Werner R G, Langlouis-Gau H, Walz F, Allgaier H, Hoffmann H
Dr. Karl Thomae GmbH, Bioengineering Techniques, Biberach an der Riss, Fed. Rep. of Germany.
Arzneimittelforschung. 1988 Jun;38(6):855-62.
Due to the biological synthesis of biotechnologically produced pharmaceuticals the product quality and safety of the drug is influenced by various factors. The correct nucleotide sequence and stability of the host cell/vector system provide the corresponding amino acid sequence of the protein. The posttranslational processing of the protein requires a well characterized production cell line. Suitable equipment for fermentation allowing a sterile production of the producing monoculture and consistent conditions are the basic requirements for the validation of the fermentation process. A constant specific productivity is one of the major criteria for the reproducibility of the production. For the validation of recovery and purification it is necessary to examine yield after each process step, product quality before and after each single process step and purification factors for removal of contaminating proteins, nucleic acids and potential viruses. In addition to the validation of the entire production process, reproducibility of quality of the formulated product has to be determined by a number of protein analytical, immunological and biochemical test methods concerning the identity, purity, safety and potency of the drug.
由于生物技术生产的药物是通过生物合成的，药物的产品质量和安全性受到多种因素的影响。宿主细胞/载体系统的正确核苷酸序列和稳定性决定了蛋白质相应的氨基酸序列。蛋白质的翻译后加工需要一个特性明确的生产细胞系。用于发酵的合适设备，能够实现生产单培养物的无菌生产以及条件的一致性，这是发酵过程验证的基本要求。恒定的比生产率是生产可重复性的主要标准之一。为了验证回收和纯化过程，有必要检查每个工艺步骤后的产量、每个单一工艺步骤前后的产品质量以及去除污染蛋白质、核酸和潜在病毒的纯化因子。除了对整个生产过程进行验证外，还必须通过一些关于药物的同一性、纯度、安全性和效力的蛋白质分析、免疫和生化测试方法来确定制剂产品质量的可重复性。
