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.

中文翻译：

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山德士 Rituximab 生物仿制药 Rixathon®/Riximyo® 在环境储存长达 21 天时的稳定性研究

目标

本研究的目的是评估山德士 Rixathon®/Riximyo® (SDZ-RTX) 在冰箱外 (OOF) 条件下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）暴露于 OOF 条件（I）25 ± 2 °C/60 ± 5，模拟了短期温度偏移对 SDZ-RTX 稳定性参数的影响% 相对湿度 (RH) 和 (II) 30 ± 2 °C/65 ± 5% RH，在长期条件 (5 ± 3 °C) 下超过声称的 36 个月保质期后最长 21 天）。使用的分析方法包括阳离子交换色谱 (CEX)、尺寸排阻色谱 (SEC) 和非还原性毛细管电泳-十二烷基硫酸钠 (nrCE-SDS)，以及补体依赖性细胞毒性 (CDC) 的生物活性-生物活性以及其他方法，例如与身份和药典测试方法相关的方法。

结果

在特性（电荷和一级结构）、药物测试（透明度、可见和亚可见颗粒分析、容器外观、着色程度、pH、渗透压、可提取体积和容器密封完整性测试）方面，所有批次均未观察到显着变化，在两种 OOF 条件下，UV 和微生物参数（无菌和细菌内毒素）的蛋白质含量。通过 SEC、CEX 和 nrCE-SDS 评估的参数仅观察到微小变化。对于效力（CDC-生物活性），只有一批显示出相关变化。即使对于这些稳定性指示测试方法，所有分析参数都符合保质期规格。

结论

SDZ-RTX 即使在最坏的情况下也可以安全使用，例如，在 OOF 条件下（25 ± 2 °C/60 ± 5% RH 或 30 ± 2 °C/65 ± 5 % RH) 在批次达到已经超过声称的保质期的年龄之后。