title: A platform analytical quality by design (AQbD) approach for multiple UHPLC-UV and UHPLC-MS methods development for protein analysis.
abstract: A platform analytical quality by design approach for methods development is presented in this paper. This approach is not limited just to method development following the same logical Analytical quality by design (AQbD) process, it is also exploited across a range of applications in methods development with commonality in equipment and procedures. As demonstrated by the development process of 3 methods, the systematic approach strategy offers a thorough understanding of the method scientific strength. The knowledge gained from the UHPLC-UV peptide mapping method can be easily transferred to the UHPLC-MS oxidation method and the UHPLC-UV C-terminal heterogeneity methods of the same protein. In addition, the platform AQbD method development strategy ensures method robustness is built in during development. In early phases, a good method can generate reliable data for product development allowing confident decision making. Methods generated following the AQbD approach have great potential for avoiding extensive post-approval analytical method change. While in the commercial phase, high quality data ensures timely data release, reduced regulatory risk, and lowered lab operational cost. Moreover, large, reliable database and knowledge gained during AQbD method development provide strong justifications during regulatory filling for the selection of important parameters or parameter change needs for method validation, and help to justify for removal of unnecessary tests used for product specifications.
authors.affiliation: Analytical Science and Technology, Global Manufacturing Science and Technology, Sanofi, MA 01710, United States. Electronic address: jianmei.kochling@genzyme.com.
authors.forename: Jianmei
authors.initials: J
authors.lastname: Kochling
authors.affiliation: Analytical Science and Technology, Global Manufacturing Science and Technology, Sanofi, MA 01710, United States.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.affiliation: Analytical Science and Technology, Global Manufacturing Science and Technology, Sanofi, MA 01710, United States.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Hua
authors.affiliation: Analytical Science and Technology, Global Manufacturing Science and Technology, Sanofi, MA 01710, United States.
authors.forename: Qian
authors.initials: Q
authors.lastname: Guan
authors.affiliation: Analytical Science and Technology, Global Manufacturing Science and Technology, Sanofi, MA 01710, United States.
authors.forename: Juan
authors.initials: J
authors.lastname: Castaneda-Merced
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D013058:Mass Spectrometry / Q000379:methods*; D010449:Peptide Mapping; D011506:Proteins / Q000032:analysis*; D013056:Spectrophotometry, Ultraviolet / Q000379:methods*
chemical_list: D011506:Proteins
keywords: Analytical quality by design; Design of experiments; Method development; Platform approach for multiple methods; Robustness; Statistical analysis