Advances in Therapeutic Development Across Modalities

Hot Topic: Bioanalytical Challenges and Strategies for Novel Drug Modalities

Wednesday, April 26, 2023

10:00 AM – 11:00 AM ET

Location: Salon B, 5th Floor

Hot Topic Speaker(s)

Eric F. Tewalt, PhD

Director
PPD, part of Thermo Fisher Scientific
Richmond, Virginia, United States
Sebastian Guelman, PhD

Senior Principal Scientist
Genentech, Inc., United States

Handouts
JD

Jason DelCarpini

Associate Director
Moderna, United States

Hot Topic Moderator(s)

Jason Pennucci (he/him/his)

Director
Moderna Therapeutics
Cambridge, Massachusetts, United States

Hot Topic Speaker(s)

Ling Morgan, PhD

Director
Moderna

Ionizable lipid and PEG lipids are the essential component of lipid nanoparticle (LNP) delivery systems used in mRNA therapies. The accurate and precise quantification of ionizable lipids is critical to monitor their in vivo post-dosing levels to understand their safety, kinetics, and metabolism. Given the nature of analytes and the required specificity and sensitivity for the bioanalytical method, LC/MS/MS is the standard choice for quantitating lipids in complex matrices like plasma, urine, and tissues. However, several bioanalytical challenges are associated with quantifying ionizable lipids in LNP formulations. These challenges include the lack of reference standards, readily available stable-isotope-labeled internal standards, interference from other LNP components and matrices, and the diversity of ionizable lipids used in LNP formulations. In addition, the instability of the lipids in biological matrices is another considerable challenge for accurately measuring lipid levels, e.g., PEG-Lipid degrades to free PEG-OH in the plasma due to esterase activity. Addressing these challenges requires interdisciplinary collaborations between multifunctional groups.

Learning Objectives:

Upon completion, participant will be able to understand why the LNP is monitored using ionizable lipids as the surrogate.
Upon completion, participant will be able to recognize the challenges in developing bioanalytical assays for ionizable lipids in LNPs to support LNP drug delivery programs.
Upon completion, participant will be able to recognize the challenges in developing bioanalytical assays for novel PEG lipids to support LNP drug delivery programs.