Silicone-free glass pre-filled syringe system for Biological Drugs.

产品说明：在医疗器械行业中，硅油是一种普遍存在的润滑剂，用于医疗部件的制造和组装，也是设备正常运行的终端润滑剂。在预充式注射器中，当硅油的微滴迁移时， 进入药物介质中，并作为污染物，可能与包装的药物发生反应。在生物药物的情况下，硅油污染与蛋白质构象变化和聚集有关，其中即使是一小部分聚集的蛋白质也会降低生物活性和/或导致不期望的免疫原性。 用于预充式应用的玻璃注射器主要使用硅油作为润滑剂。高度期望无硅树脂的玻璃预填充装置，但是新润滑剂的接受需要使用各种环境进行稳定性测试。 药物成分，以及延长储存后的颗粒和力测试。TriboFilm Research，Inc.建议开发用于玻璃预充式注射器的TriboGlide（R）无硅润滑系统。TriboGlide（R）技术基于全氟聚醚化学和气体等离子体固定，可形成耐迁移的润滑涂层，从而减少润滑剂浸提到制剂中。 一期 TriboFilm Research证明了无硅玻璃预充式注射器的概念验证。与丹佛的科罗拉多大学合作，证明了TriboGlide（R）在蛋白质聚集和注射器挤出力方面优于硅油的上级性能。在第II阶段，将开发用于生产TriboGlide（R）涂层玻璃注射器的可扩展生产工艺。最初，TriboGlide（R）润滑工艺将使用实验设计进行优化，以生产具有低注射器挤出力和低颗粒计数的涂层。将使用光阻法（HIAC）以及微流成像测量颗粒，以确定存在的颗粒数量并区分润滑剂颗粒和聚集蛋白。通过优化的包被工艺，将使用各种治疗性蛋白质评估蛋白质稳定性。将TriboGlide（R）润滑系统与硅油进行比较，以确定润滑过程的优效性。将使用荧光光谱法、质谱法和微流成像检查蛋白质稳定性。最后，将建立一个中试规模的润滑机，以证明这一过程的规模和可制造性。 医疗器械和制药行业长期以来一直希望有一种不影响溶液中包装药物稳定性的完全不含硅酮的注射器系统。如果成功，TriboGlide（R）将成为 第一个用于玻璃预充式注射器的通用无硅系统，其应用扩展到其他领域。 公共卫生相关性：病人控制的自我治疗是一个诱人的因素包装药物在单剂量预充式注射器格式，治疗慢性疾病，如类风湿性关节炎，多发性硬化症和糖尿病。预充式注射器的其他优点包括减少医疗错误、易于使用、精确剂量、消除防腐剂以及减少当药物产品包装在小瓶或安瓿中时所需的药物过量。作为润滑剂的硅油可使注射器易于操作，但可能污染制剂并与敏感药品发生不良反应。拟议的TriboGlide（R）系统将是第一个用于玻璃预充式注射器的无硅系统，它克服了润滑剂迁移和药物污染的问题。

DESCRIPTION: In the medical device industry, silicone oil is a ubiquitous lubricant used in the manufacture, assembly of medical components, and also as the terminal lubricant for proper device operation. In prefilled syringes, problems arise when micro-droplets of silicone oil migrate into the drug medium and act as a contaminant which can potentially react with the packaged drug. In the case of biological drugs, silicone oil contamination has been implicated in protein conformational changes and aggregation where even a small fraction of aggregated proteins can reduce biological activity and/or result in undesirable immunogenicity. Glass syringes for prefilled applications predominantly use silicone oil as a lubricant. A silicone-free glass prefilld device is highly desired, but acceptance of a new lubricant requires stability testing with various pharmaceutical ingredients, as well as particulate and force testing after extended storage. TriboFilm Research, Inc. proposes the development of their TriboGlide(R) silicone-free lubrication system for use in glass prefilled syringes. The TriboGlide(R) technology is based on perfluoropolyether chemistry and gas plasma immobilization to create a lubricating coating that is resistant to migration and leads to less lubricant extraction into the drug product. In Phase I TriboFilm Research demonstrated a proof-of-concept for a silicone-free glass prefilled syringe. In collaboration with the University of Colorado at Denver, the superior performance of TriboGlide(R) versus Silicone Oil was demonstrated with respect to protein aggregation and syringe extrusion forces. In Phase II, a scalable manufacturing process for producing TriboGlide(R) coated glass syringes will be developed. Initially, the TriboGlide(R) lubrication process will be optimized using a design of experiments to produce coatings with low syringe extrusion forces and low particle counts. Particles will be measured using light obscuration (HIAC) as well as microflow imaging to determine the number of particles present and distinguish between lubricant particles and aggregated proteins. With an optimized coating process, protein stability will be evaluated using various therapeutic proteins. The TriboGlide(R) lubrication system will be compared to Silicone Oil to establish superiority of the lubrication process. Protein stability will be examined using fluorescence spectroscopy, mass spectrometry, and microflow imaging. Finally, a pilot scale lubrication machine will be built to demonstrate the scale-up and manufacturability of this process. The medical device and pharmaceutical industries have long desired a completely silicone-free syringe system that does not affect the stability of the packaged drug in solution. If successful, TriboGlide(R) will be the first universal silicone-free system for glass prefilled syringes with applications extending to other fields. PUBLIC HEALTH RELEVANCE: Patient controlled self-therapy is an enticing factor for packaging drugs in single-dose prefilled syringe formats which treat chronic ailments, such as rheumatoid arthritis, multiple sclerosis, and diabetes. Other advantages of prefilled syringes include reduction in medical errors, ease of use, accurate dosage, elimination of preservatives, and reduction in the amount of drug overfill required when pharmaceutical products are packaged in vials or ampoules. Silicone oil, which serves as a lubricant for easy operation of the syringe, can contaminate the drug product and adversely interact with sensitive pharmaceutical products. The proposed TriboGlide(R) system will be the first silicone-free system for glass prefilled syringes that overcomes the problems of lubricant migration and drug contamination.