Silicone-oil-based subvisible particles: their detection, interactions, and regulation in prefilled container closure systems for biopharmaceuticals.

Recent increased regulatory scrutiny concerning subvisible particulates (SbVPs) in parenteral formulations of biologics has led to the publication of numerous articles about the sources, characteristics, implications, and approaches to monitoring and detecting SbVPs. Despite varying opinions on the level of associated risks and method of regulation, nearly all industry scientists and regulators agree on the need for monitoring and reporting visible and subvisible particles. As prefillable drug delivery systems have become a prominent packaging option, silicone oil, a common primary packaging lubricant, may play a role in the appearance of particles.

Effect of thermal stability on protein adsorption to silica using homologous aldo-keto reductases.

Gaining more insight into the mechanisms governing the behavior of proteins at solid/liquid interfaces is particularly relevant in the interaction of high-value biologics with storage and delivery device surfaces, where adsorption-induced conformational changes may dramatically affect biocompatibility. The impact of structural stability on interfacial behavior has been previously investigated by engineering nonwild-type stability mutants. Potential shortcomings of such approaches include only modest changes in thermostability, and the introduction of changes in the topology of the proteins when disulfide bonds are incorporated.

Reversibility of the adsorption of lysozyme on silica.

A central paradigm that underpins our understanding of the interaction of proteins with solid surfaces is that protein adsorption leads to changes in secondary structure. The bound proteins tend to denature, and these non-native, adsorbed structures are likely stabilized through the loss of α-helices with the concomitant formation of intermolecular β-sheets. The goal of this work is to critically assess the impact this behavior has on protein desorption, where irreversible conformational changes might lead to protein aggregation or result in other forms of instability.