Extension of quality-by-design concept to the early development phase of pharmaceutical R&D processes
Ildikó Csóka, E. Pallagi, T.L. Paál
文献索引：10.1016/j.drudis.2018.03.012
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摘要
Highlights • Extension of the ICH Q8 “Quality by Design (QbD)” model. • Enlarged QbD pathway for answering the challenges of drug R&D and industrial production. • Model proposal for implementation an extended QbD in the pharmaceutical preformulation study design. • “R&D QbD” model based on the inputs of regulatory agencies, patient-feedback and pharma industry. • Extended QbD chart for harmonized co-creation work (patient, industry and regulatory agency). Here, we propose the extension of the quality-by-design (QbD) concept to also fit the early development phases of pharmaceuticals by adding elements that are currently widely applied, but not yet included in the QbD model in a structured way. These are the introduction of a ‘zero’ preformulation phase (i.e., selection of drug substance, possible dosage forms and administration routes based on the evaluated therapeutic need); building in stakeholders’ (industry, patient, and regulatory) requirements into the quality target product profile (QTTP); and the use of modern quality management tools during the composition and process design phase [collecting critical quality attributes (CQAs) and selection of CPPs) for (still laboratory-scale) design space (DS) development. Moreover, during industrial scale-up, CQAs (as well as critical process parameters; CPPs) can be changed; however, we recommend that the existing QbD elements are reconsidered and updated after this phase.