Metal-Induced Fatty Acid Particle Formation Resulting from Hydrolytic Polysorbate Degradation.

The occurrence of visible particles over the shelf-life of biopharmaceuticals is considered a potential safety risk for parenteral administration. In many cases, particle formation resulted from the accumulation of fatty acids released by the enzymatic hydrolysis of the polysorbate surfactant by co-purified host cell proteins. However, particle formation can occur before the accumulated fatty acids exceed their expected solubility limit.

Glass Leachables as a Nucleation Factor for Free Fatty Acid Particle Formation in Biopharmaceutical Formulations.

Surfactants are essential components in protein formulations protecting them against interfacial stress. One of the current industry-wide challenges is enzymatic degradation of parenteral surfactants such as polysorbate 20 (PS20) and polysorbate 80, which leads to the accumulation of free fatty acids (FFAs) potentially forming visible particles over the drug product shelf-life. While the concentration of FFAs can be quantified, the time point of particle formation remains unpredictable.