Arexvy
respiratory syncytial virus vaccine, adjuvanted (AS01E) · RSV preF3; TLR4 (AS01E adjuvant)Not conducted for the vaccine (not required for vaccines)
Shingrix: genotox, carcinogenicity and repro: done or skipped?
zoster vaccine recombinant, AS01B-adjuvanted · VZV glycoprotein E; TLR4 (AS01B adjuvant)
Genotoxicity
Not conducted on the final vaccine formulation (considered acceptable)
“The Applicant did not provide genotoxicity data for the final vaccine formulation gE/AS01B, which is considered acceptable.”
Carcinogenicity
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.”
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
Rat EFD/pre-postnatal at 40% of human dose: no maternal toxicity or offspring effects
“Treatment of female CD rats with the candidate vaccine at 40% of the full human dose per occasion was well tolerated, did not lead to maternal toxicity, and did not adversely affect embryo-fetal or pre- and post-natal survival, growth or development of the offspring.”
Safety pharmacology
Dedicated studies: ICH S7 conscious dog with AS01B at full human dose, no cardiovascular or respiratory concern
“An ICH S7-compliant safety pharmacology study in the conscious Beagle dog with the AS01B adjuvant did not raise any concern on cardiovascular and respiratory function when a full human dose was administered.”
Genotox: Ames
DQ/QS-21 negative in Ames assay
“DQ and/or QS-21 were non-mutagenic in the Ames assay and mouse lymphoma assay.”
Genotox: in vitro mammalian
DQ/QS-21 negative in mouse lymphoma assay
“DQ and/or QS-21 were non-mutagenic in the Ames assay and mouse lymphoma assay.”
Genotox: in vivo
AS01B negative in rat micronucleus assay
“In a rat micronucleus assay, AS01B showed no evidence of causing micronuclei.”
Carcinogenicity model
Not conducted (not required for vaccines or adjuvants)
“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.”
Carcinogenicity timing
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.”
hERG / QT
No cardiovascular concern for AS01B in ICH S7 conscious dog study at full human dose
“An ICH S7-compliant safety pharmacology study in the conscious Beagle dog with the AS01B adjuvant did not raise any concern on cardiovascular and respiratory function when a full human dose was administered.”
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)
Gardasil 9
human papillomavirus 9-valent vaccine, recombinant · HPV 9-valent L1 VLPsNot conducted (vaccine guidance; CHMP agreed)
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)
HBVaxPro
hepatitis B vaccine (rDNA) · HBsAg VLPsNot stated in public reviews