Program Agenda

Saturday, September 17

Diplomate in Safety Pharmacology (DSP) Certification Exam: For more details and to register for the exam, please visit the DSP page.


Sunday, September 18

Half-Day Continuing Education Courses: For more information please visit the Continuing Education Section.

Evening Welcome Reception


Monday, September 19

Morning Sessions

Exhibits and Poster Open

Keynote Plenary: Safety Pharmacology Across the Globe: Vision of Past, Present, and Future
Dr. Jean-Pierre Valentin

The field of safety pharmacology emerged from concerns over significant gaps in the safety data that existed at the time, putting clinical trial subjects and patients at risk of pharmacodynamic toxicity. From this beginning, the field has evolved, but the risks remain of assuring the safety of novel new targeted therapies over a life-time of treatment of complex diseases. In addition to the clinical challenges, the field of safety pharmacology has emerged in a period where business models, regulatory landscape for risk-tolerance and societal challenges have evolved and molded how the field is practiced in the current day. Despite all of those challenges, safety pharmacology has demonstrated its positive impact on drug discovery and development by contributing to identification and elimination of hazards, and assessment, management and mitigation of risks. Projecting the challenges of today into the near and long term future so that the field of safety pharmacology can be positioned for next 10 to 20 years, beyond a period where most of us will be around to influence that future, is what we would like to achieve. How do we project that future, what is the roadmap to advise future generations of safety pharmacologists, what principles can we share with them today that will be relevant for tomorrow. Let us consider these together and lay out a vision and path taking into account the past and present to model the future of safety pharmacology.

Track A: Translational Cardiovascular Safety Pharmacology

In sum, the goal of all preclinical safety testing is the accurate and complete identification of effects resulting from administration of a test compound. The more accurate and complete the information, the better we are able to predict the risk associated with administration in humans. This session will examine current methods of evaluating the translational accuracy of various cardiovascular test systems, introduce emerging paradigms, and discuss their application in developing clinical risk profiles. Presentations will include consideration of various test platforms and their separate and combined contributions to a predictability index.

Track B: Clinical Relevance of Receptor Pharmacology

Advances in science related to the GPCR target family provided a wealth of drugs during the past decades. Better understanding of the structure of GPCRs and their function in physiological systems provides the pharmaceutical industry novel strategy and tools to develop more refined SAR-driven drug design, alternatives to the common approach to screen the receptors at their inactive state and consider more predictive models with high clinical relevance. This session will provide a variety of state-of-the-art scientific contributions ranging from ligand based physiological classification of GPCRs to connections between receptor heterogeneity and clinical outcome. Speakers will address the translational value of their research with a particular accent on safety aspects.

Lunch Break, Poster Presentations, Exhibits

Oral Communications


Afternoon Sessions

Track A: Advances in Technologies: In Vitro and In Silico Models

This session will provide insight into the latest knowledge and development in the fields of cardiac safety science and bioimaging. Experts will give three presentations on the in silico identification of drug-induced pro-arrhythmia, moving towards in silico drug trials in safety pharmacology and characterization of physiologically relevant 3D cardiac micro-tissues for drug safety testing, as well as a presentation focusing on the state-of-the-art imaging of live cells employing newly developed fluorogenic probes. We aim to show that these scientific innovations and developments could be of benefit for reducing attrition in drug development.

Track B: Practical Pharmacology

The Practical Pharmacology session will highlight the clinical application of pharmacology and toxicology principles in the provision of health care to patients. We will be presenting clinical cases that highlight issues related to providing optimal therapeutics and toxicological care.

Tuesday, September 20

Morning Sessions

Exhibits and Poster Open

Keynote Plenary: Using Big Data and Little Data to Understand Variable Drug Actions
Dr. Dan Roden

Initial studies to define mechanisms underlying variable response to drug therapythe fundamental goal of the discipline of Clinical Pharmacologyfocused on outlier patients or small study groups, i.e., Little Data. As the discipline turned increasingly to identify the genomic basis for variable drug actions, increasingly large datasets have been studied with and drug phenotypes coming from large networks or electronic health records (EHRs), i.e., Big Data. These large resources, in turn, have provided the starting point for new discovery in genome science and in pharmacogenomics. This talk will describe some of these advances, and how there is an emerging focus back to individual subjects both in discovery as well as in recent efforts to use DNA datasets coupled to EHRs to implement pharmacogenomics.

