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Introduction: This report summarizes and comments key talks on the five traditional senses (ear, vestibular system, vision, taste, olfaction, and touch) which were delivered during the 2015 Annual Meeting of the Safety Pharmacology (SP) Society., Areas Covered: The functional observational battery (FOB) can detect major candidate drug liabilities only on ear, touch and vision. Anatomy, physiology, pharmacology, and pathology notions on each sensory system introduce speaker talks. Techniques for evaluating drug effects on hearing functions are reviewed. Nonclinical approaches to assess vestibular toxicity leading to balance deficits are presented. Retinal explants studied with multielectrode arrays allow the identification of drug liability sites on the retina. Routinely performed Safety Pharmacology assays are not powered to address candidate drug-induced disturbances on taste and smell. This weakness needs correction since unintended pharmacological impairment of these sensorial functions may have serious health consequences. Neuropathy produced by chemotherapeutic agents may cause multiple sensorial perception distortions., Conclusions: Safety Pharmacology studies should ensure the safety of any candidate drug on the five sensorial systems., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The 2014 Annual Meeting of the Safety Pharmacology Society discussed pathophysiological mechanisms and novel investigational approaches to assess drug safety. The plenary keynote reviewed past, present, and future research on Alzheimer's disease. Polysomnography tools can uncover drug-induced sleep disturbances. FDA examiners currently assess proconvulsive liabilities on a case-by-case basis due to the lack of official guidance. In contrast, abuse liability potential is determined according to established paradigms. The FDA guideline on opioid deterrent formulations was discussed. The mechanisms and treatments of obstructive sleep apnea (OSA) and diabetes-induced neuropathic pain were reviewed. There were salient points arising from the CNS presentations but from a pharmacological point of view we note in particular that safety pharmacology should move to routinely apply polysomnographic technologies to determine whether candidate drugs exert deleterious effects on sleep quality and architecture that may markedly decrease quality of life and impair cognitive functions, including alertness and reaction time., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Introduction: The Annual Meeting of the Safety Pharmacology (SP) Society is a yearly event designed to keep attendees abreast of how to best identify and mitigate organ function liabilities of candidate drugs selected for clinical assessment., Areas Covered: Heart rate (HR) and blood pressure (BP) effects of candidate drugs in dogs/monkeys have satisfactory human translation. Mechanism-designed assays offer opportunities for innovative approaches to identify chemotherapeutic-induced peripheral neuropathy (PN). SP has a large array of methodologies to determine safety on eye functions. Video-tracking analysis of zebrafish swimming behavior accurately profiles drugs for high-level brain function liabilities. Available in vitro and in vivo assays can identify, and determine physiological and pharmacological mechanisms of, candidate drug-induced emesis. Ad hoc Working Groups have already finalized protocols for testing the comprehensive in vitro arrhythmia assay (CiPA), an innovative paradigm for assessing mechanisms conferring candidate drug proarrhythmic liabilities., Expert Opinion: The good concordance of non-clinical and clinical Phase I BP and HR effects of candidate drugs support the use of dog/monkey models for clinical outcome. Drug liabilities (e.g., PN, nausea, vomiting, etc.) affecting non-vital organs/systems require the same degree of SP attention given to vital functions as they can dramatically reduce patient quality of life.

Introduction: The 13th Annual Meeting of the Safety Pharmacology (SP) Society discussed novel therapeutic areas, recent regulatory developments, emerging biology technologies and non-pharmaceutical dairy products that may need SP evaluations for ensuring their human safety., Areas Covered: The meeting honored Willem Einthoven, the father of electrocardiography. The Comprehensive in vitro Proarrhythmia Assay (CiPA) is an under-discussion proposal for replacing the International Conference on Hamonization (ICH) S7B guideline strategy. Drugs targeting epigenetic mechanisms (e.g., histone deacetylase inhibitors) have the potential to produce proarrhythmic safety liabilities by dysregulating the synthesis of cardiac ion channel proteins as well as the intracellular machinery, moving them to sarcolemmal residence. Novel frontiers of regulatory SP investigations are functional food and probiotic (microorganisms) preparations., Expert Opinion: The CiPA initiative is a unique opportunity for concerned stakeholders to drive SP into the adoption of 21st century safety assessment platforms, which, for discovering and mitigating mechanisms conferring safety risks to drugs, apply chiefly in silico and in vitro rather than traditional in vivo pharmacodynamics assays. The SP evaluation of functional foods and probiotics needs the development of product-tailored investigational approaches.

Introduction: The 12th Annual Meeting of the Safety Pharmacology (SP) Society (SPS) covered various subjects among which safety issues concerning oncolytic drugs are reviewed and discussed in details., Areas Covered: The challenges faced by a medical oncologist during the development of new anticancer medicines were the focus of the keynote address. Romidepsin, a drug initially abandoned because of serious cardiotoxicity in dogs, was successfully rescued for clinical evaluation by tailoring the dose regimen to mitigate cardiac toxicity risks. The integration of SP endpoints into long-term toxicology offers the advantage of determining safety on organ function during chronic exposures, whilst also supporting the principal goals of the 3Rs framework. State-of-the-art imaging technologies can provide valuable, interpretable and translational (human to mouse to human) data for the detection of myocardial function impairment. The future growth of SP was discussed in terms of areas in need of innovative approaches as identified, in particular, in a worldwide sharing of SP data and methodologies., Expert Opinion: The need for epochal changes to ensure a bright future for SP should be promoted by the SPS. These comprise chiefly the expansion of the SP birth charter from primarily a regulatory discipline to include an efficiently organized experimental discovery science for which the name Exploratory SP (ESP) is proposed. Its mission would be the early and cost-effective assessment of the safety of clinical drug candidates on organ function based on mechanistic grounds and conducted outside of current expensive and time-consuming regulatory frontiers and constraints. The implementation of a high standard ESP discipline could also promote the gradual replacement of standalone safety investigations with SP assays performed within long-term toxicity studies.

