Accumulation on surfaces is a big problem for protein drug makers. Such interactions impact drug efficacy and stability and can result in the formation of aggregates that provoke dangerous allergic reactions.
Combating this accumulation, also known as adsorption, has long been a focus for developers. However, according to scientists at the University of Cork in Ireland, most efforts have focused on understanding the process, rather than looking at it in a manufacturing context.
“There have been considerable advancements in elucidating the specific mechanisms that govern protein adsorption behavior, leading to an increased understanding of how intrinsic and external factors affect adsorption characteristics.
“However, the impact of protein-formulation interactions on protein adsorption behavior during key processing steps such as filtration, fill pumping, and storage is an area of active interest owing to the complex interactions and the implications for product stability,” they write.
Technology suppliers also need to do more to examine how the materials from which their bioprocessing systems are made impact protein adsorption.
The authors write that “inadequate consideration of the surface properties of manufacturing and storage materials, specifically, surface hydrophobicity and charge, can lead to surface-induced conformational and colloidal instability.”
“Opportunity exists for the development and optimization of fill pumping units, tubing types, packaging materials, surface coatings, and most importantly, the introduction of novel excipients,” they add.
Excipients
Excipients also play a part in determining whether a protein will stick to surfaces during the manufacturing process. Yet again, according to the authors, not enough is being done to fully understand these interactions.
“Understanding how excipients influence inherent protein characteristics, including their adsorption behavior, enables the development of formulations that effectively control this phenomenon during biomanufacture and, critically, during storage.
“Protein adsorption behavior can be influenced by the effects of poor excipient stability and formulation design, including excipient-surface incompatibility, creating environments favorable for interfacial adsorption and protein instability,” they write.
Downstream
Adsorption during downstream operations is another area where more analysis is needed.
“Therapeutic proteins are exposed to considerable stresses during production, including interfacial stress, which is widely recognized as a driving force for protein unfolding, aggregation, and particle formation.
“Therefore, to minimize the impact of protein adsorption on stability during downstream manufacture and storage, it is important to carefully control the conditions under which the protein is processed and stored,” the authors write.
Drug design
Fully understanding how each of these factors influences adsorption, rather than just the mechanics of the process, is a must for industry, and the knowledge should inform everything from drug design through to formulation and storage, the authors conclude.
“It is imperative in the design of biotherapeutic products to consider the impact of interfacial stress and the interplay between protein stability and formulation.
“Additionally, there is strong evidence for the rational selection of buffer and tonicifier salts to control adsorption and stability, particularly during storage,” they write.
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