Track A: Translational Central Nervous System and Respiratory Safety Pharmacology

On the one hand, safety pharmacology is actively expanding with significant progress with in vitro drug safety screening models. On the other end of the spectrum, safety pharmacology aims to predict clinical trial outcome and clinical data can be used to validate non-clinical drug safety screening tools. This session will explore central nervous system (CNS) and respiratory safety pharmacology models across the full spectrum from single cell assays to clinical concordance. Highlighting weaknesses of older safety testing paradigms but also exploring completely new methods to improve drug safety evaluations, the session will challenge safety pharmacology boundaries and open new horizons. CNS drug safety assays are typically under-represented in the in vitro arena and the session will present cutting edge applications in this emerging field.

Track B: State-of-the-Art Methods in Pharmacology

This session will focus on the description and application of state-of-the-art methods and techniques in pharmacology as they apply to drug safety and efficacy. Session topics include pharmacometabolomics, mass spectrometry based imaging, organ-on-a-chip and will include not only “state-of-the-art technologies” but also “state-of-the-art thinking about data.” Pharmacometabolomics is the study of the metabolites in a system and how they affect drug efficacy and toxicity. This technique has been adapted as a new form of precision medicine in terms personalizing drug therapy. Recent advances in mass spectrometry have enabled mass spectrometry based imaging of organs or even entire preclinical animals. This powerful technique can aid in visualizing drug, metabolites or proteins to specific organelles within an organ. Microchips lined with human cells recapitulate the architecture of major organs such as the heart, kidney, liver, intestine, lungs, etc. These organs-on-chips can be used to assess the safety and efficacy of drugs. Non-standard approaches to data collection and interpretation will be discussed.

Lunch Break, Poster Presentations, Exhibits

Paediatric and Fetal Clinical Pharmacology Session

The inclusion of children in clinical trials is increasingly important, notably in that many drug regulatory agencies now require a paediatric plan during the process of drug approval. There are many challenges to studies in children as well as to drug discovery in children and the place of precision medicine in child health care. This symposium will address key issues in paediatric therapeutics related to drug discovery, regulation, and implementation of precision medicine for children.

Oral Communications


Afternoon Sessions

Track A: Translational Biomarkers: Bridging the Gap

This symposium will focus on recent advances in the use of biomarkers to support safety evaluations. Biomarker efforts for the central nervous system, cardiovascular, respiratory, and renal functioning will be discussed. Early data from the ILSI/HESI Subcommittee on Translational Biomarkers of Neurotoxicity collaborative project to characterize the potential markers of neurotoxicity in biological fluids for several know neurotoxins will be shared. The rationale for the protocol for the collaborative study will be described. Additional presentations on cardiovascular, renal, and respiratory biomarker development will complement the neurotoxicity discussion. Participants from different global locations will contribute to the audience’s understanding of difficulties in identifying biomarkers and the importance of biomarkers in the future regulatory and scientific environment.

Track B: CSPT Trainee Oral Presentations


Wednesday, September 21

CSPT Annual General Meeting
SPS Annual Members Meeting and Awards Ceremony
SPS Distinguished Service Award Presentation

Plenary: Global Regulatory Climate for Safety Pharmacology

Increasingly, safety pharmacology is undertaken in a global regulatory climate. While S7A guides the overall aims of safety pharmacology, new topics arise as the science and drug development advance. This session will present the similarities and—importantly—differences between Health Canada, PMDA, and FDA policies and guidances on a range of topics critical to the successful use of safety pharmacology data in support of clinical testing. The revision to S7A, progressive licensing, the CiPA and JiCSA initiatives, the recent CNS AEs in a French Phase 1 trial, and use of the British health database AMED will be discussed by regulators and safety pharmacologists.

