Continuing Education (CE) courses are 3.5 hours each and are held either Sunday morning (AM) or Sunday afternoon (PM). Preregistration is required and seating is limited.
Session Chairs: Mike Orr, Orr Nonclinical Consulting, LLC, Bethesda, MD; and Tracy Williams, Eli Lilly and Company, Indianapolis, IN
In-licensing and out-licensing within the pharmaceutical industry happens throughout drug discovery and development and occurs through varied approaches. This course is geared toward equipping the toxicologist with a general understanding of how to approach both: in- and out-licensing. For in-licensing, key elements will be outlined for evaluating a data package, identify gaps and strengths of a potential acquisition and address how to develop a productive partnership between both companies throughout the evaluation. For out-licensing, how to best represent your study designs, data, and strategies to aid an acquisition as well as being prepared to manage a due diligence assessment will be addressed. Throughout, case examples will highlight pitfalls, challenges, and successes. The ACT Early Career Professional Outreach Subcommittee developed this course.
Introduction and Overview of In-Licensing and Out-Licensing
Tracy Williams, Eli Lilly and Company, Indianapolis, IN
Practical Aspects of In-Licensing
Michael Myers, Eli Lilly and Company, Indianapolis, IN
Effective Due Diligence for Large Molecules
Patrica Ryan, MedImmune, LLC, Gaithersburg, MD
Break
Effective Due Diligence for Small Molecules
John McNulty, Shire, Lexington, MA
Practical Aspects of Out-Licensing
Ric Stanulis, Aclairo PDG, Inc., Ardsley, NY
Session Chairs: A. Wallace Hayes, Harvard University and Michigan State University, Temple Terrace, FL; and Michael Holsapple, Michigan State University, East Lansing, MI
This Continuing Education Course is intended as a learning experience for toxicologists and other scientists interested in food safety including preparing food additive and new dietary ingredient submissions to the US Food and Drug Administration (FDA). Topics will include the concept of Generally Recognized as Safe (GRAS), new dietary ingredients (NDI), issues revolving around containments in our food supply and the impact of the Food Safety Modernization Act (FSMA) on the food and dietary supplement industry. Of special importance will be a discussion of infant formula safety requirements and the process of updating the FDA Toxicological Principles for the Safety Assessment of Direct Food Additives and Color Additives Used in Food, commonly known as “the Redbook.” Speakers are from industry, government, and academia. Learning objectives: 1) understanding regulatory issues at the FDA Center of Food Safety and Applied Nutrition and 2) provide insights into preparing GRAS and NDI dossiers.
Introduction of Topic and Speakers
Michael Holsapple, Michigan State University, East Lansing, MI
Food Safety: Ingredients
Alex Eapen, Cargill, Inc, Wayzata, MN
Food Safety: Dietary Supplements
Claire Kruger, Spherix, Rockville, MD
Food Safety: Infant Formula Regulation: Nutritional Adequacy and Ingredient Safety
Carrie Assar, US FDA, College Park, MD
Importance of the Food Supply Chain in Preventing Contaminants
Roger Clemens, University of Southern California, Los Angeles, CA
Impact of FSMA on the Food and Dietary Supplement Industry
Joy Joseph, Joy’s Quality Management Systems, Los Angeles, CA
Session Chairs: Pallavi Limaye, Xenometrics LLC, Stilwell, KS; and Deven Dandekar, Xenometrics LLC, Stilwell, KS
Safety assessment of a new chemical or herbal/nutritional entity is a pivotal component of the nonclinical program prior to the clinical trials and subsequent marketing of a new drug product for human or animal health use. As per the GLP regulations, the Study Director assigned by the test facility management for a given study is the single point of study control that is responsible for the overall study conduct. In addition to taking care of the scientific aspects of the study, the study director has to ensure proper coordination with the sponsor/study monitor, study technician/coordinator, chemist, pathologist, and quality assurance. This course will provide understanding of the finer aspects of study conduct and role of each individual involved in the “study-conduct machinery;” from the study technician to the study sponsor. This course will focus on the practical approaches to the real life challenges faced during the study conduct and will provide an insight on anticipating potential problems and solutions to the problems, which may arise.
