Developability Assessment of Clinical Candidates

The role of the developability (aka preformulation) scientist at the discovery development interface has been extensively discussed in the literature. In response to shifting trends in discovery and the continued push to shorten timelines and reduce costs, the engagement of the developability scientist on discovery teams has steadily moved upstream over the past two decades. In this new and continually changing role, the developability scientist has the opportunity to influence the selection of chemistry scaffolds entering the lead optimization phase and subsequently the selection of developable compounds for clinical testing. In its current state, developability assessment of clinical candidates is an assessment of the physicochemical and biopharmaceutical properties of the compound, carried out with due consideration to the patient in question, the clinical testing plan, and the commercial landscape. This chapter describes the dynamic and integrated nature of this assessment, along with a description of the in silico, in vitro, and in vivo tools used, and illustrative case studies. Key areas of focus include: (a) Solid form design and selection. (b) Characterization of the physicochemical properties associated with the solid form, such as solubility, stability, and dissolution properties. (c) Absorption modeling, including the definition of clinical product performance criteria and the need (if any) for absorption enhancement. (d) Assessment of absorption enhancement potential using technology platforms that lend themselves to commercial development (including in vivo evaluation where relevant). (e) The assembly of a comprehensive data package that includes an assessment of potential risks to clinical and commercial development.