title: Quality by design case study: an integrated multivariate approach to drug product and process development.
abstract: To facilitate an in-depth process understanding, and offer opportunities for developing control strategies to ensure product quality, a combination of experimental design, optimization and multivariate techniques was integrated into the process development of a drug product. A process DOE was used to evaluate effects of the design factors on manufacturability and final product CQAs, and establish design space to ensure desired CQAs. Two types of analyses were performed to extract maximal information, DOE effect & response surface analysis and multivariate analysis (PCA and PLS). The DOE effect analysis was used to evaluate the interactions and effects of three design factors (water amount, wet massing time and lubrication time), on response variables (blend flow, compressibility and tablet dissolution). The design space was established by the combined use of DOE, optimization and multivariate analysis to ensure desired CQAs. Multivariate analysis of all variables from the DOE batches was conducted to study relationships between the variables and to evaluate the impact of material attributes/process parameters on manufacturability and final product CQAs. The integrated multivariate approach exemplifies application of QbD principles and tools to drug product and process development.
authors: Pharmaceutical Development Center, Wyeth Pharmaceuticals, 401 N Middletown Rd, Pearl River, NY 10965, USA. huangj16@wyeth.com
authors: Jun
authors: J
authors: Huang
authors: Goldi
authors: G
authors: Kaul
authors: Chunsheng
authors: C
authors: Cai
authors: Ramarao
authors: R
authors: Chatlapalli
authors: Pedro
authors: P
authors: Hernandez-Abad
authors: Krishnendu
authors: K
authors: Ghosh
authors: Arwinder
authors: A
authors: Nagi
mesh_terms: D002266:Carboxymethylcellulose Sodium / Q000737:chemistry; D002482:Cellulose / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D005079:Excipients / Q000737:chemistry*; D008956:Models, Chemical; D015233:Models, Statistical; D015999:Multivariate Analysis; D025341:Principal Component Analysis; D011786:Quality Control; D012995:Solubility; D013229:Stearic Acids / Q000737:chemistry; D018511:Systems Integration; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000592:standards / Q000706:statistics & numerical data*; D013997:Time Factors; D014867:Water / Q000737:chemistry
chemical_list: D005079:Excipients; D013229:Stearic Acids; D013607:Tablets; D014867:Water; C031183:stearic acid; D002482:Cellulose; D002266:Carboxymethylcellulose Sodium; C109691:microcrystalline cellulose