Drug Product Development of Lipid Nanoparticle‐Based <scp>mRNA</scp> Therapeutics and Vaccines

Lipid nanoparticles (LNP) are currently the most relevant non-viral delivery systems for mRNA and occasionally for smaller nucleic acids such as small interfering RNA. Although the manufacturing of LNP is well established and scalable equipment is available for production, LNP drug product development is not straightforward. Numerous factors influence product quality, including LNP composition, process parameters, and formulation composition. A proper understanding and control of the critical variables is essential for product development of LNP containing pharmaceuticals. This article provides an overview on the drug product development roadmap for LNP-based therapeutics and vaccines. Based on the quality target product profile and current scientific and technical knowledge, key aspects that may impact product quality will be discussed. Strategies to identify failure risks as early in the development process as possible and ways to mitigate them will be addressed. The majority of steps in the development are covered, including LNP design and LNP manufacturing process, analytical development, and formulation development to achieve a stable and safe product suitable for human application. This article is categorized under: Biology-Inspired Nanomaterials > Lipid-Based Structures.