This Master thesis explores time dependence of monoclonal antibody charge variants specially as affected by different temperatures, and in relevance for biopharmaceutical drug development. Variants -- effectively, same protein, but with a different net charge -- emerge as acidic and basic, and differ from the main ones in the value of isoelectric point or net charge. Conversion of variants may influence quality and effectiveness of therapeutics, therefore the understanding of their transformation through time is crucial for a more efficient therapeutic development and production. High temperatures accelerate the degradation processes and allow for understanding the time variation of variants. I introduced effective models that describe the conversion of variants for the measurements obtained from typical stability studies and also include both reversible and irreversible conversions between variants. The best model to describe the given data turned out to be the one involving a reversible conversion from the main variants to the acidic and basic ones, whereas other models would require more accessible data. The model is well capable of time extrapolation of data, which gives us more appropriate results comparing to the ones obtained by linear extrapolation. Because the amount of data taken from typical (experimental) stability studies is limited, complex models give us only a rough estimate of the parameters. For a more accurate estimate, more data or an alternative, simpler model would be required. Model assuming only an irreversible conversion from the main to the acidic and basic variants is also successful, to a good degree. In the given formulations, the acid variants are temperature conditioned and their values increase more rapidly with increasing temperature, whereas the basic variants are not temperature dependent. Temperature dependence allows for the use of the Arrhenius equation, which relates the temperature dependence with the reaction rate constant. Based on the model results of irreversible conversion between variants, it was possible to determine the Arrhenius equation coefficients, which well describes the time dependence of temperature conditioned variants. More generally, this work is based on the use of physical and mathematical approaches for modelling of complex protein processes and is a contribution towards the world challenge of developing novel biological drugs.
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