Nonclinical precedent Request an invite
Precedia/Protein and VLP vaccines/Fendrix/Flexibility

Fendrix: what flexibility did regulators accept, and why?

hepatitis B vaccine (rDNA), AS04C-adjuvanted · HBsAg VLPs; TLR4 (AS04C adjuvant)
Check my plan vs. these
Flexibility accepted
BiodistributionAccepted with a conditionBeyond the letter
No distribution or excretion data for the final vaccine or AS04C adjuvant
Why: Applicant assumes adsorbed materials follow unadsorbed aluminium particle distribution and elimination; applicant committed to report study results · Pharmacology or kinetics
“Only limited pharmacokinetic data were generated in this study. Neither distribution nor excretion data are available for the final HB-AS04C vaccine or the AS04C adjuvant. The Applicant committed to report the results of this study.”
✓ VerifiedEMA assessment report, p. 24Source ↗
“Neither distribution nor excretion data are available for the final HB-AS04C vaccine or the AS04C adjuvant. However, the applicant assumes that aluminium salt particles containing adsorbed materials follow the same distribution and elimination as for unadsorbed aluminium particles.”
✓ VerifiedEMA assessment report, p. 9Source ↗

Same question, other vaccines

Arexvy

respiratory syncytial virus vaccine, adjuvanted (AS01E) · RSV preF3; TLR4 (AS01E adjuvant)
Toxicity studies used AS01B adjuvant (double immunoenhancer dose) instead of the clinical AS01E formulation

Cervarix

human papillomavirus bivalent (types 16, 18) vaccine, recombinant, AS04-adjuvanted · HPV 16/18 L1 VLPs; TLR4 (AS04 adjuvant)
No genotoxicity or carcinogenicity studies with the vaccine (MPL adjuvant genotoxicity tested only)

Cyfendus

anthrax vaccine adsorbed, adjuvanted · B. anthracis PA; TLR9 (CpG 7909 adjuvant)
Effectiveness established from animal post-exposure survival studies under the Animal Rule instead of human efficacy trials

Flublok

influenza vaccine, recombinant hemagglutinin · Influenza HA
No nonclinical toxicity or pharmacology studies with the quadrivalent vaccine; package bridged from trivalent RIV3

Gardasil

human papillomavirus quadrivalent (types 6, 11, 16, 18) vaccine, recombinant · HPV 6/11/16/18 L1 VLPs
No dedicated safety pharmacology studies; physical signs monitored within toxicity studies

Gardasil 9

human papillomavirus 9-valent vaccine, recombinant · HPV 9-valent L1 VLPs
No safety pharmacology study

HBVaxPro

hepatitis B vaccine (rDNA) · HBsAg VLPs
No dedicated nonclinical studies with HBVaxPro; data extrapolated from HEXAVAC, PROCOMVAX and the thiomersal-containing vaccine

Heplisav-B

hepatitis B vaccine (recombinant), adjuvanted · HBsAg; TLR9 (CpG 1018 adjuvant)
Adjuvant-alone 8-week repeat-dose study designs not representative of the clinical dose regimen

Mosquirix

RTS,S/AS01 malaria vaccine · P. falciparum CSP-HBsAg (RTS,S) VLPs; TLR4 (AS01 adjuvant)
No reproductive and developmental toxicity studies

Nuvaxovid

COVID-19 vaccine, recombinant spike protein nanoparticle, Matrix-M-adjuvanted · SARS-CoV-2 spike (nanoparticle)
Rat DART used Matrix-M1 below the absolute human dose (maximum volume of clinical formulation)

PreHevbrio

hepatitis B vaccine (recombinant), 3-antigen · HBsAg S/pre-S1/pre-S2 VLPs
Pivotal repeat-dose toxicity study in rats not GLP-compliant

Shingrix

zoster vaccine recombinant, AS01B-adjuvanted · VZV glycoprotein E; TLR4 (AS01B adjuvant)
Vaccine DART only in rats at 40% of the human dose; no full-human-dose rabbit study

Summary across all 13 vaccines →