Mr. Speaker, Health Canada exercises stringent regulatory oversight over all pharmaceutical and biologic drugs, including vaccines. Before a drug is authorized in Canada, Health Canada conducts a rigorous scientific review of its safety, efficacy and quality.
For the quality of the mRNA COVID-19 vaccines, Comirnaty and Spikevax, impurities in lipid nanoparticles, LNPs, are assessed according to guidelines from the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, or ICH. These guidelines include ICH Q3C “Impurities: Guideline for Residual Solvents” and ICH Q3D “Guideline for Elemental Impurities”.
Assessment of the risks associated with potential and known impurities in the mRNA vaccines was performed using common industry software that is accepted as part of the ICH M7 guideline: “Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk”.
Impurities from the lipid excipients were below the limits set in the ICH Q3D and ICH Q3C guidelines. All solvents assessed were classified as non-mutagenic. Assessment of elemental impurities concluded that levels were below the permitted daily exposure, PDE. The methodologies used by the manufacturer to assess mutagenic risk from solvents and elemental impurities and their conclusions were considered acceptable.
LNPs in the mRNA vaccines were characterized and controlled using a variety of tests. The polyethylene glycol, PEG, moiety is conjugated to the lipid excipient and was assessed as part of the lipid. Residual unconjugated PEG is considered a process-related impurity in the manufacturing process of the lipid excipient and must be present below established limits. The PEG moiety itself is also classified as non-mutagenic according to ICH M7 guidelines. Each lot of drug product is tested to ensure that it conforms with approved specifications. The control strategy for the LNPs was considered acceptable.
Non-clinical safety studies were performed for the novel lipid excipients. Complement-related assays were not requested from the manufacturer as there is no established assay that can be performed to assess hypersensitivity to PEG.
For Onpattro, impurities are assessed according to guidelines from the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, ICH. These guidelines include ICH Q3C “Impurities: Guideline for Residual Solvents”, ICH Q3D “Guideline for Elemental Impurities” and the ICH M7 guideline: “Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk”.
Impurities from the lipid excipients were below the limits set in the ICH Q3D and ICH Q3C guidelines. All solvents assessed were classified as non-mutagenic or unlikely to be present. LNPs in the drug product Onpattro were assessed using a pharmacologically inactive short-interfering RNA, or siRNA, encapsulated in the same lipid particle as the one with the active siRNA, patisiran. The LNP comprised two novel excipients which were fully characterized with a complete toxicology evaluation.