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Therapeutic proteins such as monoclonal antibodies (mAb) are known to form aggregates due to various factors. Phosphate buffered saline (PBS), human serum, and human serum filtrate (HSF) are some of the models used to analyze mAb stability in physiologically relevant in-vitro conditions. In this study, aggregation of mAb in PBS and models derived from body fluids seeded with mAb samples subjected to various stresses were compared. Samples containing mAb subjected to pH, temperature, UV light, stirring, and interfacial agitation stress were seeded into different models for 2 case studies. In the first case study, %HMW (high molecular weight species) of mAb in PBS and HSF were compared using size exclusion chromatography. It was found that change in %HMW was higher in PBS compared to HSF. For example, PBS containing mAb that was subjected to UV light stress showed change in HMW by >10 % over 72 h, but the change was <5 % in HSF. In second case study, aggregates particles of FITC tagged mAb were monitored in PBS and serum using fluorescence microscope image processing. It was found that PBS and serum containing mAb subjected to stirring and interfacial agitation resulted in aggregates of >2 µm size, and average size and percentage number of particles having >10 µm size was higher in serum compared to PBS at all analysis time point. Overall, it was found that aggregation of mAb in PBS was different from that in human body fluids. Second case study also showed the importance of advanced strategies for further characterization of mAb in serum., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)