Scientific Liaison Coalition (SLC)
Improving the ability of societies to partner with other domestic and international organizations with the goal of advancing science to improve human and environmental health
For information on joining the SLC, email Heather Carskaddan at firstname.lastname@example.org.
Current Supporting and Participating SLC Organizations
Yearly Participation Dues Levels:
SOT FutureTox V: New Technologies to Evaluate Organ-Specific Effects for Drugs and Chemicals
Issue StatementCommunicating Biomedical Health-Related Research Findings: A Guide to Maintaining Balance and Avoiding Common Pitfalls
All webinars are viewable in a protected format to prevent downloading.
Virtual Roundtable: Recent Experiences Planning Virtual Scientific Meetings
Wednesday, December 2, 2020, 11:00 AM—12:30 PM ET USA
Roundtable Speakers: Kirk L. Cumpston, DO, President of the American Academy of Clinical Toxicology; Elise Madison Lewis, PhD, President of the Society for Birth Defects Research and Prevention; and Lawrence D. Sloan, CAE, CEO of the American Industrial Hygiene Association.
Moderator: Anne H. Chappelle, PhD, DABT, Chair of the Scientific Liaison Coalition (SLC).
The global COVID-19 pandemic caused significant disruptions, delays, and cancellations of scientific meetings in 2020. You are invited to attend a facilitated roundtable where leaders of three organizations will share their recent experiences in transitioning from the traditional ‘in person’ scientific meeting to a virtual experience. The goal is to engage in a discussion about:
The target audience for this roundtable includes leaders and volunteers involved in the planning of their scientific organizations’ meetings as well as staff or contractors who support the planning and execution of such meetings.
Big Data: What Is It and What Does It Mean to Me?
Thursday, April 2, 2020 at 11:00 AM—12:30 PM ET USA
Presented by Dr. Aric LaBarr and Dr. Alyson Wilson, North Carolina State University
In this ever-changing world of technology and information, data are everywhere. Everything—from the products we buy to the food we eat—can be monitored with data. With all these data coming with such variety and volume, how can we use this information to make better decisions? Data science and analytics collect and derive data-driven results from this ever-growing pile of information. This talk describes the ever-growing amount of data in the world as well as many of the latest applications of technology to gather data for making better decisions.
Dr. Aric LaBarr is a Teaching Associate Professor in the Institute for Advanced Analytics. He is passionate about helping people solve challenges using their data. Previously, he was Director and Senior Scientist at Elder Research, and was for several years earlier a member of the Institute’s faculty teaching classes in statistics, mathematics, finance, risk management, and operations research. Dr. LaBarr holds a BS in economics, as well as a BS, MS, and PhD in statistics—all from NC State.
Dr. Alyson Wilson is a Professor in the Department of Statistics, Principal Investigator for the Laboratory for Analytic Sciences, and Director of the Data Science Initiative at North Carolina State University. Her research interests include statistical reliability, Bayesian methods, and the application of statistics to problems in defense and national security. Prior to joining NC State, Dr. Wilson worked at the IDA Science and Technology Policy Institute (2011–2013), in the Department of Statistics at Iowa State University (2008–2011), in the Statistical Sciences Group at Los Alamos National Laboratory (1999–2008), and at Cowboy Programming Resources (1995–1999). She is a Fellow of the American Statistical Association and the American Association for the Advancement of Science. She holds a Ph.D. in statistics from Duke University.
Occupational Exposures and Pregnancy: A Balancing Act
Tuesday, February 11, 2020 at 11:00 AM—12:00 Noon ET USA
Presented by Richard K. Miller, PhD, University of Rochester
Women in the workplace are confronted by so many issues from this current topic to the use of opioids, vaping, smoking and therapeutic medications when preparing to conceive; however, it is well known that 50% of pregnancies are unplanned. Thus, these women and their health care providers are confronted with how the workplace exposures will impact their pregnancy and baby. Yet many working women accept and do not question their working conditions and exposures until they are pregnant. The objective of this presentation is to sensitize all working women and their health care providers to have discussions of their workplace conditions at their regular health visits, to encourage health care providers and their company counterparts to explore the workplace conditions for every woman in her reproductive years especially to prevent harmful exposures during pregnancy.
