Monday, November 9

9:00 AM–12:00 Noon

Our Microbiome is Speaking Toxicology Loud and Clear: Are We Listening? 

The human microbiome consists of the microorganisms (bacteria, fungi, viruses) that exist on our external and mucosal surfaces. Current research indicates that there are specialized niche organisms that thrive in many areas of the body and coexist as part of the human condition. The human intestine alone carries about 100 trillion microorganisms. This microbiome can change in response to environmental factors such as a change in diet, the host condition, radiation, and toxicologic insult (e.g., antibiotics or environmental toxicants). There is increasing evidence that disease processes may be exacerbated (or possibly initiated) by changes in the microbiome. Understanding the human microbiome (in relation to various human organ systems) will better inform toxicology as it relates to both environmental toxicant data and pharmaceutical data. This symposium will cover the basics of the microbiome in general, as study design limitations and considerations, and translation of nonclinical data to human condition as it relates to drug development.

  • Introduction
    Peyton Myers, US Food and Drug Administration, Silver Spring, MD
  • An Introduction to the Microbiome in Toxicity and Disease
    Victor Johnson, Burleson Research Technologies, Inc., Morrisville, NC
  • The Microbiome at the Interface of Toxicology and Risk Assessment
    Rodney Dietert, Cornell University College of Veterinary Medicine, Ithaca, NY
  • The Gut Microbiota as a Source of Variability in Animal Models/Preclinical Studies
    Aaron Ericsson, Department of Veterinary Pathobiology, University of Missouri, Columbia, MO
  • The Human Microbiome: A Drug Discovery Perspective
    James Brown, GlaxoSmithKline, Collegeville, PA
  • The Human Microbiome and Public Health: A Case for Developing Microbiome Disruption Indices
    Clifford McDonald, Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, Atlanta, GA
  • Questions and Answers

Streamlined Development of Safety Assessment Programs Supporting Orphan/Rare Diseases—Are We There Yet?

A rare/orphan disease is one that affects a small percentage of the population i.e., < 200, 000 (US) or 1 in 2000 (Europe) however has a big impact collectively, when all patients and families affected by the ~7000 rare diseases are considered. Challenges inherent to the development of drugs for rare diseases include a clinical trial population that may be limited by size, heterogeneity of disease phenotypes, and potentially, a lack of or poorly defined clinically meaningful efficacy parameters. Further, in the absence of a unifying ICH/regional guidance for nonclinical testing, preclinical assessment of therapeutics for rare, life threatening diseases is defined largely by sponsor interactions with health authorities. As such, each toxicology program would support the therapeutic candidate's unique clinical risk:benefit profile. This symposium will discuss nonclinical considerations for development of various products for rare diseases outside of the realm of oncology products developed under ICH S9. Case examples of regulatory interactions in the development of the much needed rare disease therapies, i.e., programmatic reviews from the sponsor and agency perspectives are presented. Additionally, the challenges in preclinical safety assessment for rare disease are summarized, along with the progress that has been made to date, and concluding remarks.

  • Introduction
    Krishna P. Allamneni, Jazz Pharmaceuticals, Inc., Palo Alto, CA
  • Use of Animal Models for Nonclinical Safety Programs Supporting Orphan Disease Drug Development
    Charles A. O’Neill, BioMarin Pharmaceutical Inc., Novato, CA
  • Rare Disease Drug Development: Case by Case, Patient by Patient
    Teresa Wright, Dimension Therapeutics, Cambridge, MA
  • Regulatory Perspective on the Nonclinical Studies Needed to Support Orphan and Rare Disease Drug Development
    Sruthi King, US Food and Drug Administration/CDER/ Office of Generic Drugs/Office of Bioequivalence/Division of Clinical Review, Silver Spring, MD
  • Progress and Challenges in Rare Disease Drug Development
    Laura Andrews, AbbVie, Worcester, MA

European Initiatives in the 3Rs

The symposium will cover the European initiatives in the field of the 3Rs (Replacement, Refinement and Reduction) for animal studies. The symposium will concentrate on scientific programmes run as joint efforts between the MHRA and the UK's National Centre for 3Rs (NC3Rs), focusing on the development of biosimilars, the use of microsampling for toxicokinetics, the use of recovery animals in toxicology studies and the use of human tissues for safety pharmacology assays.

