Continuing Education Courses

Hanan Ghantous

Mark your calendars for November 3, 2013, and reserve your seat early in one or two of our great Continuing Education courses. This year the Education Committee is working on seven courses covering topics on ocular toxicity and pathology, teratology and developmental toxicology screening and testing, cancer bioassays, and biologics 201. We are also offering a writing course for regulatory authorities and hands on writing drug labeling. In addition, the Society of Toxicological Pathology (STP) will offer a course on inflammatory biomarkers. These courses will be educational, covering the latest science and presented by experts in the field.
~Hanan Ghantous, Education Committee Chair

Continuing Educations (CE) courses are 3.5 hours each and held either Sunday morning or Sunday afternoon. Preregistration is required and seating is limited.

Sunday, November 3

8:00 AM–11:30 AM

Screening and Testing for Reproductive and Developmental Toxicity

Chairs: Rochelle W. Tyl, RTI International, Discovery and Analytical Sciences
Jerry F. Hardisty, Experimental Pathology Laboratories, Inc.

Assessment of reproductive and developmental toxicity is critical for both hazard identification and risk assessment. The current test guidelines require a multigenerational (typically a two-generation) study to assess reproductive toxicity typically in rats or mice and a stand-alone developmental toxicity study typically in rats or mice and rabbits, to assess developmental toxicity. The first talk will present a new optimized study design, the Modified One-Generation (MOG) study, developed by NTP to provide F1 offspring, exposed in utero, for evaluation of reproductive, developmental, nervous, and/or immunologic systems, also with subchronic (13 week), or chronic study spin-offs. This assay employs the appropriate in utero and postnatal exposures, including the critical windows of pre- and postnatal development. Subsequent speakers will present developmental windows and vulnerabilities for the rodent and human reproductive system, immune system, and nervous system, and the toxicities associated with the development of these systems.

Relevance of Animal Tumors in Assessing Human Risk of Pharmaceuticals

Chairs: Thomas J. Steinbach, Experimental Pathology Laboratories, Inc.
James A. Popp, Stratoxon LLC

Carcinogenic hazard identification of pharmaceuticals has been based on evaluation in rodents for many decades. Initially the assessment of human risk was based on a presumption of biological similarity between laboratory animals and humans. Yet species-specific responses, such as PPARα agonist-induced liver tumors in rodents and alph2µ-globulin-induced renal toxicity leading to renal neoplasia in male rats, call into question the relevance of some animal tumors when assessing human risk. This symposium will present an overview of animal tumors that may not be relevant for human risk assessment. In addition, speakers will discuss various approaches for determining relevance of animal tumors and present specific examples where additional mechanistic data impacted the risk assessment and the approval process. The symposium will also present how regulatory agencies approach the relevance of animal tumor data to assess human risk of carcinogenicity.

Writing for Regulatory Authorities

Chairs: Holly D. Dursema, Boehringer Ingelheim Pharmaceuticals, Inc.
Melissa C. Rhodes, GlaxoSmithKline

This course is to provide participants with an overview of the regulatory documentation they will be required to provide as the toxicology representative in pharmaceutical industry project teams. The course will present document timing and focus. The construct of each regulatory document will be reviewed to enable the writer to compile the information necessary for regulatory agencies to conduct their evaluations. An emphasis will be on pertinent information and the interpretation, flow, and linking of data to create the intended message.

The session will start with the Phase I enabling package, which will review the studies required, compilation of an IND, and construction of an IB that will provide sufficient information for regulators while giving an understandable overview to clinical trial physicians. Following initiation of Phase I trials, toxicology representatives must consider toxicity studies to support Phase II, which will be of longer duration and generally include women of child bearing potential. This post-Phase I support includes incorporation of that study information into the IB, yearly regulatory updates, and construction of an end of Phase II meeting briefing document. The Pediatric Investigational Plan (PIP) is typically compiled during this time and consideration must be given to the need for, design, and timing of juvenile studies in relation to the clinical pediatric plan. The third session will focus on carcinogenicity studies, which are preceded by submission of a Special Protocol Assessment (SPA) to the FDA. The assembly of toxicology information to support carcinogenicity dose level selection and a typical draft protocol will be reviewed. The final session will review the documentation required for NDA submission, including the integration of the toxicity study results, the nonclinical overview, and the presentation of compound toxicity for efficient regulatory evaluation. Time will remain at the end of the course for a Q&A session.

