Cleaning Validation of a Multipurpose Plant for Active Pharmaceutical Ingredient Bulk Production

Abstract

One of the key issues in the manufacture of active pharmaceuticals ingredients in multipurpose non-dedicated equipment is to adequately address the potential for cross-contamination. It is therefore important for a production manager to have a scientifically based and organisationally robust cleaning validation concept and program, where resources are neither over- or under-committed. In this paper technical tools, such as implementation of disassembling and cleaning SOPs, the implementation of cleaning and control levels, the definition of acceptance criteria, the execution of swab and rinse sampling methods, the development and validation of analytical methods, the use of worse-case tests, the definition of equipment-train and the preparation of validation protocols will be discussed. A cleaning validation program generates a huge amount of data. At Helsinn this data is processed, analysed and evaluated by means of tri-dimensional matrices. Cleaning validation programs have brought significant technical results that have led to production performance increases. Among them: The adopted model has permitted validation of the cleaning system in an overall manner for the entire production unit and for all products in question. It permits constant monitoring of the system and rapid theoretical verification of the impact of introducing new process/production runs. Allows earlier identification of critical cases where intervention with preventative solutions to avoid cross-contamination by use of more sophisticated cleaning/sampling/analysis methods can be implemented. The standardisation of methods for cleaning and analysis, and the introduction of the concept of cleaning levels, leading to faster product changeovers. The management has further criteria for the evaluation of new processes prior to introduction into the plant.