  • An Overview of the NC3Rs
    Kathryn Chapman, NC3Rs, London, United Kingdom
  • The Recovery Groups Project
    Paul Baldrick, Covance Laboratories Inc., North Yorkshire, United Kingdom
  • The Use of Human Tissues and Organs on Chips
    David Jones, MHRA, London, United Kingdom
  • Question and Answers
    David Jones, MHRA, London, United Kingdom

2:00 PM–5:00 PM

Safety Challenges and Decision Making for High-Risk Pharmacological Targets

Certain pharmaceutical targets are particularly challenging from a safety perspective. Sometimes these challenges are anticipated based on the biology of the target, but other times they come as a surprise as unexpected safety findings in animal studies. When critical safety findings emerge and after careful investigation these findings are deemed to be target-related, and therefore typically not solvable with cleaner molecules, this has profound implications for the program. This conclusion leads to a difficult decision-making process which can culminate in program termination, repurposing towards a therapeutic area with a lower safety bar, or challenging mitigation strategies like targeted delivery methods. This session will focus on the safety knowledge that is considered when selecting new targets, investigative strategies to establish whether a finding is target related, safety strategies that can lead to rapid and early decision making for intractable targets, and decision making around target-related safety findings (progression, termination, repurposing and mitigation). Presenters will share case studies to illustrate the challenges and internal decision making around target-related safety findings. The last session will address the myths or dogmatic believes around target-related toxicity and offer novel insights around mitigating this problem.

  • Introduction
    Dolo Diaz, Genentech, South San Francisco, CA
  • Evaluation of Target-Related Potential Safety Risks in Drug Discovery Toxicology
    Brandon Jeffy, Celgene Corporation, San Diego, CA
  • Nonclinical Safety Challenges with “Intractable” Targets
    Eric Blomme, AbbVie, North Chicago, IL
  • PAK1/2 Kinase Inhibitors Cause Acute Cardiovascular Toxicity in Mice: Investigation of MOT
    Zoe (Yu) Zhong, Genentech, South San Francisco, CA
  • Risk Assessment of Target-Based Toxicity—Scientific Absolute or Dogma with Some Wiggle Room?
    Bruce Car, Bristol-Myers Squibb Company, Princeton, NJ

Current Topics in Postnatal Behavioral Testing

Neurobehavioral evaluations are a component of a wide range of toxicity studies. The primary focus of this session will be on evaluations in pre- and postnatal development studies and juvenile toxicology studies for pharmaceuticals. However, many of the concepts covered will apply to adult safety studies and EPA/chemical assessments.

Topics to be addressed include: regulatory context for developmental neurotoxicity testing, including case studies; study design; behavioral test selection; learning and memory; other guidelines recommended neurobehavioral evaluations; age of testing and repeated testing of same animals; use of alternative animal models when rodents are not appropriate case studies; impact of findings; and extrapolation of animal results to humans.

  • Neurobehavioral Evaluations As a Component of Developmental Toxicity Testing— Regulatory Perspective
    Ikram Elayan, US Food and Drug Administration/CDER Division of Psychiatry Products, Office of Drug Evaluation I, Silver Spring, MD
  • Assessment of Core Learning and Memory Systems in Regulatory Studies
    Charles Vorhees, Cincinnati Children’s Research Foundation, Cincinnati, OH
  • Additional Neurobehavioral Evaluations in Regulatory Studies
    LaRonda L. Morford, Eli Lilly and Company, Indianapolis, IN
  • Developmental Neurotoxicity Testing in Nontraditional Animal Models
    Judith W. Henck, Consulting Toxicologist, Leeds, UT

