Senator RENNICK: Okay, then I’ll ask the professors. There was no genotoxicity study done for the rollout of the vaccine. The vaccine has been rolled out now for up to 18 or 20 months. Has any genotoxicity study been performed on the vaccine given that there are a number of modifications to the spike protein that weren’t in the initial virus? Prof. Murphy: I’ll just see if Ms Duffy from the TGA is online, and whether TGA officials can provide any information about that. They are obviously across all of the material that’s submitted as part of the vaccine evaluation. Ms Duffy: I’m sorry, I don’t have that information, but I’m happy to take it on notice and bring it back on Thursday if that suits you. Senator RENNICK: That’s fine. Initially, when you looked at the assessment it said there were no genotoxicity studies done at all, or carcinogenic or longevity studies. I’m just curious if you’ve done any since? Ms Duffy: We’ll go back and be able to provide that information on Thursday.

Question Number: 4
PDR Number: SQ22-000355
Date Submitted: 08/11/2022
Department or Body: Department of Health

The mRNA vaccines approved in Australia consist of mRNA encoding the spike protein and lipid nanoparticles (LNP). Genotoxicity studies were not conducted with the final formulation of the vaccines, which is consistent with the WHO guidelines on non-clinical evaluation of vaccines available at: www.who.int/publications/m/item/nonclinicalevaluation-of-vaccines-annex-1-trs-no-927and the approach used by major international regulators. This is because the mRNA in these vaccines does not enter the nucleus of cells, is not integrated into the human genome, and does not cause genetic damage. The LNPs in both the Moderna and Pfizer mRNA vaccines comprise four lipids. Two ingredients (cholesterol and distearoylphosphatidylcholine) in both vaccines are natural constituents of cell membranes and present at high levels in the human body. The two other lipids (SM-102 and PEG-2000-DMG) in the Moderna vaccine (SPIKEVAX) were not genotoxic in bacteria or mammalian cell assays. The two other lipids (ALC-0315 and ALC-0159) in the Pfizer vaccine (COMIRNATY) were not tested for genotoxicity. However, there were no structural alerts for genotoxicity. Similar lipids are used in a siRNA drug product, ONPATTRO (patisiran), which has been approved for use in the USA, Canada and Europe Union countries for the treatment of hereditary transthyretin-mediated amyloidosis by IV infusion every three weeks. According to the Food and Drug Administration (USA) and the European Medicines Agency evaluations, the ONPATTRO formulation including LNPs were negative in genotoxicity tests. Furthermore, the human dose of the lipids in the vaccines is very low and is below the threshold of toxicological concern for genotoxicity as outlined in the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, Guideline M7(R1), available at: https://database.ich.org/sites/default/files/M7_R1_Guideline.pdf. Based on this information, the mRNA vaccines approved for use in Australia are not considered to have genotoxic properties.