Stability and functionality of the Immunoject single-dose, auto-reconstitution de

说明(申请人提供)：为确保针对生物恐怖分子或自然发生的病原体的大规模运动的成功，需要在察觉到对公共卫生的威胁时储存疫苗、治疗药物和其他产品，并准备好立即使用。在这种情况下，存储是管理成本的主要贡献者，要求将活性产品冷藏可能会使成本增加三倍或更多。人们还普遍认为，单剂给药系统在疾病传播和微生物污染方面提供了额外的好处。免疫对象解决了这些和其他问题，这是一种新的平台设备，应用于许多药物的非肠道给药，这些药物现在可能被配制为快速溶解的粉末。单位剂量的自动重建设备紧凑、相对平坦，并呈现出经济上有吸引力的存储配置文件。它由一个整体密封的无菌薄膜袋组成，两个隔间由易碎的薄膜隔开，还有一个由注塑塑料部件制成的给药装置。袋子的一个隔室大小可容纳预定体积的注射用水，而另一个隔室容纳作为快速溶解和热稳定粉末配制的剂量的药物化合物。在四个简单易用的步骤中，医护人员将拇指按压在水箱上，进而使活性粉末溶解，然后通过针头给患者注射。该项目的主要目标是通过展示该设备将保持其功能和储存在其粉盒中的不含硫柳汞的乙肝疫苗的热稳定性，加快免疫对象走向商业化的道路。这将通过实现三个具体目标来实现。第一种方法是将疫苗制成快速溶解的纳米和微米级粉末，并完成检测，以验证乙肝表面抗原仍与明矾佐剂结合，以及粉末保持疫苗的原始效力。第二个目标是确保这些粉末在48小时内没有吸附统计上显著的水分，并测试免疫对象的功能和性能。最后，第三个目标是评估粉末和填充的免疫装置在-20℃到65℃的温度下的稳定性，储存期从一周到12个月。 公共卫生相关性：该项目寻求加速免疫对象，这是一种用于非肠道给药的新的单位剂量、自动重建设备，正在走向商业化。这种新设备将显著降低因生物恐怖分子或自然发生的病原体的传播而引发的大规模公共卫生运动的受试者存储和管理预防性或治疗性剂量的成本。免疫制剂潜力的关键是创新的有效成分配方，如热稳定和快速溶解的干粉。

DESCRIPTION (provided by applicant): Assuring the success of mass campaigns against bioterrorist or naturally occurring pathogens requires that vaccines, therapeutics, and other products are stored and ready for immediate use at the time the threat to public health is perceived. Storage is a major contributor to the cost of administration under these circumstances and a requirement to keep the active product refrigerated can increase the cost by a factor of three, or more. It is also generally accepted that single dose delivery systems provide additional benefits in terms of disease transmission and microbial contamination. These and other issues are resolved by Immunoject, a new platform device with application to the parenteral delivery of the many pharmaceutical products that may now be formulated as rapidly dissolving powders. The unit-dose auto-reconstitution device is compact, relatively flat, and presents an economically attractive storage profile. It consists of an integrally sealed aseptic film pouch with two compartments separated by a frangible membrane, together with an administration device made from molded plastic parts. One compartment of the pouch is sized to hold a pre-determined volume of water for injection while the other compartment houses a dose of pharmaceutical compound formulated as a rapidly dissolving and thermally stable powder. In four user-friendly steps, a healthcare worker applies thumb pressure to the water compartment which, in turn, causes the active powder to dissolve and then to be administered through a needle to the patient. The overarching goal of this project is to accelerate Immunoject on its path to commercialization by demonstrating that the device will maintain its functionality and the thermal stability of thimerosal-free hepatitis-B vaccine stored within its powder compartment. This will be achieved by achieving three specific aims. The first of these formulates the vaccine as rapidly dissolving nano- and micro-scale powders and completes assays to verify that the HBsAg antigen remains bonded to the alum adjuvant, and that the powders retain the vaccine's original potency. The second aim assures that the powders have adsorbed no statistically significant moisture in 48 hours and tests the functionality and performance of the Immunoject. And finally, the third aim assesses the stability of powders and filled Immunoject devices at temperatures from -20 ¿C through 65 ¿C with storage periods from one week through twelve months. PUBLIC HEALTH RELEVANCE: This project seeks to accelerate Immunoject, a new unit-dose, auto-reconstitution device for parenteral delivery, on its path to commercialization. The new device will significantly reduce the costs of storing and administering a prophylactic or therapeutic dose to subjects of a mass public health campaign provoked by the transmission of a bioterrorist or naturally occurring pathogen. Key to Immunoject's potential is the innovative formulation of active ingredients as thermally stable and rapidly dissolving dry powders.