Toxicology of E-Cigarettes

This session will discuss the present knowledge concerning the toxicological assessment of e-cigarettes, and their role in achieving harm reduction. In particular, this session will discuss the challenges associated with assessment of e-cigarettes taking into account the multitude of product variants currently on the market. While scientific understanding relating to the use of such e-cigarette is quickly building, there remains a lack of consensus regarding appropriate product standards and regulatory guidance for assessment. While there is general agreement that standards are needed, it will be important to ensure that they do not inhibit further innovation of these products. Specific topics to be discussed will include 1) characterization of e-cigarettes aerosol; 2) in vitro assessment and 3) in vivo assessment.

  • Achieving Harm Reduction in Tobacco
    Riccardo Polosa, Centre for Tobacco Research (CPCT), Catania, Italy
  • Physical Chemical Assessment of E-Cigarette Aerosol
    Jed Rose, Duke University Medical Center, Durham, NC
  • Human Studies with E-Cigarettes
    Maciej Goniewicz, Roswell Park Cancer Institute, Buffalo, NY
  • Systems Toxicology-Based Assessment of E-Liquids
    Manuel Peitsch, Philip Morris International R&D, Neuchâtel, Switzerland

Tuesday, November 10

9:00 AM–12:00 Noon

Fc/FcR-Interactions on the Safety and Efficacy of Biological Therapeutics

Biopharmaceutical products such as monoclonal antibodies and fusion proteins that contain the Fc region of immunoglobulin (Ig) have the potential to interact with Fc receptors (FcR). Fc-FcR interactions are an important aspect of understanding how monoclonal antibodies and Fc-containing proteins function. Novel biopharmaceutical products are being designed to include specific modifications to the Fc region that can either abrogate or increase binding to Fc receptors, depending on the desired pharmacological action and disease indication. Interactions with FcRn and other Fc receptors (e.g., gamma, alpha, and epsilon receptors) expressed on various cell types can impact both the efficacy and safety of biopharmaceutical products. This symposium will introduce Fc and FcR biology and how Fc structure affects function, describe the assays that measure Fc function, and outline case studies that illustrate the impact of the Fc in biological therapeutics on safety and efficacy, across disease indications, based on emerging data from both industry and the FDA.

  • Introduction
    Janice Lansita, ToxStrategies, Inc., Baltimore, MD
  • Fc Biology and Function
    Jane Sohn, US Food and Drug Administration, Division of Pulmonary, Allergy and Rheumatology Products, Silver Spring, MD
  • Fc/FcR in Nonclinical Species
    Hervé Lebrec, Amgen Inc., South San Francisco, CA
  • In Vivo Experience with mAbs with Enhanced Fc Effector Functions
    Daniel Rubio, GlaxoSmithKline, King of Prussia, PA
  • Antibody-Dependent Enhancement and Anti-Viral mAbs
    Takashi Komatsu, US Food and Drug Administration, Silver Spring, MD

Thresholds vs. Point of Departure in Genetic Toxicology

Developing drugs that elicit a positive response during genotoxicity testing is a complex endeavor. This complexity results, in part, from continued acceptance of an association between genotoxicity and linear dose-response. In cases where an indirect mechanism is suspected, follow-up testing may allow further characterization of in vivo risk. Dosing in human subjects is acceptable when quantitative in vivo data demonstrates a threshold with appropriate safety margins. No thresholds are assumed to exist for drugs that induce gene mutations/clastogenicity through direct DNA reactivity. This practical assumption is related to both the testing burden associated with establishing a threshold and concerns with regulatory acceptance. In contrast to these views, mounting scientific evidence supports the existence of thresholds regardless of genotoxic mechanism.

This symposium will cover genotoxic mechanisms, data needed to establish a threshold and/or point of departure metric, as well as current scientific and regulatory perspectives. A panel discussion will allow speakers and attendees to debate the role of thresholds in genetic toxicology.

