Developmental and reproductive toxicology (DART) studies in laboratory animals represent a valuable tool to assess the potential risk to women of child bearing potential, to the developing offspring and to the fertility of exposed men and women following exposure to an agent.
The purpose of this presentation is to discuss how DART capabilities have been introduced into an established toxicology laboratory at Southern Research, in compliance with Good Laboratory Practices (GLP). Various study types are required to meet regulatory requirements for DART, including fertility, embryo-fetal development (i.e. Teratology), and multigeneration reproduction studies. Studies must be conducted in compliance with GLPs and data are collected and reported using Provantis 8™, a validated, GLP compliant computer system. Data from positive control and training studies in rats and rabbits, as well availability of historical control data, will be discussed.
A virtual tour of the laboratory installations will include the Core Teratology Laboratory, where maternal necropsy and fetal examinations are conducted; and the Skeletal Laboratory, where processing, staining, and examination of fetal skeletal specimens are performed. Laboratories feature stereomicroscopes for micro dissection of fetuses, a dual head stereomicroscope and large screen display for training, and digital cameras for capture of images of fetal anomalies. In addition, the Andrology Laboratory, where analysis of sperm parameters is conducted, is equipped with computer-assisted rodent sperm analysis technology.
Kellye K. Daniels, Ph.D., D.A.B.T., Director, Toxicology and Pathology Services Department, Southern Research
Kellye K. Daniels, Ph.D., D.A.B.T. (Director, Toxicology and Pathology Services Department) is a board-certified toxicologist (ABT) with extensive laboratory and contract research experience in general toxicology; mechanisms of hepato-, neuro-, cardio-, and nephrotoxicity; and in identification of genomic biomarkers of toxicity/injury. She joined Southern Research in August of 2007.
Prior to this, Dr. Daniels held positions as Director of Toxicogenomics at Gene Logic in Gaithersburg, MD; Program Director at Phase-1 Molecular Toxicology in Santa Fe, NM; and Project Leader for Pharmacogenomics at CuraGen Corporation in Branford, CT.
Dr. Daniels has a B.S. degree in Biology from the Florida State University (1990), a M.S. degree in Zoology from the University of South Florida (1994), and a Ph.D. degree in Neuroscience from the University of Florida College of Medicine (1997) with postdoctoral training in Physiological Sciences at the University of Florida College of Veterinary Medicine.
She has served as study director for preclinical in vivo and in vitro toxicology studies for biotechnology and pharmaceutical companies and for U.S. governmental agencies (e.g., Toxicology & Pharmacology Branch, DTP, DCTD, NCI; Chemopreventive Agent Development Research Group, DCP, NCI), collaboratively assisting sponsors with the conduct of pharmacokinetic studies and dose range finding, acute, and subchronic toxicity studies across a diverse range of test articles, including biologicals (e.g., vaccines, gene therapy vectors), small molecules, environmental contaminants and botanical extracts. Many of these studies were designed to meet the regulatory requirements of the U.S. FDA’s Good Laboratory Practice (GLP) Regulations (21 CFR Part 58) and were conducted in a variety of species, including mouse, rat, rabbit, ferret, canine, and nonhuman primate.
Her current responsibilities include direction of all Departmental activities, including supervision of staff in the areas of Study Direction, Developmental and Reproductive Toxicology, Anatomic Pathology, Clinical Pathology, Study Coordination, and In-Life Laboratory. She is a member of the Society of Toxicology.
Eve Mylchreest, Ph.D., Program Leader, Developmental and Reproductive Toxicology (DART), Southern Research
Eve Mylchreest, Ph.D. joined Southern Research in 2010 as Program Leader to build a new program in Developmental and Reproductive Toxicology (DART). Over the past 15 years, Dr. Mylchreest has acquired the scientific and technical experience necessary to successfully implement a DART testing program. Her prior work experience includes Principal Research Scientist in Reproductive Toxicology at Pfizer (formerly Wyeth), where she was a study director and toxicologist on drug development project teams.
Dr. Mylchreest was the technical leader and manager of Reproductive Toxicology at DuPont Haskell Laboratory, where she led consulting, research, and safety testing in this area. She has extensive experience with DART studies for small molecules, proteins, vaccines, pesticides, and commodity chemicals in various species; and considerable hands-on experience with staff training, instrument validation, and procedure development.
Dr. Mylchreest completed a postdoctoral fellowship at the Chemical Industry Institute of Toxicology, and has Bachelor’s (biochemistry), Master’s and Doctorate (toxicology) degrees from the University of Montreal, Canada.
Stephen B. Harris, Ph.D., Fellow, ATS, President, Stephen B. Harris Group
Stephen B. Harris, Ph.D., Fellow, ATS, is the President of Stephen B. Harris Group in San Diego, CA, since September 1982. He has over 40 years of experience in developmental and reproductive toxicology (DART).
Dr. Harris has been an independent consultant for over 25 years. He holds an Adjunct Associate Professorship in the Graduate School of Public Health at San Diego State University. His area of expertise includes (1) scientific interpretation of data from DART studies, (2) CRO client pre-qualification site assessments, (3) CRO testing facility design, operations, and study monitoring, (4) management and training of CRO personnel especially in DART testing, (5) due diligence, and (6) product liability issues. He has authored many opinion papers and critiqued numerous technical reports for the pharmaceutical and chemical industries to assure compliance with worldwide regulatory requirements for product approval.
Dr. Harris has been invited to deliver several national and international scientific presentations and workshops. Dr. Harris is on the Editorial Board of the International Journal of Toxicology and the Journal of Environmental Science and Health, Part C, Environmental Carcinogenesis and Ecotoxicology Reviews (ECER). Dr. Harris was President of the American College of Toxicology (2006-2007) and currently is a Fellow of the Academy of Toxicological Sciences.
Who Should Attend?
Technical, regulatory and management leaders at Biotech and Pharmaceutical companies as well as students, postdoctoral scientists and experienced subject matter experts from academia interested in submitting compounds, vaccines and biologics for FDA approval with the ultimate goal of supplying marketed pharmaceutical products.
This webinar will also benefit individuals interested in setting up a GLP-compliant reproductive toxicology program in a general toxicology laboratory, benefiting from individuals with firsthand experience in establishment of a reproductive toxicology program and in the execution of reproductive toxicology studies under FDA GLP regulations.
We have one presenter with many years of program overview as an industry-leading consultant, along with staff with study director and management responsibilities for GLP-studies funded by government agencies and industry sponsors.
Functional areas include: Pre-Clinical Development, Pre-Clinical Pharmacology, Pre-Clinical Research, Operations, Pre-Clinical Drug Development, CMC, Regulatory Affairs, Quality Assurance and Quality Control
Since 1941, the people of Southern Research have contributed to scientific advancements leading to life-saving drugs, safer space exploration, cleaner air and energy production, and enhanced national defense. Southern Research is a not-for-profit, 501(c)(3) organization conducting basic and applied research in Alabama, Maryland, and North Carolina in the areas of drug discovery, preclinical drug development, advanced engineering, and environmental protection.
Southern Research has a remarkable cancer-fighting track record, having discovered seven FDA-approved drugs used in the treatment or cancer and seven currently in preclinical development or clinical trials. As a leading contract research organization, Southern Research provides preclinical drug development services to pharmaceutical and biotechnology companies on an outsourced basis. Southern Research maintains capabilities in all phases of the early-stage drug discovery and development process and provides clients with comprehensive services and support to assist them in streamlining their custom drug discovery and development programs.