Jani, Niketa, Hays, Amanda, Pennucci, Jason, Adamowicz, Wendy, Azadeh, Mitra, Benhammadi, Mohamed, Portabella, Enric Bertran, Cheng, MingLai, Colletti, Kelly, Dholakiya, Sanjay L., Doddareddy, Rajitha, Duchstein, Lara, Durham, Jennifer, Guelman, Sebastian, Gullick, Bryan, Herr, Kate, Jani, Darshana, Johansson, Oskar, John, Kaarthik, Kubista, Mikael, Lavelle, Amy, Li, Geng, Liu, Hsing-Yin, Lochmann, Timothy, Ma, Haiyan, Moritz, Benjamin, Murphy, Jacqueline, Park, Alice, Park, Jeehae, Peddigari, Suresh, Piche, Marie-Soleil, Ramaswamy, Swarna Suba, Reddy, Asha, Smet, Muriel, Stanta, Johannes, Valentine, Jenny, Veirs, Katherine, Vepachedu, Venkata, Wissel, Mark, Wu, Meizhen, Xu, Bin and Zondlo, Susan (2025) Technical Considerations of Pharmacokinetic Assays for LNP-mRNA Therapeutics by RT-qPCR. AAPS PharmSci, 27. pp. 1-18.

Abstract

Lipid nanoparticle-messenger RNA (LNP-mRNA) therapeutics are a growing class of drug modalities. The unique composition of these therapeutics requires multiple measurements to account for the different components of these drug modalities. Pharmacokinetic (PK) measurements include measurement of the encapsulated mRNA and components of the LNP in circulation to understand the effectiveness of the therapeutic mRNA. The PK measurements can utilize many different platforms including PCR. Current regulatory guidance documents for bioanalytical method validation are specific to ligand binding and chromatographic assay methods and difficult to interpret for use with molecular workflows. The purpose of this paper is to provide information on considerations for validation of regulated reverse transcription quantitative PCR (RT-qPCR) assays that are used to support the pharmacokinetic analysis of LNP-mRNA therapeutics.

Item Type:	Article
Date Deposited:	03 Oct 2025 00:45
Last Modified:	03 Oct 2025 00:45
URI:	https://oak.novartis.com/id/eprint/56510