The purpose of this guidance is to provide to sponsors nonclinical and clinical recommendations specific to the development of systemic drug products, with a focus on long-acting systemic drug products (including small molecules and monoclonal antibodies), regulated within the Center for Drug Evaluation and Research at the Food and Drug Administration (FDA) for the prevention of sexually acquired human immunodeficiency virus-1 (HIV-1) infection. Specifically, this guidance addresses FDA’s current thinking regarding the overall development program and clinical trial designs to support the development of systemic drug products for the prevention of HIV-1 infection. Investigational drug products for further development as pre-exposure prophylaxis (PrEP) can include the following: (1) an oral drug product approved for the treatment of HIV-1 infection that is subsequently developed as oral PrEP, (2) an oral drug product approved for the treatment of HIV-1 infection that is reformulated as a long-acting drug
product or other delivery system (e.g., injectable, implantable device) for PrEP, or (3) a new investigational systemic drug product that is developed for treatment and/or prevention of HIV-1 infection.

This guidance does not address the development of vaginal microbicide drug products. That topic is discussed in the guidance for industry Vaginal Microbicides: Development for the Prevention of HIV Infection (November 2014) (vaginal microbicides guidance). The following additional information can be found in the vaginal microbicides guidance: detailed nonclinical development, including in vitro virologic studies, specific information related to topical use and trials in female subjects, and more detailed information relating to protocol data collection and procedures. Except for the assessment of local microbicide effects, which are unique to vaginal microbicide development, the vaginal microbicides guidance is also generally applicable to the development of systemic drug products.

This guidance also does not discuss the general issues of statistical analysis or clinical trial design. Those topics are addressed in the ICH guidances for industry E9 Statistical Principles for Clinical Trials (September 1998) and E10 Choice of Control Group and Related Issues in Clinical Trials (May 2001), respectively. FDA recognizes the challenges in evaluating systemic drug products for the prevention of sexually acquired HIV-1 infection. FDA continues to evaluate possible approaches for the development of new therapies for HIV prevention and will update this guidance if new information becomes available.

FDA encourages the sponsor considering development of systemic drug products for the prevention of HIV-1 infection to communicate with FDA through the preinvestigational new drug application consultation program.

Posted on the FDA website on 19 March 2019