Scientific Program

We are on the brink of a sea change on antibody production. In Europe, the ECVAM Scientific advisory committee has endorsed the scientific validity of replacement methods not requiring animal immunization and the U.S. NICEATM aims to improve research quality and reproducibility by accelerating their development and use. No longer must we accept the scientific shortcomings of animal-derived antibodies. Considering the $80 billion scale of the antibodies industry, importance to all scientific disciplines, vast animal use and commitment by government authorities to the implementation of Directive 2010/63/EU, the landmark movement to animal-free sequence-defined antibodies will have an enormous global influence.

Session chair and co-chair: A. Gray, AFABILITY & University of Nottingham and K. Groff, PETA International Science Consortium Ltd

Speakers:

Abstract ID 118 - Barriers and Challenges Facing the Replacement of Animal-Derived Antibodies (ADAs)
Alison Gray, AFABILITY

Abstract ID 726 - Scientific Validity of Non-Animal-Derived Antibodies
João Barroso, European Commission, Joint Research Centre, Ispra (VA), Italy

Abstract ID 1 - Animal free multiclonal antibody generation as a replacement for polyclonal antibodies
Stefan Dübel, Technische Universität Braunschweig

Abstract ID 907 - Recombinant antibodies: a complete toolbox for academia
Pierre Cosson, University of Geneva, Faculty of Medicine

Abstract ID 127 - Recombinant antibody technology: taking antibodies from bench to bedside
Lia Cardarelli, Toronto Recombinant Antibody Centre; University of Toronto

Abstract ID 101 - STRATEGIZING TO OPTIMIZE THE DEVELOPMENT AND USE OF ANIMAL-FREE ANTIBODIES IN THE U.S.
Katherine Groff, PETA Science Consortium International e.V.

Evidence-based pain and stress assessment is essential for accurately identifying, predicting, and preventing animal suffering. It is also central for informing harm-benefit assessment of animal experimentation, thus furthering both animal welfare and regulatory compliance. Reliable and sensitive assessment is also essential for implementing refinement measures and evaluating their effect. To fulfill these goals, scientists, animal care and veterinary personnel need reliable assessment tools for providing species-relevant measurements of the animals` physical and affective state.
In this session, we aim to highlight recent scientific advances in rodent health, welfare, pain and stress assessment, such as automated grimace score assessment or thermography with the potential to further both the 3Rs and scientific quality.

Session chair: Nuno Henrique Franco, i3S, University of Porto

Speakers:

Abstract ID 84 - TOWARDS AN AUTOMATED FACIAL EXPRESSION ANALYSIS IN MICE USING DEEP LEARNING
Katharina Hohlbaum, Institute of Animal Welfare, Animal Behavior, and Laboratory Animal Science, Department of Veterinary Medicine, Freie Universität Berlin

Abstract ID 690 - Assessment of acute stress and anxiety by infrared thermography
Nuno Henrique Franco, i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto

Abstract ID 28 - Inter-laboratory variability in behavior-based severity assessment
Paulin Jirkof, University of Zurich

Abstract ID 599 - Pain assessment and management in bone-linked mouse models
Annemarie Lang, Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin; German Rheumatism Research Center

Abstract ID 310 - IDENTIFICATION OF APPROPRIATE METHODS FOR SEVERITY ASSESSMENT IN A WIDELY USED MOUSE MODEL OF ACUTE COLITIS
Christine Haeger 

A functioning central nervous system (CNS) is key for living, and ageing is a major risk factor of disfunction. With the increase in human lifespan the incidence of neurodegenerative diseases is rising. There is a demand for good models for neurodegenerative diseases, as current in vivo models have limitations and ethical concerns.
Modeling the CNS in vitro is, however, challenging. Recent discoveries in neuroscience, such as the breakthroughs of induced pluripotent stem cell technology, 3D-organotypic cultures and organs-on-chip, move the field forward. This workshop will overview how scientists are embracing new cutting-edge technologies and provide a guidemap for future developments.

