Arexvy
respiratory syncytial virus vaccine, adjuvanted (AS01E) · RSV preF3; TLR4 (AS01E adjuvant)Not conducted for the vaccine (not required for vaccines)
Heplisav-B: genotox, carcinogenicity and repro: done or skipped?
hepatitis B vaccine (recombinant), adjuvanted · HBsAg; TLR9 (CpG 1018 adjuvant)
Genotoxicity
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.”
Carcinogenicity
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.”
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 multigeneration DART study: stillbirths and skeletal anomalies only secondary to maternal toxicity at 200-fold the clinical CpG 1018 dose
“In a multigeneration reprotoxicological study in rats, effects on the offspring (stillborn pups and skeletal abnormalities) occurred secondary to maternal toxicity at a dose 200-fold the proposed clinical dose of Heplisav B with respect to 1018 ISS on a body weight basis.”
Safety pharmacology
Dedicated rabbit and baboon escalation studies: no adverse effects up to 1.6 mg/kg (rabbit) and 25 mg (baboon) CpG 1018
“No adverse effects were identified in 2 safety-pharmacology studies with doses of 1018 ISS up to 1.6 mg/kg in rabbits and 25 mg in baboons.”
Genotox: Ames
Bacterial mutation test negative up to 5 mg/plate
“In conclusion, the test article 1018 ISS did not show any evidence or genotoxicity in this in vitro test for mutagenicity when tested up to the maximum concentration of 5 mg/plate.”
Genotox: in vitro mammalian
In vitro chromosome aberration test: negative
“In conclusion, the test article 1018 ISS did not show any evidence or genotoxicity in this in vitro test for induction of chromosome damage when tested up to the maximum concentration 5 mg/plate.”
Genotox: in vivo
Mouse micronucleus assay: negative
“Therefore, 1018 ISS did not show any evidence of genotoxic activity and was found negative in the mouse micronucleus assay.”
Carcinogenicity model
Not conducted (ICH S1A; sporadic vaccine 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.”
Carcinogenicity timing
Not required for this type of product (vaccine, sporadic exposure; ICH S1A)
“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.”
hERG / QT
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.
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)
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