Protocol Development, Communication with the Sponsor and Understanding the Compound—Small Molecule, Herbal or Nutritional Products
Deven Dandekar, Xenometrics LLC, Stilwell, KS
Understanding Analytical and Bioanalytical Validation Requirements to Support Nonclinical Study
August Wilke, Eli Lilly, Indianapolis, IN
Study Conduct: Communication with the Sponsor, Quality Assurance, and Hosting a Study Monitoring Visit
Pallavi Limaye, Xenometrics LLC, Stilwell, KS
Interactions with In-Life Technical Team and Other Support Areas
David Monteith, Xenon Pharmaceuticals Inc., Burnaby, BC, Canada
Reporting of the Data: Data Compilation, Statistical Analysis, Report Writing, and Submitting a Draft Report to Quality Assurance
Suzanne Wolford, Covance Laboratories, Inc., Madison, WI
Report Review and Finalization: Responding to Quality Assurance and Sponsor’s Comments
Kenneth Hastings, Hastings Toxicology Consulting, LLC, Mount Airy, MD
Session Chairs: Denise Bounous, Bristol-Myers Squibb Company, Princeton, NJ; and William Siska, Charles River Laboratories, Reno, NV
Toxicity involving the hematopoietic system and lymphoid organs is frequently encountered in nonclinical safety studies and represents an important regulatory focus. Clinical pathology and anatomic pathology endpoints have traditionally been used for a first-line assessment of hematotoxicity and immunotoxicity, with additional specialized testing generally performed on a case-by-case basis consequent to study findings or in light of recognized drug class effects. As more specialized techniques including flow cytometry, functional assays, and other novel in vitro evaluations are increasingly utilized, it is important to understand the relationships between these modalities and traditional endpoints, and to be familiar with their advantages and limitations. This session will present comprehensive approaches to the evaluation of hematopoietic and lymphoid organ toxicity and will highlight correlations between nontraditional testing and routine endpoints through didactic presentations and integrated case examples.
Immunotoxicity: What the TDAR May Not Address
Florence Burleson, Burleson Research Technologies, Inc., Morrisville, NC
Immunotoxicity Assessment: One Size Does Not Fit All
Ellen Evans, Pfizer, Inc., Groton, CT
Correlation Among Bone Marrow Cytology, Histopathology, and Hematology Data in the Assessment of Hematotoxicity in Nonclinical Studies: Principles and Case Examples
William Siska, Charles River Laboratories, Reno, NV
Application of Flow Cytometry in Hematotoxicity Evaluation of Rodent Bone Marrow
Arlene Love, Bristol Myers Squibb, Princeton, NJ
Case Study of the Megakaryocyte Colony Forming Cell Assay As an In Vitro Model of Drug-Induced Thrombocytopenia
Jacqueline Tarrant, Gilead Sciences, Foster City, CA
Session Chairs: Paul Roney, BARDA, Arlington, VA; and Grace Furman, Paracelsus, Inc, Leucadia, CA
With the increased emphasis on outsourcing toxicology studies to specialty Contract Research Organizations (CRO), toxicologists are being asked to monitor studies being conducted outside of their organizations. In this capacity, they must ensure that the toxicology program is conducted properly and in a cost-effective manner. This presents a particular challenge to the toxicologist because many toxicologists have no training in managing these types of programs. This course will provide the participants with the tools they need to succeed in this endeavor. Specifically, this course will discuss what factors the toxicologist needs to consider when selecting a CRO including bid solicitation and bid analysis (cheapest is not always best). It will also discuss the interactions between the Study Monitor and the CRO before, during and after the study. It will conclude with a discussion of the challenges of monitoring multisite studies and the importance of Good Laboratory Practices. This course is a must for any toxicologist who is responsible for outsourcing toxicology studies, no matter what sort of company he/she works for.
Selecting the Right CRO Partner for Your Toxicology Program: Factors to Consider
Grace Furman, Paracelsus, Inc, Leucadia, CA
Monitoring versus Auditing: What Is the Difference?
David Hobson, LoneStar PharmTox LLC, Boerne, TX
What You Need to Know and Do to Be an Effective Study Monitor
David Serota, 7th Inning Stretch Consulting, LLC, Kalamazoo, MI
Study Monitor: The CRO’s Friend or Foe?
Sue McPherson, WuXi AppTec, Suzhou, Wuzhong, China
GLP’s in an Era of Multisite Studies
Robin Guy, Robin Guy Consulting, LLC, Lake Forest, IL
General Discussion
Session Chairs: Torrie A. Crabbs, EPL, Inc., Research Triangle Park, NC; and Daniel Patrick, MPI Research, Mattawan, MI
This CE course will focus on five different organ systems that commonly present as target organs during evaluation of preclinical safety studies: hepatobiliary, urinary, reproductive, lymphoid, and nervous. Each presentation will present some of the more common and/or challenging non-neoplastic spontaneous and induced findings that pathologists encounter during histopathological evaluation of preclinical safety studies. In addition to providing some general descriptions with representative photomicrographs, each presenter will also discuss how these findings are generally interpreted and their potential impacts on a study, including determination of the NOAEL. This course should be of interest to the general membership of ACT including toxicologists, regulators, scientists, and others involved in biopharmaceutical and chemical laboratory animal preclinical safety assessments.
