Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, University of Munich, Butenandtstr. 5, 81377 Munich, Germany.
Sandoz Biopharmaceutics, Biochemiestr. 10, 6336 Langkampfen, Austria.
Eur J Pharm Biopharm. 2021 Mar;160:134-142. doi: 10.1016/j.ejpb.2021.01.006. Epub 2021 Jan 30.
Monoclonal antibodies (mAbs) are valuable tools both in therapy and in diagnostic. Their tendency to aggregate is a serious concern. Since a mAb drug substance (DS) is composed of different variants, it is important for manufacturers to know the behavior and stability not only of the mAb as a whole, but also of the variants contained in the product. We present a method to separate hydrophobicity variants of a mAb and subsequently analyzed these variants for stability and aggregation propensity. We identified a potentially aggregation prone hydrophilic variant which is interrelated with another previously identified aggregation prone acidic charge variant. Additionally, we assessed the risk posed by the aggregation prone variant to the DS by spiking hydrophobicity variants into DS and did not observe an enhanced aggregation propensity. Thus we present an approach to separate, characterize and analyze the criticality of aggregation prone variants in protein DS which is a step forward to further assure drug safety.
单克隆抗体 (mAb) 在治疗和诊断方面都是非常有价值的工具。它们容易聚集是一个严重的问题。由于单克隆抗体药物物质 (DS) 由不同的变体组成，因此制造商不仅要了解整个 mAb 的行为和稳定性，还要了解产品中包含的变体的行为和稳定性。我们提出了一种分离 mAb 的疏水性变体的方法，并随后分析了这些变体的稳定性和聚集倾向。我们鉴定了一种潜在的易聚集的亲水性变体，该变体与另一种先前鉴定的易聚集的酸性电荷变体有关。此外，我们通过将疏水性变体掺入 DS 中来评估易聚集变体对 DS 带来的风险，并未观察到聚集倾向增强。因此，我们提出了一种分离、表征和分析 DS 中易聚集变体关键性的方法，这是进一步确保药物安全性的重要一步。