Session chair: J. Bajramovic, Biomedical Primate Research Centre

Speakers:

Abstract ID 850 - From microphysiological to micropathophysiological systems to study neurotoxicity and CNS diseases
L. Smirnova, Johns Hopkins

Abstract ID 578 - Transcriptome guided approaches to mimic homeostatic adult microglia in culture
R. Timmerman, Biomedical Primate Research Centre

Abstract ID 1022 - New ways of neurotoxicity testing in pre-clinical drug development
S. Kustermann, Roche

Newer alternative methods to animal tests in toxicology are increasingly using advanced techniques. These are sometimes more complex than historical animal tests and their appropriation by stakeholders, CROs, safety evaluators, regulatory bodies require new knowledge, equipment and also availability of the test systems. Their validation is a must but not always sufficient to be accepted everywhere. To be trusted and routinely used there is a need of communication and training at an international level for both current professionals and next generation of toxicologists.
In this context a number of initiatives involving private companies in partnership with educational/research institutions, learned societies and nonprofit organizations have emerged to organize theoretical as well as hands-on-training of human-relevant alternative methods. This allows students, scientists and toxicologists, to quickly become familiar with newer methods and to better understand how to use the results for GHS (global harmonization system) classification or risk assessment. In these approaches the notion of partnership is crucial. On one hand, private companies, such as methods providers or end-users, have expertise and access to technologies and methods. On the other hand, public establishments, academic institutions or learned society are representative of the intended population and have legitimacy in education.
After a short presentation of some examples involving private and public/nonprofit players conducted in Europe, South America, India or China this round table will discuss some of the barriers experienced (funding, mistrust...), definition of education and training good practices (mixing theory and practice, hosting laboratory...) and ways to improve the effectiveness and recognition of these courses (university partnership, certification, webinars...). Finally, the interest of coordination and generalization of this kind of partnerships to accelerate the spread of alternative methods to animal experimentation worldwide will be discussed.

Session chair and co-chair: Christian Pellevoisin from the Episkin Academy &  Vijay Pal Singh from CSIR-Institute of Genomics & Integrative Biology (India)575

Speakers:

Abstract ID 575 - Round Table: Industry and public sector partnerships in education to foster the implementation of alternative methods Alternatives to Animals in Education and Risk Assessment: An Overview with Special Reference to Indian Context
Akbarsha, Mohammad A., Society for Alternatives to Animal Experiments-India (SAAE-I)

Abstract ID 793 - BRAZIL is ON: Animal Testing Ban and Available OECD TG in Brazil
L. Balottin, National Institute of Metrology, Quality and Technology (INMETRO)

Abstract ID 496 - Ways to improve their effectiveness and recognition
F. Busquet, Altertox Acadamey 

Abstract ID 591 - The development of alternative methods in China and the role of the industries
C. Shujun, Shanghai Jiao Tong University

Abstract ID 670 - Feedback from 8 years of training to alternative methods in industrial and academic contexts
C. Pellevoisin, EPISKIN Academy

Several initiatives have generated a wealth of non-animal data, « new approach methodologies » -NAMs-. In 2007, the American National Academy of Science called from moving away from measuring apical endpoints to considering upstream events. Regulatory changes like in the cosmetics sector in Europe incentivized such initiatives.
NAMs have been used in different decision-making contexts. Biological effects at the molecular, cellular and/or tissue level compared to internal concentrations based on use scenarios yielded PoDs protective of human health and conservative.
The session covers cases with PoDs from NAMs with a 30 min discussion highlighting opportunities and limitations of such approaches.

Session chair and co-chair: R. Thomas, NCCT - US EPA and G. Ouedraogo - L'Oreal

Speakers:

Abstract ID 742 - Screening to Assessment: Building confidence in Bioactivity Points of Departure at Health Canada
T. Barton Maclaren, Health

Abstract ID 52 - Cosmetic Europe case studies exploring alternatives to repeated dose systemic toxicity testing
C. Mahony, P&G

Abstract ID 604 - High throughput transcriptomics to derive mode-of-action and potency information to support read across approaches
B. van de Water, University of Leiden

Abstract ID 49 - Applying In Vitro to In Vivo Extrapolation to NAM-derived PODs
N. Kleinsteuer

Abstract ID: 444 - Application of newly validated route-specific in vitro genotoxicity assays to support the safety assesment of cosmetic ingredients
R. Fautz

Session chair: Ivo Tiebosch

Speakers:

