Risk Assessment for Environmental Monitoring of the Injectable Cephalosporins and Carbapenems Production Plant

Abstract

Introduction: Operations with medicines require compliance with the requirements established in Good Practices with the objective of guaranteeing their quality, safety and effectiveness. The Quality Management System incorporates quality risk management as an integral part. In the injectable plant, the aseptic processing of Cephalosporins and Carbapenems is carried out in the form of sterile powders for injection. Production is subject to special requirements to minimize the risks of microbial, particulate and pyrogen contamination. The environmental microbiological monitoring program is one of the critical elements in the production process; it must be applied routinely and periodically. The objective of this work is to carry out risk assessment in the environmental monitoring process of controlled areas of the plant by identifying the risk points and the causes that originate them and establishing preventive and/or corrective measures to minimize their frequency and impact on processes. Materials and Methods: Failure Modal Analysis and Process Effects are used for risk assessment; it is a prevention method aimed at achieving Quality assurance. Supporting techniques such as Brainstorming and Cause-Effect Diagram were also used. Results: Through the application of this technique, reference criteria are obtained for monitoring viable and non-viable particles in the environment, monitoring frequencies, sampling frequency and number of sampling points according to m2 of the area to be monitored and determination of points by priority level. Discussion: A flow chart of the process is built to analyze the inputs of raw materials and the most critical points where contamination can be generated for different causes. The identification of risks was carried out by applying the brainstorming technique and as a result, 4 critical areas with a high probability of contamination occurrence were determined. By building the Ishikawa diagram of the process to be improved, the environmental monitoring program becomes a powerful tool to avoid the undesired effect, which is product rejection. The risk priority number was calculated for each failure mode and corrective measures were established to mitigate the effect level. Conclusions: As a result of the risk assessment in the environmental monitoring process of controlled areas, risks were identified and evaluated in order of criticality. Preventive and/or corrective measures were established for each stage in order to reduce the possibility of risks of product contamination.