Exposure-response relationships. Relationships between (1) drug substance and drug product, (2) exposure expressed as dose or systemic exposure on log scale, and (3) positive (efficacy) or negative (toxicity) outcomes. These outcomes may be measured by clinical end points, surrogate endpoints, or biomarkers. The relationships between exposure and outcomes define the optimal dose and therapeutic window. The term change introduces the concept of equivalence in outcomes before or after a specified change (eg, generic substitution, postapproval manufacturing change). CMC, Chemistry, manufacturing, and controls; BA/BE, bioavailability and bioequivalence; PK, pharmacokinetics; PD, pharmacodynamics.