A Proof of Principle Study of the Terminal Sterilization of Prefilled Syringes Using A Water Cascade Process

Abstract

Abstract Background A new development in drug compounding is the production of ready-to-administer sterilized prefilled syringes. A challenge with these syringes is the method of terminal sterilization. There is no information available whether water cascade sterilization is a suitable method. We investigated the effect of this sterilization method on cyclic olefin (co)polymer (CCP/COC) syringes. Methods For two brands ten prefilled syringes were sterilized using water cascade sterilization. The closure integrity, stopper movement, weight, diameter and physical appearance were determined before and after sterilization. As sterility test, additional syringes were filled with tryptic soy broth (TSB) and sterilized. After fourteen days microbiological growth was determined. Results Closure integrity testing showed no dye penetration inside the syringe. Together with the results for weight this showed that closure integrity is guaranteed. No significant stopper movement, deviation in diameter or visual anomalies were observed. No microbiological growth in TSB was visible. Conclusions The results of this proof of principle study show that the physical and microbiological stability of the cyclic olefin (co)polymer syringes is guaranteed during sterilization using a water cascade sterilizer. These results do not rule out the necessity for further stability experiments (e. g. interaction with drug product) to further proof the concept.