An early-phase development shipping study was designed to interrogate the stability of liquid formulations under normal shipping conditions. Parcel shipments were made between Seattle, WA, and Indianapolis, IN, during 2018-2019. Each parcel contained a data recorder that tracked the shipment by GPS and measured shock and temperature. During the transport process, the parcels received up to 40 shock events with strengths ranging from 8 to 36G. After shipment, the formulations without polysorbate showed considerable increases in submicron and visible particles while little to no change occurred when polysorbate was present. Samples dropped repeatedly from a height of 18 inches to produce a shock of ∼25G caused visible particle formation with little increase in the subvisible particles, suggesting that other factors, such as vibration, in addition to the shock, were necessary to produce particle formation. These results provide a basis for further studies in the relationships between physical stability of mAbs and the challenges introduced by the shipment network, specifically shock and vibration. The findings indicate that the shock events as measured are repeatable and attributable to the layout of the sorting facility.
Keywords: antibody; biotechnology; developability; formulation; high concentration; physical stability; protein aggregation; protein folding; protein formulation; protein structure.
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