A scientific approach was adopted in a fluid bed granulation process development and scale-up.Several new technologies have been used in process DOE study to fundamentally understand the process and to identify critical quality attributes (CQAs) and critical process parameters(CPPs).FBRM was used to gain the knowledge of granule growth kinetics and control granule size during granulation.The Compaction Simulator was equipped with a thermal couple to study temperature increase during tableting in which there existed polymorph change concern.AFM was applied to characterize granule friction forces between granules.It was found that granule size and roughness affected the temperature increase during high speed tableting.The DOE study shed light on the causal relationship between process parameters and tablet properties.Based on the DOE study results, the CQA was clearly identified.It was found that bed moisture determines the granule size distribution which in turn is the most significant factor on tablet hardness, dissolution and content uniformity.The process scale-up strategy which was to use a mathematical model developed to predict and control bed moisture has been proved successful.The scale-up batches have validated the CQA and CPP identified in DOE study.The commercial manufacturing process by using NIR technology to monitor bed moisture could effectively control the drug product quality.Through this fluid bed granulation process study, it was demonstrated that new technologies and scientific approach are useful in process understanding, development and scale-up.