Biopharmaceutical manufacturers must ensure that the quality of their manufactured medicines, both at the drug substance (DS) release stage and at the final drug product (DP) release stage, meets all of the regulatory requirements with respect to safety and efficacy. Critical quality attributes (CQAs) requirements define the needed product quality. CQAs address biomolecular structure and structural variants, biological and immunochemical properties, safety limits for process-related impurities and adventitious agents, and required compendial requirements. CQAs guide the biopharmaceutical manufacturer in demonstrating manufactured batch-to-batch consistency, supporting meaningful specifications for release, setting the product’s shelf life, and confirming product comparability after manufacturing process changes. The seven major CQA categories to be included in a biopharmaceutical Certificate of Analysis (COA), for both protein-based biopharmaceuticals (recombinant proteins and monoclonal antibodies) and gene-based biopharmaceuticals (viral and non-viral vectors, and genetically modified patient cells), will be examined in this chapter: (1) appearance/description, (2) identity, (3) purity/impurities, (4) potency, (5) quantity, (6) safety, and (7) general. The setting of specifications for these CQAs will be discussed in Chap. 16.