Such a recommendation does not exclude the male; however, the concentration for the moment is on the woman in the workplace. We will explore the history of women in the workplace, regulations, assessing exposure risk, working with the patient, primary health care provider and her employer. Lessons learned will arise from case studies presented not only for workplace exposures but also non-work exposures that can require in depth counseling, action and making difficult choices for the pregnant mother and her family. It is hoped that the participant in this discussion will leave feeling their questions have been answered, their toolbox has many more options and their confidence is enhanced to intervene when necessary to remove the woman from the workplace.
Health Hazards of Electronic Cigarettes
September 17, 2019, 11:00 AM–12:00 PM ET USA
Presented by Neal L. Benowitz MD, Professor Emeritus of Medicine, University of California San Francisco
The impact of electronic cigarette use on population health is strongly influenced by the harms and risks of e-cigarettes. The harm from cigarette smoking is to a great extent caused by toxic products of tobacco combustion. E-cigarettes deliver nicotine in an inhalable aerosol without combustion. E-cigarettes do deliver propylene glycol, vegetable glycerin, various flavoring chemicals and their various thermal breakdown products, as well as particles; some of these chemicals are potentially toxic. E-cigarettes vary considerably in design, and the risk is almost certainly greater with those with bigger batteries that operate at higher temperatures. The long-term safety of e-cigarettes is unknown at this time. Major current health concerns in the U.S. relate to e-cigarette use by youth, particularly with respect to impaired adolescent brain development, development of nicotine addiction and serving as a gateway to cigarette and other drug use. Short-term adverse effects include increased respiratory symptoms and asthma, although in smokers with chronic lung disease who switch completely to e-cigarettes their respiratory symptoms improve. Other health concerns include cardiovascular toxicity (particularly in people with pre-existing heart disease) and reproductive toxicity during pregnancy. Direct nicotine toxicity from ingestion of nicotine-containing liquids can occur, particularly in children, but is uncommon.
Maternal Morbidity and Mortality: A Primer on the Problem, and What We Can Do About It
Tuesday, February 5, 2019, 11:00 AM–12:30 PM ET USA
Presented by Suzan Carmichael, PhD, Stanford School of Medicine, Stanford, California and Emma Roberts, MPH, Hartford Hospital, Hartford, Connecticut
Despite the United States spending more money per capita on maternity care than any other country in the world, maternal mortality and severe maternal morbidity have increased substantially in recent decades. Furthermore, racial-ethnic disparities are strong for these outcomes; they are two to four times higher among black women than non-Hispanic white women. Maternal mortality is the death of a woman due to pregnancy or post-delivery complications; severe maternal morbidity encompasses a variety of conditions and procedures that identify women at highest risk of maternal mortality. Ms. Roberts will further define these outcomes and explain how they are assessed, and she will describe their prevalence, recent trends, common causes, and disparities. Dr. Carmichael will then discuss what are the potential causes of these outcomes, including their increasing prevalence and disparities. She will discuss a range of factors, including maternal sociodemographic characteristics, co-morbidities, and care. She will close with a discussion of efforts that are being made to prevent these unfortunate outcomes, including research endeavors, legislative efforts, and innovative approaches to care. Dr. Carmichael is a perinatal epidemiologist and Professor of Pediatrics at the Stanford University School of Medicine. Her research focuses on maternal and infant health and emphasizes nutrition, social determinants, environmental contaminants, and care. She is particularly interested in understanding the intersectionality of these varied types of exposures, and how they interact to impact health and health disparities, for the mother-baby dyad. Ms. Roberts is a 2018 graduate of Northeastern University. She is a member of the Teratology Society and the American Public Health Association. Her graduate capstone presentation, a critical review of maternal mortality, developed from her interest in women’s reproductive health. Ms. Roberts is currently at the Maternal Fetal Medicine Clinic, part of the Hartford Hospital.
