Abstract
Monoclonal antibodies (mAbs) are an important class of biotherapeutics; as of 2020, dozens are commercialized medicines, over a hundred are in clinical trials, and many more are in preclinical developmental stages. Therapeutic mAbs are sequence modified from the wild type IgG isoforms to varying extents and can have different intrinsic structural stability. For chronic treatments in particular, high concentration (≥ 100 mg/mL) aqueous formulations are often preferred for at-home administration with a syringe-based device. MAbs, like any globular protein, are amphiphilic and readily adsorb to interfaces, potentially causing structural deformation and even unfolding. Desorption of structurally perturbed mAbs is often hypothesized to promote aggregation, potentially leading to the formation of subvisible particles and visible precipitates. Since mAbs are exposed to numerous interfaces during biomanufacturing, storage and administration, many studies have examined mAb adsorption to different interfaces under various mitigation strategies. This review examines recent published literature focusing on adsorption of bioengineered mAbs under well-defined solution and surface conditions. The focus of this review is on understanding adsorption features driven by distinct antibody domains and on recent advances in establishing model interfaces suitable for high resolution surface measurements. Our summary highlights the need to further understand the relationship between mAb interfacial adsorption and desorption, solution aggregation, and product instability during fill-finish, transport, storage and administration.
Highlights
Introduction toProteins, Monoclonal Antibodies and AdsorptionProteins are polymers of amino acids that fold into well-defined local constructs such as helical strands, sheets and turns and three-dimensional (3D) structures
To generate octadecyl monolayer [73]. This is a mimic of a hydrophobic plastic surface and they showed generate octadecyl monolayer [73]. This is a mimic of a hydrophobic plastic surface and they showed that adsorption was greatly reduced at the hydrophobic surface with only 2 mg/m2 of Monoclonal antibodies (mAbs) adsorbed, that adsorption was greatly reduced at the hydrophobic surface with only 2 mg/m2 of mAb adsorbed, compared to around 5.5 mg/m2 on the bare SiO2 surface It was shown that standard polysorbate 80 (PS 80) could compared to around 5.5 mg/m2 on the bare SiO2 surface It was shown that standard PS 80 could displace roughly 50% of the adsorbed protein on the hydrophobic surface due to an interaction between displace roughly 50% of the adsorbed protein on the hydrophobic surface due to an interaction the fatty acid tail of the polysorbate and the modified surface
Structural changes have been observed from the work of lysozyme or bovine serum albumin highlights the power of neutron reflection to investigate the orientation of antibody adsorption in (BSA) adsorbed complex systems.to different types of stainless steel as well as therapeutic fusion proteins [43,80]
Summary
Biopharmaceuticals are highly versatile and over the past ten years or so, bioengineered proteins, especially monoclonal antibodies (mAbs), have emerged as important drugs in treating several major disease areas, including immune checkpoint inhibitors (immuno-oncology) and treatments for chronic diseases [1]. The design of mAbs rarely involves considerations for the effects of interfacial adsorption, to this end, products can sometimes face delays when incompatibilities between mAb and interfaces result in internal specification failures. Such failures can result in product batches being discarded, which is expensive and can delay important treatments to market. Studying mAb adsorption at interfaces where incompatibilities are detrimental to production could provide an insight in what is triggering unwanted aggregation, and this knowledge could be used to guide how therapeutics are formulated/designed to help prevent batch failures caused by material incompatibilities and related project delays. An outlook to future developments in interfacial science as applied to proteins will be provided
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