How long were the pivotal tox studies for approved vaccines?

“A recovery group consisting of 10 males and 10 females rats per group were sacrificed 21 days after the interim necropsy (day 67). Study duration was 13 weeks.”

“Toxicology studies supporting the safety of the 9vHPV vaccine included 3 GLP-compliant studies in rats consisting of: i) a repeat-dose toxicity study (with local tolerance and non-GLP immunogenicity assessments), ii) an intramuscular developmental toxicity and immunogenicity study with female fertility and embryo-foetal evaluation and iii) an intramuscular developmental toxicity and immunogenicity study with postnatal evaluation.”

“Group of 10 male and 10 female rabbits were treated with AS01B by intramuscular injection into the muscles of each hind limb on seven occasions 14 days apart. They were given a dose volume of 500 µL of the formulation and thus received 50 µg MPL and 50 µg QS-21 in a liposomal formulation per dose. Five rabbits per sex per group (including control group) were euthanized 3 or 28 days after the last dose.”

“SHINGRIX has been evaluated in two repeat dose toxicity studies in rabbits, one reproductive-developmental toxicity study in rats, one male fertility study in rats, two local tolerance studies in rabbits, and one safety pharmacology study in rats.”

“A 10-week repeat-dose toxicity study was performed in BALB/c mice.”

“A 10-week repeat-dose toxicity study was performed in BALB/c mice. Vaccine-treated mice received 1 or 3 doses of Gardasil at a concentration of 160/160/80/160 μg/ml of the HPV types 6/11/16/18 L1 VLPs.”

“and included a 13-week recovery period. Animals were allocated randomly to 4 groups of 10 animals each, and received intramuscular injections in the paravertebral muscles on Days 1, 15, 29 and 57.”

“The treatment regimen of up to 4 vaccine injections at 2 week intervals with up to three times the human dosage exceeds the total number of intended clinical injections.”

“rats or cynomolgus monkey received subcutaneously (SC) either 0.5, 1.5, 12.5 mg/kg/week of 1018 ISS adjuvant or PBS weekly for 8 weeks.”

“The general safety of the 1018 ISS adjuvanted HBsAg vaccine was investigated in two pivotal studies were the vaccine was administrated by the IM injection, the clinical route of administration: a repeated-dose toxicity study in mice (study 00-95) where 3 IM doses were given (at day 0, 14 and 28) and a repeated dose toxicity study in rats (study 12-728) where 4 IM doses were given (at day 0, 14, 28 and 42).”

“In the 57-day repeat intramuscular toxicity study, rabbits were administered intramuscularly 4 doses (3 weekly and one additional 21 days later) of 50 ug SARS-CoV-2 rS with 50 ug Matrix-M or 50 ug Matrix-M alone.”

“The sponsor submitted two toxicity study reports (57-day repeat intramuscular toxicity study with and without Matrix-M adjuvant in rabbits and developmental and reproductive toxicology study of intramuscular administration of SARS-C0V-2 rS nanoparticle vaccine with Matrix-M adjuvant or Matrix-M alone in rats)”

“For the third study, an 8-week repeated dose toxicity study, the testing facility was not GLP certified at the time the study was performed in 2004.”

“In this study, three groups of Wistar rats were dosed IM on Days 0, 14 and 28 with 0.5mL of PreHevbri (2 or 10 µg HBsAg per animal), or Al(OH)3 adjuvant alone, and were observed for signs of toxicity for 8 weeks.”

“Five males and five females from each group were killed on Day 45 (3 days after the last injection) and the remainder on Day 70 of study (28 days after the last injection) in order to study recovery.”

“Two groups of 20 New Zealand White rabbits (10 males + 10 females) were administered 4 intramuscular (IM) injections at 2 weeks interval (Day 0, 14, 28 and 42) of the candidate vaccine.”

“The pivotal repeat-dose toxicity study was conducted with the SC route. Results showed that five weekly SC injections with RIV3 were locally and systemically well tolerated in rats.”

“The pivotal repeat-dose toxicity study was conducted with the SC route. Results showed that five weekly SC injections with RIV3 were locally and systemically well tolerated in rats.”

“Two GLP-compliant repeated dose toxicity studies (and) were conducted in New Zealand White rabbits (10/sex/group), which received three intramuscular injections (Day 1, Day 15 and Day 29, followed by a 4- week recovery period.)”

“Two GLP-compliant repeated dose toxicity studies (and) were conducted in New Zealand White rabbits (10/sex/group), which received three intramuscular injections (Day 1, Day 15 and Day 29, followed by a 4- week recovery period.)”

“Repeated-dose toxicity studies were presented, up to 7 days in rats and 14 days in Beagle dogs, where MPL was given once daily by the intravenous route, maximising the exposure.”

“Repeated-dose toxicity studies were presented, up to 7 days in rats and 14 days in Beagle dogs, where MPL was given once daily by the intravenous route, maximising the exposure.”

“The absence of toxicity was evaluated after repeated administrations in the rat according to treatment schedules mimicking a human vaccination scheme (i.e., 3 injections at monthly intervals).”

“The absence of toxicity was evaluated after repeated administrations in the rat according to treatment schedules mimicking a human vaccination scheme (i.e., 3 injections at monthly intervals).”