Bolden Jay, Smith Kelly
Eli Lilly, Indianapolis, IN
Eli Lilly, Indianapolis, IN.
PDA J Pharm Sci Technol. 2017 Sep-Oct;71(5):405-412. doi: 10.5731/pdajpst.2017.007849. Epub 2017 Jul 20.
Recombinant Factor C (rFC) is non-animal-derived reagent used to detect bacterial endotoxins in pharmaceutical products. Despite the fact that the reagent was first commercially available nearly 15 years ago, the broad use of rFC in pharmaceutical industry has long been lagging, presumably due to historical single-source supplier concerns and the lack of inclusion in worldwide pharmacopeias. Commercial rFC reagents are now available from multiple manufacturers, thus single sourcing is no longer an issue. We report here the successful validation of several pharmaceutical products by an end-point florescence-based endotoxin method using the rFC reagent. The method is equivalent or superior to the compendia bacterial endotoxins test method. Based on the comparability data and extenuating circumstances, the incorporation of the end point fluorescence technique and rFC reagent in global compendia bacterial endotoxins test chapters is desired and warranted. Public health has been protected for over 30 years with the use of a purified blood product of the horseshoe crab, limulus amebocyte lysate. More recently, this blood product can be produced in biotech manufacturing processes, which reduces potential impacts to the horseshoe crab and related species dependent upon the crab, for example, migrating shorebirds. The pharmaceutical industry has been slow to adopt the use of this reagent, Recombinant Factor C (rFC), for various reasons. We evaluated the use of rFC across many pharmaceutical products, and in other feasibility demonstration experiments, and found rFC to be a suitable alternative to the animal-derived limulus amebocyte lysate. Incorporation of rFC and its analytical method into national testing standards would provide an equivalent or better test while continuing to maintain patient safety for those who depend on medicines and while securing pharmaceutical supply chains. In addition, widespread use of this method would benefit existing animal conservation efforts.
重组因子C（rFC）是一种非动物源试剂，用于检测药品中的细菌内毒素。尽管该试剂早在近15年前就已首次商业化，但rFC在制药行业的广泛应用长期滞后，可能是由于历史上对单一来源供应商的担忧以及未被纳入全球药典。现在多家制造商都有商业rFC试剂供应，因此单一来源不再是问题。我们在此报告，使用rFC试剂通过基于终点荧光的内毒素方法成功验证了几种药品。该方法等同于或优于药典细菌内毒素检测方法。基于可比性数据和情有可原的情况，希望并应当将终点荧光技术和rFC试剂纳入全球药典细菌内毒素检测章节。使用马蹄蟹的纯化血液制品鲎试剂已经保护公众健康超过30年。最近，这种血液制品可以通过生物技术制造工艺生产，这减少了对马蹄蟹及依赖马蹄蟹的相关物种（如迁徙滨鸟）的潜在影响。由于各种原因，制药行业采用这种试剂重组因子C（rFC）的速度一直很慢。我们评估了rFC在许多药品中的使用情况以及其他可行性示范实验，发现rFC是动物源鲎试剂的合适替代品。将rFC及其分析方法纳入国家检测标准将提供同等或更好的检测，同时继续保障依赖药品的患者的安全，并确保制药供应链的安全。此外，广泛使用这种方法将有利于现有的动物保护工作。
