Many compounded sterile preparations (CSPs) are currently sterilized by aseptic filtration and released after a USP <71> sterility test. The revised USP <797> limits batch size for CSPs requiring sterility testing to 250 units and still requires a 14-day sterility test. However, E-Beam irradiation can terminally sterilize finished CSPs and achieve a sterility assurance level (SAL) of ≤ 10-6, ten to 100 times more stringent than the SAL achieved with steam or dry-heat sterilization. Under ISO 11137-1/2 and ISO 11737-1/2, E-Beam processes are validated and monitored through bioburden determination, dose-setting studies, and routine sterilization-dose audits; ISO 11737-2 explains that sterility testing on products exposed to a complete terminal sterilization cycle provides no scientifically usable data and is not recommended. USP <71> itself states that sterility procedures “are not by themselves designed to ensure that a product or batch is sterile or has been sterilized” and that sterility assurance must come from validation of the sterilization process or aseptic processing procedures.

This analysis argues that dosimetric (parametric) batch release—where each batch is released based on dose delivery and compliance with validated process parameters—meets or exceeds the sterility assurance of USP <71> sterility testing for E-Beam-sterilized CSPs. ISO 11137 requires routine dose audits that examine bioburden levels, microbial resistance, manufacturing process controls, and the margin between the processing dose and the sterilization dose. When these audits show the validated sterilization dose continues to achieve an SAL of 10-6, the sterile product can be released based solely on dose measurements (dosimetry) and critical process parameters. This approach eliminates the 14-day sterility test and supports larger batch sizes, enabling production runs beyond 250 units while maintaining (or improving) sterility assurance. Read More >