Abstract
The monkey neurovirulence test (MNVT) is the gold standard for neurovirulence safety assessment of oral polio vaccines and has been used for 80 years for lot specific release testing. The MNVT bioassay is also required for testing new vaccine seed lots for live attenuated neurotropic viruses when there is a change to manufacturing. The dosing procedure involves direct injection of a live virus into the central nervous system to evaluate neurobehavioral effects and histopathology changes.
We have validated the MNVT model and have evaluated live attenuated viral vaccines for yellow fever. In this webinar, we demonstrate successful evaluation of the neurovirulence of master and working seed lots of 17D viruses for yellow fever in comparison to Stamaril and the WHO 17D 168-73 reference vaccine. We will present data from study endpoints including changes in clinical scores and microscopic evaluation of the brain and spinal cord, plus measurement of viral replication.
No single species or test can predict the neurovirulence of all live viral vaccines. Southern Research supports the refinement of animal use and alternatives to the MNVT. As such, we present results from a pilot study in suckling CD-1 mice that uses intracranial administration and demonstrates high sensitivity. We also discuss recent regulatory acceptance of alternative rodent models for neurovirulence testing.
Speaker: Joseph Randall
Director of Toxicology, Southern Research
Joseph C. Randall, Ph.D., is the Director of Toxicology at Southern Research. Dr. Randall has more than 20 years of experience in drug development and management of regulated toxicology studies in support of IND and NDA applications. His expertise includes lead selection and optimization, in vitro and in vivo toxicology studies, safety pharmacology, genetic toxicology, and carcinogenicity assessment in rodents. Dr. Randall has extensive experience in the safety assessment of antivirals and drugs to treat neurodegenerative diseases, cancer, and ocular indications.
Dr. Randall’s deep understanding of FDA, ICH, and OECD guidance documents pertaining to both general and specialized toxicology studies has enabled him to co-author 5 successful NDAs and 10 INDs and contribute to several successful NDAs for extended release opioids and an abuse deterrent reformulation of oxycodone. In addition, Dr. Randall has participated in several FDA advisory committees to defend the safety of investigational drug candidates.
During his career, Dr. Randall has managed bioanalytical, pharmacokinetic, and GLP toxicology studies for Phase 1 and 2 clinical trials. For 8 years, he worked at Mallinckrodt Pharmaceuticals on the safety assessment of nanoparticle reformulations of cancer chemotherapeutics, oxaliplatin and docetaxel. He also developed two extended-release acetaminophen and opioid fixed dose combinations that were FDA approved and a novel abuse deterrent reformulation of Roxicodone using plant-based polymers and aversive agents to minimize diversion and use via non-oral routes. He has held leadership roles at Covance Laboratories, Amgen, Oxigene, Inc., Idenix Pharmaceuticals, MDS Pharma Services, Chemocentryx, Inc., and Kartos Therapeutics. Dr. Randall completed his doctoral and postdoctoral research in neurotoxicology at the University of Michigan in Ann Arbor.
