Scientific, statistical, practical, and regulatory considerations in design space development. (4th March 2018)

• Record Type: Journal Article
• Authors: Debevec, Veronika; Srčič, Stanko; Horvat, Matej
• Is Part Of: Drug development and industrial pharmacy. Volume 44:Number 3(2018)
• Page Start: 349
• Page End: 364
• Publication Date: 2018-03-04
• Subjects: Quality by Design (QbD) -- Design of Experiments (DoE) -- design space -- mechanistic modeling -- empirical modeling -- hybrid modeling -- scale-independent parameters; Pharmaceutical chemistry -- Periodicals; Pharmaceutical industry -- Periodicals; Drug Industry -- Periodicals; Technology, Pharmaceutical -- Periodicals; 615.05
• DOI: 10.1080/03639045.2017.1409755
• Languages: English
• ISSNs: 0363-9045

Abstract

Abstract: The quality by design (QbD) paradigm guides the pharmaceutical industry towards improved understanding of products and processes, and at the same time facilitates a high degree of manufacturing and regulatory flexibility throughout the establishment of the design space. This review article presents scientific, statistical and regulatory considerations in design space development. All key development milestones, starting with planning, selection of factors, experimental execution, data analysis, model development and assessment, verification, and validation, and ending with design space submission, are presented and discussed. The focus is especially on frequently ignored topics, like management of factors and CQAs that will not be included in experimental design, evaluation of risk of failure on design space edges, or modeling scale-up strategy. Moreover, development of a design space that is independent of manufacturing scale is proposed as the preferred approach.