The Formulation joins the drug substance with excipients through the formulation process train to manufacture the dosage form. The material properties of the drug substance defined by the Formation process will play a role in the material properties of the formulation and its behavior in the drug product unit operations. Consequently, appropriate physical characterization of the drug substance and its consistency are important when formulating a dosage form. Understanding of particle size and material properties of the drug substance and how these characteristics might impact formulation processing or performance should be considered. First principles assessment of the impact of particle size on content uniformity and bioavailability can help establish early QbD criteria and reduce risks associated with early manufacturing QC and clinical exposure risks. Detailed understanding of the unit operations applied to manufacture the dosage form should be taken into account with respect to physicochemical risks to the drug substance form.