Systematic Review Webinar Series
The use of systematic review (SR) and evidence-based methodologies in toxicology and risk assessment have evolved from theory to practice. This webinar series is going to provide an overview of the history of SR, describe the general principles of SR, challenges encountered in adopting the methodologies from medicine to toxicology, and present case studies of its use in regulatory decision-making in different domains. The presentations will focus on efforts specifically associated with risk-based practices, such as development of health-based benchmarks (e.g., acceptable daily intakes, reference doses, etc.), rather than characterization of potential hazard (e.g., likelihood to be a hazard to humans for a given health outcome). Tools and frameworks initially developed for the field of medicine have been adapted to apply to toxicological research questions, and in many cases, new tools developed. The presentations will describe how the regulatory practitioners have addressed the challenges of toxicological data relative to that of medicine. For example, address challenges in evaluating exposures vs. interventions, multi-endpoint vs. single endpoint outcomes, well-defined diseases or conditions, complex data that is often not in humans (but rather in experimental animal studies or in vitro studies) vs. randomized controlled trials in humans, and evaluation of mixtures vs. pure substances. And beyond evaluation of individual studies and qualitative characterizations of hazard, approaches to integrate data in the context of risk–to be evaluated on a common metric, to develop health based-benchmarks–have been developed and applied. These concepts must be balanced with the rigor of a SR, a component that translates into time and resources. It is anticipated that these series will provide practical information for toxicologists and risk assessors and facilitate an understanding of how systematic review is being utilized in support of risk-based chemical assessments. Notably, speakers will also highlight how SR provides additional rigor and transparency, as well as relevance of the process in decision-making for regulated chemicals.
Practical Application of SR in Preclinical Research and Risk-based Assessments
Chaired by Katya Tsaioun, PhD, Director, Evidence-Based Toxicology Collaboration, Johns Hopkins Center for Alternatives to Animal Testing, Bloomberg School of Public Health, Baltimore. Dr. Tsaioun will introduce the History and Main Principles of Systematic Review. Kim Wever, PhD, Researcher, Radboud University Medical Center, The Netherlands, will present on Tail-ored: Applying the Concept and Methodology of SR and Meta-analysis to Preclinical Animal Studies. SR help clinicians keep abreast of the medical literature by summarizing large bodies of evidence and helping to explain differences among studies on the same question. Used to inform medical decision-making, plan future research agendas, and establish policy, SR methods are ready to be adopted in risk assessment. Dr. Wever will present several case studies on application of the principles of SR to the evaluation of preclinical animal studies conducted by SYRCLE and others. Challenges in conducing SRs in preclinical research will be addressed. Recent solutions to these challenges such as recently opened pre-registration of preclinical protocols, internal validity (risk of bias) tools, external validity (generalizability of results) will be presented. Daniele Wikoff, PhD, ToxStrategies, will present on Practical Examples of the Integration of Systematic Review to Support Development of Health-based Toxicity Values in Chemical Risk Assessments. This presentation brings together the different applications of SR in the context of quantitative risk-based assessments, differentiating how the rigor and conduct of the approach must accommodate concepts beyond identification and characterization of hazard. An overview of common challenges with respect to procedures and tools utilized in the conduct of quantitative evidence-based assessments will be provided. This will include an introduction to challenges associated with the integration of multi-endpoint and multi-stream evidence bases, as well as integration of internal and external validity as they relate to selection of candidate datasets and development of toxicity values (and how such approaches may be refined relative to application of these concepts in qualitative vs. quantitative assessments).
