Announcements

Please submit 3Rs related news items to editor@altex.org

 

EPA releases updates to CompTox Chemicals Dashboard

2024-12-11

EPA has released Version 2.5 of the CompTox Chemicals Dashboard. Updated tools include SeqAPASS and ToxCast. Some featured updates are:

  • A new default option, “Formula Contains,” for the Advanced Search > Molecular Formula Search.
  • Addition of a “Reply” column to the Comments page.
  • Updates of Hazard and high-throughput phenotypic profiling (HTPP) data and assay descriptions, respectively, to accordions to be more widely accessible.
  • Inclusion of the MS-Ready mass and MS-Ready formulae in the downloaded Batch Search file after MS-Ready SMILES are selected.

More information about EPA’s Version 2.5 updates, including resolved issues and the data sources used for release of the Dashboard, is available at https://www.epa.gov/comptox-tools/comptox-chemicals-dashboard-release-notes.

PETA Science Consortium International offers travel grant for JRC Summer School on Non-Animal Approaches in Science

2024-12-03

Early-career scientists who have been accepted into the European Commission's JRC Summer School on Non-Animal Approaches in Science and who intend to pursue a career in non-animal methods are eligible to apply for a travel award to attend the event in Ispra, Italy, in 2025.
 
Event date: 19–23 May 2025
Award application window: Applications must be submitted between 20 February and 6 March 2025
 
Click here for more information about the event and for application requirements.

Open call for CRACK IT Challenge ideas

2024-12-03

The NC3Rs is inviting new Challenge ideas for the 2025 CRACK IT competition. This is a unique opportunity to drive the development of innovative tools and technologies that tackle scientific challenges your organisation is facing and replaces, reduces or refines the use of animals in research and testing. 

The call is open to industry, academia and the charitable sector. If your idea is successful you will collaborate with the NC3Rs to develop the Challenge as a Sponsor, defining the aims and deliverables before the Challenge is presented to the scientific community to be solved as a funding competition. Sponsors support the success of the Challenge by collaborating with the awardees and providing in kind contributions (e.g. expertise, compounds, data or in-house testing) and end-user input. By being involved from the outset, you can shape the development of new technologies, ensuring they are fit for purpose and deliver 3Rs benefits for your organisation and the wider scientific community.  

CRACK IT has invested £36.7M in 49 Challenges, working with 55 Sponsors and Partners to develop 3Rs technologies that address an unmet need.

If you have a scientific or research need that you think a CRACK IT Challenge could solve, you can read more about how to submit your idea, the process and the role of a Sponsor on the Sponsor a Challenge page or get in touch with the CRACK IT team to ask questions and explore your early ideas: crackitenquiries@nc3rs.org.uk.  

Deadline for new Challenge submissions: Monday 10 February 2025.

PCRM offers travel awards to 2025 conferences

2024-11-28

The Physicians Committee for Responsible Medicine (PCRM) is sponsoring travel awards for the following conferences in 2025 for Early Career Researchers:

  • Society of Toxicology Annual Meeting, Orlando, FL, March 16, 2025
  • Joint Research Centre Summer School on Non-animal Approaches in Science, Ispra, Italy, May 19-23, 2025
  • Microphysiological Systems World Summit, Brussels, Belgium, June 9-13-2025.
  • World Congress on Alternatives to Animal Use in the Life Sciences, Rid de Janeiro, Brazil, August 31-September 4, 2025

All details can be found here: Early-Career Researchers Advancing 21st Century Science - Travel Awards

 

In silico toxicology training course available

2024-11-04

Tox Navigation has released the “NAMs – Use and Application of QSAR and Read-across” course.

The tutor-assisted eLearning course includes over 25 hours of lectures with quizzes and home assignments. The content includes how to utilize QSAR under the QSAR Assessment Framework guidance. Software demonstrations include the latest models and software releases. Subtitles throughout the course are available in English, Spanish, French, German, and Italian.

The course is recognised by EUROTOX for Continued Professional Development for ERT accredited toxicologists.

MRC/NC3Rs to support interdiscliplinary research clusters on in vitro models of complex disease

2024-11-04

The NC3Rs is collaborating with the MRC, in partnership with Wellcome, BBSRC and EPSRC, to support interdisciplinary research clusters to drive the development, validation and/or adaptation of human in vitro models of complex disease that can replace the use of animals in academia and/or industry. Research clusters could include bioengineers, biologists, biophysicists, clinicians, computational scientists and industry scientists and should focus on disease areas of high unmet need and/or address common needs to impact multiple fields.  

The aim of the call is to generate clusters which will:

  • Improve understanding of human disease mechanisms and better support therapeutic development for disease intervention.
  • Overcome limitations of current in vivo and in vitro models to represent human pathophysiology and disease heterogeneity.
  • Accelerate the development, validation and uptake of technologies and methods to accurately and reproducibly model human disease and reduce the reliance on animal models.

It is anticipated that up to five clusters will be funded from the total fund of £15M. The duration of each awarded cluster is expected to be four years.

Full applications open November 5, 2024 to March 20, 2025.
Expression of interest closes December 6, 2024.

More information: https://nc3rs.org.uk/mrcnc3rs-novel-human-vitro-models-complex-disease

MPS World Summit abstracts due January 15, 2025

2024-11-04

Abstracts are being accepted for the 2025 MPS World Summit, to be held June 9-13, 2024, in Brussels. Abstracts are invited on the topic of new developments in MPS and applications of MPS, which are divided into four themes:

  • Theme 1: MPS Development and Results Processing
  • Theme 2: MPS for Biomedical Research and Disease Modelling
  • Theme 3: MPS for Efficacy, ADME, and Toxicity Testing
  • Theme 4: MPS for Industrial and Regulatory Testing

Submit abstracts by January 15, 2025. More details on abstract submission are available at https://mpsworldsummit.org/2025-abstract-submission/

EPA publishes report as part of Agency strategy to reduce animal testing

2024-10-22

The U.S. Environmental Protection Agency (EPA) released a detailed review of major environmental statutes that summarizes which EPA laws or regulations require vertebrate animal testing, such as laboratory testing done on rats, mice, or rabbits. The report, available at https://www.epa.gov/chemical-research/epa-new-approach-methods-work-plan-reducing-use-vertebrate-animals-chemical, concludes that many statutes and regulations guiding EPA’s authority are broadly written and do not preclude the use of scientific information from NAMs, which are defined as any technology, methodology, approach, or combination that can provide information on chemical hazard and risk assessment to avoid the use of animal testing.

This report is a deliverable in EPA’s NAMs Work Plan, which was originally released in June 2020 and updated in November 2021. The Work Plan outlines the Agency’s strategies and objectives for increasing the rigor and sophistication of Agency assessments while reducing the reliance on vertebrate animals to test chemicals in regulatory, compliance, enforcement, and research activities through the use of NAMs. The assessments will remain fully protective of human health and the environment. The first objective in the Work Plan was to evaluate regulatory flexibility for accommodating NAMs, and the report accomplishes that objective.

NIH offers funding for NAMs data hub and coordinating center

2024-10-22

The National Institutes of Health (NIH) Common Fund, along with its partner NIH Institutes, Centers, and Offices has published two Notices of Funding Opportunity (NOFOs) to support the Complement Animal Research in Experimentation (Complement-ARIE) Program. Complement-ARIE will accelerate the development, standardization, validation, and use of human-based new approach methodologies (NAMs).

Investigators with expertise and insights into the area of NAMs are encouraged to consider applying for these funding opportunities, which will support Technology Development Centers and a Data Hub and Coordinating Center. NIH also encourages collaborative investigations combining expertise in in vitro, in silico, and in chemico NAMs. NIH expects to offer four or five awards with funding of approximately $18M per year.

Complement-ARIE program goals include:

  • To better model and understand human health and disease outcomes across diverse populations.
  • To develop NAMs that provide insight into specific biological processes or disease states.
  • To validate mature NAMs to support regulatory use and standardization.
  • To complement traditional models and make biomedical research more efficient and effective.

More information about Complement-ARIE is available at https://commonfund.nih.gov/complementarie

PCRM starts Animal-Free Workshop Series for Early-Career Researchers

2024-10-01

The Physicians Committee for Responsible Medicine, Johns Hopkins University Center for Alternatives to Animal Testing (CAAT), and the Animal Protection Commissioner of Berlin are launching a new workshop series focused on animal-free new approach methods (NAMs) in research and testing. The Animal-Free Workshop Series for Early-Career Researchers consists of free, online workshops that will provide a forum for early career researchers to learn about innovative nonanimal methods and gain practical career development skills. 

Registration is now open for Workshop No. 1: Understanding Translatability and Crafting Competitive Grant Applications on Tuesday, November 19, 2024 at 10 am ET/4 pm CET via Zoom.

The workshop will feature:

  • Dr. Jarrod Bailey, Director of Medical Research at the Physicians Committee for Responsible Medicine, who will explain how human-focused research provides greater clinical benefits, due to greater biological similarity and specificity of human-based methods
  • Dr. Angela Hvitved, Program Director at the Alternatives Research & Development Foundation, who will provide an overview of funding opportunities for nonanimal research methods and practical tips for crafting a strong proposal that is tailored to the target funding opportunity.

Find out more and register here! And please share with the early-career researchers in your networks.

ALTEX Prize 2024 awarded to Julia Kühnlenz

2024-09-20

We are excited to announce that Dr Julia Kühnlenz of Bayer CropScience, Lyon, France has won the ALTEX Prize 2024 as first author of the article "A microfluidic thyroid-liver platform to assess chemical safety in humans". The article was selected by the ALTEX Editorial Board, the Board of ALTEX Edition and the ALTEX editorial office as the best article published in ALTEX in 2023. The award was presented on September 19, 2024 at the EUSAAT Congress in Linz by Kristina Wagner, Vice-President of ALTEX Edition.

The ALTEX Prize is awarded annually and is kindly sponsored by the Doerenkamp-Zbinden Foundation. The prize includes a personal prize of CHF 2000.

Coalition to Illuminate and Address Animal Methods Bias (COLAAB) launches new website

2024-09-20

AnimalMethodsBias.org is now available with guidance and resources aimed at helping researchers successfully publish nonanimal biomedical studies by overcoming the preference some peer reviewers have for animal-based research methods. This animal methods bias, which is sometimes also caused by reviewers’ lack of expertise in nonanimal methods, impacts the quality or fairness of nonanimal research assessments.  

The site houses the COLAAB’s Author Guide for Addressing Animal Methods Bias in Publishing, which has several sections researchers can use when designing studies, preparing and submitting manuscripts, and responding to reviews. It includes a database of animal-free experimental platforms and tools, a database of journals with a track record of publishing nonanimal studies, and a comprehensive library of more than 800 papers and other references relevant to nonanimal research. 

NIH funding for NAM development announced

2024-08-20

The National Institutes of Health (NIH) Common Fund has announced a Notice of Intent to Publish a Funding Opportunity for the Complement Animal Research in Experimentation (Complement-ARIE) program. Complement-ARIE will accelerate the development, standardization, validation, and use of human-based new approach methodologies (NAMs) that more accurately model human biology, and complement, or in some cases, replace traditional research models.

Complement-ARIE program goals include:

  • To better model and understand human health and disease outcomes across diverse populations.
  • To develop NAMs that provide insight into specific biological processes or disease states.
  • To validate mature NAMs to support regulatory use and standardization.
  • To complement traditional models and make biomedical research more efficient and effective.

The Complement-ARIE program plans to issue a Notice of Funding Opportunity to support the Complement-ARIE Comprehensive NAMs Technology Development Centers. The goal/intent of these Centers is to stimulate the development of combinatorial NAMs in the areas of greatest need.

Publication of the funding opportunity is anticipated on October 18. The Notice of Intent to Publish a Funding Opportunity is available at https://go.nih.gov/iiuNC9v. More information about the Complement-ARIE Program is available at https://commonfund.nih.gov/complementarie/faqs. Interested persons can keep up to date with future announcements by signing up for the Complement-ARIE listserv at https://list.nih.gov/cgi-bin/wa.exe?SUBED1=COMPLEMENT-ARIE&A=1?

£2.1M funding available to UK and European-based innovators through the CRACK IT Challenges competition

2024-08-08

Are you a UK or European-based* innovator working with approaches which could be applied to replace animal use for avian toxicity testing or refine the post-operative care of rodents?

Up to £2.1M of funding is available through this year’s CRACK IT Challenges competition to solve two Challenges.

What are CRACK IT Challenges? 

The competition funds multi-disciplinary collaborations to drive the development of 3Rs products and services that are directly targeted to meet end-user needs. Sponsors (end-users) define the Challenges and work collaboratively with the awarded team, providing in-kind contributions and end-user input to support project delivery. Challenges are also supported by Partners who provide additional resources to Challenge winners. This year’s competition provides you with the opportunity to collaborate with seven international Sponsors and Partners from across the chemical, pharmaceutical and non-profit sectors.

How can you apply? 

The NC3Rs are hosting launch webinars for each Challenge in September where you will have the opportunity to find out more about the CRACK IT Challenges programme and how to apply. Further details on registering for these webinars can be found below. The competition will open for applications on Monday 23 September 2024.

*The competition is open to any UK, European Union, European Economic Area and European Free Trade Association body public or private. The competition is run using the Innovate UK Contracts for Innovation process.

Challenge 48: Wings of Change
Advancing avian toxicity assessments with new approach methodologies

Avian toxicity studies assess the potential adverse effects of chemicals in the environment on bird species. These studies are carried out for internal chemical screening and to meet regulatory requirements for the registration of new pesticides. Large numbers of birds are used and there is a significant unmet need to develop alternative approaches.

Sponsored by BASF, Bayer Crop Science, Corteva and Syngenta, and supported by Challenge Partners the American Chemistry Council and the Health and Environmental Sciences Institute, the aim of this Challenge is to develop a suite of new approach methodologies to assess acute and chronic toxicity to replace the use of birds for internal decision making and reduce the number of regulatory in vivo studies.

This Challenge will benefit from expertise across disciplines including in silico and in vitro approaches (e.g. QSARs, exposure and effects modelling, cell lines etc). Applications from those working in other fields that could be applied to avian toxicity are encouraged.

Further information: Wings of Change Challenge Register now: Launch webinar, 17 September, 14.00 - 15.30 (BST) Challenge 49: Rodent Shelter
Improving the post-operative care of rodents

The post-operative care of rodents is critical to aid recovery and minimise any pain and distress. Rodents are often singly housed for a period during their recovery and cage enrichment items are removed to avoid injuries. There are opportunities to refine the care of rodents through enhanced monitoring of parameters such as body temperature and improvements to the housing environment after surgery.

Sponsored by AstraZeneca, the aim of this Challenge is to develop an easy-to-use and affordable shelter that provides warmth and a means to monitor the animals, which can be used in any cage type to improve post-operative recovery and monitoring of rodents.

Further information: Rodent Shelter

Register now: Launch webinar, 18 September, 10.00 - 11.30 (BST)

Free NAM Use for Regulatory Application (NURA) courses move to new platform

2024-07-17

New Approach Methodology (NAM) Use for Regulatory Application (NURA) is a continuing education program designed to provide professionals in the field of toxicology with specialized resources and basic hands-on training in nonanimal new approach methodologies. NURA offers trainings, seminars, and other events to encourage the use of nonanimal approaches within various regulatory frameworks.

The NAM Use for Regulatory Application (NURA) program’s recorded content is moving to a new platform that offers easier access to NURA resources.

You can now navigate NURA content at your own pace, one presentation at a time, and the platform will keep track of your progress. Find, skip, or replay presentations easily, and earn certificates upon course completion that may be submitted for continuing education credits.

The new platform also features English and Spanish subtitle options. Access the new NURA Training platform by visiting PCRM.org/NURA.

Current courses: AI Use for Regulatory Application - Using Machine Learning to Reduce Animal Use in Toxicology
Human In, Human Out - Using Primary and Population Data for PBPK Analysis Tomorrow's Data Today - Sunsetting the 2-year Carcinogenicity Assay  

European Pharmacopoeia finally deletes the rabbit pyrogen test

2024-07-09

Pyrogen detection is essential for ensuring the safety of parenteral medicines. For decades, the rabbit pyrogen test (RPT) has been the traditional method. The RPT involves measuring the rise in body temperature in rabbits following intravenous injection of the substance to be examined.

Despite multiple efforts to encourage medicine developers to move away from the RPT, the test is still widely used to detect pyrogenic substances, consuming a large number of rabbits worldwide.

At its 179th session in June 2024, as the outcome of a broad exercise aiming at the complete removal of the RPT from the European Pharmacopoeia (Ph. Eur.), the Ph. Eur. Commission adopted 57 revised texts from which the RPT has been deleted, together with a new general chapter on Pyrogenicity (5.1.13), marking the end of the RPT era in the Ph. Eur.  

As a result, the use of the RPT will no longer be required in any text of the Ph. Eur. and it will be the responsibility of medicine developers to select a suitable in vitro test (e.g. the monocyte-activation test) to control the pyrogenicity of their product, based on a risk assessment as described in the new general chapter.

The revised texts omitting the RPT and Pyrogenicity (5.1.13) will be published in Supplement 11.8 of the Ph. Eur., with an implementation date of 1 July 2025.  

