(M1030-06-33) Loss In Weight Feeding Optimization in a Continuous Drug Product Manufacturing Line

Purpose: Loss In Weight (LIW) feeding is an integral operation used in continuous drug product manufacturing (CM). The ability to accurately dose each component of the drug formulation is crucial to the process consistency and product quality. LIW feeding is typically an upstream operation that continuously doses active drug substance and excipients at a desired mass flow set-point to downstream unit operations. In this presentation, we will discuss problems encountered in LIW feeding and the operating parameters and equipment changes that yielded process improvements. Early experimental development typically does not allocate quantities of material that allow for extended LIW feeding runtimes. After acceptable development trials, issues may not arise until after consecutive hours to days of continuous manufacturing. The processing changes of refill schedule, tuning (control gain %), and twin-screw design improved feeding performance of a micronized drug substance. The maximum mass flow deviation was reduced from 2.52 kg/hr to 0.99 kg/hr, process mass flow deviation ‘stop alarm’ rate reduced from 0.5-1.0 alarms/kg material fed to zero total LIW feeder alarms, and removed the need for physical operator intervention in response to alarms. The addition of a ‘pneumatic impactor‘ with integrated operation controlled by the feeder improved the drug substance maximum feed rate range from 2.5 kg/hr to 8.5 kg/hr. These improvements allow for a wider range of material properties to be considered feasible for LIW feeding and greater processing capability.

Methods: The LIW feeder is a KT20 K-trim feeder equipped with a rotary oyster valve for refills. The LIW feeding performance is confirmed by a standalone reference ‘catch-scale’. This scale is a K-tron K-Sampler scale that logs mass flow information on a 1-second basis.

Results: The maximum mass flow deviation was reduced from 2.52 kg/hr to 0.99 kg/hr, process mass flow deviation ‘stop alarm’ rate reduced from 0.5-1.0 alarms/kg material fed to zero total LIW feeder alarms, and removed the need for physical operator intervention in response to alarms. The addition of a ‘pneumatic impactor‘ with integrated operation controlled by the feeder improved the micronIzed drug substance maximum feed rate range from 2.5 kg/hr to 8.5 kg/hr.

Conclusion: The issues encountered after several hours to days of continuous manufacturing do not present themselves early in development when material/time are limited. The optimization of LIW feeder parameters/settings and equipment options can drastically increase the capabilities of the LIW feeder. These optimizations also allow for materials that were once considered ‘un-feedable’ to be considered again for LIW feeding.