Continuing Education Courses

Sunday, June 25 (AM)

CE 1 (Sunday AM) 8:00 AM–12:00 Noon

Impact on the Stage-Aware Assessment of the Reproductive Tract

Co-Chairs: Karen Regan, DVM, DACVP, DABT, Regan Path Tox Services, Inc.; and Karyn Colman, BVetMed, MRCVS, Novartis

The evaluation of the reproductive system in the context of toxicological pathology requires a good understanding of the normal physiology and morphology of the reproductive organs. Stage-aware assessment of the reproductive organs can provide important information on the potential of toxicity of a compound in the early phases of the drug development. However, the reproductive organs undergo major morphological and physiological changes from birth to senescence, and therefore the interpretation of reproductive morphological alterations and/or pathology sometimes becomes complex. This interactive course presents different aspects of reproductive toxicological pathology that pathologists will face during the various phases of drug development, from challenges in juvenile and immature animals to changes associated with senescence, with emphasis on the stage-aware assessments of male and female reproductive organs in typical laboratory animal species (rodents, dogs and NHP).

Stage-Aware Assessment in Adult (Sexually Mature) Males
Claudine Tremblay, DVM, MSc, DACVP, Charles River Montréal

Stage-Aware Assessment in Adult (Sexually Mature) Females
Karyn Colman, BVetMed, MRCVS, Novartis

Maturity and the Assessment of Male Reproductive Toxicologic Effects in Large Animal Species
Katharine Whitney, DVM, PhD, DACVP, Abbvie

Immaturity, Adolescence, and Puberty: Interpretation of Female Reproductive System in Nonrodents (Dog and NHP)
Justin Vidal, DVM, PhD, MPI Research

Early Senescence in Female Rodents: Recognizing and Interpreting the Changes in Preclinical Studies
Karen Regan, DVM, DACVP, DABT, Regan Path Tox Services, Inc.

CE 2 (Sunday AM) 8:00 AM–12:00 Noon

Current Practices and Challenges in Method Validation

Co-Chairs: Florence Poitout, DVM, DACVP, DECVCP, Charles River Montréal; and Mehrdad Ameri, DVM, MS, PhD, DACVP, GlaxoSmithKline

This workshop will address current practices, problems and future directions of method validation, and a review of current regulatory requirements for clinical and preclinical biomarkers validation. It will focus on non-traditional instrumentations such as Mutiplex ligand binding assays now used to support many stages of drug development, but with unique challenges compared to single-plexed assays that necessitate various adjustments for validation and sample analysis. Quantitative mass spectrometry validation may also be challenging as this technology is now an integral part of operation in a growing number of clinical pathology laboratories and could certainly gain more space in drug preclinical development. Pitfalls and Challenges encountered in the validation of biological biomarkers and flow cytometry assays in different species will be presented. The current preclinical safety biomarker qualification process and the role of pathologists and clinical pathologists will be reviewed; from the use of shared histopathology lexicons and blinded vs. open histopathology evaluation, study design, data interpretation, and data curation for statistical evaluation. Emphasis will be placed on the complementary roles of the perspective of the morphologic pathologist in the phenotypic anchoring of safety biomarker changes, and that of the clinical pathologist for understanding pathophysiological and analytical aspects unique to each novel biomarker.

Challenges in Multiplex Binding Assays
Simon Lavallee, BSc, Charles River Montréal

Challenges in Quantitative Mass Spectrometry Assay Validations
Jennifer Colangelo, PhD, Pfizer

Strategies and Pitfalls in Biological Biomarker Validations
Adam Aulbach, DVM, DACVP, MPI Research

Validation Challenges in Flow Cytometry
Marie-Soleil Piché, PhD, Charles River Montréal

The Role of Anatomic and Clinical Pathologists in Biomarker Qualification
Daniella Ennulat, DVM, PhD, GlaxoSmithKline

Sunday, June 25 (PM)

CE 3 (Sunday PM) 1:30 PM–5:30 PM

Tissue-Based Image Analysis

Co-Chairs: Jean-Rene Galarneau, DVM, MS, DACVP, Novartis, Cambridge, MA; Marielle Odin, DVM, DVSc, RochePharma; and Sasmita Mishra, DVM, MS, PhD, DACVP, AbbVie

