An Evaluation Of The Impact Of Sterilization Processes On Elastomeric Container Closure Components Used To Store And Administer Parenteral Drug Products

1.     To evaluate the impact of various sterilization processes on the chemical and physical properties of elastomeric components.

2.     To compare the extractable/leachable profile of the elastomer following steam and gamma sterilization.

3.     To examine the functionality of components used in prefillable syringe systems after steam and gamma sterilization.

 

The ideal sterilization process destroys all microorganisms rapidly with minimal adverse impact on the chemical and physical properties of the elastomeric closure. Developing and validating an acceptable sterilization process is critical to the drug product quality. This study served to help understand the potential deterioration of physical and chemical properties, the possible impact to functionality and the potential changes to the extractable/leachable profile as a result of sterilization

 

The results indicate that steam sterilization had little effect on the chemical, physical and extractable profiles of the elastomeric closures, other than a slight decrease in antioxidant content. Gamma irradiation had a greater impact to the elastomer than steam, as noted by the higher number of extractables for gamma irradiated samples, a JP pH failure at 40 kGy, and inconsistent piston release and travel forces at the higher gamma level. As expected, the number of extractables increased with increasing irradiation energy level. This confirms the importance of developing and validating a low-dose gamma level when this technique is used as the method of sterilization. The studies carried out also confirm the importance of extractable testing following the sterilization process and the importance of testing closures representative of the full process when performing drug product leachable studies.