PROJECT I – ABSTRACT Despite extensive choice and increasing availability, current contraceptive options are not meeting the needs of many women, as is evident by high levels of typical-use failure, method non-use, switching, and discontinuation. Approximately half of all pregnancies (121 million) around the world are unintended and 218 million women have an unmet need for effective contraception. New technologies having attributes more closely aligned with users’ needs and expectations are urgently needed to fill this critical gap in sexual and reproductive healthcare. The overall goal of this P50 center is to bring together some of the leading research organizations in the world with unrivalled expertise and know-how around design, manufacture and testing of intravaginal ring (IVR) technology – including Population Council (PC), Queen's University Belfast (QUB), and Weill Cornell Medical College (WCMC) – in a concerted effort to develop a new, practical, easy-to-use, long-acting, multipurpose prevention technology (MPT) IVR offering both spermicidal activity and broad antibacterial/antiviral activity against various common sexually transmitted/vaginal infections, including chlamydia, gonorrhea, bacterial vaginosis (BV), and infection with herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus (HIV). Unlike other marketed and experimental contraceptive IVR products, we are committed here to the development of a non- hormonal contraceptive strategy, referred to as the CZL-IVR, in which copper ions or copper salts (C), zinc ions or zinc salts (Z), and lactide (L) are simultaneously administered to the vagina in a sustained/controlled manner over at least 30 days. The overarching goal of Project 2, which involves a strategic and highly integrated partnership between Queen's University Belfast (QUB) and Population Council (PC), is to provide formulation support for the P50 project. Specifically, this will involve all aspects of CZL-IVR product design, formulation, manufacture and in vitro testing, according to three key aims: In Aim 1, we will develop a CZL-IVR that releases copper, zinc and lactide for at least 30 days in quantities sufficient for clinical efficacy; in Aim 2, we will design, manufacture and characterize non-medicated IVRs and sensor- embedded IVRs for end-user testing; and in Aim 3, we will complete technology transfer between QUB and PC and GMP manufacture the IVRs for clinical evaluation for Project 3. Project 1 will be closely coordinated with Projects 2 and 3 to inform IVR loading and selection of the lead IVR. Our multidisciplinary collaborative team is uniquely qualified to advance the development of this novel MPT IVR. The CZL-IVR will address a critical gap in the non-hormonal contraceptive landscape, fill a niche that users want and deliver an important public health intervention.