Read seminal ALTEX articles on the replacement of the pyrogen test:

Hartung, T., & Wendel, A. (1995). [Detection of pyrogens using human whole blood] [Article in German]. ALTEX 12, 70–75. https://www.altex.org/index.php/altex/article/view/1671

Schindler, S., von Aulock, S., Daneshian, M., & Hartung, T. (2009). Development, validation and applications of the monocyte activation test for pyrogens based on human whole blood. ALTEX 26, 265–277. doi:10.14573/altex.2009.4.265

Hartung, T. (2015). The human whole blood pyrogen test – lessons learned in twenty years. ALTEX 32, 79–100. doi:10.14573/altex.1503241

Hartung, T. (2021). Pyrogen testing revisited on occasion of the 25th anniversary of the whole blood monocyte activation test. ALTEX 38, 3–19. doi:10.14573/altex.2101051

Brown, J., Clippinger, A. J., Fritz Briglia, C. et al. (2021). Using the monocyte activation test as a stand-alone release test for medical devices. ALTEX 38, 151–156. doi:10.14573/altex.2012021

Thurman, T. L., Lahti, C. J., Mateffy, J. M. et al. (2023). Comparison of pyrogen assays by testing products exhibiting low endotoxin recovery. ALTEX 40, 117–124. doi:10.14573/altex.2202021

New Test Guidelines available from OECD

2024-07-04

The Organisation for Economic Cooperation and Development (OECD) published several Test Guidelines on 25 June 2024.

Three new Test Guidelines:

The following Test Guidelines were updated:

The following Test Guidelines were corrected/clarified:

 

WC13 calls for session proposals

2024-07-04

As of now, it is possible to submit a session proposal for the 13th World Congress on Alternatives and Animal Use in the Life Sciences. All sessions within the WC13 program will be 60 minutes long. After submitting the session proposal, the Scientific Committee will review the session based on quality, innovation, and inclusivity. Potentially overlapping sessions may be merged. The session organizer will be informed of this in advance. For more information about the general guidelines and session formats please visit the congress website. 

https://www.wc13rio.org/proposal-submission/

New webpage enables PubMed searches on specific alternatives topics

2024-06-13

A new NTP webpage will allow users to easily search PubMed for information on specific topics related to alternatives to animal testing. NICEATM and the U.S. Department of Agriculture National Agricultural Library’s Animal Welfare Information Center (AWIC) collaborated to develop search strategies, known as “hedges,” for topics specific to alternatives. Hedges are now available for the following topics:

  • Alternatives to animal use for assessing acute inhalation toxicity
  • Alternatives to animal use for assessing developmental neurotoxicity
  • In vitro to in vivo extrapolation
  • Microphysiological systems

The hedges are available at https://ntp.niehs.nih.gov/go/altbibtopics. Additional hedges are under development; please contact Catherine Sprankle at spranklec@niehs.nih.gov with suggestions of additional topics.

AWIC has developed search hedges for a number of animal welfare topics, and offers guidance and assistance for literature searches on animal use alternatives. For more information and to access these resources, visit https://www.nal.usda.gov/services/literature-searching-animal-use-alternatives

ALTEX paper chosen as NIEHS Extramural Paper of the Month

2024-05-01

The recently accepted manuscript by Han-Hsuan D. Tsai, Lucie C. Ford, Zunwei Chen, Allison N. Dickey, Fred A. Wright, Ivan Rusyn titled "Risk-based prioritization of PFAS using phenotypic and transcriptomic data from human induced pluripotent stem cell-derived hepatocytes and cardiomyocytes" (doi:10.14573/altex.2311031) was selected as NIEHS Extramural Paper for May 2024. 

Congratulations to the authors on this well-deserved recognition of their cutting edge non-animal method aiming to prioritize per- and polyfluoroalkyl substances (PFAS) for further toxicity testing based on human relevant data. The final version of the paper will appear in the next issue of ALTEX.

 

 

Updated online Animal Welfare Act training available

2024-03-20

The Animal Welfare Information Center (AWIC) within the USDA National Agricultural Library of the U.S. Department of Agriculture has updated the online version of its popular workshops on “Meeting the Requirements of the Animal Welfare Act.” The online workshop is available on demand year-round and can be completed on the user’s own schedule. Topics covered include the Animal Welfare Act, 3Rs alternatives and resources, and how to conduct a literature search for animal use alternatives. The online workshop is hosted on the website of Oregon State University and is available at https://workspace.oregonstate.edu/course/meeting-the-information-requirements-of-the-animal-welfare-act.

NICEATM releases ICE version 4.0.2

2024-03-12

NICEATM has released Version 4.0.2 of the Integrated Chemical Environment (ICE). ICE provides chemical safety data and property predictions as well as tools to help query, review, and contextualize these data. ICE is available at https://ice.ntp.niehs.nih.gov/.

Key features implemented in ICE 4.0.2 are: 

  • New data visualizations for Search tool query summary results.
  • Updated filter chain options in Search.
  • New overlays for data comparisons in the In Vitro to In Vivo Extrapolation (IVIVE) tool.
  • Curve Surfer tool optimization.
  • Updated cHTS data from the Invitrodb v3.5 release.
  • Improved support for chemical name searching in the ICE REST API.

Demonstrations of ICE and other NICEATM computational tools will be given Monday, March 11 through Wednesday, March 13 at the Society of Toxicology (SOT) 2024 annual meeting in Salt Lake City, UT. Visit https://ntp.niehs.nih.gov/go/niceatm-sot24-demos to view the demonstration schedule.

NC3Rs seeking in vitro researchers to test RIVER recommendations on preparing a manuscript

2024-03-04

The NC3Rs are looking for researchers preparing a manuscript that includes in vitro models to participate in user testing of the RIVER (Reporting In Vitro Experiments Responsibly) recommendations. RIVER aims to improve the reliability and reproducibility of in vitro studies to minimise wastage of animal-derived reagents, avoid animal experiments based on flawed data, and build confidence in alternative models.

Participants will receive expert feedback on their manuscript, improve the transparency of their work and its chances of successful publication, and receive a £50 (Euro/USD equivalent) voucher.

More info

ICCVAM document on validation, qualification, and regulatory acceptance of NAMs now available

2024-03-01

An ICCVAM document, “Validation, Qualification, and Regulatory Acceptance of New Approach Methodologies,” is now available at https://ntp.niehs.nih.gov/go/ICCVAM-submit. This document updates a model for validation and regulatory acceptance of new and alternative test methods originally described in the 1997 ICCVAM report, “Validation and Regulatory Acceptance of Toxicological Test Methods.” The updated document describes an approach to NAMs validation that reflects modern toxicity testing, placing less emphasis on replacement of an in vivo test with a single alternative method and more emphasis on integrating results from multiple in vitro and in chemico assays, and in silico approaches. Guided by the principles articulated in the 2018 ICCVAM Strategic Roadmap (available at https://ntp.niehs.nih.gov/go/natl-strategy), the new document presents a more flexible approach to how confidence is established, to help ensure the adoption of new methods by federal agencies and regulated industries once validated for a specific application or context of use.

The new document was prepared by the ICCVAM Validation Workgroup, which was established in 2021 to update the 1997 document. It reflects input from a number of federal research and regulatory agencies, as well as public comments received following the release of a draft version before the 2023 meeting of the Scientific Advisory Committee on Alternative Toxicological Methods. Materials from that meeting are available at https://ntp.niehs.nih.gov/events/past?type=SACATM.

NC3Rs launches Networks program

2024-02-13

The NC3Rs new Networks programme aims to bring researchers in key scientific fields together to establish collaborations and catalyze the uptake of 3Rs technologies. Researchers and stakeholders at all career stages from across academia and industry are invited to join the first two Networks, in cardiovascular sciences and new approach methodologies (NAMs).
The Oncology Network will be launched later this year, with further themes in development. Contact Dr Rachel Eyre (cardiovascular) or Dr Deb Milligan (NAMs) for more information.

Find out more about the benefits of joining a Network and access information on NC3Rs-funded projects, funding opportunities and resources through the Cardiovascular and NAMs Network hubs.

Register for the launch events to meet other Network members in person for the first time and discuss Network activities and priorities.

Register for the Cardiovascular Network launch event on Thursday 18 April.

Register for the NAMs Network launch event on Tuesday 30 April

NIH announces Complement Animal Research In Experimentation (Complement-ARIE) Program

2024-02-05

The NIH Common Fund’s Complement Animal Research In Experimentation (Complement-ARIE) program seeks to speed the development, standardization, validation, and use of human-based new approach methodologies (NAMs). The Complement-ARIE program will build upon ongoing efforts related to NAMs, while identifying opportunities for innovation and coordination.

Complement-ARIE will significantly advance understanding of human health and disease by providing a range of ready and standardized biomedical research models. Developing these models will require expertise in disease research, personalized medicine, and in screening therapeutics for safety and effectiveness.

Complement-ARIE will bring these expertise together through a consortium of researchers participating in the following efforts:

  • Technology development projects/centers that will develop NAMs to fill in areas of greatest need. Projects will emphasize biological complexity, high throughput techniques, combining approaches, and data sharing.
  • A data & NAM resource coordinating center that will create integrated data structures and a searchable NAMs repository. 
  • A validation network that will accelerate deployment and regulatory approval of NAMs for biomedical research.
  • Community engagement and training that will promote the development of an inclusive, diverse, biomedical research workforce with the skills to build and use new NAMs. 
  • Strategic engagement with key partners that will advance emerging opportunities in development and use of NAMs in basic, translational, and clinical research.

To learn more about Complement-ARIE strategic planning activities, visit: Complement-ARIE strategic planning. 

To learn more about related work being done at NIH, visit: NIH NCATS Tissue Chip for Drug Screening Program

ECHA launches new chemicals database

2024-02-01

ECHA CHEM is the European Chemicals Agency's new solution for publishing information on chemicals. The first release, available now, includes information from all REACH registrations – and there is more to come.

ECHA maintains the largest chemicals database in the European Union (EU), combining industry-submitted data with information generated in the EU’s regulatory processes. ECHA CHEM is the new solution to share with the public the growing amount of information hosted by the Agency.

In the first version of ECHA CHEM, you can find information from all the over 100 000 REACH registrations that companies have submitted to ECHA. Later this year, the database will be expanded with the redesigned Classification and Labelling Inventory, followed by the first set of regulatory lists.

US EPA announces new framework to assess eye irritation in new chemicals

2024-01-10

In a Federal Register notice published January 9 (available at https://www.federalregister.gov/d/2024-00169), the U.S. Environmental Protection Agency (EPA) announced a new framework for identifying eye irritation and corrosion hazards for new chemicals reviewed under the Toxic Substances Control Act (TSCA). Information about the new framework is available at https://www.epa.gov/reviewing-new-chemicals-under-toxic-substances-control-act-tsca/framework-assess-eye-irritation-or.

With this new framework, EPA will place increased weight on data from non-animal test methods that are more reproducible and provide results more relevant to humans. This will streamline the decision-making process and increase efficiency through a standard process for EPA to use each time it evaluates eye irritation or corrosion hazards test data. The new framework supports EPA’s mandate under TSCA to promote the development and implementation of alternative test methods and strategies that can provide information on chemical hazards without animal testing. This framework also supports EPA’s ongoing efforts to reduce the use of animal testing and make the Agency’s review of new chemicals more efficient, helping to bring new chemicals to market more quickly while protecting human health.

Updates to online master class in animal-free safety assessment for cosmetics

2023-12-12

The AFSA (Animal-free Safety Assessment) Collaboration has developed a “Master Class in Animal-free Safety Assessment for Cosmetics.” The goal of this class is to build confidence and global capacity in the use of animal-free data in safety decision-making.

A new module on “Global Regulatory Landscape” was released in November. This module focuses on how regulatory requirements impact cosmetic risk assessment in key global markets, including current challenges in implementing animal-free safety assessment and approaches to address them.

The Master Class is designed for stakeholders engaged in cosmetic and chemical safety assessment and regulation, and will be especially useful for:

  • Product and chemical safety assessors and regulators.
  • Regulatory affairs and compliance specialists.
  • Contract research organizations and other GLP laboratories.
  • Small and medium enterprises.
  • Graduate students.
  • Non-governmental organizations.

Course content is based on the principles of next-generation risk assessment, an exposure-led, hypothesis-driven risk assessment approach integrating existing knowledge with in silico, in chemico, and in vitro approaches in a tiered framework identifying situations in which a product or ingredient may be used safely. Students can pick and choose modules based on their interests or view them all. More information is available at https://www.afsacollaboration.org/masterclass/. Sign up and preview webinars at https://afsa.talentlms.com/.

FDA guidance available on computational modeling for medical device submissions

2023-12-12

The U.S. Food and Drug Administration (FDA) has published guidance on “Assessing the Credibility of Computational Modeling and Simulation in Medical Device Submissions.” Computational modeling and simulation (CM&S) can be used in a variety of ways in medical device applications, including to perform “in silico” device testing or as part of software embedded in a device. This guidance provides a risk-informed framework for credibility assessment of CM&S used in medical device regulatory submissions. The guidance is intended to promote consistency and facilitate efficient review of medical device submissions, to increase confidence in the use of CM&S in regulatory submissions, and to facilitate improved interpretation of CM&S credibility evidence submitted in regulatory submissions.

EFSA announces TKPlate platform for predicting acute toxicity

2023-12-07

The European Food Safety Agency (EFSA) is developing TKPlate, an online platform that offers a space and a suite of tools for scientists and regulators to model and predict toxicokinetic and toxicodynamic properties of chemicals found in food and feed. TKPlate will support modeling and predicting the toxicity of chemicals and what happens to them inside humans and animals, enabling reduction of animal use for this purpose. An overview of TKPlate is available at https://www.efsa.europa.eu/en/news/introducing-tkplate-food-safety-without-animal-testing. A detailed description of the platform is published in an article (Dorne et al.) in the EFSA Journal, available at https://doi.org/10.2903/j.efsa.2023.e211101.

Online master class in animal-free safety assessment for cosmetics now available

2023-09-26

The AFSA (Animal-free Safety Assessment) Collaboration has developed a “Master Class in Animal-free Safety Assessment for Cosmetics.” The goal of this class is to build confidence and global capacity in the use of animal-free data in safety decision-making. The Master Class is designed for stakeholders engaged in cosmetic and chemical safety assessment and regulation, and will be especially useful for:

  • Product and chemical safety assessors and regulators.
  • Regulatory affairs and compliance specialists.
  • Contract research organizations and other GLP laboratories.
  • Small and medium enterprises.
  • Graduate students.
  • Non-governmental organizations.

Course content is based on the principles of next-generation risk assessment, an exposure-led, hypothesis-driven risk assessment approach integrating existing knowledge with in silico, in chemico, and in vitro approaches in a tiered framework identifying situations in which a product or ingredient may be used safely. Students can pick and choose modules based on their interests or view them all. More information is available at https://www.afsacollaboration.org/masterclass/. Sign up and preview webinars at https://afsa.talentlms.com/.

New 3Rs resource: Refined mouse handling e-learning

2023-09-26

The NC3Rs and US-based 3Rs Collaborative (3RsC) have created the refined mouse handling e-learning course in an international collaboration with academia and industry. The course is a comprehensive and accessible overview of the evidence base, benefits and practicalities of refined handling, for the mice, the handler and the research. Designed for anyone who works with mice in research at all levels of experience it should take no longer than 45 minutes to complete.

EPAA invites participation in designathon for NAMs-based classification system

2023-09-15

The European Partnership for Alternatives to Animal Testing (EPAA) invites the submission of solutions based on NAMs to inform the development of a future classification system for systemic toxicity of human health based on the activity and potential systemic availability of chemicals.

  • The NAM-based classifications should reflect levels of concern related to, but not synonymous with, the current classification system addressing systemic toxicity.
  • The NAMs do not need to literally predict the outcomes of animal studies, nor are they expected to reproduce existing classifications.

Information about the “designathon” project is available at https://single-market-economy.ec.europa.eu/calls-expression-interest/epaa-launches-designathon-human-systemic-toxicity_en. Resources on this page include a recording of a July 13 webinar describing the project.

EPAA will provide a reference list of approximately 150 chemicals, along with identifiers reflecting three levels of concern. The number of chemicals in each class (High, Medium, and Low) will also be provided, but participants will not be told which chemical belongs to which class. Submitters will be expected to propose prototype NAM-based solutions that categorize some or all of the chemicals on the reference list. In this initial prototype phase, specific data generation is not necessarily required, but rather ideas for a NAM-based classification scheme can be explored using existing information. EPAA will provide a reporting template, including guidance. Interested persons can email zvonimir.zvonar@epaaind.eu to request updates on the designathon.

NICEATM releases ICE 4.0.1

2023-08-24

On August 18, NICEATM released version 4.0.1 of the Integrated Chemical Environment (ICE; https://ice.ntp.niehs.nih.gov/). ICE provides data and tools to help query, review, and interpret toxicological data, predictions, and tools.

Key features implemented in ICE 4.0.1 are:

  • Availability of population-level exposure predictions across multiple pathways through the ICE Search tool in addition to the ICE REST API and the ICE In Vitro to In Vivo Extrapolation tool.
  • Functional use categories added to the ICE Chemical Characterization tool.
  • A new "Curated Product Use Explorer" in the ICE Chemical Characterization tool that expands and improves upon the former "Consumer Use Explorer."
  • Improved support for chemical name searching in all ICE tools.
  • Harmonization of structure and data fields in the dermal irritation/corrosion data set to make data computationally accessible and facilitate interoperability on the ICE user interface.
  • New Chemical Quick Lists:
    • Mixtures and Formulations in ICE.
    • ToxCast Phase I, Phase II, and e1k.
  • Further development of data visualizations and query summaries for ICE Search tool results (beta version).

Presentations describing features available in ICE 4.0.1 and planned for future releases will be given next week at the 12th World Congress on Alternatives and Animal Use in the Life Sciences. A list of NICEATM and ICCVAM agency activities at World Congress is available at https://ntp.niehs.nih.gov/go/niceatm-wc12.

OECD publishes new and updated test guidelines and other documents

2023-07-28

On July 4, OECD published two new test guidelines and 19 updated or corrected test guidelines. The complete list of newly available documents is accessible at https://www.oecd.org/env/ehs/testing/oecdguidelinesforthetestingofchemicals.htm.

