A novel process system model of a roll compaction tablet manufacturing process has been developed. The model couples together multiple unit operations, namely roller compaction, milling and tablet press, providing a framework to simulate cause and effect relationships between process parameters and product performance. Models for tablet tensile strength and dissolution are implemented to evaluate tablet performance. The models for the milling and the dissolution units are based on the solution of population balance equations. The model is validated by comparison with experimental data. This work demonstrates that it is possible to develop a model for tablet manufacturing that is based on fundamental process understanding and that the resulting simulation tool, requiring limited experimental calibration, can be used easily and effectively in the workflow of pharmaceutical product development. (C) 2014 Elsevier Ltd. All rights reserved.