Introduction to SR and Their Application in Chemical Risk Assessment across the Atlantic: US EPA and European Food Safety Authority Experience
Chaired by Katya Tsaioun, PhD, Director, Evidence-Based Toxicology Collaboration, Johns Hopkins Center for Alternatives to Animal Testing, Bloomberg School of Public Health, Baltimore, MD. Dr. Tsaioun will introduce the History and Main Principles of Systematic Review. Kristina Thayer, PhD, US Environmental Protection Agency (USEPA), National Center for Environmental Assessment (NCEA) will present on Systematic Review in Support of Chemical Risk Assessment at USEPA. The USEPA NCEA is currently adapting systematic approaches for the identification, evaluation, and integration of toxicological information in chemical risk assessments. This talk will provide an overview of these approaches as summarized in the Integrated Risk Information System (IRIS) Handbook for conducting systematic reviews in support of IRIS assessments, and how multiple evidence streams influence both hazard and dose-response decisions. Updates on the gradual implementation of these methods will be presented and discussed, using examples of improvements in the consistency and transparency of the scientific decisions made, as well as the practicality of utilizing SR methods for evaluating large, complex toxicological databases. Elisa Aiassa, PhD, Scientific Officer, Assessment and Methodological Support Unit/Risk Assessment & Scientific Assistances Department and Anna F. Castoldi, PhD, Senior Scientific Officer, Unit on Food Ingredients and Packaging, European Food Safety Authority (EFSA) will present on Systematic Review in Support of Chemical Risk Assessment at EFSA. The EFSA is the keystone of the European Union risk assessment regarding food and feed safety. Within its mandate, EFSA carries out a wide range of scientific assessments (e.g., safety assessments, efficacy assessments, or full risk assessments) dealing with human and animal nutrition, animal health and welfare, plant protection, plant health and the environment. EFSA has implemented a large variety of projects to develop or adapt methods aiming at increasing the methodological rigor, impartiality, and transparency of its scientific outputs. SR is one of these methods, whose applicability, feasibility, and worthiness to the field of food and feed safety has been extensively examined by EFSA and whose implementation in EFSA assessments has considerably increased over the last decade. This talk will provide case examples of SRs utilized to support broad mandated assessments in the area of chemical risk assessment. The focus will be on the advantages, limitations, and challenges of applying SR to this field, as well as on the needs for further methodological developments.
Toxicity and Efficacy of Stem Cells as Therapeutic Products for Humans and Animals
Stem-cell based therapies are becoming very popular in humans and animals for many conditions. However, much still needs to be understood in terms of their toxicity and efficacy. We will have two speakers from the US Food and Drug Administration (US FDA). The first is from the Center for Biologics Evaluation and Research (CBER) discussing their use in humans and the second speaker is from the Center for Veterinary Medicine (CVM) who will discuss the challenges in their veterinary use.
Stem Cell-based Therapies: FDA/CBER Preclinical Regulatory Considerations presented by Wei Liang, PhD, Pharm/Tox Branch 1, Division of Clinical Evaluation and Pharmacology/Toxicology (DCEPT), Office of Tissues and Advanced Therapies (OTAT), CBER, US FDA
The conduct of a clinical trial for an investigational stem cell-based product is governed by the Code of Federal Regulations (CFR) Title 21, Part 312 to ensure the safety and rights of subjects in all phases of a clinical investigation. According to 21 CFR 312.23(a)(8), the sponsor needs to provide adequate information derived from pharmacology and toxicology studies to support a conclusion that the proposed clinical trial is reasonably safe and scientifically feasible to conduct. Preclinical evaluation of stem cell-based products in vitro and in animals is a key element in the overall benefit:risk assessment. The primary goals of preclinical studies for stem cell-based therapies are to establish the scientific rationale to support the planned clinical investigation and to assess the potential toxicities associated with administration of the stem cell-based product. Considerations for preclinical assessment of stem cell-based products are discussed in the "Guidance for Industry: Preclinical Assessment oof Investigational Cellular and Gene Therapy Products," which was released by CBER in November 2013.
This presentation will discuss (1) potential safety concerns associated with stem cell therapies, (2) preclinical testing programs for stem cell therapies to support an investigational new drug (IND) submission for a first-in-human clinical trial, and (3) early communications with FDA/CBER/OTAT via pre-pre-IND interactions and pre-IND meetings.
Safety of Cell-Based Products for Animal Use: presented by Lynne Boxer, DVM, CVM, Office of Foods and Veterinary Medicine, US FDA
Cell-based products for animal use, including stem cell products, that meet the definition of a new animal drug require US FDA approval to be legally marketed. Thus, approval of these products requires a demonstration of safety, effectiveness, and manufacturing quality. While there is increasing interest in the potential therapeutic applications for cell-based products, there are also challenges associated with assessment of the safety and quality of these products. This talk will discuss the specific safety considerations for cell-based products, as well as an overview of what is known about adverse events in veterinary species.
