
Auxiliary facilities outside the industrial areas 3 500 000 C * (D) ISO Class 8
* In operating condition according to EU GMP classification
Requirements for ventilation and air conditioning systems in aseptic production
Ventilation and air conditioning systems in aseptic production must ensure not only a given purity class, but also maintain the microclimate parameters within the specified limits. The design documentation shall determine the temperature values and, if necessary, the relative humidity of the air, ensuring the comfort of the employees and the quality of the product.
The compliance of the microclimate parameters with the requirements of the project documentation should be periodically monitored, since this directly affects aseptic technology and potential levels of contamination. Neighboring zones with different cleanliness classes should be reliably separated, according to the principle of pressure drop or displacing air flow, these parameters should also be defined in the design documentation and periodically monitored, it should be possible to adjust the pressure drop. After any reconfiguration of the airflow, it must be re-inspected.
Air filtration with HEPA filters and their testing
Air supplied to all critical production areas must be filtered using HEPA filters. The air velocity must comply with the requirements of the established cleanliness class and be monitored.
If there is a unidirectional air flow, the speed of the unidirectional air flow should be controlled for each HEPA filter in accordance with the program at certain time intervals. HEPA filters should be checked after installation / replacement and certified, and the integrity of the installed filtration system should be tested.
Filters should be tested according to standard procedures after the occurrence of any situation that may affect the integrity of the filters, or when environmental monitoring results indicate that the integrity of the filters may deteriorate.
What parameters should be monitored in the certification of clean rooms in the manufacture of medical products
If you summarize the above data from the standard GOST R ISO 13408-1-2000 "Aseptic production of medical products. Part 1. General requirements", you get the following list of tests:
measurement of particle concentration and determination of the compliance of the cleanliness class with the requirements of this standard in the exploited and equipped states,
measurement of pressure drops between adjacent rooms or displacement flow rates, in accordance with internal specifications or design data,
temperature and relative humidity control Air conditioning for compliance with the requirements of project documentation,
the speed and uniformity of the laminar flow in the presence of zones with unidirectional air flow,
integrity of HEPA filters after maintenance of the ventilation system and replacement of filters.
Test protocols for clean rooms in aseptic production
According to the results of tests conducted on clean rooms and clean zones, a test report is drawn up in accordance with GOST R ISO 13408-1-2000, including protocols and, if necessary, test reports with all primary data.
