Therapeutic monoclonal antibodies are the fastest growing class of active pharmaceutical ingredients, but face several challenges, such as the instability of monoclonal antibodies and the high viscosity of the formulation. The development of highly concentrated formulations requires the selection of appropriate excipients that maintain stability during manufacture, transport and storage, while reducing viscosity for effective injection into subcutaneous tissue.
In the context of the MSc thesis, we have designed a formulation for the incorporation of a monoclonal antibody using an appropriate combination of buffer, stabilizer and surfactant. The effect of the monoclonal antibody concentration on the viscosity of the formulation was investigated, and an exponential increase in the viscosity of the formulation with increasing monoclonal antibody concentration was observed. Formulations with concentrations up to 150 mg/mL maintained a suitable viscosity for subcutaneous administration (20 mPas), while further increases in concentration resulted in a marked increase in viscosity. In the next step of the task, we wanted to define excipients that would effectively lower the viscosity of the formulation. The selection of the tested compounds to be included in the study was based on a previous study on the effect of these compounds on the viscosity reduction of solutions of monoclonal antibodies in water. We tested the effect of arginine, proline and 11 new testing compounds on the viscosity reduction of the monoclonal antibody formulation. All tested compounds are proline mimetics. TS1, TS2, TS3, TS4, TS5, TS6, TS8 and TS11 were evaluated as effective viscosity lowering compounds for monoclonal antibody formulations as they have a relative viscosity lowering effect lower than 0,64 (relative effect of proline). In accelerated stability testing at 40 °C and 75% humidity in climate chambers and at 4 °C in a refrigerator, it was observed that compounds TS2, TS5 and TS7 are effective in stabilizing the monoclonal antibody. In general, however, the model monoclonal antibody is more susceptible to aggregation and fragmentation at higher temperatures and therefore storage of the model monoclonal antibody formulation at a reduced temperature, more specifically in a refrigerator at 4 °C, is necessary.
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