Digital pathology is in the process of revolutionizing the way pathologists conduct their art. Quantitative image analysis is a rapidly evolving area of digital pathology. The quantification of histological features on photomicrographs is not a new concept but it used to be cumbersome, resource intensive and limited to specialists and specialized laboratories. However, recent technological advances like highly efficient automated whole slide digitizer (scanner) systems, innovative image analysis platforms and the emergence of pathologist-friendly image annotation and analysis systems means that quantitation of features on histological digital images will become more and more prominent in our daily professional life. There is a plethora of potential use for quantitative image analysis in pathology including confirmation of equivocal findings noted by a pathologist, increasing the sensitivity of features detection, quantification of signal intensity, improving efficiency, etc. There is no denying that quantitative image analysis is part of the future of pathology but there are also numerous potential pitfalls when trying to estimate volumetric features from a few 2D sections. This continuing education session on quantitative image analysis will offer a broad overview of the field, a hands-on toxicologic pathologist experience with image analysis, a talk on how to apply basic stereology principle in order to avoid biases in image analysis and finally a reflection on the future of image analysis in the toxicologic pathology field.

Pathology through Pixels: Where We Are, Where We Need To Be
Robert Dunstan, DVM, PhD, DACVP, AbbVie

Image Analysis Solutions to Drive Investigative Pathology
Vanessa Schumacher, DVM, MS, DACVP, DABT, Roche Innovation Center Basel

An Investigative Toxicologic Pathologist’s Experiences with Whole Slide Image Analysis
Chandra Saravanan, DVM, MS, PhD, DACVP, Novartis

Reducing Bias in Image Analysis Data by Applying Stereological Principles
Danielle Brown, DVM, MS, DACVP, DABT, Charles River

CE 4 (Sunday PM) 1:30 PM–5:30 PM

What You Always Wanted to Know About Immunotoxicology in Pharmaceutical Development…But Were Afraid to Ask

Sponsored by the American College of Toxicology (ACT)

Co-Chairs: L. Peyton Myers, PhD, US FDA; and Michael Holsapple, PhD, ATS, Michigan State University

As evidenced by ICH S8, M3(R2), as well as S6(R1) Guidelines, the immune system has long been an important target in pharmaceutical development. Because of this attention, the science behind safety risks associated with the immune system has evolved, resulting in attention on immunotoxicology assessment tools. In recent years, as more pharmaceuticals are targeting specific immune targets, more immunotoxicology tools have been applied. This course will provide an overview of some of the most important immunotoxicology drug development platforms. Dr. Holsapple will set the stage by briefly reviewing ICH Guidelines and current paradigms in immunotoxicology. The next talks by recognized leaders in Immunotoxicology will focus on three important platforms. All of these talks will highlight how the data derived from these platforms are used to inform, highlighting strengths and limitations. Dr. Lebrec will consider the application of immunophenotyping to safety assessment. Dr. Holsapple will describe the utility of the T-dependent antibody response (TDAR) as the “gold standard” in immunotoxicology. Dr. Rao will address the dichotomy of the role of cytokines, as “friend or foe.” The final talk by Dr. Myers will provide a regulatory perspective on immunotoxicology, including trends in immunotoxicology assessment for recent FDA approvals.

Studies Setting the Stage: What You Always Wanted to Know About Immunotoxicology
Michael Holsapple, Michigan State University

Immunophenotyping: Application to Safety Assessment
Hervé Lebrec, Amgen Inc.

The “Gold Standard”: Utility of the T-Dependent Antibody Response
Michael Holsapple, Michigan State University

Cytokines: Friend or Foe?
Gautham Rao, Genentech Inc.

Immunotoxicology, Regulatory Perspective
L. Peyton Myers, US FDA

Continuing Education Chair:

Kirstin F. Barnhart, DVM, PhD, DACVP, AbbVie, Inc.

Continuing Education Co-Chair: 
Vimala Vemireddi, BVSc, MS, DACVP, DABT, Covance Laboratories, Inc.