One new Test Guideline, Test No. 444A, describes the IL-2 assay, an in vitro assay intended to be used as a part of a battery to determine immunotoxic potential of chemicals. The other new test guideline, Test No. 126, describes a method to measure hydrophobicity of nanomaterials. Among the updated and corrected test guidelines are tests describing non-animal approaches for assessing skin sensitization, eye irritation, endocrine activity, and phototoxicity.

In addition to the test guidelines, OECD also added two documents to its Series on Testing and Assessment: “Initial Recommendations on Evaluation of Data from the Developmental Neurotoxicity (DNT) In Vitro Testing Battery” and a “Workshop Report on How to Prepare the Test Guidelines for Emerging Technologies.” 

Marcel Leist wins 2023 Björn Ekwall Memorial Foundation Award

2023-06-29

The 2023 Björn Ekwall Memorial Award was presented by Dr Tuula Heinonen to Prof. Dr Marcel Leist, chair of the In Vitro Toxicology and Biomedicine Department inaugurated by the Doerenkamp-Zbinden foundation at the University of Konstanz in Germany and the director of the Center for Alternatives to Animal Testing in Europe (CAAT-Europe), on occasion of the 2nd MPS World Summit in Berlin, Germany on June 29, 2023. The award recognizes the recipient's novel and pioneering scientific work, dissemination, and promotion of non-animal science with a determined and targeted goal to replace laboratory animals in research and regulatory testing.

The Björn Ekwall Memorial Award (SEK 30,000) is bestowed annually at the scientific workshop of the SSCT or other relevant toxicological meeting, where the winner may deliver a “Björn Ekwall Memorial Lecture”.

US CPSC updates animal testing webpage

2023-06-19

The U.S. Consumer Product Safety Commission (CPSC) has updated its Animal Testing web page. It has been re-designed to be more user friendly and have direct access to necessary information and documents. The new webpage is available at https://www.cpsc.gov/FAQ/CPSCs-Policy-on-Animal-Testing.

One of the resources available on this page is CPSC’s “Guidance for Industry and Test Method Developers: CPSC Staff Evaluation of Alternative Test Methods and Integrated Testing Approaches and Data Generated from Such Methods to Support FHSA Labeling Requirements.” CPSC developed this guidance, building on its Animal Testing Policy, to assist stakeholders in determining what test methods are deemed reliable for determining compliance with the labeling requirements under the Federal Hazardous Substances Act (FHSA). This includes clarification of CPSC informational requirements and process for evaluating new approach methodologies and integrated approaches to testing and assessment.

New EUROTOX podcast series started

2023-06-12

Altertox has developed and produced a new podcast series for EUROTOX in vitro and in silico specialty section. The EUROTOX In2TOX podcast brings you the voices of those who are engineering change in toxicology. Explore the transformative potential of in vitro and in silico technologies by getting to know the people behind the science and how their work influences the way in which we look and interact with chemicals.

Listen to Ep1: learn about the difficulties of studying the effect of chemicals on brain development and why quantitative adverse outcome pathways and physiological maps can help.

Listen to Ep2: learn how toxicologists discovered that chemicals can affect the brain and why we still struggle to implement effective regulations reducing the risks associated with our exposure to neurotoxic chemicals.

In memoriam: Franz Paul Gruber

2023-04-18

It is with deep sadness that we announce the death of our esteemed colleague and friend, Franz Paul Gruber, DVM, PhD, who passed away on April 12, 2023 in Münsterlingen, Switzerland after a prolonged illness. Franz leaves behind his wife Ursula Grashey and his son Jonas Grashey. He will be greatly missed by his colleagues and friends at ALTEX Edition and the Doerenkamp Zbinden Foundation as well as by many collaborators in the field of alternatives to animal experiments. Franz was a veterinarian who dedicated his entire carrier to promoting animal welfare and alternatives to animal experimentation. He worked as an associate professor at the Free University in Berlin, academic director of the animal research facility at the University of Konstanz, scientific advisor of Animalfree Research (then FFVFF), editor-in-chief of ALTEX, and CEO of ALTEX Edition and of the Doerenkamp Zbinden Foundation. He was still active as the President of ALTEX Edition, Co-President of Ärztinnen und Ärzte für Tierschutz in der Medizin, and President of the Doerenkamp Zbinden Foundation. Franz’ life achievements were recently celebrated in an editorial published on occasion of his 80th birthday (ALTEX 40, 1). With his passing, the 3Rs field has lost one of its most dedicated pioneers. Thank you, dear Franz! Our time with you was an inspiration and a great privilege to us all.

EURL ECVAM issues Status Report on alternatives

2023-03-28

The European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) has issued its 2022 Status Report, “Non-animal Methods in Science and Regulation.” The report describes research, dissemination and promotion activities undertaken by EURL ECVAM to further the uptake and use of non-animal methods and approaches in science and regulation. It is available at https://publications.jrc.ec.europa.eu/repository/handle/JRC132525.

Specific activities described in the report include:

  • Providing guidance and training on the validation of in vitro methods, application of Good In Vitro Methods Practices, and introduction of test readiness criteria.
  • Evaluation of methods to measure cytotoxicity, skin sensitization, and genotoxicity.
  • Validation of in vitro methods measuring different modes of action relevant to the thyroid/endocrine system.

EURL ECVAM, which is part of the European Commission's Joint Research Centre, coordinates research and validation studies on alternatives to animal testing within the European Union. EURL ECVAM also shares knowledge about and promotes use of alternative methods. NICEATM and ICCVAM collaborate with EURL ECVAM via the International Cooperation on Alternative Test Methods (ICATM); more information about ICATM is available at https://ntp.niehs.nih.gov/go/icatm.

NICEATM releases ICE 4.0 and DASS App

2023-03-21

On March 20, NICEATM released version 4.0 of the Integrated Chemical Environment (ICE). ICE provides data and tools to help query, review, and interpret toxicological data, predictions, and tools. ICE is available at https://ice.ntp.niehs.nih.gov/.

Key features implemented in ICE 4.0 are:

  • Updated Search results page with improved data navigation and query summary visualizations.
  • A new Exposure Predictions data set. This can be downloaded from the Data Sets page or via the ICE REST API. Exposure predictions can also be visualized as an overlay option in the ICE IVIVE (In Vitro to In Vivo Extrapolation) tool results.
  • Updates to the ICE PBPK (Physiologically Based Pharmacokinetic) and IVIVE tools:
    • The httk R package has been updated to the newest version, v2.2.2.
    • A human gestational model from httk v2.2.2 has been added to both tools.
    • Predicted half-life and area under curve values are available in PBPK model output.
    • A new chemical concentration unit, parts per million per unit volume (ppmv), is available when modeling chemical exposure as gas.
  • Acceptance of chemical names and synonyms as input.

NICEATM has also released the DASS App, a web app for predicting skin sensitization hazard and potency. The DASS App takes a user-provided data set and applies defined approaches on skin sensitization (DASS) that are described in OECD Guideline No. 497 and by the U.S. Environmental Protection Agency. The defined approaches predict skin sensitization hazard (either a sensitizer or non-sensitizer) and potency by integrating data from in vitro assays and in silico hazard predictions. The DASS App is available at https://ntp.niehs.nih.gov/go/952311.

European Commission adopts further NAMs for REACH testing

2023-03-08

On March 3, the European Commission adopted some 100 new and updated test methods for the regulatory safety testing of chemicals under REACH, the Regulation for the registration, evaluation, authorisation and restriction of chemicals. Under these new rules, internationally approved methods (e.g.  OECD- test guidelines) for the new test methods are referred to directly in the Regulation. Lengthy procedures previously used for reproducing and translating test guidelines into all EU official languages are no longer needed and hence any approved new test methods will be included in REACH much faster.  

The majority of the newly approved toxicity test methods are New Approach Methods (NAMs) which do not involve animals. With this faster procedure, the Commission is responding to calls to speed up regulatory uptake of non-animal alternatives. It is one of the Commission’s actions to make NAMs more useful, and it will help to achieve the EU policy objective of ultimately phasing out the use of animals for regulatory testing.  

Background

REACH requires industry to manufacture, import and use chemicals safely. In order to achieve this objective, sufficient information on hazardous chemicals must be available. In some cases, the need to gather this information still requires the use of laboratory animals. Some hazardous properties of chemicals, such as endocrine disruption, cannot be sufficiently determined using currently available non-animal testing methods. Relying solely on such methods can underestimate the potentially hazardous properties of chemicals that could be harmful to humans and the environment.  

The European Commission strives to reduce and ultimately replace the use of animals for testing. REACH therefore requires companies to share data and so avoid unnecessary animal testing. Those wishing to perform tests must indicate these to the European Chemicals Agency and must then obtain approval before carrying them out. Under REACH, animal testing must be avoided in favour of alternative methods and registrants can only carry out tests involving the use of animals as a last resort.  

Through the EU Research and Innovation Framework Programmes over the past two decades more than 1 billion EUR have been dedicated to supporting over 300 projects to develop a variety of human-relevant non-animal methods and strategies. Some of these tools are now being used also for regulatory purposes. Further development of alternatives to animal testing is being pursued in the Horizon Europe Framework Programme for research and innovation that runs from 2021 to 2027. In 2022, more than 200 million EUR were allocated to this area. 

More information 

Source: EU Environment newsletter of March 3, 2023

Descroix-Vernier EthicScience Prize awarded

2023-02-03

On February 2, 2023, the Pro Anima Scientific Committee and the Descroix-Vernier Foundation recognized three teams of researchers during a ceremony at Cercle de l’Union Interalliée. The Descroix-Vernier EthicScience Prize, formerly the EthicScience Prize, is awarded every two years. This year, a total of €110,000 was awarded, the highest amount awarded by a private fund to support non-animal research in France to date.

Dr Agathe Figarol, Institut FEMTO-ST, University of Franche-Comtéwon, won the Innovation category. She and her team are working on a tumor-on-chip project to fight glioblastoma multiforme, the most common and most aggressive brain tumor.
Dr Julien Marie and Sophie Léon, Cancer Research Center of Lyon, won the Development and Applicability category. Their innovative method makes it possible to maintain the biological integrity of tumors and cellular interactions ex vivo.
Dr Nicolas Aznar, Cancer Research Center of Lyon, won the Jury’s Prize category. He and his team aim to generate patient-derived organoid cultures with a standardized and more reliable approach to improve the development of antitumor drugs.

The next Descroix-Vernier EthicScience Prizes will be awarded in February 2025, with applications to open at the start of 2024.

OECD calls for financial support of validation of new approach methodologies

2023-02-01

The Working Party of National Coordinators of the Test Guidelines Programme (WNT) of the Organisation for Economic Co-operation and Development (OECD) has called for “urgent mobilisation of national and regional resources for the demonstration of reproducibility and reliability of methods developed in single laboratories.” In a statement, the WNT notes a lack of funding for studies to demonstrate transferability and reproducibility of a new chemical safety testing method outside the developer’s laboratory. Lack of funding for such validation studies is hindering progress toward implementation of new methods with the potential to reduce use of laboratory animals and better protect human health and the environment. Read the full statement and learn more about the OECD Test Guidelines Programme at https://www.oecd.org/chemicalsafety/testing/.

New IUCLID pharmaceutical datasets support alternatives to animal testing

2023-01-26

ECHA has published IUCLID structured datasets for 348 approved pharmaceuticals, with results from non-clinical animal studies and human information. The new datasets offer robust pharmaceutical information for industry and research in a structured format. They support toxicity assessment of structurally similar chemicals with the goal of reducing the need for animal testing. They can also be used to develop predictive models and to analyse correlations based on animal and human data. Users can assess the relevance of animal models to humans by comparing results of animal tests with effects in humans. 

The datasets were built by extracting animal and human data from files provided by the United States’ Food and Drug Administration. These included studies related to carcinogenicity as well as repeat-dose, developmental and reproductive toxicity. They also have information on the effects medicines have on humans, extracted from standard product labels of approved drugs. 

Later in 2023, a total of 530 datasets for pharmaceuticals will be available. A scientific paper will also be published later this year to explain their development and architecture.

Passage of FDA Modernization Act 2.0 eliminates mandatory animal testing for new drugs

2023-01-12

The FDA Modernization Act 2.0 was unanimously passed through the United States Senate on September 29, 2022, and officially passed through the United States House of Representatives on December 23, 2022 and was signed into law by President Joe Biden. It is a bipartisan bill, sponsored by both the Republican Party and Democratic Party. The FDA Modernization Act 2.0 removes a requirement from the original Food, Drug, and Cosmetic Act of 1938 (FDCA) that mandates animal testing for new drugs approved by FDA and includes a provision to eliminate a similar mandate for biosimilars regulated by the U.S. Public Health Service.

This bill also introduced $5 million to support an FDA alternative methods program to reduce animal testing.

EPA updates NAMs resources

2023-01-10

The U.S. Environmental Protection Agency (EPA) Office of Research and Development announces availability of new and updated resources for NAMs development.

Regular updates on EPA NAMs activities are distributed via the NAMs Update email list. To subscribe, visit https://public.govdelivery.com/accounts/USEPAORD/subscriber/new.

FDA issues final guidance on carcinogenicity testing

2022-12-22

In a November 2 Federal Register notice (available at https://www.federalregister.gov/d/2022-23787), the U.S. Food and Drug Administration (FDA) announced availability of a final guidance document, “S1B(R1) Addendum to S1B Testing for Carcinogenicity of Pharmaceuticals.” The guidance was prepared under the auspices of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, and offers an integrative approach that provides specific weight-of-evidence criteria that inform whether a 2-year rat study is likely to add value in completing a human carcinogenicity risk assessment. This final guidance considered comments received from the public in response to release of the draft guidance in October 2021, and is available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/s1br1-addendum-s1b-testing-carcinogenicity-pharmaceuticals.

Slides and video available from SACATM Meeting and Population Variability Symposium

2022-12-22

The Scientific Advisory Committee on Alternative Toxicological Methods (SACATM) advises the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), the National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM), and the Director of the National Institute of Environmental Health Sciences (NIEHS) and NTP on the statutorily mandated duties of ICCVAM and NICEATM activities. The 2022 meeting of SACATM was held on September 21 and 22; slides and video from the meeting are available at https://ntp.niehs.nih.gov/events/past/index.html?type=SACATM. The 2023 SACATM meeting is planned for September 21-22 at NIEHS in Research Triangle Park, NC. Information about the meeting will be posted at https://ntp.niehs.nih.gov/events/sacatm/index.cfm as it becomes available.

Slides and video are also now available for an October 26-27 NICEATM symposium webinar on “Using New Approach Methodologies to Address Variability and Susceptibility Across Populations.” Visit https://ntp.niehs.nih.gov/go/popvar to access meeting materials. For information about other upcoming NICEATM and ICCVAM events, visit https://ntp.niehs.nih.gov/go/3Rs-wksps.

Lush Prize 2022 winners

2022-12-06

Lush Prize has announced the 2022 winners. The £250,000 prize was shared across seven categories (two of which are non-financial) - 14 winners from 11 countries. You can learn more about all the winners and see videos about their projects or watch a recording of the online awards ceremony.

Winners of the Lush Prize 2022:
Andrew Tyler Award (non-financial) - Dr Gill Langley, UK

Lobbying Prize - £50,000 - The New Zealand Anti-Vivisection Society for work to end the Forced Swim Test

Political Achievement Award (non-financial) - joint winners:
Tilly Metz, Member of the European Parliament, Luxembourg
In-soon Nam, National Assembly, South Korea
Jytte Guteland, Member of Parliament, Sweden

Public Awareness Prize - £50,000 - Carlota Saorsa & Dr Carlos Contreras, Spain - Undercover investigation at Vivotecnia laboratory

Science Prize - £50,000 - The Acute Systemic Toxicity team within RTI International, USA - Mapping mechanistic pathways of acute oral systemic toxicity using chemical structure and bioactivity measurements

Training Prize - joint winners, £25,000 each
1: University of Sarajevo Veterinary Faculty, Bosnia and Herzegovina - Dual Education System as a New Tool for Improving Practical Skills and Vocational Training of Veterinary Medicine Students.
2: Ärzte gegen Tierversuche, Germany - NAT-Database: Raising public awareness for Non-Animal Technologies to promote a human-based research generating human-relevant results

Young Researcher Award - £10,000 each
1: Artur Silva, Federal University of Goiás, Brazil - Lung-sens-on-a-chip model for mechanistic assessment of chemically-induced pulmonary sensitization: Providing building blocks for the respiratory allergy AOP
2: Prof. Dr. Francesca Grisoni, Eindhoven University of Technology, Netherlands - Combining artificial intelligence and human organoids for animal-free drug discovery: towards a paradigm shift.
3: Dr Arthur de Carvalho e Silva, University of Birmingham, UK - Integrating physiologically-based pharmacokinetic modelling and ‘omics data to derive health-based guidance values for perfluorinated chemicals.
4: Dr Sudeep Joshi, The Francis Crick Institute and King's College London, UK - A robotic process automation system for biomanufacturing animal-free in-vitro 3D tissue and organoid models for drug screening.
5: Dr Shagun Krishna, National Toxicology Program, National Institute of Environmental Health Sciences - Computational Cardiotoxicology: Building an AI-assisted alternative method-based toxicity screening pipeline.

Animal Welfare Information Center updates 3Rs literature search guidance

2022-11-30

The Animal Welfare Information Center (AWIC) within the National Agricultural Library of the U.S. Department of Agriculture has updated its 3Rs literature search webpage to help scientists find alternatives to replace, reduce, and refine animal use for research and testing. AWIC provides this information to help those conducting animal research comply with Animal Welfare Act requirements for consideration of alternatives. The 3Rs literature search webpage includes step-by-step instructions for conducting a literature search, literature search examples, worksheets and guides, and frequently asked questions.

