Protein Pharmaceutical Development, Biogen Inc., 225 Binney Street, Cambridge, Massachusetts 02142.
Protein Pharmaceutical Development, Biogen Inc., 225 Binney Street, Cambridge, Massachusetts 02142.
J Pharm Sci. 2017 Dec;106(12):3507-3514. doi: 10.1016/j.xphs.2017.08.016. Epub 2017 Aug 30.
Characterizing molecular charge variants or isoforms is essential for understanding safety, potency, and bioavailability of antibody therapeutics. However, there is little information on how they influence stability and viscosity-properties governing immunogenicity and delivery. To bridge this gap, we studied antibody stability as a function of charge variant content generated via bioreactor process. We were able to systematically vary acidic variant levels as a function of bioreactor harvest time. Importantly, we do not observe any impact on aggregation behavior of a formulated antibody at high protein concentration as a function of acidic variant level. Furthermore, we confirm that acidic variants enriched using fractionation do not influence viscosity, colloidal or conformational stability. Interestingly, variants with the most acidic isoelectric points contribute disproportionately to formulation color. We discuss our findings in context of antibody manufacturing processes that may yield increased charge variant content.
表征分子电荷变体或同种型对于理解抗体治疗药物的安全性、效力和生物利用度至关重要。然而，关于它们如何影响稳定性和粘度——影响免疫原性和递药的特性——的信息却很少。为了弥补这一空白，我们研究了作为通过生物反应器工艺产生的电荷变体含量的函数的抗体稳定性。我们能够系统地将酸性变体水平作为生物反应器收获时间的函数进行变化。重要的是，我们没有观察到作为酸性变体水平函数的高蛋白质浓度下制剂抗体的聚集行为有任何影响。此外，我们证实使用分级分离富集的酸性变体不会影响粘度、胶体或构象稳定性。有趣的是，等电点最酸的变体不成比例地影响制剂颜色。我们在可能产生增加的电荷变体含量的抗体制造工艺的背景下讨论我们的发现。
