Understanding how exposure to drone-induced vibration during transportation affects the quality of a monoclonal...

Therapeutic monoclonal antibodies essential for cancer treatments, are sensitive biomolecules requiring reconstitution in infusion bags, and administration within hours. While drone transportation presents a promising solution for reaching remote healthcare facilities, it introduces mechanical stresses that can compromise mAb stability, leading to protein unfolding and aggregation. This study aimed to evaluate the stability of reconstituted Opdivo® (nivolumab) across vibrations modelling flight. Two different reciprocating shakers were used to simulate predominant frequencies of drone-induced vibrations in a controlled laboratory setting, employing analytical techniques (UV, DLS & SE-HPLC) to assess critical parameters and support the development of risk assessments for drone transportation. Nivolumab infusions remained stable under simulated drone vibrations, with all quality attributes meeting acceptance criteria. Samples exposed to varying frequencies 8, 63, 125 Hz for 30 min; 63 Hz for 1, 2, 3 h; a 43-minute drone flight, and prepared at different concentrations (0.48, 0.86, 1.24 mg/mL) showed no significant differences from controls. Two of the three samples subjected to 125 Hz vibration for 30 min exhibited a minor increase in monomer content (≤0.16 %, p = 0.003) on Day 2, accompanied by a 3 nm reduction in particle size. However, these changes remained within pharmaceutically acceptable limits and showed no evidence of functional compromise compared to controls. The particle size shift dissipated after 24 h of storage, suggesting a reversible, vibration-induced dissociation of oligomeric species. Understanding, the impact of flight on product characteristics and stability is important. The results show that Opdivo® is not affected by the vibrations generated by the various stages of drone flight. This paper establishes a reproducible framework for evaluating monoclonal antibody stability under simulated transport conditions, contributing to the development of safer and more efficient delivery methods in cancer care.