A&M Stabtest are a quality control company specialising in stability and release testing of pharmaceuticals from small and large molecules to mRNAs and gene therapies, facilitating market entry. This presentation outlines a case study whereby they worked on identifying an inhalable mRNA formulation for a client, this involved development of a testing workflow and analytical techniques to evaluate various formulations.
Steven Watt, managing director of A&M Stabtest, presented on the quality control (QC) and formulation analysis of inhalable mRNAs and oligonucleotides. He began by introducing his background in biology, molecular biology, and biotechnology, and his experience in mass spectrometry for pharmaceutical development and QC analysis.
Nebulisation was identified as the easiest method to deliver drugs to the lungs, but the process itself stressed the samples, causing disruptions in lipid nanoparticles (LNPs) and mRNA. Various analytical methods were employed to assess formulation stability, including DLS analysis for size distribution and polydispersity, encapsulation efficiency assessments, and potency assays.
The luciferase assay was chosen for potency testing due to its sensitivity, despite the high cost of reagents. The TAMARA mixing device was used for lab-scale formulation, followed by QC checks, dialysis, and potency assessments. Aerosolisation significantly impacted formulation quality, leading to decreased encapsulation efficiency and mRNA integrity.
For antisense oligonucleotides, LC-MS was used to evaluate the oligonucleotide quality, bypassing the need for a potency assay. The presentation concluded with a brief overview of the TAMARA system's effectiveness and future plans to improve the workflow.
Watt's presentation provided valuable insights into the challenges and methodologies for developing effective inhalable mRNA and oligonucleotide formulations, highlighting the importance of robust analytical techniques and careful evaluation of formulation stability.
