Shocking Data on Parcel Shipments of Protein Solutions

Abstract

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.

Figure 1

Shock strength monitoring. Summary of the shocks that were recorded for 4 test shipments. The solid bars are shocks recorded in Seattle, the dashed bars are shocks recorded in Memphis, and the checkered bars are shocks recorded in Indianapolis. The red line indicates the shocks were performed intentionally by the recipient in Indianapolis, and in the case of trip 4, the recipients in Indianapolis and in Seattle. Because the monitoring system records data through a cell network, unavailability of the network will lead to underreporting and may have occurred here.

Figure 2

Subvisible particles. Subvisible particles were counted for each sample included in Trip 4. The total particles per mL 2 μm and more for each condition included in the shipment are shown. Panel a is the plot of all data, and panel b is the zoomed in view of the data shown in panel a.

Figure 3

Visible particles in shipped and lab dropped vials. Individual particles are counted up to 50 particles, if more than 50 particles are present TMC (too many to count) is recorded. Plates a and b were from shipping study trip 4, whereas plates c and d were after 40 drops in the laboratory from a height of 18 inches. Plate a: formulation with no polysorbate, plate b: formulation with 0.01% w/v polysorbate 80, place c: formulation with no polysorbate, plate d: formulation with 0.01% polysorbate 80.