Peer-Reviewed Publications Webinar Series: The Future of Publishing
The Future of Publishing
Presented by Gary W. Miller, PhD, Professor of Environmental Health and Associate Dean of Research in the Rollins School of Public Health at Emory University. Dr. Miller, Editor-in-Chief of Toxicological Sciences, will provide his views on some of the trends and explain what the Journal is doing to keep abreast of these challenges. Over the past decade there have been several major changes in the scientific publication landscape. Increasing access to scientific findings, through a combination of open access and making primary data more readily available, have been major drivers of these changes. Investigators are sharing more of their data through websites and data repositories. The use of preprints to share findings in advance of publication also is increasing in the biomedical sciences. There has also been rapid growth in the number of journals with a less than stellar reputation. Such predatory journals pose a threat to the research community. Dr. Miller has been a member of the Society of Toxicology since graduate school. He currently directs the HERCULES Exposome Research Center (NIEHS P30 and the Emory CHEAR (NIEHS U2C), as well at Emory’s NIEHS T32 training grant. His research is focused on environmental drivers of neurodegeneration.
Peer-Reviewed Publications Webinar Series
How to Get Published in Peer-Reviewed Journals
Presented by Mary Beth Genter, PhD, DABT, ATS, Professor, Department of Environment Health, University of Cincinnati. She is currently (2008–present) Editor-in-Chief of International Journal of Toxicology, the official journal of the American College of Toxicology. The webinar “How to Get Published in Peer-Reviewed Journals” will provide advice, examples, and guidance on writing and publishing effective scientific manuscripts. Topics will include a review of tips for good study design, a discussion of constructing an effective abstract, and important considerations when writing a manuscript, including the choice of a journal to which a manuscript will be submitted, word usage, data presentation, and authorship considerations. We conclude with a discussion of predatory journals, and how and why to avoid publishing in them. Dr. Genter also is a member of the Toxicology in Vitro Editorial Board, and a reviewer for approximately two dozen papers for other journals per year. Dr. Genter serves on the Council of the Society of Toxicology (2016–2019) and recently completed a term on the National Toxicology Program Board of Scientific Counselors (2013–2017). She is a member of the American College of Toxicology, the Society of Toxicology, the Association for Chemoreception Sciences, and Sigma Xi.
Series—Predicting Adverse Effects Before They Occur: Teratogens as an Example
The Next Thalidomide
Presented by Anthony B. Scialli, MD, a teratologist and board-certified obstetrician-gynecologist. Dr. Scialli is Adjunct Professor in the Departments of Obstetrics and Gynecology and of Pharmacology and Physiology at Georgetown University School of Medicine, where he was a full-time Professor and director of the Residency Training Program until 2003, and Clinical Professor in Obstetrics and Gynecology at George Washington University, where he continues to see patients. His presentation will address disease prevention. One reason to work in toxicology is to prevent episodes of human disease before they occur by identifying and avoiding exposures that are likely to be harmful. In developmental toxicology, this practice is sometimes called, preventing the next thalidomide. Of course, one limitation on this idea is the fact that the next thalidomide has already occurred, several times in fact. It can be instructive to review these episodes and learn from them where the failures occurred. In some cases (isotretinoin, valproic acid), well characterized warnings were not noticed by clinicians or patients. In other cases (diethylstilbestrol, warfarin), the sensitive developmental period in humans was outside the observation period of standard experimental protocols. In yet other cases (mycophenolate), the problem was the importance of the drug for the health of the patient and the need to wait for a critical epidemiological mass to establish causation. Fundamental to the use of traditional experimental protocols is the belief that laboratory animal response predicts human response, but it has been clear for decades that this belief is an artifice of the dosing regimens used in the experimental studies. By using high enough dose levels, any chemical can be made to look teratogenic, a principle enunciated by David Karnofsky in 1965. Because of this principle, experimental animal studies can look highly predictive if we accept any developmental endpoint at any dose as a positive, and if we are not too worried about false alarms. We hope that the use of alternative test strategies and better characterization of mechanisms of abnormal development will make experimental protocols more predictive of human response, but it is not a foregone conclusion that they will do so.