Spontaneous and Induced Non-Neoplastic Findings in the Liver
Russell Cattley, Auburn University–College of Veterinary Medicine, Auburn, AL
Spontaneous and Induced Non-Neoplastic Findings in the Kidney
Kendall Frazier, GlaxoSmithKline, King of Prussia, PA
Spontaneous and Induced Non-Neoplastic Findings in the Reproductive Tract
Justin Vidal, MPI Research, Mattawan, MI
Spontaneous and Induced Non-Neoplastic Findings in Lymphoid Tissues
Paul Snyder, EPL, Inc., LLC, West Lafayette, IN
Spontaneous and Induced Non-Neoplastic Findings in the Nervous System
Robert Sills, NIEHS/NTP, Research Triangle Park, NC
Session Chairs: Saryu Goel, US Food and Drug Administration, OGD, Silver Spring, MD; and William J. Brock, Brock Scientific Consulting, LLC, Montgomery Village, MD
Generic drugs have major public health impact and account for >88% of prescriptions dispensed in the United States. Starting in 2012, the Generic Drug User Fee Amendment (GDUFA) provided funding for FDA’s Office of Generic Drugs (OGD) to achieve timely review of Abbreviated New Drug Applications (ANDA’s). During this time, OGD formed a Pharmacology/Toxicology team to ensure that generics have a similar safety profile as their respective reference listed drug (RLD). This session will discuss the regulatory guidelines and Pharmacology/Toxicology safety review of impurities and excipients in generic drugs. Presenters will discuss safety issues that warrant Pharmacology/Toxicology evaluation in OGD, and provide insight on principles such as “context of use” which underpin the safety evaluation. An industry perspective on the safety evaluation of generic drugs within the context of impurities and excipients will be included in this course, and the relationship of these evaluations to the safety of generic drug in an ANDA. Furthermore, it will be a forum for the industry, academia, and regulators to discuss the common challenges and shared experience in generic drug research, development, and review practices.
Introduction
Saryu Goel, US FDA/OGD, Silver Spring, MD
Pharmacology/Toxicology Review for Generic Drugs: Why, When, and How?
Robert Dorsam, US FDA/OGD, Silver Spring, MD
Challenges in Qualifying Impurities in Generic Drugs—An Industry Perspective
S. Rajesh Sundar, Zydus Cadila, Ahmedabad, Gujarat, India
Impurity Safety Evaluation in Generic Drugs
Melanie Mueller, US FDA/OGD, Silver Spring, MD
Excipient Safety Assessment in Generic Drugs: What is the Minimum and Maximum in Toxicology?
William J. Brock, Brock Scientific Consulting, LLC, Montgomery Village, MD
Excipients in Generic Drugs—Principles, Pitfalls/Opportunities and Case Studies
Sree Rayavarapu, US FDA/OGD, Silver Spring, MD
Panel Discussion
Session Chairs: Mark W. Powley, US Food and Drug Administration, CDER, Silver Spring, MD; and Leon F. Stankowski Jr., Charles River, Skokie, IL
Genetic toxicology is a critical component of the drug safety assessment process. The overall goal of genetic toxicology testing is to identify test articles capable of damaging DNA as these compounds may also possess carcinogenic properties. Per ICH S2(R1), regulatory testing utilizes a battery approach focusing on gene mutations, structural chromosomal damage (clastogenicity), and numerical chromosomal damage (aneugenicity). Positive results from any of the initial studies may result in additional testing to further define genotoxic risk. Ultimately, genetic toxicology data is integrated into the risk:benefit analysis and may significantly impact regulatory decisions.
This course will provide attendees with a working knowledge of regulatory genetic toxicology. Topics will include reviews of regulatory studies, ICH guidelines (e.g., M3, M7, and S2), approaches to follow-up on positive results, data integration, the impact of genetic toxicology results on clinical development, and innovations in the field. Considerations unique to both API and impurities will be addressed.
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 topic of genetic toxicology will be relevant to scientists from all employment sectors.
Introduction
Mark W. Powley, US Food and Drug Administration, CDER, Silver Spring, MD
In Vitro and In Vivo Gene Mutation Assays
Leon F. Stankowski, Jr., Charles River, Skokie, IL
In Vivo and In Vitro Assays to Detect Cytogenetic Damage
in Genetox Testing
Rohan Kulkarni, BioReliance, Rockville, MD
Genetic Toxicology in Drug Development
Maik Schuler, Pfizer Global Research and Development, Groton, CT
Future of Genetic Toxicology Testing
Kerry L. Dearfield, Retired (formerly of EPA and USDA/FSIS), Burke, VA
