(Subject to Change)
Monday, October 1
AM 1—Improving Human Translation of Safety Pharmacology Models: Practical Applications of Advanced Tissue and Organ Engineering
Chairs: Blake Anson, PhD, Cellular Dynamics International, Inc. and Tony Bahinski, PhD, MBA, FAHA, Wyss Institute for Biologically Inspired Engineering at Harvard University
This intermediate-level course is intended for individuals with previous knowledge of traditional safety pharmacology studies and who are interested in learning about cutting edge and newly developing in vitro models. Recent advances in cellular models, including stem cell derived tissue cells, three-dimensional models, and micro-organ generation, have made it possible to address relevant safety pharmacology and toxicology endpoints utilizing human-based in vitro techniques. The lectures in this course will include overviews of various in vitro models and how they may be applied to cardiovascular, respiratory, and neuronal safety endpoints. Active participation from the attendees is highly encouraged.
AM 2—Safety Pharmacology Endpoints in Toxicology Studies
Chairs: Scott Tiesma, Data Sciences International and Robert Austin LaFrance, Pfizer, Inc.
Stand-alone Safety Pharmacology studies are typically conducted by exposing subjects to a single administration of a test article at multiple dose levels. Such dedicated studies provide invaluable information to assess potential risk to vital organ systems of participants in first-in-human studies. Integration of Safety Pharmacology assessments into repeat dose toxicity studies enables evaluation of functional changes following the administration of multiple doses. Such an evaluation may provide for a more robust safety evaluation—better predicting potential risk in later clinical trials where exposure to the test article is of longer duration. The course will focus on considerations when combining studies, examples of successful integrations for new chemical and biological entities, and conclude with a preview of the forthcoming Safety Pharmacology recommendations on this topic.
Lunchtime Mini Course
Safety Pharmacology Case Studies: from Discovery to the Clinics
Chair: Mark Deurinck, Novartis
In this SPS CE course, three case studies will be presented by renowned safety pharmacology experts. Each case study will consist of a 15-minute presentation followed by a 5-min Q&A. The case studies will consist of the cardiovascular, central nervous or respiratory systems and will address studies conducted, issues/risks and risk mitigation in discovery, preclinical and/or clinical development of large and small molecules.
The informal atmosphere of this CE course promotes close and interactive interactions between the experts and the attendees allowing for deeper insights in how safety pharmacology liabilities are tackled in the process of drug development at different companies.
Lunch and beverages will be provided to course attendees.
PM 1—Advanced Topics in Respiratory Safety Pharmacology
Chair: Dennis J. Murphy, PhD, DABT, GlaxoSmithKline Pharmaceuticals
The course will cover three topics important to the area of respiratory safety pharmacology. The first topic involves the ICH S7A document as it relates to respiratory function assessment in safety pharmacology. Endpoints recommended in the document will be critically evaluated both for their value in detecting respiratory dysfunction and their relevance to known drug-induced respiratory dysfunctions in humans. Alternative endpoints and a strategy for assessing drug-induced respiratory dysfunction will also be presented. The second topic will cover sleep disordered breathing. This is an emerging area of concern in human pulmonary medicine and has implications for how drug-induced effects on respiratory function should be evaluated. The presentation will provide an overview of sleep disordered breathing, including both the mechanism of action and the associated pathologies. Its prevalence and etiology will be discussed as well as the animal models used to investigate the phenomenon. In addition, the role of sleep state in the control of breathing will be examined with specific emphasis on alterations in the control of respiratory rhythm generation and reflex control of respiratory function. The implications of these data will be discussed in relation to respiratory safety pharmacology assessment of drug effects and the possible role of sleep state on such studies. The third topic will cover respiratory dysfunctions associated with inhaled drugs. This is an important topic since the lung is becoming an important route of drug delivery and the respiratory system is often the primary target of injury associated with inhaled drugs. An overview of the known pathologies commonly associated with inhaled pharmaceuticals as well as study designs and methodologies for assessing respiratory dysfunction during and following drug inhalation will be presented. Respiratory function endpoints that would be most appropriate for detecting changes associated with lung injury and airway obstruction or irritation will also be discussed.
PM 3—Gastrointestinal Safety Pharmacology: From Preclinical to Clinical
Chairs: Scott Mittelstadt, PhD, Abbott Laboratories and Mark A. Osinski, PhD, Covance Laboratories Inc.
Gastrointestinal (GI) responses to drugs, such as diarrhea, constipation and emesis, are some of the most frequently reported adverse effects in the clinical development of new chemical entities. Despite the frequency of these effects, they are not considered life threatening and preclinical assessment of the GI system is not required by regulatory agencies prior to first in human studies. Therefore, pharmaceutical scientists need to assess the importance and the type of preclinical GI assays to be conducted within their own companies. This course will focus on the basic physiology of gastric emptying, intestinal transit, absorption/secretion, and emesis. We will also discuss advantages and disadvantages of different preclinical GI models. Finally, the course will discuss potential strategies that companies can implement to reduce the risk for unexpected clinical effects on the gastrointestinal system.
PM 4—SAFETY Biomarkers—What Every Safety Pharmacologist Should Know!
Chairs: Lew Kinter, PhD, DABT, AstraZeneca and David Johnson, DVM, DACLAM, Cascades Biosciences Consultants, Inc.
“SAFTEY Biomarkers—What Every Safety Pharmacologist Needs to Know!” is an introduction to safety biomarker science and applications in nonclinical safety studies, with emphasis upon the ICH S10 Safety Pharmacology Core Battery Organ Systems. Faculty will address the origins, science, current status and regulatory expectations for safety biomarkers used in nonclinical and clinical settings, and include considerations for using traditional safety pharmacology endpoints as biomarkers, and inclusion of new biomarkers as safety pharmacology endpoints. Current status of safety biomarkers for drug-induced injury of cardiac/cardiovascular, CNS/neuromuscular, and renal systems will be presented.