Eurogroup for Animals publishes position paper on transition to non-animal science

2022-11-30

The position paper published in November 2022 reflects the key elements that Eurogroup for Animals would like to see included in a European-wide strategy for the transition to non-animal science. These include a clear statement that transitioning to non-animal science is a desirable and achievable goal, along with a strong commitment to work to get there; clear milestones; identification and prioritisation of key reserach areas where resources and efforts need to be targeted; an appropriate level of funding to support the development and uptake of new, advanced non-animal technologies; large scale support for building key infrastructure that would allow fuller exploitation of existing and new alternative methods; education and training in non-animal technologies; and more robust project evaluation and authorisation processess, and peer review and publication policies from scientific journals.

Alternative approach for carcinogenicity testing of pharmaceuticals implemented as ICH S1B(R1) addendum

2022-11-18

The International Council for Harmonisation (ICH) has integrated an addendum to the carcinogenicity testing guideline (ICH S1B) that describes an integrative weight of evidence approach as an alternative to conducting a two-year rat carcinogenicity study for assessing the human carcinogenic risk of pharmaceuticals. Application of this mechanism-based approach reduces the use of animals in the development of new pharmaceuticals. The development of the addendum was motivated by an improved understanding of the mechanisms of carcinogenicity, the limitations of rodent models, and retrospective analyses of pharmaceutical datasets on the value of the 2-year rat carcinogenicity study on risk assessment. These lead to an international prospective study under ICH S1(R1) Proposed Change to Rodent Carcinogenicity Testing of Pharmaceuticals – Regulatory Notice Document. The full process is described on the ICH website.

The new version of the guideline was implemented by Swissmedic, Switzerland on August 4, 2022; by FDA, US on November 2, 2022 (Federal Register Vol. 87, No. 211, p. 66195-66197) and by the EMA, EU on March 16, 2023 (EMA/774371/2022).

New book on balancing interests in animal experiments

2022-11-18

The Swiss foundation Stiftung für das Tier im Recht has published its latest book in the series Schriften zum Tier im Recht (Writings on the Animal in the Law). The book Güterabwägung im Tierversuchsbewilligungsverfahren (available only in German) by Dr. iur. Vanessa Gerritsen, published as volume 23, presents a comprehensive review of Swiss animal experimentation law and critically examines the strict Swiss legeal situation and its current approval practice. The book shows the various weak points in a well-founded manner and offers considerations, which, due to the analogous questions, can to a large extent be internationalized. A brief summary in English is provided.

The book "Güterabwägung im Tierversuchsbewilligungsverfahren" (book available in German only) presents a comprehensive review of Swiss animal experimentation law and critically examines the strict Swiss legal situation and its current approval practice. The book shows the various weak points in a well-founded manner and offers considerations which, due to the analogous questions, can to a large extent be internationalized.

Read more at: https://www.tierimrecht.org/en/news/2022-11-16-new-reference-work-on-the-balancing-of-interests-in-animal-experiments/ The book "Güterabwägung im Tierversuchsbewilligungsverfahren" (book available in German only) presents a comprehensive review of Swiss animal experimentation law and critically examines the strict Swiss legal situation and its current approval practice. The book shows the various weak points in a well-founded manner and offers considerations which, due to the analogous questions, can to a large extent be internationalized.

Read more at: https://www.tierimrecht.org/en/news/2022-11-16-new-reference-work-on-the-balancing-of-interests-in-animal-experiments/ The book "Güterabwägung im Tierversuchsbewilligungsverfahren" (book available in German only) presents a comprehensive review of Swiss animal experimentation law and critically examines the strict Swiss legal situation and its current approval practice. The book shows the various weak points in a well-founded manner and offers considerations which, due to the analogous questions, can to a large extent be internationalized.

Read more at: https://www.tierimrecht.org/en/news/2022-11-16-new-reference-work-on-the-balancing-of-interests-in-animal-experiments/ The book "Güterabwägung im Tierversuchsbewilligungsverfahren" (book available in German only) presents a comprehensive review of Swiss animal experimentation law and critically examines the strict Swiss legal situation and its current approval practice. The book shows the various weak points in a well-founded manner and offers considerations which, due to the analogous questions, can to a large extent be internationalized.

Read more at: https://www.tierimrecht.org/en/news/2022-11-16-new-reference-work-on-the-balancing-of-interests-in-animal-experiments/

Online Community of Practice on human-relevant research launched

2022-11-08

The Alliance for Human Relevant Science and Animal Free Research UK have launched an online Community of Practice to improve communication among biomedical scientists from around the world and bring them together to practice human-relevant research. The platform is curated by members and Animal Free Research UK coordinators. Academic researchers, early career scientists, students, industry experts and other stakeholders involved in biomedical research sector can interact online as well as attend planned events. Members are invited to add content, create, share events and resources, and to collaborate on projects such as writing reviews, articles and more. Membership is free.

Some of the activities include:

  • Networking
  • Forum discussion
  • Organising and promoting events
  • Sharing resources
  • Building new collaborations
  • Circulating information
  • Sharing and discussing negative results

 For more information, please contact Lilas Courtot - Lilas@animalfreeresearchuk.org

NC3Rs provides online tool to self-assess institutional 3Rs strategy

2022-11-02

The NC3Rs have developed a free online tool to help you self-assess and develop an institutional 3Rs strategy. The tool supports you to confidentially review your current 3Rs practices, giving tailored feedback on how you can prioritise and strengthen the 3Rs environment in your institution. It is designed to be practical and informative and suggests positive steps for putting the 3Rs into practice. To follow on from your self-assessment, guidance on developing and implementing an institutional 3Rs strategy has been developed.

ALTEX to cooperate with OECD on adverse outcome pathway (AOP) development

2022-10-27

ALTEX and the OECD have signed a memorandum of understanding on on co-operative activities in the field of adverse outcome pathway (AOP) development aiming to increase the number of AOPs developed, reviewed and published. ALTEX joins Environmental Toxicology and Chemistry and Environmental and Molecular Mutagenesis in signing a MOU with the OECD in this initiative.

ALTEX will coordinate the review of adverse outcome pathways submitted to the AOP-Wiki and publish manuscripts generated within this process as AOP Reports. An AOP Report in ALTEX provides an overview of an AOP description, which conforms with AOP development principles described in the Developers' Handbook and has been entered into the AOP-Wiki (https://aopwiki.org/), and describes its 3R relevance and potential application. Instructions for authors on submitting AOP Reports can be found on the ALTEX website.

3R articles for kids published

2022-10-12

Frontiers for Young Minds published three articles dealing with each of the 3Rs, i.e. replacement, refinement and reduction on October 11, 2022. Earlier this year, the 3Rs were introduced to young minds from the International School of Lausanne in an event sponsored by the Swiss 3RCC. The lead authors of each article presented the 3Rs to the students, and the students then learned to act as peer reviewers. The articles aim to inform children and encourage critical thinking.

Replacing animal testing - Can we and if so, how and when? doi:10.3389/frym.2022.959496
Refining research to improve the lives of laboratory mice. doi:10.3389/frym.2022.954413
Reducing the number of research animals: how imaging technologies can help. doi:10.3389/frym.2022.953662

 

OPERA now accessible via QSAR Toolbox

2022-10-10

The Open (Quantitative) Structure-activity/property Relationship App is now available as an extension to the OECD QSAR Toolbox. The Toolbox was co-developed by OECD and the European Chemicals Agency to support animal-free chemical hazard assessment. QSAR Toolbox is available at https://qsartoolbox.org/. The OPERA extension is available at https://repository.qsartoolbox.org/Tools/Details/6703ab01-9529-4f86-814f-6efc49e1f59c.

OPERA is a free and open-source/open-data suite of quantitative structure-activity relationship (QSAR) models that provides predictions for physicochemical properties, environmental fate parameters, ADME, and toxicity endpoints. OPERA is an ongoing collaboration between NICEATM and EPA and is being constantly being maintained and updated with additional models, data, and features. For more information about OPERA visit https://ntp.niehs.nih.gov/whatwestudy/niceatm/comptox/ct-opera/opera.html.

Apply for a free recombinant antibody via the Recombinant Antibody Challenge

2022-10-06

The PETA Science Consortium International, the Physicians Committee for Responsible Medicine, and the Alternatives Research and Development Foundation are offering grants for free catalogue recombinant antibodies for use in research and testing. Applications will be reviewed on a rolling basis. Click here for more information and to apply. 

Emulate launches online forum for researchers using organ chips

2022-07-12

Emulate is launching Moxi, a social network for organ-on-chip technology. Moxi is a community for researchers, by researchers, designed as a platform dedicated to connecting with peers, keeping up with the latest news, and collaborating to accelerate science into a new era.

For more information, visit https://emulatebio.com/announcing-moxi/?utm_campaign=Moxi&utm_content=209946475&utm_medium=social&utm_source=twitter&hss_channel=tw-2670800390 and see how you can win an iPad Air or a paid trip to the 2023 MPS World Summit in Berlin through the Organ on Chip image competition.

All submissions and voting will take place here: https://woobox.com/yp7ysd. Visit moxicentral.com to View Trending Topics, Explore Conversations of Interest, view entry requirements, and to join the discussion.

OECD publishes defined approaches for serious eye damage and eye irritation, stand-alone SkinEthic™ eye irritation test, GARD™skin assay

2022-07-04

On June 30, 2022, the OECD published new Test Guidelines (TGs).

While the first defined approaches were published on skin sensitization (OECD TG 497) in 2021, the new OECD TG 467 describes defined approaches for serious eye damage and eye irritation using new approach methodologies (NAMs). The methods used in the defined approaches, DAL-1 and DAL-2, encompass the Bovine Corneal Opacity and Permeability (BCOP) using the laser light-based opacitometer according to the OECD TG 437, the Reconstructed human Cornea-like Epithelium (RhCE) according to the OECD TG 492B, see below, and the Short Time Exposure in vitro (STE) according to the OECD TG 491.

OECD TG 492B describes the SkinEthic™ Human Corneal Epithelium (HCE) Time-to-Toxicity (TTT) test using a commercially available reconstructed HCE that discriminates the three UN GHS categories for serious eye damage/eye irritation, i.e. UN GHS Cat. 1, Cat. 2 and No Cat chemicals. It is recommended as a full replacement to the in vivo Draize acute eye irritation test for classification of chemicals.

OECD TG 442E, which describes in vitro assays that address mechanisms described under the key event on activation of dendritic cells of the AOP for skin sensitisation, was updated to include the Genomic Allergen Rapid Detection (GARD™) for assessment of skin sensitisers (GARD™skin) in addition to the Human Cell Line Activation test (h-CLAT), U937 cell line activation Test (U-SENS™), and Interleukin-8 Reporter Gene Assay (IL-8 Luc assay). The GARD™skin assay is the first harmonized method to use gene expression as a regulatory endpoint.

New non-animal Test Guidelines:  

  • TG 467: Defined Approaches for Serious Eye Damage and Eye Irritation
  • TG 492B: Reconstructed Human Cornea-like Epithelium (RHCE) Test Method for Eye Hazard Identification - an in vitro procedure for the identification on its own of chemicals (substances and mixtures) according to the UN GHS ocular hazard categories.
  • TG 251: Rapid Androgen Disrupter Activity Reporter (RADAR) assay - an aquatic assay that utilizes transgenic Oryzias latipes (Japanese medaka) eleutheroembryos to detect chemicals active on the androgen axis.

  
Corrections and updates:  

  • TG 442C: In Chemico Skin Sensitisation - includes updates on the amino acid derivative reactivity assay (ADRA) for skin sensitization and includes updated performance standards for the direct peptide reactivity assay (DPRA) and ADRA.
  • TG 442D: In Vitro Skin Sensitisation - minor text corrections to clarify a discrepancy regarding controls.
  • TG 442E: In Vitro Skin Sensitisation - updated to include the GARD™skin assay.
  • TG 456: H295R Steroidogenesis Assay - amendments to the data interpretation procedure.

Consult OECD Guidelines for the Testing of Chemicals for Health Effects (Section 4) and Effects on Biotic Systems (Section 2) for further OECD test guidelines.

Remembering Toni Lindl

2022-05-30

Prof. Toni Lindl passed away on May 12, 2022 in Munich. He studied chemistry and biology at the Technical University Munich and University of Freiburg and later worked at the universities of Konstanz and Bonn. Toni Lindl established the Institut für Angewandte Zellkultur – I-A-Z (Institute for Applied Cell Culture) in Munich in 1981 and became a professor at the University of Applied Sciences Weihenstephan in 1990. In 1987 Toni Lindl published the standard textbook Zell- und Gewebekultur (Cell and Tissue Culture), which is currently in its 8th edition. Alternatives to animal experimentation were a central interest of Toni Lindl’s on which he published important contributions, also in ALTEX. We will miss Prof. Toni Lindl and continue to honor his contributions to cell and tissue culture.

Gerhard Gstraunthaler

Microphysiological World Summit Abstract Book published

2022-05-26

ALTEX Proceedings has published the Abstract Book of the 1st Microphysiological World Summit, which will take place in New Orleans, LA, USA from May 30 to June 3, 2022.

We wish all participants a successful and inspiring meeting that will initiate new collaborations in this auspicious and exciting field of research, which holds so much promise to reduce and replace the use of animals for scientific purposes and to improve the health and safety of humans.

NC3Rs seeks to connect you with 3Rs technology developers via konfer platform

2022-04-29

The NC3Rs konfer platform provides a range of opportunities to collaborate with small companies and academic researchers who have developed new 3Rs technologies. This could include providing data for validation, using the technology in your lab, or supporting its further dissemination – ultimately, increasing the 3Rs impact of these new tools and approaches. If you are interested in any of the current opportunities, you can connect with the featured teams via konfer.

If you have developed a 3Rs technology you would like to showcase, email the NC3Rs at enquiries@nc3rs.org.uk to find out how they can help you find new collaborators.

EURL ECVAM issue Status Report on Alternative Methods

2022-04-14

The European Union Joint Research Centre for Alternatives to Animal Testing (EURL ECVAM) has issued its 2021 “Status Report on the Development, Validation and Regulatory Acceptance of Alternative Methods and Approaches.” The report is available at https://publications.jrc.ec.europa.eu/repository/handle/JRC127780. A news article announcing availability of the report is posted at https://joint-research-centre.ec.europa.eu/jrc-news/jrc-supporting-alternatives-animal-testing-2022-04-07_en.

The report describes research, development, and validation activities, as well as initiatives that promote the regulatory and international adoption and use of alternative approaches and their dissemination. Activities described in the report include:

  • Development of NAMs to identify chemicals with potential endocrine activity.
  • Exploration of approaches to replace, reduce, or refine animal use for batch testing of vaccines.
  • Evaluation of methods to identify potential genotoxins and sensitizers.

EURL ECVAM, which is part of the European Commission's Joint Research Centre, coordinates research and validation studies on alternatives to animal testing within the European Union. EURL ECVAM also shares knowledge about and promotes use of alternative methods.

NICEATM releases ICE 3.6

2022-04-12

On March 24, NICEATM released version 3.6 of the Integrated Chemical Environment (ICE). ICE provides data and tools to help develop, assess, and interpret chemical safety tests. This release adds new features to ICE tools, improves usability of ICE data, and adds a new reference Chemical Quick List. ICE is available at https://ice.ntp.niehs.nih.gov/.

Tool improvements in ICE version 3.6 include:

  • Ability to limit Chemical Quest searches to chemicals in user-defined lists.
  • New viewing options in Curve Surfer.
  • New filtering options in Curve Surfer and Chemical Quest Results views.
  • Updated view for uploading custom in vivo and in vitro data in the IVIVE tool.

Additions or improvements to data include:

  • Quality control annotations for curated high-throughput screening HTS data.
  • References for acute oral toxicity data.
  • New endpoints for skin sensitization data.
  • Addition and harmonization of endocrine data.
  • Downloadable flat files for all data sets available on the Data Sets page (https://ice.ntp.niehs.nih.gov/DATASETDESCRIPTION).
  • New reference Chemical Quick Lists for Cancer and Non-Cancer Assessment.

ECEAE awards first prize for animal-free antibodies

2022-04-10

The European Coalition to End Animal Experiments (ECEAE) awarded the first prize in the world dedicated to the development and application of animal-free antibodies on March 30, 2022. The two winners from Germany and Switzerland, who received €10.000 each, presented their extraordinary contributions to the field of non-animal antibodies. The event also featured talks and discussions about the importance of animal-free antibody production by members of the EU Parliament and the EURL ECVAM’s Joint Research Centre (JRC).

One award winner is the company Abcalis GmbH from Braunschweig, Germany, which is one of the pioneers in animal-free antibody production via state-of-the-art phage display technology. At the award ceremony, Abcalis’ co-founder, Dr Esther Wenzel, spoke about the company’s projects aiming to replace the largest group of animal-derived antibodies with superior, widely affordable, vegan “multiclonal” antibodies.

The other prize was awarded to Prof. Dr Pierre Cosson and his colleagues at the Geneva Antibody Facility at the University of Geneva, Switzerland. In their freely accessible ABCD database, the winners list thousands of recombinant animal-free antibodies, which are made available to all interested researchers. Dr Cosson and his colleagues also created the open access scientific journal “Antibody Reports”.

The internationally attended award ceremony was opened with welcome notes from ECEAE’s member of the board, Dr Corina Gericke. The event featured talks from two invited speakers, Tilly Metz, MEP from the Group of the Greens, and Joao Barroso, a member of the Joint Research Centre (JRC) of the European Commission and EURL ECVAM. The speakers endorsed the need to move away from animal-derived antibodies and explained how this can be achieved in the EU.

ECEAE encourages all biomedical researchers to adopt the use of animal-free antibodies and reagents in their work and urges the EU Commission, as well as individual member states to implement ECVAM’s “Recommendation on non-animal-derived antibodies”.

