Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Basic Requirements For Aseptic Manufacturing Of Sterile Medicinal Products ***

Dr. Gisela Greger (Abschlußjahr: 2004)

Health care products that must be sterile but are unsuitable for terminal sterilisation have to be processed under aseptic conditions. For example, all product parts or components that are in direct contact with aseptically-filled sterile product during the manufacturing process require pre-sterilisation. In addition, production has to take place in a controlled manufacturing environment where microbiological and particulate levels are maintained at defined low levels and where human intervention in the manufacturing process is minimised. In aseptic processing maximum efforts must be expended to use consistently qualified equipment and materials and validated systems, to use adequately trained personnel, and to control the environment. Furthermore a well documented systematic process is needed which impacts risks on product quality using the Hazard Analysis and Critical Control Points (HACCP) concept considering all aspects of qualification of equipment and materials and validation of the process (for example facility design, environment, materials, equipment suitability, supply systems, filter qualification, personnel, incubation conditions for the samples, identification of positive units, demonstration of growth promotion, process validation and quality control). Usually the validation of the whole process is performed by media fill (simulation of the manufacturing process by using nutrient media).

A lot of requirements have to be met to ensure that the aseptically manufactured drug product can be regarded as sterile.

The manuscript depicts international guidelines of EU and US and microbiological measures which should be implemented in development and performance of validation of aseptic manufacturing procedures. The whole process is only as good as any single step. The requirements in Europe and USA (for example sterile requirement for aqueous based inhalation pharmaceutical forms, clean room classification) have not yet been harmonised. In a global world the careful establishing of the requirements regarding the requirements in both regions - Europe and USA - is a precondition to supply different markets with the adequate quality of the drug products.