Farshid Mahmood, Taffs Rolf E, Scott Dorothy, Asher David M, Brorson Kurt
Office of Blood Research and Review, Center for Biologics Evaluation, Center for Drug Evaluation and Research, Food and Drug Administration, 1401 Rockville Pike, Rockville, MD 20852, USA.
Curr Opin Biotechnol. 2005 Oct;16(5):561-7. doi: 10.1016/j.copbio.2005.07.006.
The viral and transmissible spongiform encephalopathy (TSE) safety of therapeutics of biological origin (biologicals) is greatly influenced by the nature and degree of variability of the source material and by the mode of purification. Plasma-derived and recombinant DNA products currently have good viral safety records, but challenges remain. In general, large enveloped viruses are easier to remove from biologicals than small 'naked' viruses. Monoclonal antibodies and recombinant DNA biopharmaceuticals are derived from relatively homogeneous source materials and purified by multistep schemes that are robust and amenable to scientific analysis and engineering improvement. Viral clearance is more challenging for blood and cell products, as they are complex and labile. Source selection (e.g. country of origin, deferral for CJD risk factors) currently occupies the front line for ensuring that biologicals are free of TSE agents, but robust methods for their clearance from products are under development.
生物源治疗药物（生物制品）的病毒及传染性海绵状脑病（TSE）安全性受到原材料变异性的性质和程度以及纯化方式的极大影响。目前，血浆来源产品和重组DNA产品具有良好的病毒安全性记录，但挑战依然存在。一般来说，大型包膜病毒比小型“裸露”病毒更容易从生物制品中去除。单克隆抗体和重组DNA生物制药源自相对均质的原材料，并通过稳健且适合科学分析和工程改进的多步方案进行纯化。对于血液和细胞产品而言，病毒清除更具挑战性，因为它们复杂且不稳定。目前，来源选择（如原产国、因克雅氏病风险因素而延期）是确保生物制品不含TSE病原体的首要措施，但从产品中清除TSE病原体的稳健方法仍在研发之中。
