(762b) Development and Implementation of a Single-Use, Closed Depth Filtration System for Primary Clarification

Biogen Idec has developed and  implemented a single-use and completely disposable clarification platform for use within its controlled non-classified flexible volume manufacturing facility in RTP, NC.  This presentation demonstrates the capability of Millistak + POD single-use technologies for high cell density (TCD <25E6/mL) clarification while creating and maintaining a closed system for microbial control.  Major challenges with this primary clarification operation were the large volume of WFI required (>22,000L) for priming, flushing and caustic neutralization, as well as the high flow rates of >100L/min recommended for reducing leachable/extractable (L/E) substance levels.  These challenges were mitigated by assessing lower flux rates and volumes to adequately meet L/E target specs provided by the manufacturer.  Furthermore, the caustic neutralization after pre-sanitization utilized capture column equilibration instead of WFI resulting in a large reduction of volume necessary for neutralization.  Overall, the WFI volume was reduced by ~20,000L and facility fit constraints around flow rates was resolved with lower flux rates.