SATURDAY, SEPTEMBER 23
Diplomate in Safety Pharmacology (DSP) Certification Exam
For more details and to register for the exam, please visit the DSP page.
SUNDAY, SEPTEMBER 24
Half-Day Continuing Education Courses
For more information please visit the Continuing Education section.
Evening Welcome Reception
MONDAY, SEPTEMBER 25
Exhibits and Poster Open
Title: Gender Differences in Cardiovascular Diseases
Many drugs have different action in women and men. Biological differences between women and men lead to sex differences in pharmacokinetics and pharmacodynamics. The biological differences between women and men may be caused by sex-specific gene expression, by sex-specific epigenetic modifications, and by interaction with sex hormones. In addition to biology, gender (the sociocultural dimension of being a woman or a man) plays a role for drug efficacy. Women and men use drugs differently. Compliance, adherence, and self-medication with over-the-counter drugs differ. Finally, it is known that male and female physicians treat women and men as patients differently. A bias arises already in drug development: frequently drugs are only tested in animals of one sex and thereby optimized for one sex. This is based on the prejudice that sex differences are not important for clinical drug effects. Sex and gender differences were underestimated so far in clinical study and phase III studies were not prospectively designed to assess sex differences in drug effects. In conclusion, drug therapy is not yet optimized for both genders. However, the awareness increases that differences between women and men should be respected in order to provide optimal drugs in optimal doses for both genders.
Prof. Dr. Vera Regitz-Zagrosek
Location: Hall Berlin B
Date: Monday, September 25, 2017
Track A: Oncology Drug Safety Testing in the 21st Century
Recent advances in cancer diagnosis and treatment have contributed to increasing cancer survivors to nearly 14.5 million in 2014 only in the US (DeSantis et al, 2014), and this population is anticipated to reach 18 million by 2020. Most antineoplastic agents require cyclical therapies which are associated with major side effects (Kounis et al, 2016). Illustrating this medical concern, cardiac side effects such as cardiac systolic dysfunction, ischemia, arrhythmias, hypercoagulable state, and hypertension have been correlated with increased risk for cardiovascular deterioration; childhood cancer survivorship study reported that survivors present an increased risk of cardiac disease (Meachem et al, 2010). Similar observations were made in regards to neurotoxicity. Standard single-dose safety pharmacology studies are limited in their ability to detect side effects from chronic dosing. Front-loading the safety assessment in parallel with other drug properties (e.g., efﬁcacy, pharmacokinetics, pharmacodynamics) may help conceive the best overall features during chemical design and permit timely investigation/characterization of toxicity mechanisms for identiﬁed liabilities. An open dialogue and synergistic collaborations between toxicologists, safety pharmacologists, and oncologists is required for optimal anticancer medication development. This session will appraise several angles of the non-clinical risk assessments from translational considerations to animal models and the global regulatory landscape as they relate to oncology drugs. The game-changing global safety pharmacology regulatory landscape of all new I/O treatments and combo-therapies will be discussed.
Track B: Updates on the Hot Topics within CNS: Preclinical Suicidality, Update on the Abuse Potential FDA Guidance, Seizure Assessment, and Getting a CNS Drug to the Brain: A Case Study
One of the primary organ systems evaluated in classical Safety Pharmacology studies is the Central Nervous System, following ICH S7A as guidance. In these standard studies, motor activity, behavior, coordination, reflexes, and body temperature are evaluated. This session will focus on the emerging topics within Safety Pharmacology as it relates to the Central Nervous System and hopes to stimulate discussion on new areas of evaluation or focus within Safety Pharmacology for assessing Central Nervous System effects. The topics covered are based upon recent events, such as the issuance in January 2017 of the final rule for “Assessment of Abuse Potential of Drugs: Guidance to Industry,” as well as the FDA's box warning for Valeant's Siliq for suicidal behavior and ideation. Updates and case studies will also be provided on Consortia initiatives and issues related to drug delivery into the Central Nervous System.
Lunch Break, Poster Presentations, Exhibits
Track A: Current Topics in the Translation and Validation of Safety Pharmacology Studies
Safety pharmacology seeks to identify, predict, and understand potential clinical liabilities and adverse effects of new therapeutics. This session will focus on translational safety pharmacology beginning with an understanding of off-target interactions and their ability to predict clinical consequences. The second talk will describe the role of non-excitable cells like fibroblasts in cardiac biophysics, a potentially new target for cardiac risk assessment. This will be followed by a presentation of the recent data generated by the Japanese Safety Pharmacology Society on the predictability of non-rodent data to clinical cardiovascular risk. The final talk will provide an update on incorporation of intensive ECG collection in early clinical development and how this impacts the need for a thorough QT study.
Track B: Best Practices New Modalities and New Biological Entities (NBEs)
This session will focus on the contribution of safety pharmacology to the safety assessment of two of the main new therapeutic modalities, the biologics and the oligonucleotide based therapeutics. After an overview of the specific requirements and challenges for each modality updated according to the learnings of the past decade, the experimental strategy and methods will be addressed.