Helena Kandárová wins the Björn Ekwall Memorial Award

2022-04-04

Björn Ekwall Memorial Foundation Award committee has announced that the winner of the 2022 Björn Ekwall Memorial Award (BEMA) is Dr Helena Kandárová, a senior scientist at the Institute of Pharmacology and Toxicology, Centre of Experimental Medicine, Bratislava, Slovakia and ESTIV president. In the words of the committee, she is awarded the prize in recognition of her active involvement in the development, validation, and subsequent implementation of in vitro tests through acceptance in OECD, EU and other test guidelines. Her work on 3D-reconstructed human tissue models for topical toxicity and phototoxicity testing of chemicals, cosmetics, pesticides and medical devices has substantially contributed to the replacement of animal experiments.

The award will be presented at the BEMA ceremony at the ESTIV 2022 Congress followed by BEMA lecture of the awardee.

FRAME seeks applications for Innovation grants

2022-04-02

FRAME has launched the annual Innovation grant scheme to address a gap for small funding pots for proof of principle research and pilot projects. The Scheme offers grants of around £5,000 but will consider applications asking up to £15,000. Projects should last for between 6 months and 2 years. The first year of this scheme proved very popular and we funded some diverse and interesting projects.

FRAME exists to promote better science and a more humane and compassionate society by the replacement of animals in medical experiments, drug development and testing.

FRAME believes that the accepted practice of using animals for researching human drugs and diseases is fundamentally flawed; however viable human-focussed methods do not yet exist in all areas.

We accept that the path to animal-free medical research, drug development and testing will be long.  It requires both the existence of suitable alternative methods, and culture change by scientists, regulators, funders, and journals.

The Innovation Grants are a pilot project funding stream designed to provide small grants to enable scientists to explore innovative ideas, methods and techniques, and where relevant help generate proof of principle data to support applications for larger grants in the future.

Closing date for round 1 applications: Sunday 7th August 2022

Provisional dates for next stages:

  • Invitations for round 2 will be sent out: First week of September 2022
  • Deadline for round 2 applications: 1st October
  • Announcements of winners: First week of November

3RCC 2021 awards presented to Bernhard Voelkl and Pauline Zamprogno

2022-03-21

The Swiss 3RCC has awarded Bernhard Voelkl from the Vetsuisse Faculty of the University of Bern the 2021 3Rs Award in recognition of his work supporting researchers to better design animal studies to improve research quality and reduce animal use. The 2021 Young 3Rs Investigator Award went to Pauline Zamprogno from the ARTORG Center for Biomedical Engineering Research, also at the University of Bern, for her contribution to a lung-on-chip model, which aims at replacing animals testing. With their research the awardees not only help promote the 3Rs principle, they communicated their projects in an exemplary manner to encourage other researchers to adopt these novel approaches in their work. The jury consisted of independent external experts from the Charité 3Rs (Berlin, DE) and the North American 3Rs Collaborative/University of Washington (USA) as well as from the Swiss Federal Food Safety and Veterinary Office (FSVO). The jurors emphasised the importance of comprehensive communication as demonstrated by the award winners. The 3Rs Award 2021 and Young 3Rs Investigator Award recipients will receive CHF 4,000 and CHF 1,000 respectively to acknowledge their work in advancing the 3Rs. Furthermore, they will get the opportunity to present their awarded research at the Swiss 3Rs Day 2022 and in a featured video. More information.

ECHA seeks feedback on initiative to delete six animal tests from REACH Annex and update methods list

2022-03-18

The European Chemicals Agency has launched an initiative for which it requests feedback by April 7, 2022. The initiative is an amendment to Regulation (EC) No 440/2008, which lays down test methods pursuant to Regulation (EC) no 1907/2006 (The REACH Regulation).
The proposed amendment recognizes that there have been delays in adapting the Regulation to scientific progress with regard to aligning the accepted methods with up-to-date versions and adding new international test methods. It further recognizes that such delays could hinder the replacement of animal experiments with methods that do not entail the use of a live animal, which is a legal obligation under Directive 2010/63/EU once such methods are adopted at international level.
The initiative includes a table of updated test methods and proposes to delete six animal methods no longer considered appropriate from the Annex. The methods to be deleted are:
B.22. Rodent dominant lethal test;
B.25. Mouse heritable translocation;
B.34. One-generation reproductive toxicity study;
B.35. Two-generation reproductive toxicity study;
B.39. Unscheduled DNA synthesis (UDS) test with mammalian liver cells in vivo;
C.15. Fish, Short term toxicity test on Embryo and Sac Fry Stages.

The table of updated test methods includes test methods for physicochemical, toxicological and ecotoxicological properties adopted up to 2021. The test methods for toxicological and ecotoxicological properties include in vitro and in vivo OECD test guidelines. Current in vitro OECD test guidelines adopted in 2021, which are included in the table, are:
OECD TG 439: In vitro Skin Irritation: Reconstructed Human Epidermis Test Method (2021),
OECD TG 494: Vitrigel Eye Irritancy Test (2021),
OECD TG 442C: In chemico skin sensitisation: Direct peptide reactivity assay (DPRA) (2021),
OECD TG 497: Defined Approaches on Skin Sensitization (2021),
OECD TG 406: Skin sensitisation (2021),
OECD TG 498: In vitro phototoxicity test method using the Reconstructed human Epidermis (RhE) (2021)
OECD TG 249: Fish cell line acute toxicity - the RTgill-W1 cell line assay (2021)

EPA announces collaborative research program to support new chemical reviews

2022-02-25

On Feb. 24, 2022, the U.S. Environmental Protection Agency (EPA) announced a new effort under the Toxic Substances Control Act (TSCA) to modernize the process and bring innovative science to the review of new chemicals before they can enter the marketplace.

Through this effort, the Office of Chemical Safety and Pollution Prevention (OCSPP)is proposing to develop and implement a multi-year collaborative research program in partnership with the Agency’s Office of Research and Development (ORD) and other federal entities focused on approaches for performing risk assessments on new chemical substances under TSCA. The results of the effort are expected to bring innovative science to new chemical reviews, modernize the approaches used, and increase the transparency of the human health and ecological risk assessment process.

“Science is the backbone of our chemical safety work, and strong science ensures we put measures in place to protect human health and the environment, when necessary,” said Assistant Administrator for the Office of Chemical Safety and Pollution Prevention Michal Freedhoff. “This exciting and collaborative effort announced today will modernize the processes and bring innovative science into the evaluation of new chemicals under TSCA, leading to a more sustainable program.”

“This collaborative effort between OCSPP and ORD will draw on ORD’s innovative science, expertise, and leadership in relevant areas such as high-throughput testing, computational toxicology and exposure approaches, and development of databases and tools to make data accessible and informative for chemical assessments. Work on this collaborative effort furthers ORD’s commitment to translating research into application and is complementary to efforts on EPA’s New Approach Methods Work Plan,” said Deputy Assistant Administrator for Science Policy in the Office of Research and Development Chris Frey.

EPA is holding a virtual public meeting on April 20 and 21, 2022, from 1:00 PM to approximately 5:00 PM (EDT) to provide an overview of the TSCA New Chemicals Collaborative Research Program and give individual stakeholders an opportunity to provide input. 

Prior to the public meeting, EPA will release a draft document describing this collaborative research program for a 60-day public comment period. Following the public meeting, EPA intends to update the draft document as appropriate and will place the updated document in the docket. Later in 2022, the Agency plans to release a revised version of the collaborative research plan for an additional public comment period and peer review by the Board of Scientific Counselors (BOSC).

This multi-year research program will refine existing approaches and develop and implement new approach methodologies (NAMs) to ensure the best available science is used in TSCA new chemical evaluations. Key areas proposed in the TSCA New Chemicals Collaborative Research Program include:

  • Updating OCSPP’s approach using data from structurally similar chemicals to determine potential risks from new chemicals, also known as read-across. This will increase the efficiency of new chemical reviews promoting the use of the best available data to protect human health and the environment.
  • Digitizing and consolidating information on chemicals to include data and studies that currently only exist in hard copy or in disparate TSCA databases. The information will be combined with publicly available sources to expand the amount of information available, enhancing chemical reviews and enabling efficient sharing of chemical information across EPA. Safeguards for confidential business information will be maintained as appropriate in this process.
  • Updating and augmenting the models used for predicting a chemical’s physical-chemical properties and environmental fate/transport, hazard, exposure, and toxicokinetics to provide a suite of models to be used for new chemicals assessments. The goal of this effort is to update the models to reflect the best available science, increase transparency, and establish a process for updating these models as science evolves.
  • Exploring ways to integrate and apply NAMs in new chemicals assessments, reducing the use of animal testing. As this effort evolves, the goal is to develop a suite of accepted, fit-for-purpose NAMs that could be used by external stakeholders for data submissions under TSCA as well as informing and expanding new chemical categories. 
  • Developing a decision support tool that integrates the various information streams specifically used for new chemical risk assessments. The decision support tool will more efficiently integrate all the data streams (e.g., chemistry, fate, exposures, hazards) into a final risk assessment and transparently document the decisions and assumptions made. Simply put, this will facilitate the new chemicals program tracking decisions over time and evaluating consistency within and across chemistries.

Register for the public meeting.

Learn more about the Collaborative Research Program to Support New Chemical Reviews.

SOT session on cross-species extrapolation: Input requested from members

2022-02-25

A session titled “Cross-Species Extrapolation: Opportunities in a 21st-Century Regulatory Nonanimal Testing World” is planned for Tuesday, March 29 during the upcoming annual meeting of the Society of Toxicology (SOT). Four invited speakers will share their views on the changing regulatory context that provides opportunities for cross-species extrapolation to inform a nonanimal testing paradigm for assessing human and environmental health. The session will be held as a roundtable to encourage discussion between researchers and regulators.

The session is being organized by the SOT Sustainable Chemistry through Contemporary Toxicology Specialty Section, the In Vitro and Alternative Methods Specialty Section, and the Women in Toxicology Special Interest Group. The session organizers invite interested SOT members to provide their opinions on the opportunities and challenges of using cross-species extrapolation and bioinformatics to support regulatory decision-making. More information and a link to the survey can be found at http://SocietyOfToxicology.informz.net/z/cjUucD9taT0yNDMyNjE5JnA9MSZ1PTUyMTAzNzM5MCZsaT0yNDIxNDIzNQ/index.html. Please respond by March 1.

JRC report discusses evidence needs for chemicals policy development

2022-02-16

The European Union Joint Research Centre has issued a report, “Addressing Evidence Needs in Chemicals Policy and Regulation.” The report provides insights into key stakeholder perceptions of the main challenges facing chemicals regulation. It also examines stakeholder views on alternative approaches to conducting toxicological studies and the role and value of the adverse outcome pathway framework. The report puts forward a set of actionable recommendations including how knowledge management systems can be designed in a user-centric fashion to address current challenges. It is available at https://publications.jrc.ec.europa.eu/repository/handle/JRC126724. The Joint Research Centre is planning a webinar in March to raise awareness of the report.

Grants offered for US Cancer Tissue Engineering Collaborative Research Program

2022-02-16

The National Cancer Institute is offering grants to support the development and characterization of state-of-the-art biomimetic tissue-engineered technologies for cancer research. Projects supported by this funding will become part of the Cancer Tissue Engineering Collaborative (TEC) Research Program. The goals of the Cancer TEC Program are to (1) catalyze the advancement of innovative, well-characterized in vitro and ex vivo systems available for cancer research, (2) expand the breadth of these systems to several cancer types, and (3) promote the exploration of cancer phenomena with biomimetic tissue-engineered systems.

Applications for funding will be accepted beginning on May 5, with applications due June 5 and quarterly thereafter through February 2025. Grants of up to $400,000 will be awarded to fund projects that can continue up to five years. Eligibility for these grants is open to for-profit and nonprofit institutions within and outside the United States. For more information about the grants and instructions on how to apply, visit https://grants.nih.gov/grants/guide/pa-files/PAR-22-099.html. More information about the Cancer TEC Program is available at https://www.cancer.gov/about-nci/organization/dcb/research-programs/tec.

Amy Clippinger receives SOT Enhancement of Animal Welfare Award

2022-01-24

Amy J. Clippinger, PhD, President of PETA Science Consortium International e.V., has received the 2022 SOT Enhancement of Animal Welfare Award to honor her extensive efforts to develop and integrate predictive methods that advance toxicology while reducing and replacing animal use.

Her recent articles published in ALTEX are:

Groff, K., Allen, D., Casey, W. and Clippinger, A. J. (2020). Increasing the use of animal-free recombinant antibodies. ALTEX 37, 309-311. doi:10.14573/altex.2001071

Brown, J., Clippinger, A. J., Fritz Briglia, C., Casey, W., Coleman, K., Fritsch, A., Hartung, T., Maouyo, D., Muller, T., Reich, J., Robert, L., Roeder, R., Sanchez, G., Sawyer, A. Y., Solati, S., Tirumalai, R., Zwisler, W. and Allen, D. (2021). Using the monocyte activation test as a stand-alone release test for medical devices. ALTEX 38, 151-156. doi:10.14573/altex.2012021

Petersen, E. J., Nguyen, A., Brown, J., Elliott, J. T., Clippinger, A. J., Gordon, J., Kleinstreuer, N. and Roesslein, M. (2021). Characteristics to consider when selecting a positive control material for an in vitro assay. ALTEX 38, 365-376. doi:10.14573/altex.2102111

Sullivan, K. M., Allen, D. G., Clippinger, A. J., Wilson, D. M., Edwards, S. W., Glover, K., Mansouri, K., Settivari, R., Wijeyesakere, S. J. and Casey, W. (2021). Mind the gaps: Prioritizing activities to meet regulatory needs for acute systemic lethality. ALTEX 38, 327-335. doi:10.14573/altex.2012121

Helena Hogberg joins NICEATM

2022-01-07

On December 6, Helena Hogberg joined NICEATM as a staff scientist at the National Institute of Environmental Health Sciences (NIEHS). Hogberg will conduct research drawing on her broad expertise in applying in vitro methods to assess developmental neurotoxicity (DNT) potential of chemicals.

Hogberg received her Ph.D. in toxicology from Stockholm University and performed her doctoral research at the European Centre for the Validation of Alternative Methods in Ispra, Italy. She developed new in vitro approaches to detect chemicals with DNT potential, focusing on gene expression and electrical activity recordings. During a postdoctoral fellowship at the Center for Alternatives to Animal Testing (CAAT), Johns Hopkins University Bloomberg School for Public Health, Hogberg explored the application of a broader set of in vitro models to DNT, including organotypic models, induced pluripotent stem cells, and transcriptomics and metabolomics approaches. After completing her fellowship, she was appointed as a research associate and later deputy director of CAAT. In these roles Hogberg administered a variety of CAAT programs and research activities and continued her own research on DNT.

Hogberg currently serves on the DNT expert group of the Organisation for Economic Co-operation and Development (OECD); the U.S. Environmental Protection Agency (EPA) Scientific Advisory Panel for the Federal Insecticide, Fungicide, and Rodenticide Act; the EPA expert group on new approach methodologies (NAMs) for DNT assessment; and the Scientific Advisory Board for the European Commission-funded Horizon 2020 grant, “Novel Testing Strategies for Endocrine Disruptors in the Context of Developmental NeuroToxicity (ENDpoiNTs).”

Videos available from September 2021 SACATM Meeting

2022-01-07

Videos from the September 28-29 meeting of the Scientific Advisory Committee on Alternative Toxicological Methods (SACATM) are now available at https://ntp.niehs.nih.gov/events/past/index.html?type=SACATM. Minutes from the meeting will be posted to this page following review and approval by the committee.

SACATM is a federally chartered external advisory group of scientists from the public and private sectors that advises ICCVAM, NICEATM, and the Director of the National Institute of Environmental Health Sciences and NTP regarding statutorily mandated duties of ICCVAM and activities of NICEATM. The September 2021 meeting’s agenda included detailed discussion of two topics of current interest to ICCVAM: reducing or replacing animal use for ecotoxicity testing and new approaches to validation of new testing methods.

The next SACATM meeting is scheduled for September 21-22. Information about the meeting will be posted at https://ntp.niehs.nih.gov/events/sacatm/index.cfm when it is available.

EPA drops target date to end mammalian toxicity testing by 2035

2021-12-20

In the 2021 New Approach Methods Work Plan published by US Environmental Protection Agency (US EPA) on December 12, 2021, no reference is made to the memo signed by EPA Administrator Andrew Wheeler in 2019, directing “the agency to aggressively reduce animal testing, including reducing mammal study requests and funding 30% by 2025 and completely eliminating them by 2035“. Instead, the new workplan discusses short- and long-term strategies up until 2024 to accomplish its objectives, which are specified as “to ensure its [EPA’s] regulatory framework is robust and flexible enough to accommodate the development and the use of NAMs; establish baselines, measurements and reporting mechanisms to track progress in meeting its goals; establish scientific confidence in NAMs and demonstrate application to regulatory decisions; develop NAMs that fill critical information needs; and continue to engage and communicate with stakeholders to incorporate their knowledge and address concerns as EPA moves away from vertebrate animal testing.”

According to a statement made by EPA to Inside TSCA, the deadlines were dropped because, “While the goals/dates in the original work plan may have been intended to spur focus and action, the dates themselves became the primary focus of discussion within the scientific and stakeholder communities as opposed to what actions or path the Agency should take in the near-term. As a result, the goals/dates were removed to shift the focus towards these actions as represented by the objectives, strategies, and deliverables outlined in the document”.

