Validation of a radiation sterilization process for product or component can sometimes be difficult when testing large or bulk products and components; especially those that are complex with multiple components or with large volumes. For these products this difficulty exists in bioburden and sterility testing as well as delivering the verification dose. Also, the typical approach of using the entire product bioburden of a large/complex/bulk product often results in an overestimation of bioburden and subsequently high sterilization doses. This is especially true in the case of large single-use systems and bulk drug substances for bioprocessing and pharmaceutical manufacturing. A review of the underlying principles of product bioburden and radiation processing (e.g., Table 1 and Clause 4 of ISO 11137-2) reveals an alternative approach to testing large, complex products that can greatly simplify bioburden/sterility testing and verification dose delivery.

This presentation/poster will review these underlying principles and provide alternatives to the SIP approach commonly used for large, complex products or bulk materials that will enable for the determination of a more representative product bioburden and validation using the appropriate verification dose. Examples will be shared to clarify the proposed approach and a case study to demonstrate how one might select the representative product portion to be used in future testing.