Chemistry, manufacturing and controls strategies for using novel excipients in lipid nanoparticles

• Published in: Nature nanotechnology Vol. 20; no. 3; pp. 331 - 344
• Main Authors: O’Brien Laramy, Matthew, Foley, David A., Pak, Roger H., Lewis, Jacob A., McKinney, Eric, Egan, Patricia M., Yerabolu, Ravikiran, Dane, Eric, Dirat, Olivier, Saunders Gorka, Lindsey, Martinelli, Joseph R., Moussa, Ehab M., Barthuet, Julie
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.03.2025; Nature Publishing Group
• Subjects: 631/61/350/354; 631/61/54/152; 639/638/11; 639/925/352/152; 639/925/357/341; Chemistry and Materials Science; Developmental stages; Drug Industry; Excipients; Excipients - chemistry; Humans; Lipids; Lipids - chemistry; Liposomes; Manufacturing; Materials Science; Nanoparticles; Nanoparticles - chemistry; Nanotechnology; Nanotechnology and Microengineering; Nucleic acids; Perspective; Pharmaceutical industry; Pharmaceuticals; Pharmacodynamics; Pharmacokinetics; Structure-function relationships
• ISSN: 1748-3387; 1748-3395; 1748-3395
• DOI: 10.1038/s41565-024-01833-9

Lipid nanoparticles (LNPs) for nucleic acid delivery often use novel lipids as functional excipients to modulate the biodistribution, pharmacokinetics, pharmacodynamics and efficacy of the nucleic acid. Novel excipients used in pharmaceutical products are subject to heightened regulatory scrutiny and often require data packages comparable to an active pharmaceutical ingredient. Although these regulatory requirements may help to ensure patient safety they also create economic and procedural barriers that can disincentivize innovation and delay clinical investigation. Despite the unique structural and functional role of lipid excipients in LNPs, there is limited specific global regulatory guidance, which adds uncertainty and risk to the development of LNPs. In this Perspective we provide an industry view on the chemistry, manufacturing and controls challenges that pharmaceutical companies face in the use of novel lipid excipients at each stage of development, and propose consensus recommendations on how to streamline and clarify development and regulatory expectations. This Perspective discusses some of the challenges that pharmaceutical companies face in the use of lipid excipients at each stage of development, and proposes recommendations on how to streamline regulatory expectations.