(T1430-08-48) Optimizing Biologics Formulation: Synthetic Sugars for Improved Stability and Viscosity

Purpose: High-concentration biologic formulations often face challenges related to elevated viscosity and protein instability, which can hinder manufacturability, reduce therapeutic efficacy, and affect patient comfort and compliance. Conventional viscosity-lowering excipients may compromise protein stability, particularly at higher concentrations, highlighting the need for more effective formulation strategies. This work explores the complex interplay between viscosity and stability in biologics development and emphasizes the need for novel excipients that can address both simultaneously. Here we present case studies demonstrating the potential of Hovione synthetic sugars to function as multifunctional excipients- reducing viscosity while enhancing protein stability and mitigating aggregation. These advances represent a promising step toward improving the performance, shelf life, and patient experience of biologic therapies.

Methods: Viscosity Measurements Commercial monoclonal antibody (mAb) formulations were reformulated in buffer and concentrated in the presence of Hovione synthetic sugars (100 mM) to a final concentration of 150 mg/mL. Viscosity measurements were performed using m-VROC™ technology (RheoSense, California, USA) at a shear rate of 3000 s⁻¹. Stability Studies High concentration protein formulations (150 mg/mL in buffer) were incubated at room temperature with 100 mM of Hovione synthetic sugars. At defined timepoints, aliquots were collected and analyzed for protein purity using SEC-HPLC.

Results: The viscosity-reducing potential of Hovione synthetic sugars was evaluated using high-concentration formulations of a monoclonal antibody (Evolocumab) and a fusion protein (Etanercept). For high concentration Etanercept formulations at 150 mg/mL and 100 mM excipient concentration, the synthetic sugar HSS202B significantly reduced viscosity, outperforming conventional excipients such as arginine. In Evolocumab formulations, Hovione synthetic sugars demonstrated a robust viscosity-lowering effect while maintaining protein stability over three months of storage at room temperature. High protein purity was retained, as confirmed by SEC-HPLC analysis, and stability was superior to that observed with arginine under identical conditions. These results highlight the dual functionality of Hovione synthetic sugars in improving both processability and long-term stability of biologic formulations.

Conclusion: These findings demonstrate that Hovione synthetic sugars offer a dual advantage by effectively reducing viscosity and enhancing protein stability in high-concentration biologic formulations. Their superior performance compared to conventional excipients such as arginine underscores their potential as valuable formulation tools for overcoming the challenges associated with next-generation biologics.

Figure 1. Viscosity-reducing effect of Hovione synthetic sugars at 100 mM. True viscosity of Etanercept (150 mg/mL) was measured at a shear rate of 3000 s⁻¹ and 25 °C.

Figure 2. Viscosity-reducing effect and Stabilizing effect of Hovione synthetic sugars at 100 mM. a) True viscosity of Evolocumab (150 mg/mL) was measured at a shear rate of 3000 s⁻¹ and 25 °C. b) Stability study of high concentrated Evolocumab solutions (150 mg/mL) in the presence of Hovione sugars at 100 mM over 3 month at rt (25 ºC).