Analytical Research and Development, Merck & Co., Inc., Rahway, NJ 07065, United States.
Pharmaceutical Sciences and Clinical Supply, Merck & Co., Inc., Rahway, NJ 07065, United States.
J Pharm Sci. 2024 May;113(5):1330-1338. doi: 10.1016/j.xphs.2023.12.014. Epub 2023 Dec 17.
Formulation screening, essential for assessing the impact of physical, chemical, and mechanical stresses on protein stability, plays a critical role in biologics drug product development. This research introduces a Reciprocal Injection Device (RID) designed to accelerate formulation screening by probing protein stability under intensified stress conditions within prefilled syringes. This versatile device is designed to accommodate a broad spectrum of injection parameters and diverse syringe dimensions. A commercial drug product was employed as a model monoclonal antibody formulation. Our findings effectively highlight the efficacy of the RID in assessing concentration-dependent protein stability. This device exhibits significant potential to amplify the influences of interfacial interactions, such as those with buffer salts, excipients, air, metals, and silicone oils, commonly found in combination drug products, and to evaluate the protein stability under varied stresses.
制剂筛选对于评估物理、化学和机械应力对蛋白质稳定性的影响至关重要，是生物制品药物产品开发的关键环节。本研究介绍了一种往复注射装置（RID），旨在通过在预装注射器中探测强化条件下的蛋白质稳定性来加速制剂筛选。该多功能装置可适应广泛的注射参数和不同的注射器尺寸。采用一种商业药物产品作为模型单克隆抗体制剂。我们的研究结果有效突出了 RID 在评估浓度依赖性蛋白质稳定性方面的功效。该设备具有显著的潜力，可以放大界面相互作用的影响，如与缓冲盐、赋形剂、空气、金属和硅油的相互作用，这些相互作用通常存在于组合药物产品中，并评估在不同应激条件下的蛋白质稳定性。
