Improved Anthrax Vaccine Stability & use of Adjuvants

描述（由申请方提供）：本申请描述了一个开发稳定性显著改善的炭疽rPA疫苗的四阶段计划。该计划的一个产出将是一种候选疫苗，当成功获得许可时，不需要冷藏或供应链，为政府提供维护和部署成本较低的库存。这种疫苗在承受极端温度的能力方面将更加强大，从而简化了在该领域的使用。该计划还检查了不含alhyrdrogel的配方，可能会产生更安全的产品。 该计划研究了冻干，微胶囊化，微粒结晶和玻璃化四个阶段，旨在只发展那些显示稳定性可测量的改善，而不影响动物挑战试验和使用替代标记物的免疫反应的效力的技术。在第1阶段，将使用所有技术进行初始工艺开发和优化，以生产可用于第2阶段加速稳定性试验的制剂，并将使用大量先前开发的原料药和制剂表征检测和测定来检查技术对疫苗的影响。在第3阶段，将开发一种技术工艺，用于GMP中试工厂生产，以生产将用于第4阶段毒性测试的材料。然后，这些数据将用于设计，成本和计划非临床和临床项目，以获得许可证。 该计划的目标是开发一种比现有产品稳定性更好的炭疽疫苗。该计划的成功完成将产生一种炭疽疫苗候选人，当获得许可证时，将降低维持国家储备的成本。此外，提高使用中的稳定性和耐用性将大大简化在紧急情况下部署疫苗的后勤工作，从而为公众提供更大的保护。

DESCRIPTION (provided by applicant): This application describes a four stage program to develop an Anthrax rPA vaccine with a significantly improved stability. An output from this program would be a vaccine candidate that when successfully licensed does not require refrigerated storage or supply chain, providing the government with a stockpile that is less costly to maintain and deploy. The vaccine would be more robust in terms of it's ability to withstand temperature extremes simplifying use in the field. The program also examines formulations that do not contain alhyrdrogel potentially yielding a safer product. The program studies lyophilization, micro-encapsulation, micro-particle crystallization and glassification in four stages designed to progress only those technologies showing a measurable improvement in stability without compromising potency in an animal challenge test and immunological response using surrogate markers. In stage 1 initial process development and optimization will be carried out using all technologies to produce formulations useable for accelerated stability trials in stage 2 and extensive previously developed Drug substance and Drug Product characterization tests and assays will be used to examine the effect of the technologies on the vaccine. In Stage 3 will develop one technology process to GMP pilot plant manufacture to produce material that will be used in stage 4 for toxicity. This data will then be used to design, cost and plan a non-clinical and clinical program to achieve license. Relevance This program targets the development of an anthrax vaccine with improved stability over currently available products. The successful completion of the program would yield an anthrax vaccine candidate that when licensed would reduce the costs of maintaining a National Stockpile. In addition, improved stability and robustness in use would greatly simplify the logistics for deploying the vaccine in an emergency yielding greater protection to the public.