1:00 PM–4:30 PM

Inclusion of Nonclinical Data in Drug Labels: Current and Upcoming Labeling Guidance, Practice, and Initiatives

Chairs: Mary Ellen Cosenza, Amgen Inc.
Lynnda Reid, US FDA, CDER

Pharmaceutical labeling serves many purposes and is used for communicating efficacy and risks associated with approved indications. In February 2013, a guidance proposed by US Food and Drug Administration (US FDA) was released that changes the requirements for the content and format of labeling for human prescription drug and biological products, called the Physician Labeling Rule (PLR). This class will introduce the portions of the label covered by the new PLR, and will include speakers with real world experience and a hands-on label writing session. The product label is used by a variety of audiences, but is written primarily for medical practitioners and patients. Animal and in vitro data should be conveyed in a clinically meaningful way to ensure its relevance to the patient population is clearly communicated. This session will describe what, where, and how nonclinical information should be included in pharmaceutical product labeling. The talks will focus on presentation of data in clear language with an emphasis on relevance to the prescribing health care professional and patient. Sections to be covered will include labeling highlights, pharmaceutical class and mechanism of action (Section 12.1), communication risk to special populations (Section 8), and presentation of carcinogenicity, genotoxicity, fertility and animal toxicology (Section 13) results. New pregnancy labeling initiatives at FDA in preparation for the removal of pregnancy categories will also be discussed.

Biologics 201: Advanced Topics in Nonclinical Safety Assessment of Biotechnology-Derived Drug Products

Chairs: Patricia C. Ryan, MedImmune, LLC
T. Scott Manetz, MedImmune, LLC

This course will provide insight into the unique considerations important for designing, executing and interpreting nonclinical safety programs for biotechnology-derived drug products (also known as biologics). Approaches used for interpreting nonclinical safety results relevant to human safety to support regulatory filings and clinical development of biologics will be described using a combination of general principles, regulatory guidelines, best practices, and case examples. Given that many of the biologics products on the market and in development are monoclonal antibodies, the majority of the topics will relate to this class of biologics. This course is intended for those interested in expanding their understanding of nonclinical safety aspects of biologics drug development.

Inflammatory Biomarkers

Chairs: Lila Ramaiah, Huntingdon Life Sciences
William Reagan, Pfizer Drug Safety R&D

Drug-induced toxicity to the immune and inflammatory systems encompasses a wide variety of adverse effects, ranging from exaggerated pharmacology (intended immunomodulation), to immunotoxicity (unintended immunosuppression or immune stimulation), drug-induced hypersensitivity and autoimmunity. Inflammatory biomarkers are valuable tools for the identification, characterization and monitoring of effects. Inflammatory biomarkers, often themselves mediators of inflammatory and immune responses, include cytokines, acute phase proteins, complement, and hemostatic proteins. This session explores the current use of inflammatory biomarkers in preclinical safety assessment. Topics encompass the evaluation of acute phase proteins, cytokines and complement in rodent and large animal models of inflammation. Emphasis is on relevance, utility, application, and use of inflammatory biomarkers, as well as on their translatability and predictivity from in vitro to in vivo models and from nonclinical to clinical settings. Factors that influence study design and biomarker selection, including preanalytical and analytical considerations, technologies and platforms, and species differences will be discussed. The session also includes short case studies with opportunity for open discussion with audience members.

All Eyes Focused on Ocular Toxicology and Pathology

Chairs: Brian J. Christian, Covance Laboratories, Inc.
Margarita M. Gruebbel, Experimental Pathology Laboratories, Inc.

The eye is often a target organ in toxicology studies. In order to evaluate the toxicological significance of effects on the eye, it is necessary to understand the basic structure and function of ocular tissues. Differences in the ocular anatomy and physiology among laboratory animal species are important factors to consider when designing protocols for ocular toxicology studies as they can influence the ability to collect and interpret data. Likewise, it is important to understand the value and limitations of current methods used for evaluation of ocular structures and their function. This session will provide detailed reviews of the anterior and posterior ocular segments of common laboratory animal species with regard to comparative anatomy and physiology, common methods used to determine treatment-related effects in ocular structures, as well as a description of spontaneous and induced changes observed in each segment of the eye.