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

描述（由申请人提供）：在医疗器械行业，硅油是一种普遍存在的润滑剂-用于部件的制造和组装，也用作设备正常运行的终端润滑剂。对于预充式注射器，当硅油微滴迁移到药物介质中并作为污染物和包装药物的可能反应物时，问题就出现了。在生物药物的情况下，这种硅油污染已涉及蛋白质构象变化和聚集。用于预填充应用的玻璃注射器主要使用硅油作为润滑剂。一种无硅油的玻璃预填充装置是非常需要的，但在它被接受之前，需要进行各种药物成分的稳定性测试以及延长储存后的颗粒和力测试。我们建议开发基于全氟聚醚化学的TriboGlide(r)无硅润滑系统的玻璃预填充注射器。提出了加速储存条件对注射器断裂力和挤压力的影响，并比较了标准硅油润滑注射器和TriboGlide(r)无硅注射器的颗粒生成情况。与科罗拉多大学丹佛分校（UCD）合作，TriboGlide(r)注射器将与标准硅化注射器作为蛋白质配方包装设备进行比较。将评估蛋白质沉淀（UV/Vis光谱）、可溶性蛋白质损失（SE-HPLC）、吸附蛋白质对注射器力的影响以及注射水中pH值的变化。本研究选用的蛋白为人血清白蛋白、人IgG、胰岛素和abatecept （Bristol Myers Squibb单克隆抗体）。在第二阶段，我们建议使用圆二色性和荧光光谱来评估TriboGlide(r)玻璃注射器对蛋白质二级和三级结构变化的影响。差示扫描量热法将用于检测在注射器中延长储存后蛋白质热力学稳定性的变化。最后，凭借UCD的LaToya Jones Braun博士带来的丰富疫苗经验，我们将评估储存在注射器中的各种疫苗配方的稳定性。医疗设备和制药行业长期以来一直希望有一种完全无硅的系统，不影响包装药物在溶液中的稳定性。如果成功，TriboGlide将成为第一个用于玻璃预填充注射器的通用无硅系统，其应用范围将扩展到其他医疗设备。公共卫生相关性：患者控制的自我治疗是用于治疗慢性疾病（如风湿性关节炎和糖尿病）的单剂量预填充注射器包装药物的一大驱动因素。其他优点包括减少错误、易于使用、剂量准确、在多剂量疫苗情况下不使用防腐剂，最重要的是减少了用小瓶包装所需的药物过量。硅油作为润滑剂，便于注射器操作，但会污染药品，并与敏感药物产生不良反应。提出的TriboGlide系统将是第一个用于玻璃预填充注射器的无硅油系统，克服了润滑剂迁移和药物污染的问题。

DESCRIPTION (provided by applicant): In the medical device industry, silicone oil is a ubiquitous lubricant - used in the manufacture and assembly of components and also as the terminal lubricant for proper device operation. For prefilled syringes, the problem arises when micro-droplets of silicone oil migrate into the drug medium and act as a contaminant and possible reactant for the packaged drug. In the case of biological drugs, such silicone oil contamination has been implicated in protein conformational changes and aggregation. Glass syringes for prefilled applications predominantly use silicone oil as a lubricant. A silicone oil-free glass prefilled device is highly desired, but before it would be accepted, stability testing with various pharmaceutical ingredients as well as particulate and force testing after extended storage is required. We propose the development of glass prefilled syringes with the TriboGlide(r) silicone-free lubrication system based on perfluoropolyether chemistry. The effect of accelerated storage conditions on break-loose and extrusion syringe forces along with comparison of the particulate generation between standard silicone oil lubricated and TriboGlide(r) silicone-free syringes is proposed. In collaboration with the University of Colorado Denver, UCD, TriboGlide(r) syringes will be compared to standard siliconized syringes as devices for packaging of protein formulations. Protein precipitation (UV/Vis spectroscopy), loss of soluble protein (SE-HPLC), influence of adsorbed protein on syringe forces, and pH shifts in water for injection will be assessed. The proteins selected for this study are human serum albumin, human IgG, insulin, and abatecept (monoclonal antibody by Bristol Myers Squibb). In phase II, we propose to evaluate the TriboGlide(r) glass syringes for effects on secondary and tertiary structural changes of the proteins, using circular dichroism and fluorescence spectroscopy. Differential scanning calorimetry will be used to detect changes in the thermodynamic stability of the proteins after extended storage in the syringes. Finally, with the extensive experience in vaccines brought by Dr. LaToya Jones Braun from UCD, we will evaluate the stability of various vaccine formulations stored in the syringes. The medical device and pharmaceutical industries have long desired a completely silicone-free system that does not affect the stability of the packaged drug in solution. If successful, TriboGlide will be the first universal silicone-free system for glass prefilled syringes with applications extending to other medical devices. PUBLIC HEALTH RELEVANCE: Patient controlled self-therapy is a big driving factor for drugs packaged in single-dose prefilled syringe formats for treatment of chronic ailments such as rheumatoid arthritis and diabetes. Other advantages include reduced errors, ease of use, accurate dosage, elimination of preservatives in case of multi-dose vaccines and above all reduced overfill of drugs that are required for packaging in vials. Silicone oil, which serves as a lubricant for easy operation of the syringe, can contaminate the drug product and adversely interact with the sensitive drugs. The proposed TriboGlide system will be the first silicone oil-free system for glass prefilled syringes that overcomes the problems of lubricant migration and drug contamination.