Similarly, in the Netherlands, The State Secretary for Economic Affairs of the Dutch government, Martijn van Dam, in 2016 expressed the ambition to phase out animal testing for research on the safety of chemicals by 2025, stating that the Netherlands wanted to be a “world leader” in innovation without the use of laboratory animals. This ambition was based on an NCad opinion. The current Minister of Agriculture, Nature and Food Quality, Carola Schouten, launched the Transition Programme for Innovation without the use of animals (TPI) in June 2018; however, as stated in a letter by Minister Schouten to the lower house of parliament in December 2018, the ambition was reformulated as ‘The Netherlands as a forerunner in the international transition with animal-free innovation’, and the target date was less strictly defined, because, „By letting go of the year, and with it resistance, progress can be made. But this does not mean that the ambition for animal-free innovation has been abandoned or lessened”.

 

NICEATM-organized workgroup supporting research efforts for COVID Omicron variant

2021-12-17

A workgroup co-organized by NICEATM and the UK National Centre for the 3Rs (NC3Rs) is coordinating activities among investigators to apply microphysiological systems (MPS) to investigations of the Omicron variant of the SARS-CoV-2 virus that causes COVID-19. Workgroup members met with representatives of the World Health Organization (WHO) on December 3 to discuss research needs relevant to the biology and treatment of Omicron and the potential for MPS to provide human-relevant platforms for rapidly addressing those needs. A spreadsheet detailing relevant research capabilities is available on the WHO website.

The MPS for COVID Research working group was established by NICEATM and NC3Rs to coordinate the use of MPS to reduce animal use in studies of COVID-19 and future emerging infectious diseases. Workgroup members include researchers, MPS model developers, therapeutic/vaccine manufacturers, and international regulators; new members are welcome.

Recordings of webinar series on replacing basement membrane extracts available

2021-12-17

This webinar series from a cross-European group of 3Rs centres, delivered during October-December 2021, aimed to explore the challenges and opportunities when it comes to replacing BMEs, from research through to application.

Reliable and reproducible in vitro models are essential for replacing the use of animals in scientific procedures. The availability of complex 3D models, including organoids and microphysiological systems, has in recent years strengthened this replacement potential. However, many in vitro models are dependent on animal-derived products, for example to support cell growth or differentiation, which can show batch-to-batch variation and can involve animal suffering in their production. Replacing these with non-animal derived products provides an opportunity to increase the reproducibility of in vitro models and remove the use of animals completely.

The series is aimed at researchers (academics, clinicians and industry), but also potentially regulators, funding organisations and publishers and is a chance to hear from experts from across the field, to pose questions and to be part of the wider discussions around the implementation of these alternatives.

NC3Rs publishes ARRIVE Action Plans for universities, journals and funders

2021-12-17

The ARRIVE guidelines – a checklist of information that should be included in all publications that describe experiments involving animals – are designed to promote transparent and accurate reporting, addressing increasing concern from researchers, funders and policy makers around the irreproducibility of animal research.

Despite the guidelines’ widespread endorsement since their original 2010 publication (by over 1,000 journals, universities, learned societies and major funders), studies show that reporting of important items found in them, including measures to reduce subjective bias of studies and improve their reliability, is still very often missing from animal research publications. These findings have driven a recent, thorough revision of the guidelines, and the development of a variety of resources designed to help put them into practice.

As part of this programme, these Action Plans lay out discrete activities that various organisations can undertake to implement the guidelines in their policies and procedures. Three action plans are available, for:

The Action Plans are divided into three sequential levels, with an increasing expectation of compliance with the guidelines at each. Many organisations will already be at Level 1 and should relatively quickly be able to move on to more active use of the guidelines.

They are available via the ARRIVE guidelines website. If you have questions about their use, suggestions for additional activities to help with ARRIVE implementation, or would like any more information, contact arrive@nc3rs.org.uk.

 

NC3Rs publishes guidance for archiving and sharing genetically altered mouse strains

2021-12-17

Archiving genetically altered mouse strains reduces animal wastage and maintains genetic integrity, maximising data reproducibility. Cryopreserved resources are also often the best means of sharing genetically altered strains, providing further opportunities for reduction in animal use and minimising the need for strain duplication. Working with colony management experts, the NC3Rs has updated existing guidance to provide an overview of current best practice, highlighting the reduction and refinement opportunities from archiving and sharing.

More information

German Animal Protection Research Prize awarded

2021-12-17

The 40th Animal Protection Research Prize was awarded in Berlin to Dr Jan Bruder and Dr Hendrik Renner of the Max-Planck-Institute for Molecular Biomedicine in Münster, Germany for developing an automated process to produce human midbrain organoids that can be used to model diseases of the human nervous system such as Alzheimer's or Parkinson's disease and amyotrophic lateral sclerosis and reduce the number of animal experiments performed in this area of research. The prize is awarded annually and includes prize money of €25,000.

New webinar series of the 3R-Network Baden-Württemberg starts Thursday

2021-12-13

The webinar series of the 3R-Network Baden Württemberg is organized by the 3R-Center Tübingen together with CAAT-Europe at the University of Konstanz, the 3R-Center Rhine-Neckar and the University of Ulm. The 20-30 minute keynote presentations given by experts in the field are intended to provide exciting thought-provoking impulses for the subsequent discussion. The focus of the event is the interactive exchange between speakers and interested parties.

In addition to scientists, people and decision-makers with prior scientific knowledge from politics, regulatory authorities, industry, or ethics committees are invited to participate in the discussion rounds. The webinar series (mainly in English language) will start on December 16, 2021 from 05:00-06:00 pm (CET). In the first webinar, Prof. Dr. Peter Loskill (Faculty of Medicine, Eberhard Karls University and NMI Natural and Medical Sciences Institute at the University of Tübingen) and Prof. Dr. Marcel Leist (CAAT Europe, University of Konstanz) will talk about why is it crucial to dialogue on novel technologies for risk assessment and disease modeling right here and now. From 2022 forward, exciting impulses and discussions will continue at the same time every last Thursday of a month.

 

Free Registration is possible online on the website of the 3R-Center Tübingen. More information about the activities in the 3R-Network Baden-Württemberg as well as about the work of the 3R-Center Tübingen are also to be found there.

 

German BMBF calls for applications for projects on alternatives to animal experiments

2021-11-05

The German Ministry for Education and Research (BMBF) aims to consolidate and strengthen Germany's leading international position in the field of alternative methods. Funding applications for excellent projects aiming to develop new methods to replace or reduce animal experiments (module I) and concepts that support the widespread use of alternative methods (e.g. education and training courses) and strategies to implement alternative methods (module II) will be considered.

Universities, research institutions and companies may apply. The project duration is three years. Projects may be submitted by March 15 every year beginning with 2022. Project applications received after the deadline will be considered for the following funding period.

More information [in German]

NICEATM releases ICE 3.5

2021-10-29

On October 11, NICEATM released version 3.5 of the Integrated Chemical Environment (ICE; https://ice.ntp.niehs.nih.gov/). ICE provides data and tools to help develop, assess, and interpret chemical safety tests. This release adds expanded capabilities and new data to the existing ICE resources.

ICE version 3.5 includes the following expanded capabilities:

  • New result selection options in the Chemical Quest and Curve Surfer tools.
  • Application of Saagar fingerprints (described in Sedykh et al. 2021: https://doi.org/10.1021/acs.chemrestox.0c00464) to Chemical Quest searches.
  • Ability to display AC50 plots in Search results.

In addition, updated data have been added for acute oral toxicity, cancer, and skin sensitization, and modeling tools are using updated absorption, distribution, metabolism, and excretion data.

NC3Rs launches organ-on-a-chip online resource

2021-10-15

Organ-on-a-chip (OoC) technologies are promising tools to reduce the reliance on animal models in basic and applied research. The NC3Rs has created a new resource bringing together their OoC activities as well as other global programmes and initiatives. As well as showcasing the NC3Rs' portfolio of reports and projects in this area, the resource provides information and support for the OoC community, including technology developers, end-users, regulators and in vivo researchers who are looking to adopt alternative approaches.

Thomas Hartung wins EUROTOX Merit Award

2021-10-01

Prof. Heather Wallace, President of EUROTOX, presented the EUROTOX Merit Award to Thomas Hartung at the opening ceremony of the Virtual 2021 EUROTOX Congress on September 27, 2021.

Thomas Hartung, MD, PhD, is the Doerenkamp-Zbinden-Chair for Evidence-based Toxicology at Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA with joint appointments at The Whiting School of Engineering Molecular Microbiology and Immunology Georgetown University, Washington, DC and the University of Konstanz, Germany. He also is Director of the Centers for Alternatives to Animal Testing (CAAT) in the US and Europe. He is the former Head of the European Commission’s Center for the Validation of Alternative Methods (ECVAM), Ispra, Italy. He is Chief Editor of Frontiers in Artificial Intelligence and has authored more than 580 scientific publications.

The EUROTOX Merit Award is presented annually at the EUROTOX Congress to a European toxicologist with a long and outstanding career in the discipline. Achievements in academia, public service or industry may be recognized. Emphasis should be put on individual contributions strengthening the science of toxicology.

EMA implements new measures to minimise animal testing during medicines development

2021-09-30

 

EMA is putting in place special support to developers to replace, reduce and refine animal use for the development, manufacturing and testing of human and veterinary medicines. The Agency is promoting these three principles — replace, reduce and refine; commonly referred to as 3Rs — through EMA’s Innovation Task Force (ITF). This action will facilitate the development and implementation of New Approach Methodologies (NAMs) that are in line with the European Union legislation on the protection of animals used for scientific purposes.

ITF is a dedicated forum for early dialogue between regulators and developers of medicines to discuss innovative aspects such as emerging therapies, methods and technologies. Set up to ensure coordination across the Agency, the ITF is a multidisciplinary group that includes scientific, regulatory and legal competences. It will provide an opportunity to discuss 3R-compliant methods and facilitate their integration into the development and evaluation of medicinal products.

The ITF’s service is free of charge and any NAMs adhering to the 3Rs principles that can be used to fulfil testing requirements are eligible for consideration.

Alternative approaches to animal models, such as improved tests based on human and animal cells, organoids, organ-on-chips and in silico modelling, provide opportunities to develop better and more predictive scientific tools to protect human and animal health as well as the environment.

Opening the ITF platform to discussions of 3Rs-compliant methodologies is expected to encourage prioritising and speeding up the integration of alternative methods into the regulatory framework. This action supports the reduction of animal use and is in line with EMA's Regulatory Science Strategy to 2025 aiming to build a more adaptive regulatory system that will encourage innovation in human and veterinary medicine.

EMA press release, 29/09/2021

QSAR Toolbox 4.5 for animal-free assessment of skin sensitisation released

2021-09-23

The updated QSAR Toolbox (version 4.5) includes an automated workflow for defined approaches for skin sensitisation. The recently published OECD guideline includes computational methods for assessing skin sensitisation without testing on animals. The Toolbox is the only freely available tool that can be used to do that. The new version also has a simplified web interface and enables structural searches in IUCLID databases.

The QSAR Toolbox is a free software supporting chemical hazard assessment, co-developed by ECHA and OECD. It helps to minimise testing on animals. Its results are based on existing experimental data and knowledge on the mechanisms of toxicity.

NIH NCATS supports the first three Microphysiological Systems World Summits with grant

2021-09-20

The initiative to create a series of MPS World Summits has been awarded a grant by the National Center for Advancing Translational Sciences (NCATS), one of 27 Institutes and Centers at the National Institutes of Health (NIH) in support of the organization of the first three Microphysiological Systems World Summits.

About 40 organizations (and counting) as well as a continuously expanding Scientific Advisory Committee of experts in the field have teamed up to organize the May 30-June 3, 2022 inaugural World Summit in New Orleans and similar events in Europe 2023 and the US West Coast in 2024. The series was kicked-off with a virtual conference on June 24, 2021 with the theme "Towards regulatory acceptance", which will be followed by a second virtual event on December 9, 2021 on "Systems engineering of microphysiological systems".

The MPS (Microphysiological Systems) World Summit will bring together a global audience, including institutions (government, health foundations, charities), the academic research community (universities, research institutes), environmental and human toxicity researchers, the pharmaceutical and other industries (cosmetics, chemical, and food industries), medical centers and practitioners, patient associations, and policy makers and testing centers—in a series of global conferences to create a roadmap for MPS technologies. This will be a first step in establishing an international MPS society. 

The MPS World Summit offers multiple sponsoring opportunities as detailed on the website to which the companies listed below have already committed:

  • Gold sponsor: Emulate
  • Silver sponsors: AxoSim, Hesperos, InSphero, Obatala
  • Bronze sponsor: Nortis
  • Exhibitors: Aracari, Mimetas, Vitrocel Systems GmbH, TissUse

In related good news, the latest issue of Science features the article:

Roth, A. and MPS-WS Berlin 2019 [Marx, U., Vilén, L., Ewart, L., Griffith, L. G., Hartung, T., Ingber, D. E., Mendrick, D. L., Steger-Hartmann, T. and Tagle, D. A.]. Human microphysiological systems for drug development. Science 2021, 373:1304-1306. doi: 10.1126/science.abc3734

which was a direct result of the hightly cited t4 workshop report published in ALTEX:

Marx, U., Akabane, T., Andersson, T. B. et al. (2020). Biology-inspired microphysiological systems to advance patient benefit and animal welfare in drug development. ALTEX 37, 365-394. doi:10.14573/altex.2001241

Joint motion for a resolution to accelerate the transition to innovation without the use of animals adopted by European Parliament

2021-09-14

A joint motion for a resolution entitled “European Parliament resolution on plans and actions to accelerate the transition to innovation without the use of animals in research, regulatory testing and education (2021/2784(RSP))” was submitted to European Parliament on September 13 by representatives of the PPE, S&D, Renew, Verts/ALE, ECR and The Left Groups and adopted on September 15. The motion calls on the Commission to establish a high-level inter-service taskforce to design an EU-wide action plan with a clear and ambitious timeline and a list of milestones to phase-out live animal use for scientific purposes as soon as this is scientifically possible and without lowering the level of protection for human health and the environment. The motion acknowledges the important contributions of animal-based research to date and states that alternative methods are not available to replace all animal testing yet, however experiments that are carried out on animals should take place in optimal conditions that minimize pain, distress, and suffering. To achieve the transformation, the motion highlights that the development of alternative animal-free methods, technologies, and instruments necessary for change must be accelerated by preferential funding of non-animal methods across all EU research and innovation initiatives. It further calls on the Commission to set reduction goals in consultation with ECHA, EFSA and other relevant agencies, and to support education and training in advanced non-animal models.

Recordings of WC11 keynote lectures, talk shows, awards & closing ceremony available online

2021-09-13

The keynote lectures given during the 11th World Congress on Alternatives and Animal Use in the Life Sciences held virtually on August 23 to September 2, 2021 are available on-demand at the following links:

André Kuipers: https://vimeo.com/591569100

Russel Thomas: https://vimeo.com/591478966

Donald Ingber: https://vimeo.com/592069625

Jason Ekert: https://vimeo.com/592667886

Malcolm McLeod: https://vimeo.com/593173630

Anna Deplazes: https://vimeo.com/595249036

Tharanga Thoradeniya: https://vimeo.com/599376359

Ger Janssen: https://vimeo.com/599359072

Joseph Wu: https://vimeo.com/599403130

 

Recordings of the talk shows can be viewed here:

TALK SHOW 1 (SAFETY): https://vimeo.com/592090451 

TALK SHOW 2 (DISEASE): https://vimeo.com/594695667

TALK SHOW 3 (INNOVATIVE TECHNOLOGIES): https://vimeo.com/599362733

The WC11 Award Ceremony can be rewatched here:https://vimeo.com/599420643

Rewatch the WC11 Closing Ceremony here:https://vimeo.com/599432825

2021 ALTEX Prize awarded to Taylor Rycroft

2021-09-02

We are pleased to announce that Dr Taylor Rycroft of the Environmental Laboratory, U.S. Army Engineer Research and Development Center, Vicksburg, MS, USA has won the ALTEX Prize 2021 as first author of the article "AOPERA: A proposed methodology and inventory of effective tools to link chemicals to adverse outcome pathways". The article was selected by the ALTEX Editorial Board, the Board of ALTEX Edition and the ALTEX editorial office as the best article published in ALTEX during 2020. The award was presented on September 2 at the 11th World Congress on Alternatives and Animal Use in the Life Sciences in Maastricht in 2021.

The ALTEX Prize is awarded annually and is kindly sponsored by the Doerenkamp-Zbinden Foundation.

Helena Kandárová announced as winner of the 2021 Doerenkamp-Zbinden Prize

2021-09-02

The Board of Trustees of the Doerenkamp-Zbinden Foundation for Animalfree Research has chosen the Slovak scientist Dr. Helena Kandárová, ERT from the Centre of Experimental Medicine at Slovak Academy of Sciences, in Bratislava, Slovakia, as the Doerenkamp-Zbinden Prize winner in the year 2021. The 10 000 CHF Prize was presented to her on September 2 at an online ceremony during the 11th World Congress on Alternatives and Animal Use in the Life Sciences in Maastricht. Helena Kandarova receives the prize for her outstanding achievements in the field of alternatives to animal testing.

NICEATM releases ICE 3.4

2021-07-18

On June 7, NICEATM released version 3.4 of the Integrated Chemical Environment (ICE). ICE provides data and tools to help develop, assess, and interpret chemical safety tests. This release adds new tools and expanded capabilities to the existing ICE resources.

ICE version 3.4 includes the following new tools and expanded capabilities:

  • Chemical Quest (Beta): uses fingerprints to predict structure similarity.
  • Drawing of 2D structures (part of the Chemical Quest tool): users can draw their own structures and query ICE for all chemicals that are similar to the drawn structure.
  • Query by multiple chemical identifiers: CASRNs, DTXSIDs, SMILES or InChiKeys are now accepted as inputs into all ICE tools.
  • Send assays to other ICE tools: users can switch between ICE tools and keep the same assays selected.