In Bed with the Devil: Recognizing Human Teratogenic Exposures
Presented by Jan Friedman, MD, PhD, a clinical geneticist and Professor of Medical Genetics at the University of British Columbia (UBC). In the past decade, Dr. Friedman has been a pioneer in the development and application of cytogenetic and genomic tools to understand the genetic causes and clinical consequences, and improve diagnosis of, intellectual disability syndromes. His presentation will address the challenge to recognize that an exposure is teratogenic when the fewest possible babies have been harmed. Recognizing exposures that are teratogenic in humans requires: (1) babies who have been harmed by the exposure; (2) a way to associate the maternal exposure to the babies’ birth defects (hypothesis generation); and (3) a way to prove that the observed association is causal (hypothesis testing). Proving an association is probably causal as quickly as possible means making this call before the definitive study has been done. A weight-of-evidence approach is used, taking each study for what it is worth, but no more. Dr. Friedman has published more than 270 peer-reviewed papers and has written six books and edited two others. He is the Director of CAUSES Clinic at BC Children’s Hospital. This research clinic provides advanced DNA testing, clinical interpretation, genetic counselling, and personalized recommendations for treatment for children with complex, undiagnosed medical conditions.
Epidemiology of Vaccine Refusal
Presented by Presented by Saad B. Omer, MBBS MPH PhD FIDSA, William H. Foege Professor of Global Health and Professor of Epidemiology & Pediatrics at Emory University, Schools of Public Health and Medicine. He also is a faculty member at the Emory Vaccine Center. Vaccines are among the most efficacious and cost-effective prevention tools. However, the success of an immunization program depends on high acceptance and coverage. There is evidence of an increase in vaccine refusal in the United States and of geographical clustering of vaccine refusers resulting in outbreaks. Children with exemptions from school immunization requirements (a measure of vaccine refusal) are at increased risk of measles and pertussis and can infect others who are too young to be vaccinated, cannot be vaccinated for medical reasons, or were vaccinated but did not have a sufficient immunological response to the vaccine. Parents of children with non-medical exemptions to immunization requirements have been documented to have perceptions of lower susceptibility to and severity of vaccine preventable diseases and perceptions of lower safety and efficacy of vaccines compared to parents of vaccinated children. Moreover, compared to parents of vaccinated children, vaccine hesitant parents had less trust in the government and the health care system. There is a need for development of a robust evidence base of effective interventions for reducing vaccine hesitancy. Potential interventions include: effective provider-parent communication tools, rational administrative requirements for granting exemptions, and informed declination. Given the geographic clustering of refusers, theses interventions must be locally relevant.
Polypharmacy and the Challenges of Optimizing Pharmacotherapy in Complex Patients
Presented by Cathy Yeung, Pharm D, PhD, MPH; Assistant Professor, Department of Pharmacy, University of Washington School of Pharmacy, Seattle, Washington. One of the greatest challenges facing clinical pharmacists is the rapid growth of polypharmacy, in which patients are prescribed 10 or more medications, and the associated increased risks of adverse drug reactions, drug-drug interactions, and drug-disease interactions. Selection of drugs, doses, and timing of doses is particularly difficult in patients who are elderly or have accompanying organ impairment (liver, kidney). Drug pharmacokinetics in the setting of polypharmacy and organ impairment is complicated by overlapping clearance modalities, including drug metabolizing enzymes and drug transporters. In this webinar, we will review major pathways of drug metabolism and identify clinically relevant drug transporters. The impact of renal impairment on non-renal drug clearance will be discussed. Finally, a clinically relevant drug metabolism/drug transporter/food interaction will be presented. Dr. Yeung’s training encompasses clinical pharmacy, medicinal chemistry, pharmacokinetics, and epidemiology. Her research focuses on optimizing pharmacotherapy in patients with chronic kidney disease using molecular tools to probe proximal tubule transport, mathematical modeling of substrate transit in the proximal tubule, innovative 3-dimensional microfluidic models, and clinical pharmacokinetics studies.
