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为什么需要冻融工艺的步骤

时间:2019-08-05 浏览次数:238

Regulations mandate that biopharmaceutical product quality be controlled throughout manufacturing, storage, transportation, and delivery to patients (1). Operations often include freezing and thawing of a bulk drug substance, dilution of that purified substance to a target concentration, filtration, filling into a selected container–closure system, additional processing (e.g., lyophilization), inspection, packaging, storage, transport, and delivery (2).

法规要求在制造,储存,运输和交付给患者的过程中控制生物制药产品的质量(1)。 操作通常包括将原液冷冻和解冻,将纯化后原液稀释至目标浓度,过滤,灌装到选定的封闭容器系统,额外工艺(例如,冻干),检查,包装,储存,运输和交付(2

Freezing is a common processing step used to maintain stability and quality of a drug substance during development and production of biopharmaceutical products. It is generally agreed upon that freezing drug substance maximizes productivity and reduces overall production costs by decoupling bulk solution manufacture and storage steps from final product manufacture.

冷冻是用于在生物制药产品的开发和生产期间维持药物的稳定性和质量的常见工艺步骤。 人们普遍认为,通过将散装原液生产和储存步骤与终成品过程分离,冷冻药物大限度地提高了生产率并降低了总体生产成本。

Freezing provides flexibility and cost savings by enabling batch processing: Large volumes of an expensive biological drug substance can be frozen in batches to allow the drug product to be manufactured based on real-time commercial or clinical demands. Freezing a drug substance before drug product manufacture also reduces microbial growth risk and eliminates mechanical (agitation) stresses during transportation.

通过批量处理,冷冻提供了灵活性、节约成本:可以批量冷冻大体积昂贵的原液,以允许基于实时商业或临床需求来制造药物产品。 在药品生产之前冷冻药物也降低了微生物生长风险并消除了运输过程中的机械(搅动)压力。

Most important, this allows for a longer shelf life. Freezing decelerates chemical degradation (because reaction kinetics depend directly on temperature) and physical degradation (immobilizing drug substance in a frozen matrix limits protein–protein interactions) (3–13). Furthermore, application of freeze–thaw processes extends to storage of process intermediates, allowing for longer hold steps between manufacturing operations. Although freezing is considered to be a conservative approach, frozen storage is one of the most efficient and reliable methods to minimize protein interactions with container–closures and extend the shelf life of biological products in solution-based formulations (13).

重要的是,这可以延长保质期。 冷冻减缓化学降解(因为反应动力学直接取决于温度)和物理降解(固定药物在冷冻基质中限制蛋白质间相互作用)(3-13)。 此外,冻融工艺的应用延伸到工艺中间体的存储,允许制造操作之间更长的保持步骤。 虽然冷冻被认为是一种保守的方法,但冷冻储存是有效和可靠的方法之一,可以大限度地减少蛋白质与容器封闭物的相互作用,并延长生物制品在溶液型配方中的保质期(13)。

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