Mueller Claudia, Dietel Elke, Heynen Severin R, Nalenz Heiko, Goldbach Pierre, Mahler Hanns-Christian, Schmidt Johannes, Grauschopf Ulla, Schoenhamnmer Karin
Int J Pharm Compd. 2015 May-Jun;19(3):261-7.
MabThera is an essential component of the standard-of-care regimens in the treatment of non-Hodgkin lymphoma and Chronic Lymphatic Leukemia. MabThera for subcutaneous injection is a novel line extension that has been approved by the European Medicines Agency for the treatment of patients with follicular lymphoma and diffuse large B-cell lymphoma. This study aimed to evaluate in-use stability data of MabThera subcutaneous drug-product solution in single-use syringes for subcutaneous administration according to the European Medicines Agency guideline. The drug-product solution was exposed to material contact surfaces of five different administration setups commonly used in subcutaneous drug delivery. MabThera subcutaneous was transferred under aseptic conditions into polypropylene and polycarbonate syringes and stored for 1, 2, and 4 weeks at 2°C to 8°C followed by 24 hours at 30°C. After storage, subcutaneous administration was simulated and MabThera subcutaneous drug-product solution quality attributes were evaluated by using compendial physico-chemical tests, as well as suitable and validated molecule- and formulation-specific analytical methods. MabThera subcutaneous vials were treated and analyzed in parallel. The physico-chemical results of MabThera subcutaneous in the different setups were comparable to the control for all timepoints. No change in drug-product quality after storage and simulated administration was found compared to the control. However, since single-dose products do not contain preservatives, microbial contamination and growth needs to be avoided and product sterility needs to be ensured. The results showed that MabThera subcutaneous remains compatible and stable, from a physico-chemical perspective, for up to 4 weeks at 2°C to 8°C followed by 24 hours at 30°C with the contact materials tested in this study. In order to avoid and minimize microbial growth, MabThera subcutaneous should be used immediately after removal from the original packaging container and strict aseptic handling conditions need to be followed.
美罗华是治疗非霍奇金淋巴瘤和慢性淋巴细胞白血病的标准治疗方案的重要组成部分。皮下注射用美罗华是一种新型的产品线扩展产品，已获欧洲药品管理局批准用于治疗滤泡性淋巴瘤和弥漫性大B细胞淋巴瘤患者。本研究旨在根据欧洲药品管理局指南评估皮下注射用美罗华药品溶液在一次性注射器中用于皮下给药时的使用稳定性数据。该药品溶液与皮下给药常用的五种不同给药装置的材料接触表面接触。皮下注射用美罗华在无菌条件下转移至聚丙烯和聚碳酸酯注射器中，在2℃至8℃下储存1、2和4周，随后在30℃下储存24小时。储存后，模拟皮下给药，并使用药典中的物理化学测试以及合适且经过验证的分子和制剂特异性分析方法评估皮下注射用美罗华药品溶液的质量属性。同时对皮下注射用美罗华小瓶进行处理和分析。在所有时间点，不同装置中皮下注射用美罗华的物理化学结果与对照相当。与对照相比，储存和模拟给药后未发现药品质量变化。然而，由于单剂量产品不含防腐剂，需要避免微生物污染和生长，并确保产品无菌。结果表明，从物理化学角度来看，皮下注射用美罗华在2℃至8℃下最多可稳定保存4周，随后在30℃下保存24小时，与本研究中测试的接触材料兼容。为避免和尽量减少微生物生长，皮下注射用美罗华应在从原包装容器中取出后立即使用，并需遵循严格的无菌操作条件。
