Background Automated devices have recently come onto the market as an alternative to manual preparation of drugs for intravenous administration. Automated methods have so far been focused on rapid and time-saving procedures that might harm delicate substances such as monoclonal antibodies (mAbs). Many summaries of product characteristics (SmPCs) of mAbs state that they require gentle swirling to aid reconstitution and that drawing into a syringe should be done slowly.
Purpose To assess whether automated preparation can be performed with mAbs without affecting the aggregation state of the proteins.
Materials and Methods Three frequently used mAbs were studied: infliximab (Remicade) and trastuzumab (Herceptin) in lyophilised form, and bevacizumab (Avastin) as a liquid formulation. Brand names are mentioned because biosimilars exist. The effects of different procedures to prepare the patient doses on antibody aggregation were evaluated. Remicade and Herceptin were reconstituted both manually and by an automated arm (i.v.STATION, Health Robotics). Additionally, the effect of vigorous shaking during reconstitution was investigated. The effects of rapid aspiration and dispensing on antibody aggregation were investigated for all three mAbs. The aggregation state was assessed by UV-Vis absorbance, 90° light scatter, fluorescence spectroscopy, Nile red fluorescence microscopy, and field flow fractionation without cross and focus flow.
Results Samples reconstituted by an automated process showed similar findings compared to manual reconstitution if performed exactly according to the summary of product characteristics (SmPC). Vials that were shaken vigorously showed a significant increase in aggregates. Similarly, rapid aspiration/dispense cycles resulted in a strong increase in the number and sizes of aggregates for all three mAbs; this result was observed after just one rapid aspiration/dispense cycle.
Conclusions Our study showed that automated preparation of mAbs is feasible if the machine is programmed exactly according to the SmPC, indicating that automated preparation can be used to achieve reproducible high-quality preparation for delicate formulations.
No conflict of interest.
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