1. Scope

1.1 Lipid nanoparticles (LNPs) have emerged as an important nanoscale drug delivery technology for the in vivo intracellular delivery of therapeutic proteins and nucleic acids for the treatment of a wide range of human diseases (e.g., cancers, infectious diseases, etc). 1.2. This guide has been prepared to describe the key technical considerations and recommended analytical methodology for establishing high quality characterization of mRNAs encapsulated in LNPs. 1.2.1 Recommended industry best practices including suitable analytical methods and tools for characterizing the mRNA encapsulation efficiency (e.g., the amount of free versus total mRNA encapsulated in LNP vectors) are described within this guide. 1.2.2 Recommended industry best practices including suitable analytical methods and tools for either the qualitative or quantitative extraction of LNP encapsulated mRNA are described within the guide. 1.2.3 Recommended industry best practices including appropriate analytical methods and tools for characterizing the identity, integrity, and purity of mRNA before and after encapsulation in LNP vectors are described within the guide. 1.3 The technical recommendations in the guide may also have direct applicability to the characterization of self-amplifying RNAs (saRNAs), short interfering RNAs (siRNAs), as well as to other nucleic acid drug substances encapsulated into LNP vectors. 1.4 The scope of this guide is limited to the characterization of mRNA payloads and does not describe the physical characterization of the LNP nor methods to assess in vitro or in vivo potency of the drug product. 1.5 UnitsThe values stated in SI units are to be regarded as the standard. No other units of measurement are included in this standard. 1.6 This standard does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility of the user of this standard to establish appropriate safety, health, and environmental practices and determine the applicability of regulatory limitations prior to use. 1.7 This international standard was developed in accordance with internationally recognized principles on standardization established in the Decision on Principles for the Development of international Standards, Guides and Recommendations issued by the World Trade Organization Technical Barriers to Trade (TBT) Committee.

Keywords

lipid nanoparticles; nanoscale, drug, delivery, intracellular, nucleic acids, mRNA

Rationale

Lipid nanoparticles (LNPs) are widely used as vectors for the delivery of protein- and nucleic acid-based therapeutic agents in the treatment of cancers, neurological disorders, and infectious diseases, etc. As an example, the use of LNPs to deliver mRNA to cells is an important therapeutic avenue for combating the current COVID-19 pandemic. This standard guide will benefit government (regulators), industry (biopharma) and academia (drug discovery) in establishing and ensuring that the quality attributes of mRNA therapeutic agents are maintained throughout the timeline of the drug development and manufacturing process

The title and scope are in draft form and are under development within this ASTM Committee.