Arexvy
respiratory syncytial virus vaccine, adjuvanted (AS01E) · RSV preF3; TLR4 (AS01E adjuvant)Not conducted for the vaccine (not required for vaccines)
Gardasil 9: genotox, carcinogenicity and repro: done or skipped?
human papillomavirus 9-valent vaccine, recombinant · HPV 9-valent L1 VLPs
Genotoxicity
Not conducted (vaccine guidance; CHMP agreed)
“The in vitro and in vivo genetic toxicity/mutagenic potential of the 9vHPV vaccine were not evaluated.”
Carcinogenicity
Not conducted (not required for vaccines)
“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.”
Instead of carcinogenicity
Not stated in public reviews
Not reported in the public reviews. Reviewers summarise selectively, so this usually means it wasn't discussed publicly, not that it wasn't studied.
Instead of genotoxicity
Not stated in public reviews
Not reported in the public reviews. Reviewers summarise selectively, so this usually means it wasn't discussed publicly, not that it wasn't studied.
DRG histopathology
Not stated in public reviews
Not reported in the public reviews. Reviewers summarise selectively, so this usually means it wasn't discussed publicly, not that it wasn't studied.
Reproductive & developmental
Two GLP rat studies (fertility/EFD and postnatal); no adverse effects; up to 240 and 160 times human dose (mg/kg)
“Reproduction studies have been performed in rats at doses up to 240 and 160 times the human dose on mg/kg basis and revealed no evidence of impaired fertility or harm to the fetus due to V503 vaccine.”
Safety pharmacology
Not conducted; no CNS, respiratory, cardiovascular or renal signs in toxicity or clinical studies (CHMP accepted)
“Therefore, given that there were no signs of CNS, respiratory, cardiovascular and renal effects for the 9vHPV vaccine, a nonclinical safety pharmacology study was deemed to be not necessary for the 9vHPV vaccine. This was found acceptable by the CHMP under the current requirements.”
Genotox: Ames
Not conducted (vaccine)
“No studies have been performed in animals to evaluate the carcinogenic potential and the genotoxic risk of V503 vaccine.”
Genotox: in vitro mammalian
Not conducted (vaccine)
“No studies have been performed in animals to evaluate the carcinogenic potential and the genotoxic risk of V503 vaccine.”
Genotox: in vivo
Not conducted (vaccine)
“No studies have been performed in animals to evaluate the carcinogenic potential and the genotoxic risk of V503 vaccine.”
Carcinogenicity model
Not conducted (not required for vaccines)
“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.”
Carcinogenicity timing
Not required for vaccines
“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.”
hERG / QT
Safety pharmacology not conducted
“Safety pharmacology studies were not performed for the 9vHPV vaccine.”
Same question, other vaccines
Cervarix
human papillomavirus bivalent (types 16, 18) vaccine, recombinant, AS04-adjuvanted · HPV 16/18 L1 VLPs; TLR4 (AS04 adjuvant)Vaccine not tested; MPL adjuvant negative in Ames, CHO clastogenicity and in vivo micronucleus
Cyfendus
anthrax vaccine adsorbed, adjuvanted · B. anthracis PA; TLR9 (CpG 7909 adjuvant)Not conducted
Fendrix
hepatitis B vaccine (rDNA), AS04C-adjuvanted · HBsAg VLPs; TLR4 (AS04C adjuvant)MPL only: negative in Ames and CHO clastogenicity tests; vaccine not tested
Flublok
influenza vaccine, recombinant hemagglutinin · Influenza HANot conducted (not normally required for viral vaccines; no adjuvant)
Gardasil
human papillomavirus quadrivalent (types 6, 11, 16, 18) vaccine, recombinant · HPV 6/11/16/18 L1 VLPsNot conducted (CPMP/SWP/465/95 vaccine guidance)
Heplisav-B
hepatitis B vaccine (recombinant), adjuvanted · HBsAg; TLR9 (CpG 1018 adjuvant)CpG adjuvant negative in Ames, in vitro chromosome aberration and in vivo mouse micronucleus tests
Mosquirix
RTS,S/AS01 malaria vaccine · P. falciparum CSP-HBsAg (RTS,S) VLPs; TLR4 (AS01 adjuvant)Not conducted on the final vaccine; adjuvant system components tested instead
Nuvaxovid
COVID-19 vaccine, recombinant spike protein nanoparticle, Matrix-M-adjuvanted · SARS-CoV-2 spike (nanoparticle)Matrix-M1 adjuvant negative in GLP Ames and in vitro CHO micronucleus assays; in vivo testing judged unnecessary
PreHevbrio
hepatitis B vaccine (recombinant), 3-antigen · HBsAg S/pre-S1/pre-S2 VLPsNot conducted (in line with applicable guidelines)
Shingrix
zoster vaccine recombinant, AS01B-adjuvanted · VZV glycoprotein E; TLR4 (AS01B adjuvant)Not conducted on the final vaccine formulation (considered acceptable)
HBVaxPro
hepatitis B vaccine (rDNA) · HBsAg VLPsNot stated in public reviews