山德士利妥昔单抗生物仿制药Rixathon®/Riximyo®在环境储存长达21天时的稳定性研究

IF 2.2 4区医学 Q3 PHARMACOLOGY & PHARMACY Drugs in Research & Development Pub Date : 2022-09-01 Epub Date: 2022-08-07 DOI:10.1007/s40268-022-00393-4

Roman Borišek, André Mischo, Ida Šmid

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引用次数: 1

摘要

目的:本研究的目的是评估山德士Rixathon®/Riximyo®(SDZ-RTX)在冰箱外(OOF)条件下暴露后的扩展物理化学和生物稳定性。材料和方法:通过随后将三批SDZ-RTX(100和500 mg)暴露在(I) 25±2°C/60±5%相对湿度(RH)和(II) 30±2°C/65±5% RH的OOF条件下(5±3°C)，模拟短期温度偏移对SDZ-RTX稳定性参数的影响，在超过声称的36个月保质期的长期条件下(5±3°C)储存长达21天。所用的分析方法包括阳离子交换色谱法(CEX)、粒径排除色谱法(SEC)和非还原性毛细管电泳法-十二烷基硫酸钠(nrCE-SDS)，以及补体依赖性细胞毒性法(CDC)-生物活性法以及其他方法，例如与鉴定和药典测试方法相关的方法。结果:在两种OOF条件下，所有批次在鉴定(电荷和初级结构)、药物测试(透明度、可见和不可见颗粒分析、容器外观、着色程度、pH、渗透压、可提取体积和容器封闭完整性测试)、紫外线测定的蛋白质含量和微生物参数(无菌性和细菌内毒素)方面均未观察到显著变化。通过SEC、CEX和nrCE-SDS评估的参数仅观察到微小的变化。效力(cdc -生物活性)只有一个批次显示相关变化。即使对于这些稳定性指示测试方法，所有分析的参数都符合保质期规范。结论:即使在最恶劣的条件下，SDZ-RTX也可以安全使用，例如，在批次达到保质期后，在OOF条件下(25±2°C/60±5% RH或30±2°C/65±5% RH)放置长达21天。

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Study of the Stability of Sandoz Rituximab Biosimilar Rixathon^®/Riximyo^® When Subjected for up to 21 Days to Ambient Storage.

Aim: The purpose of this study was to evaluate the extended physicochemical and biological stability of Sandoz Rixathon®/Riximyo® (SDZ-RTX) after exposure to out-of-fridge (OOF) conditions.

Materials and methods: The impact of the short-term temperature excursion on stability parameters of SDZ-RTX was simulated by subsequently exposing the three batches of SDZ-RTX (100 and 500 mg) to OOF conditions, (I) 25 ± 2 °C/60 ± 5% relative humidity (RH) and (II) 30 ± 2 °C/65 ± 5% RH, for up to 21 days after more than the claimed 36-month shelf-life storage in long-term conditions (5 ± 3 °C). Analytical methods used included the cation exchange chromatography (CEX), size exclusion chromatography (SEC), and non-reducing capillary electrophoresis-sodium dodecyl sulfate (nrCE-SDS), as well as biological activity by complement-dependent cytotoxicity (CDC)-bioactivity as well as further methods, for example, related to identity and pharmacopoeia test methods.

Results: No notable changes were observed across all batches with respect to identity (charge and primary structure), pharmaceutical tests (clarity, visible and subvisible particles analytics, container appearance, degree of coloration, pH, osmolality, extractable volume, and container closure integrity testing), protein content by UV and microbiological parameters (sterility and bacterial endotoxins) under both OOF conditions. Only minor changes were observed for parameters evaluated via SEC, CEX, and nrCE-SDS. For potency (CDC-bioactivity) only one of the batches showed a relevant change. Even for these stability-indicating test methods, all analyzed parameters complied with the shelf-life specifications.

Conclusion: SDZ-RTX is safe for use even under worst-case conditions, for example, after subjecting it for up to 21 days at OOF conditions (25 ± 2 °C/60 ± 5% RH or 30 ± 2 °C/65 ± 5% RH) after the batches had reached an age that was already beyond the claimed shelf-life.

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来源期刊

Drugs in Research & Development Pharmacology, Toxicology and Pharmaceutics-Pharmacology

CiteScore

5.10

自引率

0.00%

发文量

审稿时长

8 weeks

期刊介绍： Drugs in R&D is an international, peer reviewed, open access, online only journal, and provides timely information from all phases of drug research and development that will inform clinical practice. Healthcare decision makers are thus provided with knowledge about the developing place of a drug in therapy. The Journal includes: Clinical research on new and established drugs; Preclinical research of direct relevance to clinical drug development; Short communications and case study reports that meet the above criteria will also be considered; Reviews may also be considered.