Regeneron Pharmaceuticals Inc., Formulation Development, 777 Old Saw Mill River Road, Tarrytown, New York, NY 10591, USA.
Regeneron Pharmaceuticals Inc., Formulation Development, 777 Old Saw Mill River Road, Tarrytown, New York, NY 10591, USA.
J Pharm Sci. 2023 Dec;112(12):3045-3055. doi: 10.1016/j.xphs.2023.08.020. Epub 2023 Aug 27.
Host-cell lipases can be present in monoclonal antibody drug products and can degrade polysorbates present in the formulations as stabilizers. We hypothesized that the in-use stability of the IV admixture prepared from such a drug product might be impacted by decreasing levels of polysorbate 20. Host-cell lipase activity has, in fact, been observed during development of one of our therapeutic monoclonal antibody drug products. Throughout the course of the product shelf life, polysorbate 20 levels decreased but no other quality attributes of the drug product were impacted. An experimental approach was developed to simulate how the prepared IV admixture in-use stability is affected as polysorbate 20 concentration in the drug product decreased over the shelf life, and from that a minimum level of polysorbate 20 required in the drug product was determined to estimate the in-use stability of the IV admixture as the polysorbate 20 in the drug product degrades. The results indicate that although the observed degradation of polysorbate 20 does not affect quality attributes of this drug product, in-use stability of the IV admixture as a function of polysorbate degradation can be impacted and should be assessed to ensure sufficient quality.
宿主细胞脂肪酶可能存在于单克隆抗体药物产品中，并可降解制剂中作为稳定剂的聚山梨酯。我们假设，从这种药物产品制备的 IV 混合物的使用稳定性可能会受到聚山梨酯 20 水平降低的影响。事实上，在我们的一种治疗性单克隆抗体药物产品的开发过程中已经观察到了宿主细胞脂肪酶的活性。在整个产品货架期内，聚山梨酯 20 的水平下降，但药物产品的其他质量属性没有受到影响。开发了一种实验方法来模拟随着药物产品货架期内聚山梨酯 20 浓度的降低，制备的 IV 混合物的使用稳定性如何受到影响，并由此确定药物产品中所需的最低聚山梨酯 20 水平，以估计药物产品中聚山梨酯 20 降解时 IV 混合物的使用稳定性。结果表明，尽管观察到聚山梨酯 20 的降解不会影响该药物产品的质量属性，但作为聚山梨酯降解的函数，IV 混合物的使用稳定性可能会受到影响，应进行评估以确保足够的质量。
