Objectives To determine prospectively the risk reducing measures of non-sterility during aseptic handling and to develop a method for prioritising these measures. Methods In the first part of this series of articles, we identified all sources of risk which could contaminate a product during aseptic handling, and calculated the remaining risks of non-sterility using a risk assessment (RA) model. We concluded that additional research of some risk sources was needed before risk control (RC) could be executed on all risk sources. The chances of technical problems with a laminar airflow cabinet or safety cabinet (LAF/SC) were collected from 10 hospital pharmacies using a questionnaire. The chances of blocking first air were examined by airflow visualisation (smoke studies). For checking the way of working during aseptic handling, a checklist for an audit was developed. Risk control was executed by a multidisciplinary team of (hospital) pharmacists and technicians, a consultant experienced in aseptic processing and an independent facilitator. They determined the risk reducing measures for each source of risk and the influence of these measures on the remaining risk (expressed as risk prioritisation number). Results The chances of defects of the LAF/SC were low. Airflow visualisation is a sensible method to find the correct location of materials and equipment inside the LAF/SC and to detect a way of working without blocking first air on critical spots. Audits will provide valuable information about the way aseptic handling is executed and the remaining risks as a consequence. The risk of non-sterility caused by needle or spike contact with critical spots of vials and ampoules (stopper or ampoule neck), blocking first air under downflow and touching critical spots cannot be eliminated completely. Conclusion The RA/RC model shows the impact of risk reducing measures on the probability of non-sterility during aseptic handling. The calculated risk prioritisation numbers are helpful in prioritising these measures. Audits result in risk reduction for nearly all sources of risk.

No abstract

No abstract

Background According to the Dutch GMP-hospital pharmacy directive (1) three types of microbiological controls are required when aseptic dispensing is performed: 1. microbiological monitoring of the air in the working area, the gloved hands of the operator and the work surface at the critical place in the laminar airflow cabinet; 2. microbiological validation of the operators through media fill runs; 3. validation of the aseptic process by repeating the procedures with an appropriate broth. Purpose To develop a web-based program for data of microbiological controls on aseptic dispensing for Dutch hospital pharmacies for: simple processing of environmental monitoring data; trending of environmental monitoring data; comparing individual data with other hospital pharmacies nationwide. Materials and methods The web-based program MICROBIO was designed in collaboration with an expert group of hospital pharmacists. Participating hospital pharmacies collected microbiological control data and entered them into the program. Limits for microbiological contamination are based on EU-GMP recommendations (2). Results Currently 49 of 80 Dutch hospital pharmacies use MICROBIO. More than 85% of the microbiological controls on monitoring comply with the results (air 87%, gloved hands 90%, work surface 86%). Conclusions MICROBIO is a standardised tool which fully supports processing data and evaluation for all three types of microbiological controls and presents them in diagrams and histograms. The results show that the directive on aseptic dispensing in GMP-hospital pharmacy is met. Literature 1. Aseptic dispensing. In GMP-hospital pharmacy. The Hague: Dutch Association of Hospital Pharmacists; 2005; www.nvza.nl. 2. The rules governing medicinal products in European Union. Volume 4. Good manufacturing practices. Medicinal products for human and veterinary use. Annex I. Manufacture of sterile medicinal products. European Commission, revision May 2003.

Objectives To describe the application of the model described in part A and part B of this series of articles for risk assessment (RA) and risk control (RC) of non-sterility during aseptic handling. The model was applied in nine hospital pharmacies. Methods The starting point was an audit of each hospital pharmacy. The determined risk reduction and remaining risks were entered into a risk assessment model. The corresponding risk prioritisation numbers (RPNs) for each source of risk were calculated and these values were summed up to a cumulative RPN. Subsequently, all hospital pharmacies started an improvement programme, using the risk assessment as input. Results of aseptic process simulation (APS) and microbiological monitoring (MM) were also collected. The participants were informed about their progress of risk reduction and results of APS and MM during the study period. At the end of the study (about 4 years after the start), a final assessment was executed by using a checklist with risk reducing measures for each source of risk. Additional risk reduction and remaining risks were put in an RA and RC template and corresponding RPN values and a new cumulative RPN were determined. Results At the start of the study differences in cumulative RPN values were relatively small (from 630 to 825). At the end they were relatively great (from 230 to 725), which illustrates a different sense of urgency for reducing the risk of non-sterility. Of all the risk reducing measures, a yearly audit of all operators had the greatest impact on reducing the risk of non-sterility. Except for glove prints, there was no correlation between process improvement (lower cumulative RPN) and results of microbiological controls. Conclusion A systematic and science-based reduction of the risks of non-sterility can be done by using a checklist with risk reducing measures and an RA & RC template. Prospectively, the relevance of each risk reducing measure can be demonstrated by RPN calculations. Microbiological controls are an important part of the overall assurance of product quality. However, the results are less useful for assessing the risk of non-sterility.