title: Shipping-Induced Aggregation in Therapeutic Antibodies: Utilization of a Scale-Down Model to Assess Degradation in Monoclonal Antibodies.
abstract: It is vital to understand the impact of transportation on monoclonal antibody (mAb) product quality during drug product development. Fully representative real-time shipment studies are resource intensive, so in this work, we studied laboratory agitation methods to mimic the effect of real-time shipment on aggregation, specifically subvisible particle formation. The agitation methods studied include a rotator, orbital shaker, vortexer, and shipping simulator vibration table. The simulator is able to predict the particle formation behavior during real-time shipment for a number of mAbs in vial and prefilled syringe configurations, with a correlation of about 90%, whereas the other methods of agitation were inconsistent. This study demonstrates that using a shipping simulator vibration table provides an opportunity for consistent and predictive development studies of shipping stress with minimal resource requirements during early- or late-stage drug product development.
authors.affiliation: Formulation Sciences, MedImmune, Gaithersburg, Maryland 20877.
authors.forename: Marianna L
authors.initials: ML
authors.lastname: Fleischman
authors.affiliation: Drug Delivery and Device Development, MedImmune, Gaithersburg, Maryland 20877.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Chung
authors.affiliation: Formulation Sciences, MedImmune, Gaithersburg, Maryland 20877.
authors.forename: Eden P
authors.initials: EP
authors.lastname: Paul
authors.affiliation: Formulation Sciences, MedImmune, Gaithersburg, Maryland 20877. Electronic address: lewusr@medimmune.com.
authors.forename: Rachael A
authors.initials: RA
authors.lastname: Lewus
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000378:metabolism*; D002626:Chemistry, Pharmaceutical / Q000379:methods / Q000592:standards*; D066329:Protein Aggregates / Q000502:physiology; D013314:Stress, Mechanical; D014186:Transportation / Q000592:standards*
chemical_list: D000911:Antibodies, Monoclonal; D066329:Protein Aggregates
keywords: biopharmaceutical characterization; microparticles; monoclonal antibody; physical stability; protein aggregation; protein formulation