Abstract ID 81 - Systematic reviews to validate alternatives to specific animal models
Cathalijn Leenaars

Abstract ID 143 - DO WE ACT LIKE CAR SALESMEN OR AIRLINE PILOTS? PREPARING FOR ROBUST AND HUMANE RESEARCH
Adrian Smith

Abstract ID 212 - SENSITIVITY OF MOUSE BEHAVIOURAL TESTS OF ANXIETY TO ANXIOLYTIC DRUGS APPROVED FOR TREATMENT OF ANXIETY IN HUMANS: A SYSTEMATIC REVIEW
Marianna Rosso

Abstract ID 244 - Criterion guided interviews to validate competence in designing animal experiments
Ivo Tiebosch

Abstract ID 289 - SATORI-BTR: DEVELOPING PRELIMINARY GUIDANCE ON EVALUATING QUALITY AND HUMAN RELEVANCE OF IN VITRO STUDIES IN BRAIN TUMOUR RESEARCH
Karen Pilkington

Abstract ID 1113 - AN URGENT CALL FOR FULLY XENO-FREE STEM CELL CULTURE CONDITIONS AND CERTIFICATION IN DISEASE MODELING 
Eizleayne M. Edrosa

Malcolm Macleod is Professor of Neurology and Translational Neurosciences at the University of Edinburgh, member of the UK Commission for Human Medicines and the UK Reproducibility Network. He also leads the European Quality in Preclinical Data IMI project and the SE Scotland Stroke Research Network. He was co-CI of the EuroHYP trial of brain cooling for acute stroke and is UK coordinator for the PRECIOUS trial of preventing complications following stroke.

Since founding the Collaborative Approach to Meta-analysis and Review of Animal Data form Experimental Studies (CAMARADES) in 2004 his research has largely focussed on how best to increase the value of biomedical research. This has included work with funders, journals (including randomised studies of different approaches to improve quality, and the proposed MDAR Minimum Standards Framework) and most recently with institutions (recently appointed Research Improvement lead at the University of Edinburgh).
He led the development and implementation of the SyRF platform (app.syrf.org.uk) which supports systematic reviews of in vivo research.

Warlow’s Stroke: Practical Management (ISBN: 978-1-118-49222-2)

The 3Rs represent a framework for the advancement of animal welfare by supporting the Reduction, Refinement, and Replacement of animals within scientific research. While specific government regulations aim to ensure minimum animal welfare standards, the scientific community has a responsibility to actively investigate refinement and alternatives to animal use and to minimize the number of animals used, along with promoting animals’ wellbeing in the research environment and for procedures that are performed. Although animal use is often mandated or deemed necessary for research and safety testing, there are opportunities to implement 3Rs improvements within current toxicology testing strategies and individual study designs. Improvements in data quality and increased predictivity to human outcomes can facilitate the provision of new therapies to benefit patient health.

The main objective of this session is to highlight some of the different approaches used to advance the science of the 3Rs in drug development, bringing together global colleagues from various sectors and collaborative projects within the toxicology field. This session will summarize the current understanding, recent advancements and data from retrospective analyses and introduce emerging technologies to challenge you to consider how best to design your preclinical toxicology and efficacy studies to maximize data quality and clinical relevance whilst promoting animal welfare. We posit that a well-defined development strategy includes a suite of tools to help better predict clinical translatability. These may include in silico modeling or in vitro tests replacing animal experiments, or as a supplement to reduce subsequent animal use. Emerging technologies, digital and non-digital, provide an opportunity for identification of novel clinically relevant endpoints and increased understanding of animal models. When animal models are required, modifications in study designs including endpoints and real-time data access can limit animal use while maximizing scientific utility, whilst refinements in animal housing, welfare and data driven enrichment that decrease or eliminate pain and/or distress can improve data quality.

Session chair: D. W. Lee, Genentech 

Speakers:

Abstract ID 899 - INCREASE PREDICTIVITY AND TRANSLATABILITY FROM ANIMAL MODELS - UNDERSTANDING HOW DIFFERENT FACTORS CONTRIBUTE TO (IR)REPRODUCIBILITY 
Emily Sena, University of Edinburgh

Abstract ID 359 - Reimagining preclinical studies through digital transformation; leveraging computer vision, machine learning,
mixed reality & informatics platforms to maximize data quality and clinical relevance of preclinical studies
Szczepan Baran, Novartis Institutes for BioMedical Research (NIBR), Inc.

