What is bracketing approach in media fill validations?

Bracketing approach is a methodology employed in aseptic media simulation experiments to mimic a manufacturing environment's filling process and provide confidence in biopharmaceutical product sterility during media-fill validation studies. The intent is to determine if interventions applied after the point of filling can render a container-closure imperfect during the production phase.

When executing a media-fill study using the bracketing approach, the parameters (e.g., time and temperature for cooling product-filled containers, capping machine settings) are intentionally chosen to generate a "bracket" around the aseptic production process.

By executing media fill simulations that encompass conditions beyond standard operating procedures, the approach allows evaluation of the sterility of the simulated product in situations where minor excursions or disruptions may occur. This approach enhances the validation scope and robustness by examining borderline process parameters that can influence container-closure integrity and potential microbial ingress.

Ultimately, bracketing ensures the aseptic processing can withstand foreseeable deviations and assures manufactured product sterility under normal handling and processing conditions.