Specific issues related to drug development will be of interest to scientists from the pharmaceutical industry, regulatory agencies, contract research organizations, and consultants. The general concept of thresholds in genetic toxicology will be of interest to scientists from all sectors.

  • Dose-Response Assessment in Genetic Toxicology: An Overview
    Bhaskar Gollapudi, Exponent, Inc., Midland, MI
  • Non-Linear and Non-Mutagenic Mode-of-Action Determinations in Environmental Chemical Risk Assessment
    David Eastmond, University of California, Riverside, Riverside, CA
  • Genotoxic Thresholds in Drug Development
    Mark W. Powley, US Food and Drug Administration/CDER, Silver Spring, MD
  • Case Study: EMS
    Robert Heflich, US Food and Drug Administration/National Center for Toxicological Research, Jefferson, AR
  • Practical Recommendations for Determining Dose-Response Relationships
    Maik Schuler, Pfizer Global Research and Development, Groton, CT
  • Panel Discussion

The First Cut Is the Deepest: The History and Development of Safe Treatments for Wound Healing and Tissue Repair

As the skin is the primary barrier to infection, the importance of wound healing and tissue repair has been understood since ancient times. This presentation will focus on how wounds were traditionally treated, what models and endpoints exist to study wound healing and the clinical relevance of such models. Toxicology and pathology endpoints and special considerations for appropriate treatment and assessment of wounds will also be discussed. A perspective on military research and treatment of wounds will be included. An overview of regulatory aspects of new pharmaceutical and medical device development will be included. In addition, clinical aspects of treating small and large wounds and emerging therapies will be discussed.

  • Introduction
    Maralee McVean, PreClinical Research Services, Inc., Fort Collins, CO
  • History of Wound Healing
    David W. Hobson, LoneStar PharmTox LLC, Bergheim, TX
  • Pathologic Evaluation of Wound-Healing Models and Relevance to Human Tissue Healing
    JoAnn C.L. Schuh, JCL Schuh, PLLC, Bainbridge Island, WA
  • Acinetobacter Baumannii: A Bacterial Pathogen that Causes Wound Infections in Wounded Warriors and Civilians
    Daniel V. Zurawski, Walter Reed Army Institute of Research and Clinical Research Management Inc., Silver Spring, MD
  • Nonclinical Regulatory Considerations of New Drug Development for Wound Healing
    Jianyong Wang, US Food and Drug Administration, Division of Dermatology and Dental Products, OND/CDER, Silver Spring, MD
  • Clinical Considerations of Wound Healing
    Sam Arbabi, University of Washington, Seattle, WA

2:00 PM–5:00 PM

Immune Function Monitoring in Nonclinical Safety Assessment of Immunotherapies: Challenges, Methods, and Translational Aspects

Immune function monitoring is a critical component of the assessment for potential immunotoxicity during nonclinical development of pharmaceuticals. Historically, most concerns have been related to the potential for adverse immunosuppression. Consequently, most of the nonclinical models like the TDAR or the NK cell assays were designed to detect immunosuppression. However, recent advancements in the field of cancer immunotherapy has refocused the attention on measuring immune activation as part of the pharmacodynamics characterization, or to identify and mitigate potential safety concerns regarding exaggerated immune stimulation. Consequently, the detection and quantification of the immune response following antigen exposure in nonclinical species and the determination of adversity requires a careful re-evaluation of the existing experimental models. Available protocols and methods need to be re-assessed regarding their sensitivity to adequately detect not only immunosuppression; but also immune activation and translatability to the clinic.

The session will discuss the current knowledge, challenges, and translational relevance when assessing immune responses in nonhuman primates (NHP), and other nonclinical species for the development of cancer vaccines and T cell targeting immunotherapies for cancer, will provide a regulatory perspective on safety concerns and immune function monitoring for cancer immunotherapies, and will discuss the usability and translatability of alternative animal models.

