The industrial design, translation, and development strategies for long-acting peptide delivery
Bin Yang, Ana Gomes dos Santos, Sanyogitta Puri, Annette Bak, Liping Zhou
Abstract
INTRODUCTION: Peptides are widely recognized as therapeutic agents in the treatment of a wide range of diseases, such as cancer and diabetes. However, their use has been limited by their short half-life, due to significant metabolism by exo- and endo-peptidases as well as their inherent poor physical and chemical stability. Research with the aim of improving their half-life in the body and thus improving patient compliance (by decreasing the frequency of injections) has gained significant attention. AREAS COVERED: This review outlines the current landscape and industrial approaches to achieve extended peptide exposure and reduce dosing frequency. Emphasis is placed on identifying challenges in drug product manufacturing and desirable critical quality attributes that are essential for activity and safety, providing insights into chemistry and design aspects impacting peptide release, and summarizing important considerations for CMC developability assessments of sustained release peptide drugs. EXPERT OPINION: Bring the patient and disease perspective early into development. Substantial advances have been made in the field of sustained delivery of peptides despite their complexity. The article will also highlight considerations for early-stage product design and development, providing an industrial perspective on risk mitigation in developing sustained release peptide drug products.