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18 Pharmaceutical Technology Regulatory Sourcebook October 2020 P h a r mTe c h . c o m Process Development ing process that will be reflected in planned master production and control records. CQAs should be identified in this stage based on the QTPP and/or prior knowledge using quality risk management (1) according to the iterative approach specified in Part 1. Table II, adapted from the FDA document on quality-by-design for ANDAs (4), summa- rizes the CQAs of an immediate-release solid oral form. In this example, assay, uniformity of dosage units, degradation products, water content, dis- integration time, dissolution, hardness, friability, powder/granule bulk properties, and polymor- phism are identif ied as t he subset of CQAs that have the potential to be impacted by the for- mulation and/or process variables. Therefore, these attributes will be investigated and discussed in de- Table I. Quality target product profile (QTPP) examples for different immediate release solid oral dosage forms (powders, granules, tablets). ICH is International Council for Harmonization. QTPP element Target Reference/Requirement Powder Granules Tablet Dosage form Solid, loose, dry particles of varying degrees of fineness Solid, dry aggregates of powder particles sufficiently resistant to withstand handling Solid dosage forms usually obtained by single or multiple compression of powders or granules Commercial requirement Route of administration Oral Oral Oral Commercial requirement Dosage strength Single-dose: the nominal dose per container (mg/vial, mg/sachet) Multi-dose: the amount of active ingredient in a suitable quantity by weight Nominal dose (mg/tablet) Clinical requirement Container closure system Vial or sachet Vial or sachet Blister or bottle Stability and commercial requirements Composition Precedented and safe inactive ingredients Precedented and safe inactive ingredients Precedented and safe inactive ingredients Quality and regulatory aspects Drug product quality attributes Appearance Appearance Appearance Regulatory requirement Identification Identification Identification Regulatory requirement Assay Assay Assay Regulatory requirement Uniformity of dosage units (weight variation or content uniformity) Uniformity of dosage units (weight variation or content uniformity) Uniformity of dosage units (weight variation or content uniformity) Harmonized requirements for content uniformity Degradation products Degradation products Degradation products ICH and compendial standards Single-dose: uniformity of mass Multi-dose: uniformity of mass of delivered doses from multi-dose containers Uniformity of mass Compendial standards Water content Water content Water content Compendial standards Drug product quality attributes Residual solvents (if relevant) Residual solvents (if relevant) Residual solvents (if relevant) Compendial standards --- --- Hardness Compendial standards --- --- Friability Compendial standards --- --- Disintegration Compendial standards Dissolution Dissolution Dissolution Compendial standards Microbial purity Microbial purity Microbial purity Compendial standards Shelf life Variable Variable Variable Commercial requirement Administration instructions Variable Variable Variable Clinical requirement Stability during administration Variable (if multi-dose to be reconstituted) Variable (if multi-dose to be reconstituted) Not applicable Quality and safety requirements