  • Session Introduction: Immune Function Monitoring
    Michael P. Holsapple, Michigan State University, East Lansing, MI
  • Tracking Antigen-Specific T-Cell Responses Induced by a Recombinant Attenuated Listeria-Based Cancer Vaccine in an IND-Enabling NHP GLP Toxicology Study
    Meredith Leong, Aduro Biotech Inc, Berkeley, CA
  • Reassessment of Available Antigen Challenge Models in NHPs to Support Cancer Immunology Drug Development
    Rodney Prell, Genentech, South San Francisco, CA
  • Nonclinical Safety Evaluation for Development of Cancer Immunotherapies
    Shawna L. Weis, Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD
  • Immune Function Monitoring Beyond CIT: Experience and Challenges When Testing Adjuvants in Nonclinical Species
    Marie-Soleil Piche, Charles River Preclinical Services, Quebec, Canada
  • General Discussion and Questions and Answers
    Jorg Blumel, Genentech, South San Francisco, CA

Leachables and Extractables: Current Best Practices for Qualification of Container Closure Leachables in Drug Products 

Safety and analytical thresholds for leachables from container-closure systems in drug products have helped to ensure public health by establishing scientifically justified limits for chemical identification and risk assessment of these chemicals. Minimization of leachables in drug products is a critical and significant part of the pharmaceutical development process as it is a key area of ensuring the quality and safety of the final product. Safety thresholds for leachables in drug products can be developed using well-established, robust databases and quantitative risk assessment approaches. Currently, there are no globally accepted guidelines to identify and qualify leachables in drug products. The Product Quality Research Institute (PQRI) has developed best practice recommendations for inhaled, nasal and parenteral drug products. Recently the United States Pharmacopeia (USP) has developed general chapters to address qualification of leachables and extractables in drug products. This workshop will provide a broad overview of the PQRI best practices, USP general chapters, regulatory perspective, and case studies to demonstrate how to qualify leachables in drug products.

  • PQRI Safety Qualification Classification Strategy for Parenteral Drug Products
    William Beierschmitt, Pfizer, Inc, Groton, CT
  • Extractables and Leachables in Biotechnology Products—Points to Consider in Conducting Product Safety and Quality Assessments
    Kim Li, Amgen, Inc, Thousand Oaks, CA
  • Determining Suitability of Plastic Packaging Materials and Systems for Therapeutic Products: Extractables and Leachables Testing
    Desmond Hunt, United States Pharmacopeia (USP), Rockville, MD
  • Regulatory Review of Extractables and Leachables in Inhalation and Parenteral Drug Product
    Timothy Robison, US Food and Drug Administration/DPARP, Silver Spring, MD

Applied Toxicology Workshop: GLP Issues

This workshop will focus on Good Laboratory Practices (GLP), one aspect of applied and practical toxicology. After a brief introduction to GLPs, followed by guidelines for the session, this will be an interactive workshop with the Chairs, an FDA inspector, and participants discussing GLP concerns, issues and questions. Case reports are welcome if they do not breach confidentiality. If preferred, questions may be submitted to the Chair prior to the start of the session to maintain anonymity. Students and those new to GLPs are encouraged to attend to learn more about laboratory situations in a regulated environment.

  • Good Laboratory Practice (GLP) Introduction and Workshop Guidelines
    Robin Guy, Robin Guy Consulting, LLC, Lake Forest, IL
  • FDA GLP “Modernization” Update
    Charles Bonapace, US Food and Drug Administration/CDER/Office of Translational Sciences/Office of Study Integrity and Surveillance, Silver Spring, MD
  • GLP-Interactive Session
    Robin Guy, Robin Guy Consulting, LLC, Lake Forest, IL; Charles Bonapace, US Food and Drug Administration/CDER/Office of Translational Sciences/Office of Study Integrity and Surveillance, Silver Spring, MD; Mark Seaton, US Food and Drug Administration, Silver Spring, MD; David W. Hobson, LoneStarPharmTox, LLC, Bourne, TX; and Charles B. Spainhour, Calvert Laboratories, Scott Township, PA
  • GLP-Interactive Session—Continued
    Robin Guy, Robin Guy Consulting, LLC, Lake Forest, IL; Charles Bonapace, US Food and Drug Administration/CDER/Office of Translational Sciences/Office of Study Integrity and Surveillance, Silver Spring, MD; Mark Seaton, US Food and Drug Administration, Silver Spring, MD; David W. Hobson, LoneStarPharmTox, LLC, Bourne, TX; and Charles B. Spainhour, Calvert Laboratories, Scott Township, PA

