(428f) Model-Aided Development of a Continuous Drug Product Manufacturing Process

Authors: 
Luciani, C., Eli Lilly & Co.
Shi, Z., Eli Lilly & Co.
Roth, W., Eli Lilly & Co.
Butterbaugh, A. S., Eli Lilly & Co.
Hanson, J., Eli Lilly and Company
Manley, L., Eli Lilly & Co.
Barnes, L., Eli Lilly & Co.
Leavesley, I., Eli Lilly & Co.
Almaya, A., Eli Lilly & Co.

This work involves the use of mathematical tools to aid the development of an integrated Powder to Drug Product Continuous Manufacturing Process. Fundamentally driven dynamic models of the different units of the system are the basic frame of a holistic model capable of describing the overall system dynamics. Such a model is used to justify the appropriate usage of process analytical technology (PAT) tools to monitor the critical quality attributes (CQA’s) and fundamentally increase the observability of the states of the system. State estimation along with data reconciliation techniques are used to fuse all available measurements and identify the best estimate of the de-noised signals of concentration of active pharmaceutical ingredient (API). Such reconciled values (along with other diagnostics) are then proposed as an integral component of the control strategy.