(207d) Systematic Control Strategy Development for a Continuous Direct Compaction Line Via the Control Strategy Evaluation Tool (CET)

Being able to track materials through a continuous manufacturing process is crucial to the implementation of a quality control strategy for solid oral dosage forms. Typically, residence time distribution (RTD) models are developed and parameterized for that purpose. RTD models allow for the prediction of the concentration of the active pharmaceutical ingredient (API) at specific locations in the manufacturing line. If the deviation in the API concentration from the setpoint exceeds a threshold, the generated material is considered out-of-specification (OOS) and needs to be discarded. The discharge of OOS material can then be triggered based on the output signal from the RTD model.

Any change in material attributes (e.g., due to a change of raw material batch) or process settings (e.g., due to an adjustment of the mass flow rate through the manufacturing line) can also change the RTD and affect the discharge decision. Therefore, a comprehensive knowledge of the critical factors and their impact on the RTD is essential during control strategy development. Because an extensive experimental characterization of the RTD is often not feasible, a simulation based on the discrete-element-method (DEM) is adopted. The RTD obtained from the DEM simulations at selected process settings or for specified material attributes is then approximated by suitable reduced order models and interpolation techniques, which significantly reduce the computational cost needed for a real time control strategy.

Finally, a control strategy evaluation tool (CET) is introduced, which has the functionality to test material discharge strategies in a systematic manner without running costly experiments. Three main components of the CET include: i) a modular simulation model of pharmaceutical manufacturing lines based on the RTD models mentioned above, ii) a library of typical disturbance scenarios, and iii) a discharge algorithm that implements a certain control strategy in terms of material discharge. The functionality of the CET is demonstrated using selected scenarios.

Disclaimer: This abstract reflects the views of the authors and should not be constructed to represent FDA’s views or policies.