9 Monitoring Microbial Contamination EU GMP Annex 1 Clean areas for the production of sterile products are classified according to the required characteristics of the environment. Each manufacturing operation requires an appropriate environmental cleanliness level for minimizing the risks of particulate and microbial contamination of the concerning starting material or product. EU GMP Annex 1 sets limits for microbial contamination for each of the four identified cleanroom grades (Table 5). The air in risk zone areas, particularly vulnerable to biocontamination, needs to be protected from viable particles, consisting of one or more live organisms. Methods for evaluation and control are provided by ISO 14698 (Biocontamination Control). The Role for Air Filtration Especially for aseptically prepared parenteral medicine (such as injectables and infusions), no contamination can be accepted, otherwise severe harm or life-threatening health risks to the patient can result. It is exactly in this area where air filtration comes in as the critical link in the overall chain. Air in critical areas should always be supplied at the terminal stage by HEPA filtered unidirectional airflow, preceded by sequential prefiltration steps. A leak-free and high filtration efficiency performance of the HEPA filter is vital for ensuring that air purity is optimized, the pressure differentials between rooms are met, and healthy working conditions are achieved. Table 5: Cleanroom Classification According to EU GMP Annex 1 Maximum Permitted Number of Particles /m3 Equal to or Greater than the Tabulated Size At-rest In Operation International Cleanroom Standard Comparison for “At-rest” Grade 0.5 µm 5.0 µm 0.5 µm 5.0 µm FED 209E FED 209D ISO 14644 A 3,520 20 3,520 20 M 3.5 Class 100 ISO 5 B 3,520 29 352,000 2,900 M 3.5 Class 100 ISO 5 C 352,000 2,900 3,520,000 29,000 M 5.5 Class 10,000 ISO 7 D 3,520,000 29,000 Not Defined Not Defined M 6.5 Class 100,000 ISO 8
RkJQdWJsaXNoZXIy MjgzNzA=