Jiskoot W, Hawe Andrea, Menzen Tim, Volkin David B, Crommelin Daan J A
Coriolis Pharma Research GmbH, Fraunhoferstr. 18 b, 82152 Martinsried, Germany; Leiden Academic Center for Drug Research (LACDR), Leiden University, 2300 RA Leiden, the Netherlands.
Coriolis Pharma Research GmbH, Fraunhoferstr. 18 b, 82152 Martinsried, Germany.
J Pharm Sci. 2022 Apr;111(4):861-867. doi: 10.1016/j.xphs.2021.11.008. Epub 2021 Nov 20.
Although many subcutaneously (s.c.) delivered, high-concentration antibody formulations (HCAF) have received regulatory approval and are widely used commercially, formulation scientists are still presented with many ongoing challenges during HCAF development with new mAb and mAb-based candidates. Depending on the specific physicochemical and biological properties of a particular mAb-based molecule, such challenges vary from pharmaceutical attributes e.g., stability, viscosity, manufacturability, to clinical performance e.g., bioavailability, immunogenicity, and finally to patient experience e.g., preference for s.c. vs. intravenous delivery and/or preferred interactions with health-care professionals. This commentary focuses on one key formulation obstacle encountered during HCAF development: how to maximize the dose of the drug? We examine methodologies for increasing the protein concentration, increasing the volume delivered, or combining both approaches together. We discuss commonly encountered hurdles, i.e., physical protein instability and solution volume limitations, and we provide recommendations to formulation scientists to facilitate their development of s.c. administered HCAF with new mAb-based product candidates.
尽管许多皮下（s.c.）给药的高浓度抗体制剂（HCAF）已获得监管批准并在商业上广泛使用，但在开发基于新单克隆抗体（mAb）和基于mAb的候选药物的HCAF过程中，制剂科学家仍面临许多持续的挑战。根据特定基于mAb分子的具体物理化学和生物学特性，这些挑战各不相同，从药物属性（如稳定性、粘度、可制造性）到临床性能（如生物利用度、免疫原性），最后到患者体验（如对皮下给药与静脉给药的偏好和/或与医护人员的首选互动）。本评论聚焦于HCAF开发过程中遇到的一个关键制剂障碍：如何最大化药物剂量？我们研究了增加蛋白质浓度、增加给药体积或两者结合的方法。我们讨论了常见的障碍，即蛋白质物理稳定性和溶液体积限制，并为制剂科学家提供建议，以促进他们开发基于新mAb的候选产品的皮下给药HCAF。
