Vaccine not tested; MPL adjuvant negative in Ames, CHO clastogenicity and in vivo micronucleus
“The in vitro mutagenicity (Ames) and clastogenicity (CHO cells) tests, and in vivo micronucleus assay demonstrated no genotoxic potential of the MPL adjuvant.”
Not conducted; accepted as the vaccine is L1 protein without HPV oncoproteins
“The mutagenic and carcinogenic potential of the Cervarix vaccine was not further evaluated, which is accepted since the vaccine is based on L1 protein and HPV oncoproteins are absent.”
influenza vaccine, recombinant hemagglutinin · Influenza HA
Genotoxicity
Not conducted (not normally required for viral vaccines; no adjuvant)
“No genotoxicity and carcinogenicity studies were carried out in line with relevant guidelines. Studies evaluating genotoxicity and carcinogenicity are normally not required for viral vaccines.”
Not conducted (not normally required for viral vaccines; no adjuvant or novel excipients)
“Studies evaluating genotoxicity and carcinogenicity are normally not required for viral vaccines. Since no adjuvants or novel excipients are used in this product absence of those studies is considered acceptable.”
“The oncogenic/carcinogenic potential of the 9vHPV vaccine in long and short-term studies was not evaluated. According to current requirements as mentioned above, carcinogenicity studies are generally not required for vaccines and this is acceptable also for Gardasil 9.”
CpG adjuvant negative in Ames, in vitro chromosome aberration and in vivo mouse micronucleus tests
“No genotoxicity was observed in the standard battery of tests composed of in vitro bacterial mutation, chromosome aberration and in vivo mouse erythrocyte micronucleus test.”
Not conducted (vaccine and adjuvant guidelines, ICH S1A; sporadic exposure)
“No studies assessing the carcinogenicity of Heplisav B or 1018 ISS adjuvant have been performed. This is acceptable for this type of product in line with EMAs guidelines for vaccines and adjuvants and compliant with ICH S1A, considering that the exposure to this vaccine will be sporadic.”
Not conducted on the final vaccine; adjuvant system components tested instead
“Vaccines are not used in the long term and this reduces risk from consequences of genotoxicity. However, the genotoxic potential of the Adjuvant System and its components should be understood.”
Not conducted (not required for vaccines, adjuvant systems or immunoenhancers per WHO/EMA guidance)
“According to the WHO Guidelines on Nonclinical Evaluation of Vaccines (WHO, 2005), the EMEA Note for Guidance on Preclinical Pharmacological and Toxicological testing of Vaccines (CPMP/SWP/465/95) and the Guideline on adjuvants in vaccines for human use (EMEA/CHMP/VEG/134716/2004), carcinogenicity studies are not required for final vaccine formulations, Adjuvants Systems and/or immunoenhancers.”
Matrix-M1 adjuvant negative in GLP Ames and in vitro CHO micronucleus assays; in vivo testing judged unnecessary
“The confirmatory GLP-compliant bacterial reverse mutation assay and Mammalian Cell Micronucleus assay in CHO Cells with Matrix-M1 confirmed the absence of any indication for a genotoxic potential of Matrix-M1. Further in vivo studies were therefore not considered necessary.”
Not conducted (WHO vaccine and adjuvanted vaccine guidelines)
“No carcinogenicity studies have been performed with the SARS-CoV-2 rS vaccine and Matrix-M1 adjuvant in accordance with the WHO Guidelines on Non-clinical Evaluation of Vaccines (2005) and Guidelines on the Non-clinical Evaluation of Vaccine Adjuvants and Adjuvanted Vaccines (2014).”
Not conducted (not required for vaccines, adjuvant systems or immunoenhancers)
“Carcinogenicity studies were not performed. As carcinogenicity studies are not required for final vaccine formulations, adjuvants systems and/or immunoenhancers based on current guidelines, this was considered acceptable.”