A Rapid Sterility Method Using Solid Phase Cytometry for Cell-Based Preparations and Culture Media and Buffers

Area of Science:

• Biotechnology
• Microbiology
• Pharmaceutical Science

Background:

• Traditional compendial sterility testing (CST) is time-consuming.
• Cell-based therapies and their associated media require robust sterility assurance.
• Rapid detection methods are crucial for efficient biopharmaceutical manufacturing.

Purpose of the Study:

• To demonstrate and validate a rapid sterility test (RST) for non-filterable cell-based preparations.
• To evaluate the RST for in-process control of media and buffers.
• To establish the suitability of solid-phase cytometry for sterility testing.

Main Methods:

• Utilized the ScanRDI® system based on solid-phase cytometry for microorganism detection.
• Validated the RST for a CAR-T cell-therapy product with a 4-day time to detection (TTD).
• Assessed the RST for in-process control of media/buffers using real-time detection with representative microorganisms.

Main Results:

• The RST demonstrated high sensitivity, detecting down to one microbial cell.
• Validation parameters including limit of detection, specificity, robustness, and repeatability were met.
• Statistical evaluation confirmed equivalence between the RST and CST methods, with no significant differences detected.

Conclusions:

• Solid-phase cytometry technology, via the ScanRDI® system, is a validated and effective alternative for sterility testing of cell-based preparations.
• The RST is suitable for in-process control of media and buffers, offering significant time savings.
• This rapid method meets regulatory standards (USP <1223>, Ph. Eur. 5.1.6, PDA TR No. 33).