Lamanna William C, Heller Katharina, Schneider Daniel, Guerrasio Raffaele, Hampl Veronika, Fritsch Cornelius, Schiestl Martin
1 Sandoz Biopharmaceuticals, Sandoz GmbH, Kundl, Austria.
2 Biopharmaceuticals Process and Product Development, Biologics Technical Development and Manufacturing, Novartis, Sandoz GmbH, Kundl, Austria.
J Oncol Pharm Pract. 2019 Mar;25(2):269-278. doi: 10.1177/1078155217731506. Epub 2017 Sep 26.
The purpose of this study was to evaluate the in-use physicochemical and biological stability of the Sandoz rituximab biosimilar, marketed under the trade names Rixathon® and Riximyo® in the European Union, upon preparation for intravenous infusion.
Three batches of Rixathon®/Riximyo® in the final month of their 36 month shelf life were exposed to room temperature and light for 14 days to recapitulate a major temperature excursion. Samples were diluted to the lowest allowable concentration of 1 mg/mL in 0.9% NaCl solution in either polypropylene or polyethylene infusion bags and stored for 14 or 30 days at 5 ± 3℃ followed by an additional 24 h at room temperature to simulate product handling. Samples stored in infusion bags were analyzed using SEC, CEX, non-reducing CE-SDS, peptide mapping and CDC to assess physicochemical and biological stability.
Analysis of Rixathon®/Riximyo® diluted to the lowest allowable concentration in 0.9% sodium chloride in either polypropylene or polyethylene infusion bags revealed no change in molecular weight variants, charge variants, deamidation, oxidation, overall composition or potency over a 31-day period.
Physicochemical and biological analyses demonstrate that Rixathon®/Riximyo® stability is not impacted by dilution and formulation conditions required for intravenous infusion, even under worst case conditions with regard to product shelf life, temperature excursion, light exposure, dilution factor and infusion bag storage time over a 31-day period.
本研究旨在评估欧盟市场上以商品名Rixathon®和Riximyo®销售的山德士利妥昔单抗生物类似药在制备静脉输注制剂时的使用中物理化学和生物学稳定性。
三批处于36个月保质期最后一个月的Rixathon®/Riximyo®在室温及光照条件下暴露14天，以模拟一次重大温度偏差。样品在聚丙烯或聚乙烯输液袋中用0.9%氯化钠溶液稀释至最低允许浓度1mg/mL，并在5±3℃下储存14或30天，随后在室温下再储存24小时，以模拟产品处理过程。使用尺寸排阻色谱（SEC）、阳离子交换色谱（CEX）、非还原毛细管电泳-十二烷基硫酸钠（CE-SDS）、肽图分析和细胞毒性试验（CDC）对储存在输液袋中的样品进行分析，以评估物理化学和生物学稳定性。
对在聚丙烯或聚乙烯输液袋中用0.9%氯化钠稀释至最低允许浓度的Rixathon®/Riximyo®进行分析，结果显示在31天内，其分子量变体、电荷变体、脱酰胺、氧化、总体组成或效价均无变化。
物理化学和生物学分析表明，即使在产品保质期、温度偏差、光照暴露、稀释倍数和输液袋储存时间等方面处于最坏情况的条件下，Rixathon®/Riximyo®的稳定性也不会受到静脉输注所需的稀释和制剂条件的影响，在31天内均保持稳定。
