title: Establishing column batch repeatability according to Quality by Design (QbD) principles using modeling software.
abstract: Column technology needs further improvement even today. To get information of batch-to-batch repeatability, intelligent modeling software was applied. Twelve columns from the same production process, but from different batches were compared in this work. In this paper, the retention parameters of these columns with real life sample solutes were studied. The following parameters were selected for measurements: gradient time, temperature and pH. Based on calculated results, batch-to-batch repeatability of BEH columns was evaluated. Two parallel measurements on two columns from the same batch were performed to obtain information about the quality of packing. Calculating the average of individual working points at the highest critical resolution (R(s,crit)) it was found that the robustness, calculated with a newly released robustness module, had a success rate >98% among the predicted 3(6) = 729 experiments for all 12 columns. With the help of retention modeling all substances could be separated independently from the batch and/or packing, using the same conditions, having high robustness of the experiments.
authors.affiliation: Budapest University of Technology and Economics, Budapest, Hungary.
authors.forename: Norbert
authors.initials: N
authors.lastname: Rácz
authors.affiliation: Egis Pharmaceuticals PLC, Budapest, Hungary.
authors.forename: Róbert
authors.initials: R
authors.lastname: Kormány
authors.affiliation: Budapest University of Technology and Economics, Budapest, Hungary.
authors.forename: Jenő
authors.initials: J
authors.lastname: Fekete
authors.affiliation: Molnár-Institute for Applied Chromatography, Berlin, Germany. Electronic address: imre.molnar@molnar-institute.com.
authors.forename: Imre
authors.initials: I
authors.lastname: Molnár
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006863:Hydrogen-Ion Concentration; D015203:Reproducibility of Results; D012984:Software; D013678:Technology, Pharmaceutical / Q000295:instrumentation*; D013696:Temperature
keywords: DOE; DryLab; QbD; Robustness; UPLC-column comparison