Purpose <p>Therapeutic monoclonal antibodies (mAbs) are prone to degradation via&#xa0;aggregation and fragmentation. In this study, forced degradation of trastuzumab (TmAb) was explored in saline and <i>in-vitro</i> models having H₂O₂ and exposed to UV light (case study 1)_, both bleomycin (BML) formulation and ferrous ions (Fe²⁺) (case study 2)_, and sodium hypochlorite (NaOCl) (case study 3).</p> Methods <p>Size exclusion chromatography, dynamic light scattering, spectroscopic analysis, and fluorescence microscope image processing was carried out for characterizing TmAb degradation.</p> Results <p>Saline samples containing TmAb and 0.1% H₂O₂ incubated at 40ºC for 1&#xa0;h in the presence of UV light showed increased monomer loss by more than 40% compared to TmAb sample without H₂O₂ exposed to UV light. Saline containing TmAb having both 0.1-unit BML and 0.25&#xa0;mM Fe²⁺ showed increased monomer loss by more than 50% compared to TmAb in saline having only Fe²⁺ or BML. A higher&#xa0;TmAb degradation was also observed in saline containing 0.01% NaOCl compared to saline without NaOCl. Samples containing aggregates of mAb showed altered protein structure. Degradation of TmAb in saline increased with time, temperature, and concentrations of H₂O₂, Fe²⁺_, and NaOCl. At different analysis time points, TmAb monomer loss was higher in saline compared to human serum filtrate, an <i>in-vitro</i> model. Aggregate particles (&gt; 2&#xa0;µm size) of TmAb were also observed in serum containing both Fe²⁺ and BML.</p> Conclusion <p>It can be concluded that rapid TmAb degradation significantly enhanced due to various stress factors, and the aggregates could&#xa0;result in enhanced immunogenic risk to the patients.</p>