Project 5: IND-enabling Critical Path Project: GMP Manufacture of a Combination I

项目 5：支持 IND 的关键路径项目：组合 I 的 GMP 生产

• 批准号: 9316531
• 负责人: Amanda Malone
• 金额: $ 50.02万
• 依托单位: OAK CREST INSTITUTE OF SCIENCE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9316531
• 关键词: AIDS prevention; Acyclovir; Adherence; Animals; Anti-Retroviral Agents; Antiviral Agents; Beds; Biological Assay; Clinical; Clinical Data; Clinical Research; Clinical Trials; Collaborations; Contracts; Critical Pathways; Cyclic GMP; Data; Development; Dose; Drug Kinetics; Endotoxins; Environment; Evaluation; Formulation; Fumarates; Funding; Future; GMP lots; Goals; HIV Infections; Human Volunteers; In Vitro; Inferior; Laboratories; Lead; Liquid substance; Macaca; Methods; Modeling; Molds; Outcome; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Phase I Clinical Trials; Placebos; Prevention; Prevention strategy; Procedures; Process; Production; Recurrence; Research Contracts; Safety; Sheep; Techniques; Tenofovir; Time; TimeLine; Toxic effect; Toxicology; Translating; United States National Institutes of Health; Vaginal Ring; Woman; Work; animal data; base; clinical development; clinical lot; clinically relevant; cost; design; emtricitabine; genital herpes; insight; microbial; novel; pre-clinical; prevent; programs; safety study; screening; sexual HIV transmission; systemic toxicity; tool

PROJECT SUMMARY: PROJECT 5 Successful transition from the laboratory to manufacture is an essential step in the development of a topical non-vaccine biomedical prevention (nBP) candiadate. For intravaginal rings (IVRs) delivering antiretroviral (ARV) drugs, the timeline for this process can be as long as, or longer than, the initial development, and be much more expensive. The overarching goal of this IPCP-MBP effort is to develop IVR formulations of multiple ARV combinations for prevention of sexual HIV transmission, emphasizing the needs of women in the developing world. The specific objectives of Project 5 are to establish GMP manufacturing capability to advance the best-performing combination ARV IVR identified through Project 1 (pharmacokinetics), Project 2 (safety), Project 3 (efficacy), and Project 4 (pre-Phase I clinical trial) efforts into post-IPCP Phase 1 clinical trials. Our overall pod-IVR manufacturing strategy is to apply a combination of established pharmaceutical manufacturing techniques to a novel production process, already validated with NIH R44 funding for a single- ARV IVR, minimizing both the cost and timeline for translating an efficacious ARV combination IVR to clinical trials and, ultimately, protecting women from HIV infection. Aim 1 is to develop procedures for pre-GMP small- scale manufacture based on the formulation results from Core B. Completed manufacturing methods will be transferred to and validated in a GMP environment in Aim 2 to develop the capacity for production of clinical lots of ARV IVRs under cGMP. A clinical lot of the best-performing candidate will be manufactured and evaluated in an IND-enabling, GLP, safety study in sheep (Aim 3). In Aim 4, an amended IND, or a new IND application depending on the final ARV IVR candidate selected by the IPCP, will be prepared and submitted to the FDA, in collaboration with Core A, in anticipation of future Phase 1 clinical trials. Upon completion of this Project, the capability and capacity to provide ARV pod-IVRs manufactured under cGMP to the IND-enabling GLP toxicology study and post-IPCP clinical trials will be achieved. The manufacturing capacity established in the IPCP-MBP will enable the transition of the final selected combination IVR into clinical trial and allow other nBP strategies based on the pod-IVR to be rapidly advanced in the future.

项目摘要：项目5 成功从实验室过渡到制造是局部发展的重要一步 非疫苗生物医学预防（NBP）糖果。对于载肠内环（IVRS），输送抗逆转录病毒 （ARV）药物，此过程的时间表可以长度或更长的时间，而不是初始发展，并且 贵得多。 IPCP-MBP工作的总体目标是开发多个的IVR公式 预防性HIV传播的ARV组合，强调女性的需求 发展中国家。项目5的具体目标是建立GMP制造能力 推进通过项目1（药代动力学）确定的表现最佳组合ARV IVR，项目2 （安全），项目3（功效）和项目4（第I临床试验）在IPCP后1阶段临床上的工作 试验。我们的整体POD-IVR制造策略是应用已建立的药物的组合 制造技术到新的生产过程，已经用NIH R44资金验证了单一的资金 ARV IVR，最大程度地减少将有效ARV组合转化为临床的成本和时间表 试验，最终保护妇女免受艾滋病毒感染的侵害。目的1是开发用于GMP前小型的程序 根据核心B的配方结果制造规模。完成的制造方法将是 在AIM 2中转移到GMP环境中并在GMP环境中进行验证，以发展生产临床的能力 CGMP下的许多ARV IVR。临床上最出色的候选人将制造出来，并 在绵羊的索引，GLP，安全研究中进行评估（AIM 3）。在AIM 4，修订的IND或新的IND 根据IPCP选择的最终ARV IVR候选者的申请，将准备并提交给 FDA与核心A合作，预计将来的1阶段临床试验。完成此任务后 项目，提供在CGMP下制造的ARV POD-IVR的能力和能力 将实现GLP毒理学研究和IPCP后临床试验。建立的制造能力 IPCP-MBP将使最终选定组合IVR转变为临床试验，并允许其他 基于POD-IVR的NBP策略将来会迅速发展。