Abstract ID 732 - Advanced Human Cell Models to support Safety assessment of bi-specific Antibodies
Adrian B. Roth, Hoffmann-La Roche

Abstract ID 408 - Applying the 3Rs within Regulatory Toxicology Studies in Drug Development
Helen Prior, NC3Rs

Abstract ID 18 - 3Rs opportunities in preclinical safety testing: A CRO perspective
Gerhard Weinbauer, VP Global DART

Abstract ID - Improving the 3Rs in Drug Development Takes Collaborative Effort
Donna Lee, Genentech 

While one can think there is failure to improve experimental design and increase 3Rs principle uptake in the scientific community, this session aims at bridging science quality and the 3Rs:
- providing concrete scientific perspectives on how rigor, relevance and reproducibility foster the best use of research models and deliver scientific results that ultimately benefit the 3Rs;
- illustrating the continuity and complementarity in the use of non-animal and animal research models as the best approach to shift from animal to non-animal methods over time through knowledge sharing;
- ultimately aligning researchers and regulators to the same ultimate 3Rs goal.

Session chair and co-chair: S. Rao, SANOFI R&D and A. L Andreu, EATRIS

Speakers:

Abstract ID 890 - Rigor, relevance and reproducibility in the use of in vivo models in the pharmaceutical industry
S. Rao, Sanofi R&D 

Abstract ID 761 - Increasing the reliability of preclinical data: enabling approaches
I. Lefevre, Sanofi R&D

Abstract ID 112 - Reproducibility crisis in preclinical research
A. Andreu,  EATRIS

Adult- and induced pluripotent stem cells are unique sources of somatic human cells from patients and healthy individuals, challenging to obtain reproducibly in large numbers from primary tissue samples. Immune cells and inflammation are major disease triggers and identifying renewable sources of these cells would benefit attempts to model disease as in patients. These stem cell derivatives can be cultured in 2D or 3D and in single or multiple cell type combinations and thus form Micro-physiological Systems that can “stand alone” as research or drug screening models or may be incorporated into Organ-on-Chip models for inclusion of appropriate biophysical parameters.

Session chair: C. Mummery, LUMC C. Denning

Speakers:

Abstract ID 945 - HUMAN PLURIPOTENT STEM CELL MODELS FOR CARDIOTOXICITY
Chris Denning, University of Nottingham, Biodiscovery Institute, Faculty of Medicine & Health Sciences

Abstract ID 944 - GASTRULOIDS FROM STEM CELLS: MODELS OF EARLY DEVELOPMENT.
Alfonso Martinez Arias, University of Cambridge, Department of Genetics

Abstract ID 908 - BUIDING VESSELS ON A CHIP TO MODEL GENETIC VASCULAR DISEASES USING PATIENT-SPECIFIC INDUCED PLURIPOTENT STEM CELLS 
Valeria Orlova, Leiden University Medical Center

Abstract ID 948 - A standardized platform for miniaturized cortical organ
Steven Kushner, Department of Psychiatry, Erasmus Medical Center Rotterdam

Next Generation Risk Assessment (NGRA) is an exposure-led, hypothesis-driven approach that uses new approach methodologies (NAMs) to ensure the chemical safety without the use of animal data. Whilst some NAMs have been validated and adopted by regulators (e.g. OECD test methods for skin sensitization) there is a need amongst both industry and regulatory risk assessors for more examples to demonstrate the utility of NAMs for decision-making on effects that are associated with systemic exposure to chemicals. This symposium will increase awareness and confidence in the use of NAMs for decision-making, by showcasing several of the components of an NGRA framework

Session chair and co-chair: C. Westmoreland, Unilever and M. Varçin, Cosmetics Europe

Speakers:

Abstract ID 677 - Perspectives on the Use of High Throughput Profiling Assays in Next Generation Risk Assessment
J. Harrill, US Environmental Protection Agency (EPA)

Abstract ID 628 - Predictive value of PBK-model predictions based on in vitro and in silico input data as essential tool in next generation (animal-free) risk evaluations
A. Punt, Wageningen Food Safety Research (WFSR)