New data and data updates include:

  • Developmental/reproductive in vivo assays from NTP and the European Chemicals Agency.
  • Dermal irritation in vivo assays (rat Draize skin irritation/corrosion test).
  • Updates to ICE curated high-throughput screening data and data from the Open Structure-activity/property Relationship App (OPERA).

ICE is available at https://ice.ntp.niehs.nih.gov/

NC3Rs launches interactive 3Rs self-assessment tools

2021-07-14

The NC3Rs has launched two online 3Rs self-assessment tools that research groups and institutions can use to collate, track and benchmark their 3Rs activities. These interactive tools, which are secure and free-to-use internationally, help researchers, ethics committee members and others to identify and implement 3Rs opportunities.

Leaders of research groups and institutions who want to ensure an optimal 3Rs culture need to be able to evaluate their current activities, understand their strengths and establish what should be improved and how. Through consultation with the scientific community, NC3Rs has developed two 3Rs self-assessment tools: one for individual research groups and one for research institutions (i.e. universities and other academic, research-intensive organisations). Each tool consists of a series of questions on the 3Rs, divided into categories that reflect the breadth of potential 3Rs activities across different levels. Once each question set is completed, the system automatically scores the responses and provides bespoke feedback on what is being done well and what improvements the research group or institution could make.

ECHA reports critical issues with EOGRT studies, review ongoing

2021-07-08

Experts from ECHA and Member States have found critical issues in the design and conduct of extended one-generation reproductive toxicity (EOGRT) studies. The issues can compromise data analysis and may raise questions over compliance or requests for further studies if there is a concern. ECHA encourages registrants and test laboratories to consider the issues and improve ongoing and future EOGRT studies accordingly.

The EOGRT study (EU B.56, OECD TG 443) has been the information requirement for reproductive toxicity in REACH since March 2015. 

ECHA’s advice on improving EOGRT studies

European Pharmacopoeia to put an end to the rabbit pyrogen test

2021-07-01

At its 170th session in June 2021, the European Pharmacopoeia (Ph. Eur.) Commission took the decision to engage on a path that should ultimately lead to the complete replacement of the rabbit pyrogen test (RPT) in the Ph. Eur., within approximately 5 years.

The Ph. Eur. test for pyrogens (general chapter 2.6.8) consists of measuring the rise in body temperature evoked in rabbits by the intravenous injection of a sterile solution of the substance to be examined. It was first published in the Ph. Eur. in 1986.

The majority of pyrogens are bacterial endotoxins and these can be detected using the bacterial endotoxins test (BET) described in Ph. Eur. general chapters 2.6.14. Bacterial endotoxins and 2.6.32. Test for bacterial endotoxins using recombinant factor C. However, in some cases, non-endotoxin pyrogens may also be present and these are not detected by the BET. A test covering all types of pyrogens is therefore required to confirm the absence of non-endotoxin pyrogens.

General chapter 2.6.30. Monocyte-activation test (MAT) was added to the Ph. Eur. in 2009, providing an in-vitro alternative to the RPT that is capable of detecting both endotoxin and non-endotoxin pyrogens. The publication of this chapter was a significant step forward in terms of animal welfare, in accordance with the Council of Europe’s European Convention for the Protection of Vertebrate Animals used for Experimental and Other Scientific Purposes.

However, despite multiple efforts since then to encourage developers to apply the MAT instead of the RPT, rabbits continue to be used extensively to detect pyrogenic substances.

There are currently 59 Ph. Eur. texts – covering a variety of topics including vaccines for human use, blood products, antibiotics, radiopharmaceuticals and containers – that refer to the RPT and will be affected. The Ph. Eur. is committed, for all these texts, to replacing the test for pyrogens with a suitable in-vitro alternative, ultimately leading to the complete elimination of the RPT. In the meantime, users are actively encouraged to seek alternatives to chapter 2.6.8, the best option being the MAT.

Throughout the process, users will have the opportunity to comment on a case-by-case basis, since each of the texts concerned will go through the standard public enquiry in Pharmeuropa.

OECD adopts new Guideline on Defined Approaches on Skin Sensitisation

2021-06-18

The OECD has published a new Guideline on Defined Approaches for Skin Sensitisation (OECD GL No. 497). This is a new type of OECD Guideline that uses several types of combined information to provide chemical safety information and can replace the need for animal test data. The project to develop this new Guideline started in 2017 and was led by the United States, the European Commission Joint Research Centre and Health Canada, supported by a group of nominated experts. The Defined Approaches (DAs) were validated using an extensively curated large set of human and mouse reference data on skin sensitisation. A supporting document providing details on the data curation and performance characteristics of the DAs on skin sensitisation will be published soon in the OECD Series on Testing and Assessment. 

A Defined Approach (DA) consists of selected information sources (e.g. in silico predictions, in chemico, in vitro data) used in a specific combination, and resulting data are interpreted using a fixed data interpretation procedure (DIP) (e.g. a mathematical, rule-based model). DAs are intended to overcome some limitations of the individual methods. 

The first three DAs included in this Guideline use combinations of OECD validated in chemico and in vitro test data, in some cases along with in silico information.  The DAs included in this Guideline have shown to either provide the same level of information or be more informative than the LLNA (OECD TG 429) for hazard identification (i.e. sensitiser versus non-sensitiser).  In addition, two of the DAs provide information for sensitisation potency categorisation that is equivalent to the potency categorisation information provided by the LLNA.

 This new Guideline is intended to be the first of more harmonised defined approaches adopted across OECD member countries and countries adhering to the Mutual Acceptance of Data system to 1) address regulatory needs, 2) enhance the utility of individual methods when used in testing strategies, and 3) reduce use of animal testing.

 

Further new test guidelines and updates include:

Section 4

Test No. 498: In vitro Phototoxicity - Reconstructed Human Epidermis Phototoxicity test method

Test No. 250: EASZY assay - Detection of Endocrine Active Substances, acting through estrogen receptors, using transgenic tg(cyp19a1b:GFP) Zebrafish embrYos

Test No. 494: Vitrigel-Eye Irritancy Test Method for Identifying Chemicals Not Requiring Classification and Labelling for Eye Irritation or Serious Eye Damage

Test No. 455: Performance-Based Test Guideline for Stably Transfected Transactivation In Vitro Assays to Detect Estrogen Receptor Agonists and Antagonists
Test No. 439: In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method

Test No. 442C: In Chemico Skin Sensitisation

Test No. 405: Acute Eye Irritation/Corrosion

Test No. 406: Skin Sensitisation

 

Section 2

Test No. 249: Fish Cell Line Acute Toxicity - The RTgill-W1 cell line assay

Test No. 211: Daphnia magna Reproduction Test

Einstein Center for Alternative Methods in Biomedical Research in Berlin established

2021-06-17

The Einstein Center for Alternative Methods in Biomedical Research will officially commence work on July 1, 2021. The Einstein Foundation will provide financial support amounting to €5.3 million until the end of 2026, but will make part of its funding subject to the Center's positive interim assessment by the Foundation’s independent research board in 2024. Additional funding will be made available by the State of Berlin.

The Einstein Center 3R (Replace, Reduce, Refine) aims to develop new therapies for human diseases by improving the transferability of research while also taking into view animal welfare. Research will focus on 3D human organoids designed to replace animal testing. These organoids shall resemble human organs as closely as possible in terms of maturity and complexity, i.e., “micro-organs” with vascular or immune systems.

The Einstein Center will accommodate six research projects focusing on the intestines, lung, heart, brain, liver, and neuromuscular junctions, respectively. These will be complemented by two cross-sectional quality assurance projects designed to improve the models and define measures and principles to guide the projects’ research. In addition, the Center will set up an imaging and analysis platform in order to improve the comparability of human and animal-based models regarding the specific characteristics of diseases such as COVID-19.

The Center’s long-term aim is to build a Berlin-wide research network that explores tissue models and develops cutting-edge projects. It will also be involved in education and training as well as communication and outreach programs.

Three new Horizon 2020 research projects kick off

2021-04-30

The EU is funding the three multi-partner research projects PrecisionTox, ONTOX and RISK-HUNT3R under the call „Advancing safety assessment of chemicals without use of animal testing” with a total funding volume of € 60 million over five years.

PrecisionTox, with 15 partners led by the University of Birmingham, started on February 1. The goal of the project is to identify molecular key event (KE) biomarkers that predict chemically induced adverse health effects in humans and to facilitate their uptake into regulatory and industry practice. This goal is supported by three core concepts: PhyloToxicology, which replaces mammalian models with an evolutionarily diverse suite of non-sentient animal species from across the tree of life; Quantitative Susceptibility, which determines safety factors based on genetic variability; and Embedded Translation, which engages key stakeholders in project planning, selection of chemicals for investigation, and case studies for regulatory application.

ONTOX, with 18 partners led by the Vrije Universiteit Brussels, will kick off on May 1. The consortium aims to deliver a generic strategy to predict systemic repeated dose toxicity effects. This will be combined with tailored exposure assessment to enable human risk assessment. The focus will be on 6 new approach methodologies (NAMs) addressing adverse outcomes in the liver (steatosis and cholestasis), kidneys (tubular necrosis and crystallopathy) and developing brain (neural tube closure and cognitive function defects). The NAMs will integrate available data into physiological maps, quantitative adverse outcome pathway networks and ontology frameworks and use artificial intelligence technology to identify data gaps to be filled by targeted in vitro and in silico testing. The NAMs will be evaluated and applied in collaboration with industrial and regulatory stakeholders to maximize end-user acceptance and regulatory confidence.

RISK-HUNT3R, with 37 partners led by the Universiteit Leiden, will start on June 1. The vision of the RISK-HUNT3R consortium is to provide a fully human-centric risk assessment strategy encompassing exposure assessment, information on chemical distribution in the body, hazard characterization, adverse outcome prediction, and determination of actual risk in defined scenarios, also factoring in human (disease) genetics and exposome data. The applicability of all critical test systems integrated into the next generation risk assessment strategy will be assessed. Engagement with all key stakeholders from different industry sectors and international regulatory agencies based on real-world case studies will allow critical evaluation and warrant genuine acceptance of the novel safety testing framework that will be in concordance with the European Commission’s “Green Deal”. The project will seek commercial exploitation of the validated safety assessment approaches to ensure sustainability of the project outcomes and fortify the innovation capacity of the industry sectors involved.

Interactive map of global 3R resources online

2021-03-31

Norecopa has published an interactive world map to highlight a range of resources relevant to laboratory animal science and welfare. These are divided into two groups called Centres (which highlight organisations at specific locations) and Associations (networks between countries). Filters in the right margin can be used to turn these on and off. Suggestions for additions are welcome, and may be sent to Adrian Smith.

NICEATM releases ICE 3.3

2021-03-22

On March 12, NICEATM released the version 3.3 update of the Integrated Chemical Environment (ICE). ICE provides data and tools to help develop, assess, and interpret chemical safety tests. This release adds two new tools, new features including expanded activity visualization, and new datasets to existing ICE resources.

New tools:

  • Curve Surfer: allows users to view and interact with concentration-response curves from curated high-throughput screening data.
  • Physiologically Based Pharmacokinetics (PBPK) tool: this tool, based on the the U.S. Environmental Protection Agency (EPA) httk package (https://cran.r-project.org/web/packages/httk/index.html), allows users to generate predictions of tissue-specific chemical concentration profiles following a dosing event.

Updates to existing tools:

  • Search tool: users can get detailed visualization of query results.
  • In Vitro to In Vivo Extrapolation (IVIVE) tool: users can now upload their own in vivo data to overlay on the results.
  • Chemical Characterization: new visualizations include bioactivity PCA plots and Consumer Use Explorer, which allows users to view chemical use categories from the EPA Consumer Products Database (CPDat).

New data:

  • Cancer data from multiple sources, including detailed data from NTP two-year cancer bioassays and in vivo and in vitro genotoxicity studies.
  • Developmental and reproductive toxicity (DART) in vivo bioassays from the EPA’s Toxicity Reference Database (ToxRefDB).
  • Updated in vivo human predictive patch test data set for skin sensitization characterization compiled by NICEATM and the German Federal Institute for Risk Assessment (BfR).

ICE is available at https://ice.ntp.niehs.nih.gov/.

NC3Rs releases new research culture hub

2021-02-22

The NC3Rs is committed to facilitating a good research culture, supporting reproducible and ethical research through effective application of the 3Rs. They have produced a new hub that features a range of resources to help you strengthen the research culture of your group, department or institution. These focus on experimental design and reporting, open research and communication, and promoting a culture of care. As a funder the NC3Rs also has a responsibility to help foster a fair and inclusive research culture.

The term research culture encompasses the actions and behaviours of individuals and the values and ethos of institutions, both of which can have a significant impact on the effective application of the 3Rs and the humane use of animals.

The research culture hub one element of the NC3Rs Resource hubs.

Recordings of online symposium on animal euthanasia available

2021-02-08

The Swiss Federal Food Safety and Veterinary Office (FSVO), UFAW (the Universities Federation for Animal Welfare) and HSA (the Humane Slaughter Association) together organised the 3rd symposium on Humanely Ending the Life of Animals as a virtual meeting on November 3rd and 4th. Recordings of the sessions are available. This symposium continues a growing initiative to identify, refine and implement alternative methods to CO2 for humanely ending the life of mice, rats, poultry and pigs to improve animal welfare in the laboratory, the slaughterhouse and during emergency depopulation. Carbon dioxide is commonly used for stunning animals prior to killing. It allows several animals to be killed at once, reduces the need for handling, and is a reliable method. However, research in laboratory rodents, poultry, and pigs has indicated that it causes considerable aversion at concentrations above ambient conditions. Currently, there are no available alternatives with desirable characteristics.

More information: https://www.hsa.org.uk/news-events/fsvo-ufaw-hsa-online-symposium-a-humanely-ending-the-life-of-animals

Switzerland initiates national research programme to advance the 3Rs 

2021-02-08

On 3 February 2021, the Swiss Federal Council initiated a new national research programme "Advancing 3Rs - Animals, Research and Society". The main objectives of NRP 79 are to reduce the number of animal experiments in scientific research, to improve animal experimentation, and to develop basic principles on ethical and societal aspects in this field. The programme, which is endowed with 20 million Swiss francs, will run over five years. The Swiss National Science Foundation is responsible for the implementation of the NRP 79. The Swiss 3RCC is coordinating its activities with those of the new NRP.
More information: https://www.admin.ch/gov/de/start/dokumentation/medienmitteilungen.msg-id-82212.html 

EPA list of alternative test methods to animal testing updated

2021-02-08

EPA has updated its list of alternative test methods or strategies (New Approach Methodologies or NAMs) that do not require new vertebrate animal testing. This action helps meet the requirements of the Toxic Substances Control Act to reduce and replace, to the extent practicable and scientifically justified, the use of vertebrate animals in the testing of chemical substances or mixtures.

The updated list incorporates the following changes from the 2019 List:

  • Added one new test guideline that relates to human health effects.
  • Incorporated two additional EPA guidance documents that reduce the use of animal testing.
  • Added version 9.0 of the organic chemicals’ module of OncoLogicTM, a more user-friendly version of the most widely used piece of this system that evaluates a chemical’s potential to cause cancer.

For more information on alternative test methods and strategies to reduce vertebrate animal testing, please visit: www.epa.gov/assessing-and-managing-chemicals-under-tsca/alternative-test-methods-and-strategies-reduce.

EPA finalizes guidance to waive dermal toxicity tests for pesticides

2021-01-20

Today, the U.S. Environmental Protection Agency (EPA) delivered on EPA Administrator's directive to reduce animal testing by finalizing guidance that will allow researchers to forego testing chemicals on animal skin in certain circumstances to determine whether pesticides lead to adverse effects. 

“Today’s action is another example of how EPA is moving closer to achieve our goal  of eliminating  the use of mammals in chemical testing by 2035,” said EPA Office of Chemical Safety and Pollution Prevention Assistant Administrator Alexandra Dapolito Dunn. “Our guidance expands the ability for waivers for dermal toxicity studies while allowing the agency to continue to make  science-based decisions about pesticide registrations without the need to conduct unnecessary additional animal tests.”  

In October 2020, EPA released the proposed guidance for a 30-day comment period which received stakeholder input. In developing the guidance, EPA conducted a retrospective analysis with the U.S. Department of Health and Human Service. The joint analysis found that requirements for such studies provides little to no added value in the regulatory decision making process.   

The final dermal toxicity guidance will allow registrants to apply for waivers for studies on single-active ingredients used to develop end use products. This guidance is expected to save up to 750 test animals annually from unnecessary testing as well as EPA, industry and laboratory resources. 

Background 

In September 2019, Administrator Wheeler issued a directive  calling for the Agency to reduce animal testing and funding 30 percent by 2025 and eliminate it by 2035. In support of this directive, EPA has taken many steps since then to reduce, replace, and refine animal testing requirements: 

  • In September 2019, EPA announced $4.25 million in funding for five universities to research and develop alternative test methods for evaluating chemical safety. 
  • In December 2019, EPA convened a conference for achieving reduced animal testing in chemical safety research 

and updated its list of NAMs that could be used in the agency's work under the amended TSCA. The updated list includes 21 new test guidelines related to health and ecological effects and six additional EPA policies that reduce the use of animal testing. 

FDA publishes report on advancing alternative methods

2021-01-13

The U.S. Food and Drug Administration has published the report, “Advancing New Alternative Methodologies at FDA,” which demonstrates the significant progress that the FDA has made in laying the groundwork for integrating alternative approaches into regulatory programs.

