Lubiniecki A S
SmithKline Beecham Pharmaceuticals, King of Prussia PA, USA.
Dev Biol Stand. 1996;88:9-11.
Viral contaminants are less amenable then chemical contaminants to analytical detection due to the lower sensitivity, specificity and precision of existing assays. In combination with the potential for biological amplification of viral contaminants in cell substrates or product recipients these analytical limitations lead directly to potential risk of virus infection of product recipients. While less than perfect, a broad spectrum of assays is available to characterize cell banks for the presence of adventitious and endogenous agents. Each product lot can be tested by an appropriate subset of assays for selected viruses of concern. Engineering and procedural controls over facilities, equipment and operations are necessary to minimize the possibility of viral contamination. Processes can be designed to include unit operations to remove or inactivate specific viruses of potential concern; the efficacy of these measures can be evaluated. While each of these measures has value, each also has limitations. None is solely adequate by itself to the task of preventing potential exposure to viral contaminants in product recipients. Biopharmaceuticals (purified characterizable macromolecules) are prepared by using a combination of such preventive measures. Specific measures will vary from product to product, depending on the nature and origin of the cell substrate, cell bank characterization results, raw materials used, physicochemical properties of the biopharmaceutical, effectiveness of assays, available facilities, and the agents of concern. Thus, flexibility in approach is necessary, resulting in different combinations of measures for each set of circumstances. So far, this approach has been successful in preventing viral infection in large populations treated to date with cell culture-derived biopharmaceuticals. Current issues for discussion include appropriate assays for adventitious and endogenous agents, appropriateness of current control systems and the scientific basis for standards.
由于现有检测方法的灵敏度、特异性和精密度较低，病毒污染物比化学污染物更难通过分析检测出来。再加上病毒污染物在细胞基质或产品接受者中具有生物扩增的可能性，这些分析上的局限性直接导致产品接受者面临病毒感染的潜在风险。虽然并不完美，但有一系列广泛的检测方法可用于鉴定细胞库中是否存在外来因子和内源性因子。每个产品批次都可以通过适当的检测方法子集来检测选定的相关病毒。对设施、设备和操作进行工程和程序控制，对于将病毒污染的可能性降至最低是必要的。工艺可以设计成包括去除或灭活潜在相关特定病毒的单元操作；这些措施的效果可以进行评估。虽然这些措施都有价值，但也都有局限性。没有一种措施本身足以完成防止产品接受者潜在暴露于病毒污染物的任务。生物制药（纯化的可表征大分子）是通过结合使用这些预防措施来制备的。具体措施会因产品而异，这取决于细胞基质的性质和来源、细胞库鉴定结果所用的原材料、生物制药的物理化学性质、检测方法的有效性、可用设施以及相关因子。因此，方法上的灵活性是必要的，这导致针对每种情况采取不同的措施组合。到目前为止，这种方法在防止使用细胞培养衍生的生物制药治疗的大量人群中发生病毒感染方面一直很成功。当前讨论的问题包括针对外来因子和内源性因子的适当检测方法、当前控制系统的适当性以及标准的科学依据。
