IMPACT OF ENVIRONMENTAL STRESS FACTORS ON THE STABILITY AND EFFICACY OF MONOCLONAL ANTIBODIES DURING REAL-LIFE PROCESSES IN AN ONCOLOGY REFERRAL CENTER

Monoclonal antibodies (mAbs) are biological drugs that are susceptible to environmental stresses, which may potentially compromise their physicochemical stability and therapeutic efficacy. [1] Although verifying physicochemical stability is a requirement for market authorization (ICH Q5C Guidelines), in real-world practice, variations in temperature, mechanical stress, and light exposure can negatively affect their quality. It is therefore necessary to monitor stress factors in order to implement operational solutions that improve the safety and efficacy of oncological therapies.To evaluate the effect of environmental stressors on biological drug infusion bags during handling, transport, and administration, in order to ensure their physicochemical stability and clinical efficacy. RESULTS Duplicate infusion bags were prepared using two of the most commonly used mAbs in clinical practice. For some of them, administration was scheduled at the site housing the compounding laboratory, while the other two bags were transported for 40 minutes and administered at a different location. Smart labels, applied from the very first step of formulation handling to monitor stress conditions—through preparation, transport, and administration with an exposure time simulating real clinical practice—indicate that both handling and transportation of mAb bags, as well as exposure to artificial/natural light during administration, represent critical phases for their stability and efficacy. Specifically, as an example, the graphs below show the light doses, expressed in lux, to which IV bags are exposed in the clinical practice setting. In these still preliminary results, it is clearly observable that: A) Light exposure is constant (average: 540 lux) during handling under the hood in the Antiblastic Drug Unit (UFA); B) During storage in the Alibox, light exposure drops drastically (average: 99 lux); C) During internal transport, the bag seems to be shielded from direct light for a certain period (average: 138 lux); D) During the premedication phase, when the bag is kept on the tray waiting for administration, light exposure is constant but lower than direct light under the hood (average: 334 lux); E) During patient administration on a rainy day, the bag receives a lower light dose (average: 185 lux) compared to a sunny day (average: 1330 lux) (F). These data will later be correlated with the impact of individual stress factors on the physicochemical stability and the preservation of the biological activity of therapeutic mAbs. DISCUSSION AND CONCLUSION C Real-time schedule on the day of mAb exposure Real-time schedule on the day of mAb exposure D F Real-time schedule on the day of mAb exposure Real-time schedule on the day of mAb exposure Confronted with the problem of safe product delivery to different care wards, many chemotherapeutic compounding units require full-time employees who are responsible for delivering the correct drug to the appropriate care service while ensuring that they are quickly supplied and correctly stored. The monitoring of stress factors using smart labels, aimed at future assessments of physicochemical stability and therapeutic activity, allows for the identification of critical issues at various stages throughout the real-life process of a mAb. This highlights the importance of raising awareness among healthcare professionals regarding handling, transport, and administration conditions to ensure optimal management of biological drugs and to promote the revision of current operational practices.REFERENCES 1. Le Basle Y, Chennell P, Tokhadze N, Astier A, Sautou V. Physicochemical Stability of Monoclonal Antibodies: A Review. J Pharm Sci. 2020;109(1):169-190. This work has received support from the EU/EFPIA Innovative Medicines Initiative Joint Undertaking (H2020-JTI-IMI2) RealHOPE grant n°101007939.