**4. Conclusions**

We have presented results for exploring the operational flexibility for a fluid bed drying unit that is at the heart of formulation processes for tablet manufacture. The methodology obtains a feasible operating envelope which is then reduced to one that allows constrained flexibility in two key parameters (T and V) but maintains an optimal distance from the feasible boundary. Finally, when using this optimal set of conditions, it is possible to explore the trade-off between the envelope size and a key parameter, the drying time. We have demonstrated the value of this approach to a process which is known to have considerable uncertainty and which is key to operational excellence. We aim to broaden the analysis to embrace all elements of the formulation process to explore operational flexibility and demonstrate the value of using a model-based optimisation approach to managing uncertainty in the pharmaceutical industry. It can add to the toolkit of the Quality by Design approach being brought in to pharmaceutical process development and operations. The approach seeks to support systematic development processes: in this case to systematically identify operating flexibility with robustness guarantees subject to model accuracy. Further work in tandem with experimental pilot plant work is needed to fully validate the approach within the tight regulatory regime of pharmaceutical manufacture.

**Author Contributions:** Conceptualization, V.M.C., I.D.L.B. and L.G.P.; methodology, V.M.C., L.G.P. and S.-L.J.; software, S.-L.J. and V.M.C.; validation, S.-L.J.; formal analysis, S.-L.J. and V.M.C.; writing— original draft preparation, S.-L.J. and I.D.L.B.; writing—review and editing, all; supervision, I.D.L.B.; project administration, I.D.L.B.; funding acquisition, S.-L.J. All authors have read and agreed to the published version of the manuscript.

**Funding:** National Natural Science Foundation of China Grant No. 61873042 funded S.J.-L. visit to UCL.

**Acknowledgments:** The authors acknowledge LiGe Wang of PSEnterprise Ltd. for his help with using gPROMS and the model and to PSEnterprise Ltd. for use of gPROMS software.

**Conflicts of Interest:** The authors declare no conflict of interest.
