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

项目总结：项目5

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.