Biology of Vaccines and Molecular Evolution of Viruses
Animal Models of Human Disease for Nonclinical Safety—Why, What and When…
Presented by Sherry J. Morgan, DVM, PhD, ACVP, ABT, ABVT joined Abbott/AbbVie, Inc. in 1990. She currently serves a dual role as a pathologist and a Director of Scientific Projects, providing toxicology and pathology guidance for Discovery and Development projects. Dr. Morgan also provides interpretative nonclinical risk assessment summaries of numerous potential in-licensing compounds, helping to guide the selection process of novel compounds. She is board certified by the American College of Veterinary Pathologists, the American Board of Veterinary Toxicologists, and the American Board of Toxicology. Her publication list includes approximately 30 journal articles, 20 book chapters, and 30 abstracts/posters. Topics on the use of animal models span therapeutic indications including oncology, joint diseases, neurodegeneration, cardiovascular disease, and endocrine and metabolic diseases. She also has contributed to the validation of non-invasive imaging technologies using traditional pathology endpoints. In this presentation, the rationale for the use of animal models of disease will be discussed as it pertains to different adverse drug reactions for which there is relatively low predictability with conventional animal models. Some of the possible reasons for lack of concordance between different organ systems will be covered as well. The presentation will conclude with general recommendations when considering using an animal model of animal disease as well as some examples of studies involving animal models of disease.
This presentation was sponsored by AbbVie, which contributed to the design, research, and interpretation of data, writing, reviewing, and approving the publication. Sherry Morgan is an employee of AbbVie.
Regulatory Perspective on the Use of Animal Models of Disease in Drug Development
Presented by: Sruthi King, PhD, Pharmacology/Toxicology Team Leader in the Division of Clinical Review in the Office of Generic Drugs within the Center for Drug Evaluation and Research at the US Food and Drug Administration (CDER/FDA). Prior to her current role, Dr. King was a primary nonclinical reviewer for seven years in the Division of Gastroenterology and Inborn Errors Products in the Office of New Drugs within CDER/FDA. She has spoken on the topic of using animal models for nonclinical safety assessment and their utility in supporting rare disease drug development, most recently at the 2015 Annual Meeting of the American College of Toxicology. Dr. King also has co-authored a chapter on this topic in second edition of Pediatric Drug Development: Concepts and Applications. The objective of this presentation is to highlight current regulatory practices within CDER/FDA with case studies in which animal models of disease were used in nonclinical safety studies. At this time, the FDA recommends the use of animal models of disease be used in “proof of concept” studies, unless the sponsor provides acceptable justification that the animal model is the most relevant species for pharmacology and toxicology testing. However, the use of animal models, particularly for rare disease drugs, is increasing and regulators are tasked with determining whether the data generated in these models are adequate to support drug development and approval of safe and effective therapies, with limited clinical trial data. In general, nonclinical studies to support clinical trial initiation and ongoing development of small molecules and biologics are guided by ICH M3 and ICH S6; however, review divisions may apply regulatory flexibility.
The Use of Animal Models of Disease in Safety Assessments
Presented by: Diann L. Blanset, PhD, DABT, Boehringer Ingelheim. Preclinical safety studies for proposed pharmaceutical products are usually conducted in healthy animals. The appropriate species for these studies are selected based on the relative pharmacological activity/potency and metabolite profiles between the proposed species and humans. The studies are then designed to mimic the clinical dosing regimen with respect to the route of administration, duration of treatment, and dosing interval. As these studies are conducted in healthy animals, they generally mimic the characteristics of the clinical population for first in human (FIH) Phase I trials in normal subjects (healthy volunteers). However, they do not mimic the characteristics of subjects in later clinical trials or in FIH Phase I trials conducted in subjects with disease. This deviation from the principle of mimicking the clinical conditions of use can be very important in certain disease indications where the disease condition can dramatically affect the safety of the pharmaceutical. The aim of this webinar is to review the use of animal models of disease in the evaluation of exaggerated pharmacology and toxicity to improve the relevance and extrapolation of the assessments to the intended disease population. The basic principles of the use of animal models of disease will be reviewed as well as the advantages and disadvantages of these models. In addition, specific examples of the use of these models in safety assessments will be presented.
