為什麽需要凍融工藝的步驟

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).

法規要求在製造，儲(chu) 存，運輸和交付給患者的過程中控製生物製藥產(chan) 品的質量（1）。 操作通常包括將原液冷凍和解凍，將純化後原液稀釋至目標濃度，過濾，灌裝到選定的封閉容器係統，額外工藝（例如，凍幹），檢查，包裝，儲(chu) 存，運輸和交付（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.

冷凍是用於(yu) 在生物製藥產(chan) 品的開發和生產(chan) 期間維持藥物的穩定性和質量的常見工藝步驟。 人們(men) 普遍認為(wei) ，通過將散裝原液生產(chan) 和儲(chu) 存步驟與(yu) 終成品過程分離，冷凍藥物大限度地提高了生產(chan) 率並降低了總體(ti) 生產(chan) 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.

通過批量處理，冷凍提供了靈活性、節約成本：可以批量冷凍大體(ti) 積昂貴的原液，以允許基於(yu) 實時商業(ye) 或臨(lin) 床需求來製造藥物產(chan) 品。 在藥品生產(chan) 之前冷凍藥物也降低了微生物生長風險並消除了運輸過程中的機械（攪動）壓力。

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，這可以延長保質期。 冷凍減緩化學降解（因為(wei) 反應動力學直接取決(jue) 於(yu) 溫度）和物理降解（固定藥物在冷凍基質中限製蛋白質間相互作用）（3-13）。 此外，凍融工藝的應用延伸到工藝中間體(ti) 的存儲(chu) ，允許製造操作之間更長的保持步驟。 雖然冷凍被認為(wei) 是一種保守的方法，但冷凍儲(chu) 存是有效和可靠的方法之一，可以大限度地減少蛋白質與(yu) 容器封閉物的相互作用，並延長生物製品在溶液型配方中的保質期（13）。