Physikalische und mikrobiologische Umgebungskontrollen bei der aseptischen Herstellung von peripheren Blutstammzelltransplantaten

The transplantation of peripheral blood stem cells (PBSC) is used for reconstitution of the hematopoietic system after high-dose chemotherapy. PBSC are harvested by leukapheresis from the circulating blood upon successful mobilisation by growth factors and/or chemotherapy. The cells are then processed and cryopreserved. The processing is considered to be a drug production and has to follow the principles of Good Manufacturing Practices (GMP). To ensure quality and safety of the final cell preparation, strict hygiene standards are required for the aseptic processing of ready-to-use sterile products. The new version of the supplementary guide for the production of sterile pharmaceuticals of the EU-Guide to Good Manufacturing Practices gives detailed information on limits and frequencies for air, surface and personnel testing. The purpose of this study was the analysis of the airborne particulate and microbial contamination during our non-batch-production of PBSC-transplants. The testing program was based upon the use of various methods such as particle counting, volumetric air sampling, settle plating and contact plating. Analyses of the effectiveness of the standard cleaning and desinfection procedures were also performed. Samples were taken in multiple locations at rest and in operation conditions to determine a baseline count. The sample mean in the different locations were mostly within the limits set by the EU-GMP-Guide. The concentration of airborne particles ≥ 5 μm in the production room exceeded the limits as well as the microbial contamination in 2 locations in this room. The analysis was used to evaluate critical sites and a routine monitoring program. Alert and action limits were set based upon this baseline count. The limits and their significance for clinical practices were assessed.