Does transport through a pneumatic tube network affect the physicochemical stability of ready-to use infliximab bags ?

Philip Chennell , Nicolas Tokhadzé, Valérie Sautou
Université Clermont Auvergne, CHU Clermont-Ferrand, CNRS, SIGMA Clermont-Ferrand, ICCF, Clermont-Ferrand, France

Objectives
Monoclonal antibodies like infliximab are known to be sensitive to agitation induced stress, however little is known about their stability after transport through high velocity pneumatic tube networks which could be used to convey prepared infusion bags directly from the pharmacy to the clinical ward. This study therefore aimed to evaluate the physicochemical stability of solutions of infliximab after being shaken during transport through a pneumatic tube network

Methods
Biosimilar Infliximab CT-P13 (INFLECTRA®) solutions diluted to 0.4 mg/mL and 2 mg/mL in 0.9% NaCl in polyolefin bags were sent through an approximatively 200 m long pneumatic tube network. The solutions were subjected to the following analyses before and 2 hours after transit : visual inspection, turbidimetry, subvisible and nanoparticle counting, size exclusion chromatography, pH, osmolality measurement, cation exchange chromatography, second derivative Fourier Transform infrared, second derivative ultraviolet spectroscopy and total protein quantification.

Results
Transport time was of 1’45”. Most employed analytical techniques did not highlight any signs of infliximab instability for both concentration conditions. Formation of foam was noticed when sending 2 mg/mL infliximab solutions in NaCl bags through the pneumatic tube network, but not for the 0.4 mg/mL concentration. A significant increase in subvisibles particles was noted at 0.4 mg/mL when compared to pre-transport values, for particles ranging from 2-5 µm (702 particles/mL versus 172), 5-10 µm (405 particles/mL versus 89) and 10-25 µm (187 particles/mL versus 46). An increase was also noted for the 2 mg/mL bags, but of lesser magnitude. Size exclusion chromatography results also indicated an evolution in high molecular weight products, increasing to 0.81% and 0.93% after transport, up from 0.69% and 0.84% initially for respectively the 0.4 and 2 mg/mL concentrations

Discussion – Conclusion
No signs of chemical or secondary/tertiary structural instability were noted. Concerning physical stability, an increase in subvisible particles was noted, which could be linked to possible reversible and irreversible monoclonal antibody aggregation. 0.4 mg/mL bag volume were bigger (250mL) than the 2 mg/mL bags (100mL) and may induce an increase of the air-liquid and bag-liquid interface which could be the cause of the difference between the two concentrations. As infliximab solutions must be infused to the patient through a 1.2 μm or smaller pore diameter filter, the clinical impact of an increase in subvisibles particles might be limited, unless it leads to a decrease in infliximab concentration by retaining infliximab aggregates. Further studies evaluating the quantity of infliximab CT-P13 present after the inline filter should be performed to before any recommendation for use of a pneumatic tube network can be made.

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