Advanced Formulations/Drug Delivery Systems for Subcutaneous Delivery of Protein-Based Biotherapeutics

Multiple advanced formulations and drug delivery systems (DDSs) have been developed to deliver protein -based biotherapeutics via the subcutaneous (SC) route. These formulations/DDSs include high-concentration solution, co-formulation of two or more proteins, large volume injection, protein cluster/complex, suspen-sion, nanoparticle, microparticle, and hydrogel. These advanced systems provide clinical benefits related to efficacy and safety, but meanwhile, have more complicated formulations and manufacturing processes com-pared to conventional solution formulations. To develop a fit-for-purpose formulation/DDS for SC delivery, scientists need to consider multiple factors, such as the primary indication, targeted site, immunogenicity, compatibility, biopharmaceutics, patient compliance, etc. Next, they need to develop appropriate formula-tion (s) and manufacturing processes using the QbD principle and have a control strategy. This paper aims to provide a comprehensive review of advanced formulations/DDSs recently developed for SC delivery of pro-teins, as well as some knowledge gaps and potential strategies to narrow them through future research.(c) 2022 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.