title: An improved methodology for data analysis in accelerated stability studies of peptide drugs: practical considerations.
abstract: Although the basic science behind current methods for studying biopharmaceutical drug stability has not changed significantly, the techniques available for predicting stability have evolved over the years. This paper therefore describes and discusses various options of data analysis for accelerated degradation studies of peptide and protein drugs based on the Arrhenius equation. Both linear and non-linear regression analyses are also discussed. The results indicate that the simultaneous treatment of all data, as opposed to determining individual rate constants is clearly preferable, combined with the use of the reparameterized Arrhenius equation. The estimated shelf-life at 5 °C varied between 2.2 and 4.0 years in function of the temperature range and procedure used, whereas the precision of the estimated parameter is reflected in the width of the 95% confidence intervals, the classic Arrhenius analysis was maxima. All these results were evaluated by the bootstrap approach.
authors.affiliation: Departamento de Ingeniería Química y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de La Laguna, 38200 Tenerife, Spain. amoliva@ull.es
authors.forename: Alexis
authors.initials: A
authors.lastname: Oliva
authors.forename: José B
authors.initials: JB
authors.lastname: Fariña
authors.forename: Matías
authors.initials: M
authors.lastname: Llabrés
mesh_terms: D001688:Biological Products / Q000032:analysis*; D002853:Chromatography, Liquid; D056148:Chromatography, Reverse-Phase; D004355:Drug Stability; D006801:Humans; D007700:Kinetics; D013058:Mass Spectrometry; D012044:Regression Analysis; D012107:Research Design; D013696:Temperature; D013758:Tetragastrin / Q000032:analysis*; D013816:Thermodynamics
chemical_list: D001688:Biological Products; D013758:Tetragastrin