Precision Medicine—Getting Personal on Safety
Presented by: Sian Ratcliffe, PhD, is General Toxicology Site Lead in Drug Safety R&D at Pfizer, Groton, Connecticut, USA. Prior to holding her current role, Dr. Ratcliffe was the Global Head of Safety Pharmacology. During her 16 year tenure at Pfizer, she also has held other senior leadership roles in Clinical Development, Safety Risk Management, and Regulatory Affairs, managing projects throughout development stages from research to post-approval in the Neurology, Psychiatry, Pain, Women’s Health, Pulmonary Vascular Disease, and Respiratory therapeutic areas. Dr. Ratcliffe has a keen research interest in precision medicine, translational, and predictive safety projects and is actively engaged with the US Food and Drug Administration and the National Cancer Institute on PredicTox, a systems pharmacology project to examine cardiotoxicity associated with tyrosine kinase inhibitors. Prior to joining Pfizer, Dr. Ratcliffe worked for Elsevier as an editor for a number of the Trends journals. Sian has a PhD in Pharmacology from the University of Cambridge (1996) where she also held postdoctoral research and academic posts.
Industry Perspective on Biomarkers: The Use of Biomarkers in Clinical Development of Novel Drugs
Biomarker Utility and Acceptance in Drug Development and Clinical Trials: An FDA Regulatory Perspective
Presented by: Shashi Amur, PhD, Scientific Lead of the Biomarker Qualification Program in the Office of Translational Sciences, Center for Drug and Evaluation Research (CDER), US Food and Drug Administration (FDA) and Christopher L. Leptak, MD, PhD, Biomarker and Companion Diagnostics Lead for the Office of New Drugs within CDER/FDA and Co-Director of the Biomarker Qualification Program. Dr. Amur's current research interests include biomarkers in Autoimmune Diseases and in Alzheimer’s disease, drug-induced liver toxicity, pharmacogenomics, and HLA-associated adverse events. She is Past Chair of the Pharmacogenomics Focus Group, American Association of Pharmaceutical Scientists. The focus of Dr. Leptak's work is on biomarker development and diagnostic device utility in clinical trials and drug development, both for drug-specific programs as well as qualification. He is charged with identifying policy, process, and regulatory science needs within the co-development space and is involved in multiple inter-office and inter-center working groups to address those needs.View Webinar Recording
Gatekeeper and Watchman: the Microbiome Enters the Picture
Presented by: Ellen Silbergeld, PhD, Professor, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. Her research and professional activities bridge science and policy, with a focus on the incorporation of mechanistic toxicology into environmental and occupational health policy. Dr. Silbergeld also directs a Fogarty Training Program in NonCommunicable Diseases, which is collaboration between Hopkins and the School of Public Health of Mongolia.
Nonclinical Safety Testing
Presented by: Thomas W. Jones, PhD, Chief Scientific Officer, Toxicology & Pathology, Eli Lilly and Company
On Wednesday, February 4, 2015, the Scientific Liaison Coalition (SLC) hosted a webinar, “Prediction Is Very Difficult, Especially If It Is About the Future: How Well Does Toxicology Testing Predict Clinical Outcomes?“
Dr. Jones is the Chief Scientific Officer, Toxicology and Pathology, Eli Lilly and Company. He is currently Past Chair of the Preclinical Safety Leadership Group within the International Consortium for Innovation and Quality in Pharmaceutical Development. He also serves as the nonclinical safety representative for the Development Special Emphasis Panel supporting the National Cancer Institute Experimental Therapeutics (NExT) Program.
Progress Made on Tox21: A Framework for the Next Generation of Risk Science
Moderator: Daniel Krewski, PhD, MHA, McLaughlin Centre for Population Health Risk Assessment, University of Ottawa
On October 1, 2014, the Scientific Liaison Coalition (SLC) hosted a webinar, Progress Made on Tox21: A Framework for the Next Generation of Risk Science, presented by Daniel Krewski. The Society of Toxicology (SOT) is a participating member of the SLC. Dr. Krewski is currently Professor of Epidemiology and Community Medicine and Scientific Director of the McLaughlin Centre for Population Health Risk Assessment at the University of Ottawa. He served as Chair of the National Research Council’s Committee on Toxicity Testing and Assessment of Environmental Agents, which published its influential report, “Toxicity Testing in the 21st Century: A Vision and a Strategy,” published in June of 2007.
*Note to Mac users: Due to software incompatibilities, it is advisable that you view this recording on a PC.