Automation of GMP manufacturing of HIV microbicide rings

 描述(由申请人提供)：这项工作的广泛长期目标是使发展中国家的妇女能够通过使用艾滋病毒杀微生物剂阴道内环来保护自己免受艾滋病毒感染。在这个项目的第一和第二阶段，我们开发了技术平台，在我们的“Pod”静脉注射受体中提供广泛的抗逆转录病毒药物。我们证实了绵羊分娩的安全性和药代动力学，以及这些环在猕猴模型中预防感染的能力。我们还开发了制造方法，以生产足以进行临床试验的cGMP环。在这个IIB阶段计划中，我们建议 发展具有成本效益的商业批量生产HIV杀微生物剂阴道内环的能力。吊舱环制造包括3个步骤：空白环制造、吊舱生产和组装。我们已经成功地实现了前两个步骤的自动化，从而具备了商业批量生产的能力。这一阶段IIB提案的具体目标是开发和实施自动化组装和包装战略。我们的方法将包括在第一年进行试点和可行性研究，并在第二年过渡到cGMP。这一目标的成功实现将使商业批量生产成为可能，这将使向发展中国家提供具有成本效益的杀微生物环成为可能。

 DESCRIPTION (provided by applicant): The broad long term goal of this work is to empower women in the developing world to protect themselves against HIV infection through the use of an HIV microbicide intravaginal ring. In Phase I and II of this project we developed the technology platform to deliver a broad range of antiretrovirals in our "Pod" IVRs. We confirmed the safety and pharmacokinetics of delivery in sheep and the ability of these rings to prevent infection in the macaque model. We also developed manufacturing methods to produce cGMP rings at a volume sufficient for carrying out clinical trials. In this Phase IIB program we propose to develop the capacity for cost effective manufacture of commercial lots of HIV microbicide intravaginal rings. Pod ring manufacture comprises 3 steps: blank ring manufacture; pod production; and assembly. We have successfully automated the first two steps to have the capacity for commercial lot production. The specific aim of this Phase IIB proposal is to develop and implement an automated assembly and packaging strategy. Our approach will comprise pilot and feasibility studies in the first year and transfer to cGMP in the second year. The successful completion of this aim will allow commercial lot manufacture which will allow cost-effective provision of microbicide rings to the developing world.