title: Use of a quality-by-design approach to justify removal of the HPLC weight % assay from routine API stability testing protocols.
abstract: Due to the high method variability (typically > or = 0.5%, based on a literature survey and internal Merck experience) encountered in the HPLC weight percent (%) assays of various active pharmaceutical ingredients (APIs), it is proposed that the routine use of the test in stability studies should be discouraged on the basis that it is frequently not sufficiently precise to yield results that are stability-indicating. The high method variability of HPLC weight % methods is not consistent with the current ICH practice of reporting impurities/degradation products down to the 0.05% level, and it can lead to erroneous out-of-specification (OOS) results that are due to experimental error and are not attributable to API degradation. For the vast majority of cases, the HPLC impurity profile provides much better (earlier and more sensitive) detection of low-level degradation products. Based on these observations, a Quality-by-Design (QbD) approach is proposed to phase out the HPLC weight % assay from routine API stability testing protocols.
authors: Merck & Co., Inc., P.O. Box 2000, 126 East Lincoln Avenue, RY818-B205, Rahway, NJ 07065, USA. peter_skrdla@merck.com
authors: Peter J
authors: PJ
authors: Skrdla
authors: Tao
authors: T
authors: Wang
authors: Vincent
authors: V
authors: Antonucci
authors: Thomas
authors: T
authors: Dowling
authors: Zhihong
authors: Z
authors: Ge
authors: Dean
authors: D
authors: Ellison
authors: John
authors: J
authors: Curran
authors: Ganapathy
authors: G
authors: Mohan
authors: Jean
authors: J
authors: Wyvratt
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods* / Q000592:standards*; D002851:Chromatography, High Pressure Liquid / Q000379:methods* / Q000592:standards*; D004339:Drug Compounding; D004340:Drug Contamination; D004345:Drug Industry; D004355:Drug Stability; D004364:Pharmaceutical Preparations / Q000032:analysis; D011786:Quality Control; D015203:Reproducibility of Results; D013678:Technology, Pharmaceutical / Q000379:methods / Q000592:standards
chemical_list: D004364:Pharmaceutical Preparations