Wednesday, November 11

9:00 AM–12:00 Noon

Gene Therapy Products: A Promising Descendant of Precision Medicine?

The pharmaceutical industry is aware that the clinical testing paradigm yielding average responses is not always the best way forward for treating disease. Gene therapy products are being developed to treat a variety of diseases including cancer, in-born mutations, genetic deficiencies, and other orphan indications. Delivery of a therapeutic gene attempts to restore deficient genes or enhance downstream molecular processes. Gene therapy fits the profile of Precision Medicine as it provides patients the right treatment at the right dose and time with minimum side effects and maximize efficacy. However, will gene therapy lead to improved efficacy and fewer side effects? This symposium will highlight the development of a gene therapy product from multiple viewpoints consisting of nonclinical, CMC, regulatory and clinical. The pharmacological aspects of gene therapy will be addressed. The nonclinical safety risks will be discussed as well as its translation to a safe first clinical starting dose. The nonclinical development program will be compared to the nonclinical testing strategy of other pharmaceuticals from both an US and EU perspective. The CMC requirements of a gene therapy product will be highlighted and clinical experience with a gene therapy product will be shared.

  • Nonclinical Safety Aspects of Viral Gene Therapy Products: Hurdles to Overcome
    Bert Haenen, 3D PharmXchange, Tilburg, The Netherlands
  • Preclinical Development of Gene Therapy Products: A US FDA Perspective
    Jinhua Lu, US Food and Drug Administration/CBER/OCTGT, Silver Spring, MD
  • Gene Therapy CMC: Considerations Across the Product Development Spectrum
    Maritza McIntyre, Consultant, Rockville, MD
  • Clinical Evaluation and Development of a Gene Therapy Medicinal Product
    Barbara Matthews, BioDirect, Silver Spring, MD

Development of Anticoagulant Therapies

The clinical benefits of anticoagulant therapy are well established for prevention of thrombosis in patients with existing cardiovascular disease such as atrial fibrillation and post-myocardial infarction or following knee or hip surgery because of deep vein thrombosis or pulmonary embolism. The prevention of thrombosis is continually balanced by the potential complications and risks associated with excess bleeding. This symposium will provide insight into the advances in the development of anticoagulant therapies.

  • Introduction
    Holly D. Dursema, Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, CT
  • Hemostasis and Coagulation
    Thulasi Ramani, Envigo, Somerset, NJ
  • Animal Models for Thrombosis and Bleeding Risk Assessment
    Karin Conde-Knape, Johnson & Johnson Innovation Centre, London, United Kingdom
  • Practical Aspects of Bleeding Time Assessments
    Jennifer Sheehan, Envigo, Somerset, NJ
  • Oral Anticoagulants: The Old and the New, and How Do I Stop the Bleeding?
    Holly D. Dursema, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT
  • Choosing the Right Anticoagulant for the Right Patient: Opportunities and Challenges
    Jeffrey Weitz, McMasters University, Ontario, Canada

A, B, C, D and X are Gone, OH MY!: How to Communicate Risk Without Categories

The Pregnancy and Lactation Labeling Rule (PLLR) was published on December 4, 2014.  The PLLR revises the information required for Section 8: Use in Special Populations for all human prescription drug and biological products subject to the Physicians Labeling Rule (PLR).  It specifically amends the regulations previously governing the content and format of the "Pregnancy," "Labor and delivery," and "Nursing mothers" subsections.  The new rule requires the removal of the pregnancy categories A, B, C, D, and X and replaces these categories with a risk statement which summarizes the risks of using a drug during pregnancy and lactation, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy and lactation.  The rule also requires that the labeling include relevant information about pregnancy testing, contraception, and infertility for females and males of reproductive potential.  The PLLR creates a consistent format for providing information about the risks and benefits of prescription drug and/or biological product use during pregnancy and lactation and by females and males of reproductive potential.  This session will review the rule and the accompanying guidance giving examples of new labeling using PLLR formatting.