TUESDAY, SEPTEMBER 26
Exhibits and Poster Open
Title: The Pathophysiology and Treatment of Tinnitus
Tinnitus is a symptom that can accompany various disorders (hearing loss, cardiovascular diseases, metabolic disorders such as diabetes, TMJ disorder, and many other conditions). If the main disorder responds well to the medical treatment, then often also the associated symptoms disappear. However, if either the treatment is not quite effective or if tinnitus is present for longer time, then the therapy for tinnitus should focus on a tinnitus-related distress. Medical therapy for chronic tinnitus and therapy strategies will be discussed.
Prof. Dr. med. Birgit Mazurek
Location: Hall Berlin B
Date: Tuesday, September 26, 2017
Track A: Disease Models and Personalized Medicine
Personalized medicine opens a new era of medical product development with impactful therapeutic approaches. In this session, experts will cover in vitro and in vivo models—such as the use of stem cells and genomics—aiming at improving early translation into the clinics. The advantages and challenges of novel methods such as CRISPR/CAS9 in this field will also be discussed. (Another key talk will also provide more insight into practical applications of personalized medicine).
Track B: In Vitro Microphysiological Systems to Predict Safety
Development of safe and effective drugs is currently hampered by the poor predictive power of existing preclinical animal models that often lead to failure of drug compounds late in their development after they enter human clinical trials. There is a crucial need for new technologies that can reliably predict drug safety and efficacy in humans in preclinical studies. Advances in bioengineering, material sciences, microfabrication, and microfluidics technologies have enabled the development of microphysiological systems that mimic the functional units of an organ. These systems recreate the specialized multicellular architectures, tissue-tissue interfaces, physicochemical microenvironments, and vascular perfusion necessary to recapitulate organ-level physiology in vitro. These biomimetic devices provide a window on human physiology as they enable real-time, high resolution microscopic imaging as well as analysis of biochemical, genetic, and metabolic activities of living cells when they are positioned within the context of functional tissue and organ units. An integrated microphysiological platform could further enhance our understanding of disease etiology and fill the critical need for improved model systems to predict efficacy, safety, bioavailability, and toxicity outcomes for candidate compounds. This session will examine diverse microphysiological systems and their application in safety pharmacology.
Lunch Break, Poster Presentations, Exhibits
Track A: In Silico Modeling—From Bench to Bedside
This session will start with a comparison of various in silico models for drug safety testing and a discussion of their integration into early drug development. Next, improvements of the CiPA consensus cardiomyocyte model of O‘Hara Rudy will be addressed; in particular, dynamic drug channel interaction will be captured and a novel metric for risk classification will be offered. Then, the association of early afterdepolarizations with bifurcations in action potential models will be highlighted and distance to bifurcation will be discussed as a possible tool for measuring a compound's potential to cause arrhythmic behaviour. Finally, computational challenges posed by the bidomain equations for cardiac excitation propagation will be mentioned and state of the art methods for their simulation will be presented.
Track B: Animal Models and Species Selection
Safety Pharmacology studies designed to address ICHS7A & ICHS7B guidelines generally use the same rodent and non-rodent species as the toxicology program for the specific compound of interest (usually the rat for CNS and respiratory assessments and the dog or NHP for cardiovascular assessments, or for combinations of all three vital organ systems). However, during early in vivo testing and research of atypical supplementary organ systems, the species used can be different and tends to be the one deemed most relevant for the pharmacological model or endpoint of interest. This session will highlight two examples of infrequently studied systems (chronobiology and sleep) where drug-induced adverse effects can impair quality-of-life, and where the choice of research species can be critical. Two further speakers will discuss options for alternative species use within the regulatory phases, covering the minipig as a non-rodent alternative and the importance of species selection for biologics.
Evening Event: Berlin TV Tower Dinner
(Space is limited, registration required)
Join your colleagues for a social evening in the sky at the Berlin TV Tower! Enjoy a unique panorama and unforgettable view of the entire city while socializing and dining with your friends and colleagues. Visit our General Information page for more information and be sure to add the ticket when registering for the Meeting.
WEDNESDAY, SEPTEMBER 27
Annual Members Meeting and Awards Ceremony
Distinguished Service Award Presentation
CiPA Challenges and Opportunities from Non-Clinical, Clinical, and Regulatory Perspectives
The objective of the session is to engage members of the Safety Pharmacology Society (SPS) in the development of the CiPA guidelines. This will be achieved by running the session as a ‘debate’ and asking members of the audience a number of questions; the responses to these questions can be fed back to the CiPA working groups. Six short presentations, in which each presenter will discuss either the challenges or opportunities of CiPA from a non-clinical (Discovery and Drug Safety), clinical (early and full development), and regulatory point of view, will be followed by a short Q&A. After a round table panel discussion, SPS members will be asked to vote on a question that aims to solicit views on the confidence of CiPA to enable compounds to be progressed that otherwise have been abandoned.
