Mohnicke Mandy, Blecher Arnd, Beichert Kathrin, Bidlingmaier Bernd, Todt Ernst-Josef, Dette Christoph, Rotthaeuser Baerbel, Mukherjee Bhaswati
Sanofi, Industriepark Höchst, 65926, Frankfurt am Main, 65926, Germany.
Sanofi, Industriepark Höchst, 65926, Frankfurt am Main, 65926, Germany.
J Pharm Sci. 2023 Apr;112(4):963-973. doi: 10.1016/j.xphs.2022.12.006. Epub 2022 Dec 13.
SAR341402 (Insulin aspart Sanofi®) is an insulin aspart biosimilar that can be used for continuous subcutaneous insulin infusion (CSII) in pump systems. The physicochemical stability of SAR341402 for CSII use was evaluated in several in vitro experiments. Insulin aspart products (SAR341402, NovoLog®, NovoRapid®) were filled into pump reservoirs and pumped through Medtronic insulin pumps (MiniMed 530G-Model 751, Medtronic, Northridge, CA) and their related infusion sets under simulated stress conditions, including elevated temperature and mechanical agitation on a continuously vibrating platform, up to 13 days. Samples pumped through the infusion sets and retained in reservoirs (non-pumped) were analyzed using suitable analytical methods. All products showed stable insulin aspart content and no unwanted impurities. Minor pH changes were seen in all products but were not considered relevant. A time-dependent increase in high-molecular-weight proteins and largest other insulin aspart impurities was observed for each product but each remained within acceptance limits. Concentrations of phenol and metacresol decreased but remained at levels to ensure preservative efficacy. Samples collected from the infusion sets were clear of visible particles and showed comparable subvisible particle counts. No occlusion events were observed. Leachable profiles from pump and reservoir samples were similar in all product batches. Like NovoLog®/NovoRapid®, SAR341402 demonstrates appropriate physicochemical stability when used in these insulin pump systems.
SAR341402（赛诺菲®门冬胰岛素）是一种门冬胰岛素生物类似药，可用于泵系统中的持续皮下胰岛素输注（CSII）。通过多项体外实验评估了用于CSII的SAR341402的物理化学稳定性。将门冬胰岛素产品（SAR341402、诺和锐®、诺和锐特充®）装入泵储液器，并在模拟应激条件下通过美敦力胰岛素泵（MiniMed 530G - 751型号，美敦力公司，加利福尼亚州北岭）及其相关输注装置进行泵送，模拟应激条件包括高温以及在持续振动平台上的机械搅拌，最长持续13天。使用合适的分析方法对通过输注装置泵送并保留在储液器中的样品（未泵送）进行分析。所有产品的门冬胰岛素含量均稳定，且未出现有害杂质。所有产品均出现了轻微的pH值变化，但认为无关紧要。观察到每种产品的高分子量蛋白质和其他最大的门冬胰岛素杂质随时间增加，但均保持在可接受范围内。苯酚和间甲酚的浓度降低，但仍保持在确保防腐效果的水平。从输注装置收集的样品没有可见颗粒，亚可见颗粒计数相当。未观察到堵塞事件。所有产品批次的泵和储液器样品的可提取物概况相似。与诺和锐®/诺和锐特充®一样，SAR341402在这些胰岛素泵系统中使用时表现出适当的物理化学稳定性。
