LAUSR

Poor adherence to prescribed medications significantly impacts the U.S. health care system.1–4 Given the human and financial consequences, the development of strategies for improving adherence to prescribed medications is imperative. Long-acting injectable (LAI) drug products are 1 of several interventions for improving patient adherence to prescription medications.5–8 LAIs are formulated to achieve extended-release drug action over days and months, when administered via intramuscular and subcutaneous routes. These products can help to improve adherence in patients who need medications to be administered frequently. Several LAIs have been approved by the U.S. Food and Drug Administration (FDA), for example, paliperidone palmitate, aripiprazole, naltrexone, and buprenorphine. LAI products have unique pharmacokinetic (PK) characteristics. Their pharmacokinetics generally are characterized by a rate of drug absorption that is slower than their rate of elimination; hence, they exhibit flipflop kinetics. In these products, the terminal phase of the drug profile reflects the rate of absorption, rather than the rate of elimination, as is usually observed in classical linear drug PK.9–13 The long terminal phase of these products poses several challenges for the development of new versions, as well as generic copies. Modelinformed drug development (MIDD) has the potential to make drug development of LAI more efficient by integrating mechanistic understanding and improving study designs. Therefore, gathering stakeholders to discuss the current status and application of MIDD in drug development and regulatory decision making for LAI products is both important and timely. A symposium titled, “Model-Informed Drug Development for Long-Acting Injectable Products” was organized and presented at the American College of Clinical Pharmacology meeting in Chicago, Illinois, on September 16, 2019.14 Goals and objectives of this symposium were to describe opportunities and challenges in the development of LAI products, to identifyMIDD opportunities for new and generic LAI products, and to discuss challenges and opportunities from a regulatory perspective. This report summarizes the presentations and discussions that made up the symposium.