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

用于生物药物的无硅玻璃预填充注射器系统。

• 批准号: 7669963
• 负责人: LaToya Jones Braun
• 金额: $ 22.95万
• 依托单位: TRIBOFILM RESEARCH, INC.
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-15 至 2011-03-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7669963
• 关键词: Address; Adhesions; Affect; Automobile Driving; Biochemistry; Biological; Cells; Chemistry; Chronic; Circular Dichroism; Collaborations; Colorado; Development; Devices; Diabetes Mellitus; Differential Scanning Calorimetry; Dose; Drug Contamination; Drug Formulations; Drug Industry; Drug Packaging; Drug-sensitive; Ensure; Environment; Fluorescence Spectroscopy; Generations; Glass; Grant; Hormonal; Human; Immunoglobulin G; Industry; Injection of therapeutic agent; Insulin; Life; Liquid substance; Lubricants; Lubrication; Marketing; Measures; Medical Device; Monitor; Monoclonal Antibodies; Operative Surgical Procedures; Oxygen; Particulate; Particulate Matter; Patients; Peptides; Performance; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Plasma; Plastics; Precipitation; Procedures; Process; Property; Proteins; Protocols documentation; Research; Research Design; Rheumatoid Arthritis; Self-control as a personality trait; Serum Albumin; Silicone Oils; Silicones; Small Business Innovation Research Grant; Solutions; Spectrum Analysis; Surface; Syringes; System; Technology; Testing; Thermodynamics; Universities; Vaccines; Vial device; Water; base; biological systems; crosslink; dosage; experience; migration; perfluoropolyether; protein aggregate; protein aggregation; public health relevance; stability testing; water vapor

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.

描述（由申请人提供）：在医疗器械行业中，硅油是一种普遍存在的润滑剂 - 用于部件的制造和组装，也可作为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成为包装药物的污染物和可能的反应物时，就会出现问题。就生物药物而言，这种硅油污染与蛋白质构象变化和聚集有关。用于预填充应用的玻璃注射器主要使用硅油作为润滑剂。非常需要一种无硅油的玻璃预填充装置，但在它被接受之前，需要对各种药物成分进行稳定性测试以及长期储存后的颗粒和力测试。我们建议开发带有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松开和挤压注射器力的影响，以及标准硅油润滑和 TriboGlide(r) 无硅注射器之间颗粒生成的比较。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制剂包装设备进行比较。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用水的 pH 变化。本研究选择的蛋白质是人血清白蛋白、人 IgG、胰岛素和 abatecept（百时美施贵宝公司的单克隆抗体）。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注射器中长期储存后蛋白质热力学稳定性的变化。最后，凭借来自UCD的LaToya Jones Braun博士带来的丰富的疫苗经验，我们将评估注射器中储存的各种疫苗配方的稳定性。医疗器械和制药行业长期以来一直希望获得一种完全不含有机硅的系统，该系统不会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充式注射器的通用无硅系统，其应用范围可扩展到其他医疗设备。公共健康相关性：患者自控自我治疗是单剂量预装注射器包装药物用于治疗类风湿性关节炎和糖尿病等慢性疾病的一大推动因素。其他优点包括减少错误、易于使用、剂量准确、多剂量疫苗无需防腐剂，最重要的是减少了包装在小瓶中所需的药物溢出。硅油作为注射器易于操作的润滑剂，可能会污染药品并与敏感药物产生不利的相互作用。拟议的TriboGlide系统将是第一个用于玻璃预充式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。