The keynote address of 2011 Annual Meeting of the Safety Pharmacology Society examined the known and the still to be known on drug-induced nephrotoxicity. The nominee of the Distinguished Service Award Lecture gave an account of his career achievements particularly on the domain of chronically instrumented animals for assessing cardiovascular safety. The value of Safety Pharmacology resides in the benefits delivered to Pharma organizations, regulators, payers and patients. Meticulous due diligence concerning compliance of Safety Pharmacology studies to best practices is an effective means to ensure that equally stringent safety criteria are applied to both in-licensed and in-house compounds. Innovative technologies of great potential for Safety Pharmacology presented at the meeting are organs on chips (lung, heart, intestine) displaying mechanical and biochemical features of native organs, electrical field potential (MEA) or impedance (xCELLigence Cardio) measurements in human induced pluripotent stem cell-derived cardiomyocytes for unveiling cardiac electrophysiological and mechanical liabilities, functional human airway epithelium (MucilAir™) preparations with unique 1-year shelf-life for acute and chronic in vitro evaluation of drug efficacy and toxicity. Custom-designed in silico and in vitro assay platforms defining the receptorome space occupied by chemical entities facilitate, throughout the drug discovery phase, the selection of candidates with optimized safety profile on organ function. These approaches can now be complemented by advanced computational analysis allowing the identification of compounds with receptorome, or clinically adverse effect profiles, similar to those of the drug candidate under scrutiny for extending the safety assessment to potential liability targets not captured by classical approaches. Nonclinical data supporting safety can be quite reassuring for drugs with a discovered signal of risk. However, for marketing authorization this information should be complemented by a clear clinical proof of safety. The ongoing outsourcing process of Regulatory Safety Pharmacology activities from large Pharmas to contract research organizations should be taken as an opportunity to establish long-overdue in-house Exploratory Safety Pharmacology units fully dedicated to the optimization of clinical candidates on organ safety.

The keynote presentation of the Safety Pharmacology (SP) Society 9th Annual Meeting addressed the urgency, for pharmaceutical organizations, to implement strategies for effectively communicating drug risks to all concerned stakeholders and, in particular, the general public. The application of chronobiology to SP investigational protocols can improve the search of drug-induced adverse effects. The Distinguished Service Award Lecture reviewed a life-long journey through trials and tribulations in the quest of the ever-distant scientific truth. The revision process of Directive 86/609/EC for improving animal welfare should be conducted with the purpose of maintaining a fair balance among animal protection, human health and research imperatives in order to prevent the migration of pharmaceutical activities outside Europe. Additional topics of interest were the behavioral, metabolic and cardiovascular problems experienced by small animals housed at the standard laboratory temperature. A technology for the automated collection of blood and urine samples in rats implanted with telemetry sensors was presented. Non-clinical, clinical, regulatory and legal aspects of abuse liability were expertly reviewed. The 'degradability' of pharmaceuticals into environment-friendly chemicals should be an actively searched and optimized feature of future pharmaceuticals in order to prevent drug pollution of ecosystems. Transgenic and diseased animal models should be selected whenever they can facilitate the determination of drug-induced adverse effects. SP strategies to investigate the safety of drug combination products were exemplified and analyzed in depth. The future of SP was proposed to lie not in the performance of regulatory studies of pharmacodynamic nature but in developing and early applying an array of screening assays for clearing clinical candidates against known drug-induced organ function injuries. In conclusion, the 2009 SP Society annual meeting offered a wealth of thought-provoking material to attendees for improving SP investigation strategies.

Of the numerous topics discussed during the eighth annual meeting of the Safety Pharmacology (SP) Society the author identified the following key topics: i) the impact of hERG (human ether-à-go-go related gene) channel data on drug development, ii) safety evaluation of biological products, iii) opportunities and expectations from SP, iv) human stem cell derived cardiomyocytes for safety assessment, v) role of cellular calcium pathways in drug-induced arrhythmias, vi) collaboration initiatives for finding solutions to cardiac repolarisation and other recognised SP risks, vii) Pharma and FDA perspectives on ICH S7B guideline, viii) joint PhRMA-FDA dialogue on drug abuse potential assessment, ix) frontloading SP strategies for mitigating non-clinical and clinical attrition; and x) approaches to measure non-clinical assay predictability for human outcome. The establishment of consortia to accelerate the solution of critical SP issues and the implementation of Frontloading SP or Exploratory SP strategies for an early selection of safe clinical candidates are promising avenues for consolidating SP as an indispensable drug development discipline and for transforming established regulatory SP investigations into a risk-known exercise.