  • Introduction
    Kok-Wah Hew, Takeda Pharmaceutical International Co., Deerfield, IL
  • Labeling Without Categories: An Overview of the Physician Labeling Rule
    Lynnda Reid, US Food and Drug Administration/Division of Bone, Reproduction, and Urology Products, Office of New Drugs, Center for Drug Evaluation and Research
  • Clinical Considerations: How Pregnancy Labels Are Used By Clinicians
    Jan Friedman, University of British Columbia, Vancouver, Canada
  • Replacing Pregnancy Categories with Risk Summaries
    Daniel Minck, US Food and Drug Administration/Division of Metabolic and Endocrine Products, Office of New Drugs, Center for Drug Evaluation and Research, Silver Spring, MD
  • Section 8.3: Women and Men of Reproductive Potential
    Jay Chang, US Food and Drug Administration/Division of Anesthesia, Analgesia, and Addiction Products, Office of New Drugs
  • Panel Discussion

Use of Genetically Modified or Surgically Adapted Animal Models of Human Disease in Nonclinical Drug Discovery and Development

Animal models of human disease are commonly utilized to gain insight into the potential efficacy and mode of action of novel pharmaceuticals.  However, conventional (healthy) rodent and non-rodent models are generally utilized in nonclinical safety testing. Animal models of human disease may be helpful in understanding safety risks of compounds in nonclinical or clinical development, with their greatest value being in targeted or hypothesis-driven studies to help understand the mechanism of a particular toxicity. Limitations of animal models of disease in nonclinical safety testing include a lack of historical control, heterogeneity in disease expression, a limited life span, and confounding effects of the disease. In most instances, animal models of human disease should not be utilized to supplant testing in conventional animal models. While of potential benefit, testing in an animal model of human disease should only be taken after adequate consideration of relevance along with benefits and limitations of the proposed model.  The intent of this presentation is to outline recommendations for the use of animal models of human disease in drug discovery and safety assessment.

  • Introduction
    Paul W. Snyder, Experimental Pathology Laboratories, Inc., W Lafayette, IN
  • Nonclinical Models with an Edge: Utilizing Genetic Diversity, Humanized Organs, or Animal Models of Human Disease for Safety Assessment
    Kathleen Heinz-Taheny, Eli Lilly and Company, Indianapolis, IN
  • Animal Models for Immune Assessment
    Gary R. Burleson, Burleson Research Technologies, Inc., Morrisville, NC
  • Of Men in Mice: Chimeric Animal Models for Drug Discovery Research and Safety Assessment
    Kristina Howard, US Food and Drug Administration, Silver Spring, MD
  • Rodent Osteoarthritis Models Used for Preclinical Drug Development
    Pamela Blackshear, Covance Inc., Greenfield, IN

1:30 PM–4:30 PM

Hot Topics

  • Health Issues Related to Use of Hookahs
    Terry Gordon, New York University, New York, NY
  • Advances in Organ on Chip Development: An Update
    Kristen Fabre, National Institutes of Health, Bethesda, MD
  • Discussion of FDA Draft Guidance on Male-Mediated Developmental Risk for Pharmaceuticals
    Lynnda Reid, US Food and Drug Administration/CDER, Silver Spring, MD
  • Updates from FDA’s Office of New Drugs
    Karen Davis-Bruno, US Food and Drug Administration/CDER/OND, Silver Spring, MD
  • Updates from MHRA/EU
    David Jones, MHRA, London, United Kingdom