title: Thermally induced degradation pathways of three different antibody-based drug development candidates.
abstract: Protein-based medicinal products are prone to undergo a variety of chemical and physical degradation pathways. One of the most important exogenous stress condition to consider during manufacturing, transport and storage processes is temperature, because antibody-based therapeutics are only stable in a limited temperature range. In this study, three different formats of antibody-based molecules (IgG1, a bispecific scFv and a fab fragment) were exposed to thermal stress conditions occurring during transport and storage. For evaluation, an analytical platform was developed for the detection and characterization of relevant degradation pathways of different antibody-based therapeutics. The effect of thermal stress conditions on the stability of the three antibody-based formats was therefore investigated using visual inspection, different spectroscopic measurements, dynamic light scattering (DLS), differential scanning calorimetry (DSC), electrophoresis, asymmetric flow field-flow fractionation (AF4) and surface plasmon resonance technology (SPR). In summary, thermal stress led to heterogeneous chemical and physical degradation pathways of all three antibody-based formats used. In addition, identical exogenous stress conditions resulted in different kinds and levels of aggregates and fragmentation products. This knowledge is fundamental for a systematic and successful stabilization of protein-based therapeutics by the use of formulation additives.
authors.affiliation: Analytical Development, Bayer Pharma AG, Berlin, Germany. Electronic address: anja.fincke@bayer.com.
authors.forename: Anja
authors.initials: A
authors.lastname: Fincke
authors.affiliation: Analytical Development, Bayer Pharma AG, Berlin, Germany.
authors.forename: Jonas
authors.initials: J
authors.lastname: Winter
authors.affiliation: Hilberstraße 4, 12307 Berlin, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bunte
authors.affiliation: Formulation Development Liquids, Bayer Pharma AG, Berlin, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Olbrich
mesh_terms: D002152:Calorimetry, Differential Scanning; D002942:Circular Dichroism; D004355:Drug Stability; D006358:Hot Temperature; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry*; D007074:Immunoglobulin G / Q000737:chemistry*; D057127:Single-Chain Antibodies / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D057127:Single-Chain Antibodies
keywords: Aggregation; Analytical platform; Antibody-based therapeutic; Degradation; Thermal stress