President’s Summary/Meeting Adjourned


Continuing Education

AM Courses

8:00–12:00

AM1: For or Against Stem Cell Safety Screening
Co-Chairs: Bernard Fermini and Frederick Sannajust

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and human embryonic stem cell-derived cardiomyocytes (hESC-CMs) are increasingly used in drug discovery, toxicity assessment, and cell-based disease treatments. In vitro screening assays are also used to make decisions about which drug candidates should progress to First-In-Human (FIH) and successive development clinical phases II & III studies. Assessing the cardiac toxicity risk liability of any new chemical entities (NCEs) is essential before embarking into long-lasting and expensive development phases. The goal of this CE course is to assess the current state of our understanding of hiPSC-CMs and hESC-CMs and whether these cells are appropriate for use in high-throughput screening and regulatory assays. Since these cells are currently used to assess QT prolongation and proarrhythmia effects, we will define where do we stand? While some of the studies conclude that these cells represent a suitable predictive model, others question their value based on reports of mixed phenotype(s), unforeseen pharmacology, beta-adrenoceptor signaling, issue with maturity (adult ventricular, atrial, nodal CMs), 2D vs. 3D construct configuration, acute vs. chronic exposure, and conflicting ion channel profile(s) pending on cells characteristics and specific conditions to culture the cells. We will review some of the more controversial issues and attempt to provide a current view of the field: Are stem cells ready for prime time safety screening? Strengths and weaknesses of hiPSC-CMs? What are the major advantages and flaws? How may this application and related methodologies impact safety screening in the near future? In fact, Donald Trump has reportedly said that there are a lot of gaps and it would be a HUGE mistake to invest in this unproven tool. In light of the potential utility of this emergent technology and new tool, this CE course will therefore critically evaluate the use of hiPSC-CMs and hESC-CMs for preclinical drug safety assessment and share expert experiences using hiPSC-CMs and hESC-CMs for the testing of electrophysiological effects of NCEs and assessment of other drug-induced safety risks such as effects on contractility, Ca2+ transient dynamics/homeostasis, cardiac mitochondrial toxicity, cardiac drug-drug interaction (significant increase or decrease in field potential duration, beating rate, impedance amplitude, conduction) and cardiac morphological cell features via use of High Content Assay (HCA) imaging techniques, etc. Consequently, the future decisional regulatory use of hiPSC-CMs or hESC-CMs and then, the acceptable translation of effects in these cells with NCEs to human exposure levels, will require a thorough understanding of all these parameters to predict the proarrhythmic potential of all NCEs as proposed by the new HESI/ILSI-FDA Comprehensive In Vitro Proarrhythmic Assay (CiPA) initiative.

CE Book   (Registration Required)

 

AM2: Disease Models: Safety Assessment and EfficacyReading through the Disease Model to Assess Possible Liabilities
Co-Chairs: Kristy D. Bruse and Greet Teuns

Early discovery/safety studies are typically conducted in healthy animals with the species for these studies being selected based on the estimated pharmacological activity/potency and metabolite profiles. The studies are then designed to mimic the clinical dosing regimen with respect to the route of administration, duration of treatment, and dosing interval. These studies are conducted in healthy animals and mimic the characteristics of the first in human (FIH) clinical population.

However, both the preclinical and Phase I clinical trials do not mimic the characteristics of the targeted [disease] patient. Performing preclinical studies that mimic the clinical patient can be very important in certain disease indications where the disease condition can dramatically affect the safety of the pharmaceutical. In this course, we will review the use of animal models for selected diseases in the evaluation of exaggerated pharmacodynamics and toxicity in order to improve the relevance and extrapolate the preclinical findings to the intended targeted population. The basic principles of the use of diseased animal models will be reviewed as well as the advantages and disadvantages of these models. In addition, case studies of the use of these models in safety assessments will be presented.

CE Book  (Registration Required)

 

AM3: Enhanced Cardiovascular Risk Identification: Leveraging Cardiac Contractility Assessments on Cardiovascular Safety Studies
Chair: Mathew Abernathy

Blood pressure is highly regulated so as to maintain blood flow to organ systems. Baroreceptors are located in the vasculature and are responsible for driving changes in cardiac output and peripheral vascular resistance to maintain blood pressure. Under normal conditions, fluctuations in blood pressure will trigger autonomic reflexes inducing compensatory changes in heart rate, inotropy, and vascular tone. Off-target drug effects on blood pressure and/or heart rate are commonly observed on cardiovascular safety studies, but with these limited datasets elucidating a mechanism can be challenging. Adding measures of cardiac contractility to safety studies can help more thoroughly reveal effects on cardiac output as well as aid in proarrhythmia risk detection. This CE course will cover current methods used to measure cardiac contractility and the sensitivity of these measures across animal models for prediction of clinical drug reactions. Additionally, this course will also cover the use of electrophysiological measures of cardiac function to predict Torsades de Pointes (TdP).

