The advancements in lipid nanoparticle (LNP) delivery systems have been paramount in the performance, stability, safety, and eventual regulatory approval of novel drugs and vaccines, such as the mRNA COVID-19 vaccine by Moderna, Pfizer/BioNTech, and others. These encapsulated LNPs can deliver drugs using a wide range of sizes based on the LNP components and route of administration. However, the lipophilic nature and complexity of LNPs can present difficulties in the cleaning process. Laboratory cleaning models can be used to efficiently screen the optimum aqueous cleaning agent and define critical cleaning parameters. This presentation explores the concerns with cleaning pharmaceutical products utilizing LNP delivery vehicles and provides a general cleaning recommendation based on laboratory and field testing.