Abstract ID 851 - In silico approaches to link adverse outcomes to molecular initiating events through AOPs
T. Allen, University of Cambridge

Abstract ID 262 - An industry perspective on strategies for integrating new approach methodologies for NexGen Risk Assessment: coumarin as a case study
M. Baltazar, Unilever

Abstract ID 337 - Integrating toxicokinetics and toxicodynamics for decision-making in an NGRA context: 2 Cosmetics-Europe case studies
G. Ouedraogo, L’Oreal

in3 is a EU's Marie Skłodowska-Curie Action - Innovative Training Network project funded by the EU Horizon 2020 under grant no. 721975. In3 focuses on research and training of 15 PhD students in utilising integrated in silico and in vitro tools for animal-free toxicity assessment. There is a particular interest in the project on utilising human induced Pluripotent Stem Cells (hiPSC) differentiated to toxicologically relevant target tissues such as brain, lung, liver, vasculature and kidney, but also anchoring this information to mechanistic toxicology and utilising read across and adverse outcome pathways.

Session chair: M. Culot, Universitè d’Artois

Speakers:

Abstract ID 938 -The in3 project - An integrated interdisciplinary approach to animal-free nanomaterial and chemical safety assessment
P. Jennings, Vrije Universiteit Amsterdam

Abstract ID 837 - Study the effect of Cycloporin A on functionality of endothelial cells differentiated from induced pluripotent stem cells as in vitro toxicity model
Z. Mazidi, Evercyte GmbH

Abstract ID 809 - Exploiting the use of iPSC derived renal proximal tubular like cells to investigate megalin mediated aminoglycosides toxicity
V. Chandrasekaran, Vrije Universiteit Amsterdam

Abstract ID 654 - iPSC-derived human BrainSpheres: a multifaceted and powerful 3D model for
neurotoxicity testing
C. Nunes, Université de Lausanne

Abstract ID 768 - Probabilistic modelling of an Adverse Outcome Pathway network for developmental neurotoxicity
N. Spinu, John Moores Liverpool University

Abstract ID 608 - New read across modules for safer chemicals
A. Caballero, Istituto di Ricerche Farmacologiche Mario Negri

The Center for Alternative to Animal Testing in Europe (CAAT-Europe), housed at the University of Konstanz, coordinates transatlantic activities to promote the development of new and improved methods in toxicology, to provide a platform for different stakeholders for exchanging ideas, and to support the 3R’s principle of human science. CAAT-Europe is going to celebrate the 10th anniversary of its foundation, with a session focused on the most relevant CAAT articles that have been published in the last years. The presentations will cover several topics, as in vitro regulatory, systemic and investigative toxicology, including the application of omics, microphysiological systems and good practice guidance for supporting a human-centered toxicity testing paradigm change. Each speaker will introduce a single publication to tell the story behind its compilation and to discuss its implication and impact on the actual and future discussion in the 3Rs field.

Session chair and co-chair: M. Leist, CAAT-Europe and University of Konstanz / G. Pallocca, CAAT-Europe and University of Konstanz

Speakers:

(2010) CAAT-EUROPE’S BIRTH
Thomas Hartung, CAAT/ Johns Hopkins University

(2011) ‘How are reproductive toxicity and developmental toxicity addressed in REACH dossiers?’
Costanza Rovida, CAAT-Europe

(2013) ‘Metabolomics in toxicology and preclinical research’
Bennard Van Ravenzwaay, BASF SE 

(2014) 'Consensus report on the future of animal-free systemic toxicity testing'
Martin Stephens, Johns Hopkins Bloomberg School of Public Health

(2015) ‘Animal use for science in Europe’
Francois Busquet, Altertox 

(2016) ‘Biology-inspired microphysiological system approaches to solve the prediction dilemma of substance testing’
Thomas Steger Hartmann, Bayer AG

(2017) ‘Good Cell Culture Practice for stem cells and stem-cell-derived models’
Sandra Coecke, JRC EURL-ECVAM

(2019) ‘Optimizing drug discovery by Investigative Toxicology: Current and future trends’
Mario Beilmann, Boehringer Ingelheim

The impact of the CAAT publication series on ALTEX
Sonja von Aulock, ALTEX