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Pharmaceutical Technology Regulatory Sourcebook October 2020 5 cake has sub-optimal appearance, cycles are longer than required: unnecessarily long primary drying times are often adopted, and long secondary dry- ing times can result in drug degradation). Quality target product profile (QTPP) and critical quality attributes (CQAs) The QTPP is a strategic guide to the formulation scientists allowing their activities to be focused on the development objectives (1). Therefore, the QTPP is strictly related to identity, strength, pu- rity, and stability, which are the four pillars of the common technical document (CTD) quality sec- tion. Based on the physicochemical characteristics of the drug substance and the general quality at- tributes of the drug product, the QTPP for a paren- teral liquid and a freeze-dried product is reported as an example in Table I. Table I. Quality target product profile (QTPP) examples for liquid and freeze-dried parenteral products. ICH is International Council for Harmonization. QTPP element Target Reference/Requirement Liquid form Freeze-dried form Dosage form Sterile liquid, clear and clean solution (concentrate for solution for infusion) free from visible particles Sterile powder or cake for reconstitution (sterile powder or cake for concentrate, for solution for infusion) Commercial requirement Route of administration Intravenous infusion Intravenous infusion Commercial requirement Dosage strength Nominal dose (mg/container) or concentration (mg/mL) Nominal dose (mg/container) Clinical requirement Container closure system Single dose, clear Type I glass vial or ampoule, or polymer for blow-fill-seal container, X mL capacity closed with a rubber stopper and sealed with an aluminum metal cap with flip-off or flame sealed, or top mold sealed Single dose, clear Type I glass vial, X mL capacity closed with a rubber stopper and sealed with an aluminum metal cap with flip-off Stability and commercial requirements Composition Precedented and safe inactive ingredients Precedented and safe inactive ingredients Quality and regulatory aspects Drug product quality attributes Appearance Appearance Regulatory requirement Identification Identification Regulatory requirement Assay Assay Regulatory requirement Not applicable Uniformity of dosage units (weight variation or content uniformity) Harmonized requirements for content uniformity Degradation products Degradation products ICH and compendial standards Sterility Sterility Compendial standards Bacterial endotoxins Bacterial endotoxins Compendial standards Osmolality Residual solvents (if relevant) Tolerability and safety requirements pH Water content Regulatory requirement Particulate matter Reconstitution time Regulatory requirement Not applicable pH of reconstituted solution Regulatory requirement Appearance of reconstituted solution Regulatory requirement Particulate matter on reconstituted solution Regulatory requirement Shelf-life Variable Variable Commercial requirement Administration instructions Variable Variable Clinical requirement Stability during administration Variable Variable Quality and safety requirements