Interactive Case Studies
President’s Summary/Meeting Adjourned
AM1: Safety Pharmacology: Understanding Safety and Preclinical Derisking Strategies
Co-Chairs: Kristy Bruse and Nancy Poy
This course aims to define the discipline of safety pharmacology by discussing relevant guidelines for required studies, including follow-up and supplemental studies and team discussions on scenarios for early safety assessment. In addition, an introduction to safety pharmacology assessment of non-small molecule modalities (e.g., nanoparticles and conjugated biologic/small molecules) will be presented, including definitions, regulatory requirements, and study designs. Animal models and veterinary care with focus on Refinement, Reduction, and Replacement alternatives will also be presented, e.g., best practices for: animal numbers, statistics (power analysis), selection of species, model, and methodologies for sample collection.
Finally a session about “Guidance of a Project Team Member” will be presented:
- Monitoring a safety pharmacology study. How to be a good Study Monitor/Director.
- The SP “sponsor monitor role” in toxicology studies.
- How to be a good SP representative.
AM2: The Role of Classical Pharmacology in Nonclinical Safety Assessment
Co-Chairs: Malar Pannirselvam and Kathy Derakhchan
Gain an introduction to classical pharmacology and its application on safety pharmacology strategies. Quantification of drug actions requires an appreciation of classical bioassay and concentration—response relations and is a basic skill essential for a clear understanding of all aspects of pharmacological research. Topics covered include: receptor structure/function using classical techniques such as tissue bath, Langendroff in vitro systems to anesthetized and conscious animal models measuring complex physiological end points such as preload, intrinsic cardiac contractility, and peripheral resistance. Finally, the course will end with real-time case studies and how the learned skills can be applied to understand the integrated safety pharmacology issues.
AM3: Hands-On Training in Electrocardiography of Laboratory Animals (Interactive Course)
Chair: Jeffrey Richig
This course will cover a brief review of ECG basics, followed by advanced ECG interpretation and evaluation including hands-on evaluation and measuring of the waveforms. Also covered will be normal values and variants, arrhythmias and conduction disturbances and their modalities, plus actual drug-related case studies. The course will be both educational and entertaining, and will include audience participation.
Lunchtime Mini-Course: What’s That Elephant in the Room? SEND Submissions for Safety Pharmacology
Co-Chairs: Michael Pugsley and Marc Ellison
Now that Standard for Exchange of Nonclinical Data (SEND) v3.0 has been supported by the FDA since 2011, it is time for Safety Pharmacology to take center stage with SEND v3.1. This presentation will focus on how the CDISC SEND v3.1 standard applies to vital core battery Safety Pharmacology cardiovascular and respiratory studies, and how organizations that sponsor and/or perform these studies can prepare for its use. It will also provide an overview of the roadmap for Safety Pharmacology in SEND for the future and discuss Safety Pharmacology study endpoints included in repeat dose toxicology studies. Finally, some of the challenges that are frequently faced when implementing SEND in an organization will be discussed, with suggested approaches to smooth the transition.
PM1: Current Topics and Best Practices for Central Nervous System Safety Pharmacology
Co-Chairs: Annie Delaunois and Bruce Morimoto
The objective of CNS safety pharmacology is to evaluate the potential adverse risk of drug candidates for the central nervous system in humans. The ability to translate the nonclinical findings to the clinic therefore becomes critically important and is dependent not only on validation of the assays but also on the predictability of the models.
This course will focus on recent advances and best practices in CNS safety pharmacology with an emphasis on translation from nonclinical to clinical. In addition to the predictability of the standard functional observational battery (FOB) or modified Irwin test, topics will include assessment of convulsion liability using EEG and the evaluation of sleep using various electrophysiological modalities.
PM2: Building on the Classics: The Emerging Role of Stem Cell-Based Techniques in Safety Pharmacology Assessments
Co-Chairs: Blake Anson and Amy Pointon
Human stem cell technology is bringing new tools to drug discovery, toxicity testing, and safety pharmacology. This CE course will build on traditional safety pharmacology topics to cover how this technology is being developed for use as a safety tool as well as a therapeutic. Lectures will cover the use of stem cell derived cardiomyocytes and neurons in simple and complex culture systems to understand and predict traditional drug-induced effects on cardiomyocyte electrophysiology, contractility, and neuronal seizureogenic behavior. The course will then expand to include a discussion on stem cell-based regenerative medicine applications and related potential safety considerations. Where appropriate, speakers will compare and contrast stem cell models with more traditional models to highlight the potential advantages and limitations. Attendees will come away from the course with a practical understanding of how and when to apply current stem cell-based models, the limitations of such models, and ultimately how the technology is evolving in both the therapeutic and safety arenas.
PM3: “Non-Trivial Pursuit:” A Game Challenging Safety Pharmacologists for a Piece of the (IND) Pie
Co-Chairs: Carrie Markgraf and Tomas Mow
Join your fellow safety pharmacologists in a fun and challenging game of advancing a drug candidate from late Discovery through GLP studies to IND. Teams of 4–6 people will work together to decide whether to advance a fictional compound through the core safety pharmacology studies as well as any supplementary studies that may be necessary. Teams will receive a description of their compound’s attributes, a list of available studies with prices and a budget. The challenge is to select studies, receive the data, and decide what next steps to take to get to IND or to decide to terminate the compound without going over budget. The teams will be guided by the CE chairs and share their approaches so that everyone can learn about the different paths that can get to the same goal.