CE Book   (Registration Required)

 

Lunchtime Mini-Course

12:30–13:30

Lunchtime Mini-Course: Introduction to Safety Pharmacology
Co-Chairs: Nancy S.J. Poy and Kristy D. Bruse

Safety Pharmacology has evolved significantly over the past 15 years with many new scientists entering or transitioning over into this field. This mini-course will cover the current regulatory guidelines for the FDA, EU Canada, and Japan as well as some of the new proposed guidelines currently in discussion. We will address the core assays as well as secondary (Tier 2) and supplemental assays. Attendees will be able to have a “crash course” in Safety Pharmacology in order to better understand the current issues discussed at this year’s meeting.

CE Book  (Registration Required)

 

PM Courses

14:00–18:00

PM1: Cardiac Risk Assessment: Translational Medicine Approaches from Preclinical to Clinical Evaluation
Co-Chairs: Bruce Morimoto and Lorraine M. Rusch 

It has been nearly 20 years since the EMA published the first Points to Consider document on the assessment of QT prolongation by non-cardiovascular drugs, which later became part of ICH S7A. And the clinical evaluation of QT prolongation and pro-arrhythmic potential (ICH E14) was published more than 10 years ago. Since then, the assessment of QT-prolongation and arrhythmia risk has been a significant focus of the pharmaceutical industry and the Safety Pharmacology Society.

This course will focus on understanding the current best practices for conducting nonclinical cardiovascular safety studies, case studies on the translation from preclinical-to-clinical, and a discussion of the clinical evaluation of cardiovascular safety including thorough QT (TQT) studies and the more recent intensive ECG evaluation in early clinical research.

CE Book  (Registration Required)


PM2: Age and Safety Pharmacology: Considerations for Neonatal/Pediatric Indications and Geriatric Animal Models
Co-Chairs: Mathew Abernathy and Mary Jeanne Kallman

The practice of safety pharmacology as indicated in ICH S7a specifies that core battery assessments should be conducted in animals that are of an age that is scientifically justifiable. As most drugs are developed to treat diseases across the adult lifespan, there is a large body of background literature for CNS, cardiovascular, and respiratory endpoints in adult rodents, canines, and monkeys. The appropriateness of conducting safety pharmacology studies in adult animals becomes a question when developing a drug to treat a disease specific to pediatric/neonatal or elderly populations. This CE course will cover topics related to known age differences in CNS, cardiovascular, and respiratory endpoints as well as how the execution and application of data collection methods may differ with age. Additionally, this course will discuss therapeutic indications where using young or old animals for drug safety evaluations may be scientifically justifiable. Examples of disease models and case studies will be integrated throughout the course to facilitate interactive learning.

CE Book  (Registration Required)


PM3: Best Practices, Study Designs, NOEL, and NOAEL in Safety Pharmacology
Co-Chairs: Robert Austin-LaFrance and Tomas Mow

This course will highlight factors to consider in developing best practices and optimal safety assessment within core battery safety pharmacology studies. Areas for consideration will include sampling rate, number of samples, sample period(s), and sample duration applied to the acquisition and analysis of telemetered data. Cross-over vs. ascendant dosing, parallel control group, number of test subjects required to provide sufficient power to discern a change of X, Y, or Z (msec, mV, bpm, mmHg, etc.) for both chronic (in-dwelling) and acute (jacketed, etc.) acquisition methodologies. Similar discussions will include other core battery central nervous (e.g., FOB, locomotor) and common cardiopulmonary testing methodologies. The goal is to secure study designs with high translatability and predictive data value allowing for accurate evaluation of NOEL and NOAEL setting criteria for each of the relevant test parameters.

CE Book   (Registration Required)


Meeting Materials

Please view the Mobile App, or the Meeting Materials page for the most up to date program information. The meeting materials and App are restricted to 2016 Meeting Registrants. When prompted, please provide your registrant login information emailed to you in mid-August.