Cleaning validation of a multipurpose plant for active pharmaceutical ingredient bulk production

One of the key issues in the manufacture of active pharmaceuticals ingredie nts in multipurpose nondedicated equipment is to adequately address the pot ential for cross-contamination, It is therefore important fora production m anager 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 disasse mbling and cleaning SOPs, the implementation of cleaning and control levels , the definition of acceptance criteria, the execution of swab and rinse sa mpling methods, the development and validation of analytical methods, the u se of worse-case tests, the definition of equipment-train and the preparati on of validation protocols will be discussed. A cleaning validation program generates a huge amount of data. At Helsinn this data is processed, analys ed and evaluated by means of tri-dimensional matrices. Cleaning validation programs have brought significant technical results that have led to produc tion performance increases. Among them: The adopted model has permitted val idation of the cleaning system in an overall manner for the entire producti on 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 cas es where intervention with preventative solutions to avoid cross-contaminat ion 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 produ ct changeovers. The management has further criteria for the evaluation of n ew processes prior to introduction into the plant.