Not the Usual Suspects: Alternative Surfactants for Biopharmaceuticals

Area of Science:

• Biopharmaceutical formulation
• Protein aggregation and stabilization
• Surfactant chemistry

Background:

• Therapeutic proteins can aggregate at interfaces, leading to loss of activity and immunogenicity.
• Current biotherapeutics rely on limited surfactants like polysorbates (PS20/80) and poloxamer 188, which have degradation and impurity issues.
• These issues increase risks of particle generation, protein degradation, and adverse immune reactions.

Purpose of the Study:

• To identify and screen alternative surfactants for biotherapeutics.
• To evaluate surfactant efficacy in preventing protein aggregation and degradation.
• To assess the chemical and enzymatic stability of candidate surfactants.

Main Methods:

• Screened 40 alternative surfactant candidates across four protein modalities and six formulations.
• Employed a three-gate screening process including agitation-induced aggregation, particle analysis, and surface tension measurements.
• Conducted long-term stability studies assessing protein purity and particle formation, followed by degradation propensity analysis.

Main Results:

• Identified novel alpha-tocopherol derivatives, VEDG-2.2 and VEDS, as promising alternative surfactants.
• These candidates demonstrated protein stabilization comparable or superior to polysorbates.
• VEDG-2.2 and VEDS exhibited enhanced resistance to chemical and enzymatic degradation.

Conclusions:

• VEDG-2.2 and VEDS represent valuable alternatives to current surfactants in biotherapeutics.
• These novel surfactants offer improved stability and reduced degradation, mitigating risks associated with protein aggregation.
• The findings support the development of safer and more effective biopharmaceutical formulations.