Developed by the FDA’s Alternative Methods Working Group, the report and its outlined activities build upon the Predictive Toxicology Roadmap, a framework to spur the development and evaluation of emerging technologies that can help potentially replace, reduce, and/or refine animal testing and to incorporate them into the agency’s regulatory review. The roadmap ensures that the end users of this new technology—FDA regulators—are involved up front as these technologies evolve from design to testing to qualified context of use.

As noted in the report, the FDA has developed the Advancing Alternative Methods webpage, which hosts related publications, presentations, and a webinar series that enables developers to showcase their pioneering technologies to FDA scientists. The FDA will continue to update its progress on alternatives in real time for stakeholders on its website.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of the U.S. food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

Baden Württemberg limits use of animals for higher education

2020-12-17

On December 16, the parliament of the State of Baden Württemberg voted for a change in the Higher Education Act, which will allow students to complete their studies without using animals. The amendment states that animals shall not be killed for teaching purposes if scientifically equivalent alternatives are available. Universities and colleges are to develop such alternative methods to avoid and reduce animal use, and study courses are to be designed in such a way that animals are not used to illustrate biological, chemical or physical processes if scientifically equivalent alternatives are available. In case alternatives are not available, students must be given the option to fulfill the course requirements without the use of animals.

The amendment, which will come into effect early 2021, follows similar provisions in seven other German states (Bremen, Hessen, Nordrhein-Westfalen, Rheinland-Pfalz, Saarland, Sachsen-Anhalt and Thüringen).

Virtual Human Platform based exclusively on human biology gains funding

2020-12-14

How great would it be if we could assess the safety of chemicals and pharmaceuticals without the use of laboratory animals? To be able to test the safety of chemicals solely based on human physiology and biology, including such vulnerable groups as infants, the elderly or the sick? Researchers from, among others, Utrecht University, University of Applied Sciences Utrecht and the National Institute for Public Health and the Environment (RIVM) are developing a Virtual Human Platform to assess the safety of chemicals and medicines without the use of laboratory animals. The consortium will receive 9.9 million Euros from the Dutch Research Agenda: Research on Routes by Consortia (NWA-ORC) for this purpose. Thanks to the contribution of foundations, government and private sector organisations, the total funding comes to 11.2 million Euros. The project is led by Juliette Legler (Utrecht University), Cyrille Krul (University of Applied Sciences Utrecht) and Anne Kienhuis (RIVM). 

More information

USP includes in vitro batch release test for insulins

2020-12-03

The United States Pharmacopeia has added an in vitro cell-based assay for the batch release of two insulins (glargine and lispro) as an alternative to the rabbit blood sugar bioidentity assay to Chapter <121> Insulin Assays. The rabbit assay, which requires 8-24 animals per batch, is not required in the European Union. Sanofi, which exports insulin to the US, began to validate an experimental in vitro test as an alternative to the rabbit assay in 2012, which was accepted in 2016 (see Hack et al., 2017, doi:10.14573/altex.1708091) and included in the guideline in December 2020.

Joint statement on implications of recent ECHA Board of Appeal decisions

2020-11-24

Cruely Free Europe, The European Coalition to End Animal Experiments (ECEAE), Eurogroup for Animals, Humane Society International (Europe) and PETA UK have issued a joint statement regarding the use of animals to test cosmetics ingredients under the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) regulation. Even though the testing of cosmetics ingredients on animals is banned under the EU Cosmetics Regulation, the European Chemicals Agency and the European Commission have argued that even ingredients used exclusively in cosmetics may still be tested on animals under REACH if there is a possibility of workforce exposure during the manufacturing process. For cosmetics ingredients also used in other types of products, tests on animals may, they say, be required regardless of any potential for workforce exposure.

The statement reads as follows:

When the European Union banned the testing of cosmetics products on animals in 2004 and prohibited the sale of cosmetics ingredients that relied on newly generated animal test data in 2013, consumers, companies and animal protection organisations rightly claimed a ground-breaking victory after decades of campaigning. These bans have since been a beacon of change for animals around the world, and in 2018, their significance was reinforced when the European Parliament overwhelmingly supported a call for a global end to animal testing for cosmetics. Now, this progress is substantially weakened by the current stance of the European Chemicals Agency (ECHA) and the European Commission.
A series of testing decisions by ECHA made with the backing of the European Commission, along with recent decisions by the ECHA Board of Appeal, have challenged a basic principle of interpreting EU legislation by disregarding the clear intention of legislators and thereby seriously undermining the cosmetics testing ban. In addition, the European Commission's Chemicals Strategy for Sustainability is set to re-open the Cosmetics Regulation, with the potential to introduce new testing requirements at the expense of many more animals' lives.
Already, thousands of animals are being condemned to suffer in additional testing of cosmetics ingredients that have been manufactured and marketed safely under the EU's Cosmetics Regulation for decades – and the bans that animal advocates fought so hard to achieve, and that the public and many scientists support, are effectively being rendered meaningless.
It is imperative that the purpose of the Cosmetics Regulation – that cosmetics products are safely brought to market using only non-animal data – be met without compromising the bans. For ingredients marketed under the Cosmetics Regulation that have a history of safe use by consumers and of controlled handling on the factory floor, robust protection of both workers and consumers is already enabled through a variety of non-animal assessment methods and the careful application of exposure assessments. When regulators decide that a new ingredient cannot be brought safely to market without animal testing, its introduction should be delayed until additional non-animal test methods are available.
Continued requests for renewed testing of existing cosmetics ingredients are set to severely limit the availability of products and ingredients marketed within the cruelty-free sector. The European Commission must come clean to consumers and parliamentarians, who still believe that cosmetics in the EU must be free from animal testing, over measures taken to weaken the bans. European consumers expect to be able to buy cosmetics that have not been tested on animals, and the European Commission and ECHA have a duty to ensure that this is the case by applying the law properly.
The recent administrative decisions are not the end of the road for the cosmetics testing and marketing bans. We maintain that new safety assessment data for cosmetics substances imported into, manufactured or sold within the EU may only rely on non-animal assessment methods. The wishes of citizens and legislators are clear: ECHA and the European Commission must be held accountable and compelled to uphold the terms of the EU cosmetics animal test and marketing bans as originally intended.
As animal protection organisations, we call for the European Parliament and the European Commission to ensure that the following mandates are urgently carried out:
- The EU bans on animal testing for cosmetics and the marketing of ingredients tested on animals must be fully upheld and implemented as intended by the legislators.
- EU test requirements – including requirements set out in REACH – must not undermine the bans but instead must apply a substance-tailored approach to ensure consumers, workers, and the environment are protected without further tests on animals.
- The European Commission must devise a robust testing strategy for cosmetics ingredients using only available non-animal assessment strategies so that the implementation of the Chemicals Strategy for Sustainability reflects the overwhelming support for strengthening – rather than weakening – the protection of animals in Europe.

Doerenkamp-Zbinden Prize 2020 awarded

2020-11-18

Marcel Leist, Thomas Hartung, Bas Blaauboer, Pierre Cosson, and Mohammad Abdulkader Akbarsha, the five endowed chairs of the Doerenkamp-Zbinden Foundation, have jointly received the Doerenkamp-Zbinden Prize 2020 in acknowledgement of their outstanding work in the promotion of alternatives to animal testing. The prize was presented on November 5, 2020. 

More information about the prize can be found here. 

FDA partnership to apply lung chips to safety evaluation of COVID-19 vaccines and therapies

2020-11-17

The U.S. Food and Drug Administration (FDA) has entered into a Cooperative Research and Development Agreement (CRADA) with Emulate, Inc. to enable multiple studies using Emulate’s Organ-Chips across FDA offices in priority research areas. Organ-Chips are in vitro systems that recreate the natural physiology of specific human tissues and organs. Some projects will evaluate COVID-19 vaccines or investigate human immune response against SARS-CoV-2, the virus that causes COVID-19. Under the CRADA, FDA will use a range of Organ-Chips to study the safety, efficacy, and mechanisms of action of drugs regulated by the FDA. This new CRADA agreement follows the successful completion of the first Emulate CRADA with the FDA initiated in 2017 that focused on toxicity studies using Emulate’s Liver-Chip. Details on the CRADA are provided in Emulate’s October 29 press release, available at https://www.emulatebio.com/press/fda-organ-chip-crada-2020.

Presentations and video available from EPA NAMs Conference

2020-11-17

The U.S. Environmental Protection Agency (EPA) hosted the Second Annual “Conference on the State of the Science on Development and Use of New Approach Methods (NAMs) for Chemical Safety Testing” virtually on October 19-20. The virtual conference was presented in response to the September 2019 directive by EPA Administrator Andrew Wheeler to reduce the EPA’s use of mammalian studies.

Conference topics included:

• Implementation of animal testing reduction at EPA.
• State of the science in development of NAMs.
• Current limitations of NAMs.
• Developing scientific confidence in NAMs.

To view the conference presentations and recordings, visit the conference website at https://www.epa.gov/chemical-research/second-annual-conference-state-science-development-and-use-nams-chemical-safety-0#2b. If you attended the conference and would like to submit feedback on the EPA New Approach Methods Work Plan, email NAM@epa.gov.

Lush Prize 2020 winners announced

2020-11-12

The nine winning projects, organisations and scientists from seven countries, plus two commendations, as well as a winner of the Andrew Tyler Award were announced at a virtual prizegiving on November 11, 2020. The winners share a total prize fund of £250,000. The 2020 LUSH Prize saw the highest number of submissions to date, with 137 entries from 34 countries. No awards were given this year in the categories Political Achievement Award or Public Awareness (Future).

LOBBYING

Environment and Animal Society of Taiwan (EAST)
Taiwan
east.org.tw
£50,000
Project: Erasing mandatory animal testing requirements and prioritising non-animal testing methods in the chemical registration process.

Also commended:
Medical Device In Vitro Irritation Team (MD-IV-IT)
USA
Project: In Vitro Irritation Testing of Medical Devices.

PUBLIC AWARENESS

SOKO Tierschutz
Germany
soko-tierschutz.org
£50,000
Project: Undercover investigation at the Laboratory of Pharmacology and Toxicology.

SCIENCE

Dr Tim Allen, The MIE Atlas Team, Cambridge University
UK
researchgate.net/profile/Timothy_Allen10
£50,000
Project: In Silico Models to Predict Human Molecular Initiating Events.

Also commended:
Dr Azra Raza, MDS Centre, Columbia University
USA
azraraza.com
Project: Tissue Repository.

TRAINING

Helpathon Team
The Netherlands
tpihelpathon.nl
£50,000
Project: TPI Helpathon.

YOUNG RESEARCHERS

All Young Researcher winners receive £10,000 each.

Edoardo Carnesecchi
Institute for Risk Assessment Sciences, Utrecht University, The Netherlands
Project: Early neurodevelopmental disturbances during sensitive periods of stem cell differentiation.

Nadine Dreser
researchgate.net/profile/Nadine_Dreser
University of Konstanz, Germany
Project: An innovative software platform to assess chemical mixtures toxicity and exposure.

Dr Domenico Gadaleta
researchgate.net/profile/Domenico_Gadaleta
Computational Toxicology Unit, Laboratory of Environmental Chemistry and Toxicology, Istituto di Ricerche Farmacologiche Mario Negri, IRCCS, Italy
Project: Development of an Integrated Screening Method Based on Quantitative Structure-Activity Relationships Predicting Molecular Initiating Events of Neurotoxicity.

Dr Johanna Nyffeler
researchgate.net/profile/Johanna_Nyffeler
US Environmental Protection Agency, USA
Project: High-throughput phenotypic profiling of human neural progenitor cells to identify putative modes-of-action of developmental neurotoxicants.

Dr Yuan Pang
researchgate.net/profile/Yuan_Pang
Tsinghua University, China
Project: Construction of advanced in vitro tissue models based on 3D bioprinting and their application in drug discovery and toxicity test.

ANDREW TYLER Award

The Andrew Tyler Award for outstanding contribution to ending animal testing (a non-financial prize)

Andrew Rowan PhD
wellbeingintl.org
USA
Andrew is President of Wellbeing International, and former CEO of Humane Society International. He has also served on the committees of several animal protection groups, including the World Society for the Protection of Animals.

Sandra Coecke announced as winner of 2020 Björn Ekwall Memorial Award

2020-11-03

Dr Sandra Coecke, senior scientist at European Commission Joint Research Centre, Ispra, Italy, is the recipient of the Björn Ekwall Memorial Award for the year 2020 in recognition of her work on the development and validation of new in vitro cell- and tissue-based methods for in vitro toxicity testing for the replacement of animal experiments. Sandra Coecke is also highly recognized for her leading role in the development of the European Commission Joint Research Centre’s guidance document on Good Cell Culture Practice (GCCP) and the OECD’s guidance document on Good In Vitro Method Practices (GIVIMP). The Scandinavian Society for Cell Toxicology (SSCT) established the Björn Ekwall Memorial Foundation in 2001. The main goal of the BEMF is to honour the memory of Dr. Björn Ekwall by giving a reward to the scientists who have substanctially contributed to the field of cell toxicology, e.g. by developing new in vitro tests or via mechanistic or validation studies.

NICEATM releases ICE 3.2

2020-10-26

On October 20, NICEATM released an update of the Integrated Chemical Environment (ICE). ICE provides data and tools to help develop, assess, and interpret chemical safety tests. This update adds the following features to these ICE tools.

  • In Vitro to In Vivo Extrapolation (IVIVE): a new inhalation model from the U.S. Environmental Protection Agency (EPA) httk package (https://cran.r-project.org/web/packages/httk/index.html) is available that allows estimation of an equivalent administered dose based on a gas exposure. The IVIVE tool also now allows the user to specify whether experimental or predicted data are used for absorption, distribution, metabolism, and excretion (ADME) parameters.
  • Chemical Characterization: query results are now displayed using two principal component analysis plots: a static plot that compares query chemicals to a background of a larger chemical set and a dynamic plot that compares query chemicals to one another based on physicochemical properties or molecular descriptors.

Other new resources in ICE 3.2 include:

ICE is available at https://ice.ntp.niehs.nih.gov/.

Recordings of "The 3Rs across Europe" webinar series available

2020-10-15

Europe is home to a vibrant 3Rs community with a range of organisations who fund or promote science and technology developments that lead to opportunities to replace, reduce and refine the use of animals in research. To celebrate the 3Rs in Europe, six organisations came together in September 2020 to organise a virtual event highlighting the latest 3Rs advances over three days of talks. Recordings of each talk are now available to watch online.

OECD releases eight IATA case studies

2020-10-12

The Organisation for Economic Co-operation and Development (OECD) supports the development of integrated approaches to testing and assessment (IATA). IATA provide a means by which all relevant and reliable information about a chemical is used to answer a defined hazard characterization question. Information considered can include toxicity data, exposure routes, use cases, and production volumes.

The OECD IATA Case Studies Project allows countries to share and explore the use of novel methodologies in IATA for chemical hazard characterization within a regulatory context. Eight new case studies illustrate the use of NAMs for predicting systemic toxicity, developmental and reproductive toxicity, and neurotoxicity from chemicals such as caffeine, p-alkylphenols, and carboxylic acids. Information about the Case Studies Project and links to the new case studies are available at http://www.oecd.org/chemicalsafety/risk-assessment/iata-integrated-approaches-to-testing-and-assessment.htm.

EPA announces guidance to waive toxicity tests on animal skin

2020-10-09

The U.S. Environmental Protection Agency (EPA) is continuing to follow through on EPA Administrator Andrew Wheeler’s commitment to reduce animal testing by seeking public comment on draft guidance that would allow researchers to forego testing chemicals on animal skin in certain circumstances to determine whether pesticides lead to adverse effects.

“This proposed guidance is a great example of how we can continue to protect human health and the environment and make science-based decisions about pesticide registrations without needing to conduct unnecessary tests on the skin of animals,” said EPA Administrator Andrew Wheeler. “Today’s action puts EPA on a path of eliminating the need for all mammal testing by 2035.”

“With this draft policy the Agency continues to make real progress in reducing animal testing requirements, saving animals and resources while maintaining environmental and human health protections,” said Physicians Committee for Responsible Medicine Vice President for Research Policy Kristie Sullivan. “The Physicians Committee encourages companies to consider this draft guidance to avoid dermal toxicity tests and thanks those involved in this analysis and resulting policy.”

The proposed dermal toxicity guidance would allow waivers for studies on single-active ingredients used to develop end use products to apply for waivers. In developing the guidance, EPA conducted a retrospective analysis and concluded that its requirement for such studies provides little to no added value in regulatory decision making. This guidance, when finalized, is expected to save up to 750 test animals annually from unnecessary testing as well as EPA, industry and laboratory resources.

EPA will take comments on the proposed guidance for 30 days after publication in the Federal Register. Comments can be submitted online at http://www.regulations.gov (Docket ID No. EPA-HQ-OPP-2016-0093). After carefully considering public input, EPA will finalize the Guidance.

In addition, EPA has launched a new webpage  that provides metrics and strategies for reducing and replacing animal testing, including links and resources to all pertinent guidance and workplans tied to the larger Toxicology in the 21st Century Initiative across the federal government.

Background

In September 2019, Administrator Wheeler issued a directive calling for the Agency to reduce animal testing and funding 30 percent by 2025 and eliminate it by 2035. To support these efforts:

EPA will host its Second Annual Conference on the State of the Science on Development and Use of New Approach Methods (NAMs) for Chemical Safety Testing  virtually on October 19 and 20, 2020.

To learn more about EPA efforts to reduce animal testing, visit: https://www.epa.gov/research/efforts-reduce-animal-testing-epa.

Center for Contemporary Sciences launches to advance human-specific research models that will end animal testing

2020-09-22

A new organization in the biomedical field has launched with a mission to improve lives through education, funding and championing scientific innovation based on human biology.

Center for Contemporary Sciences (CCS) is an independent 501(c)3 organization that is advancing human-specific research methods and testing to improve lives. The organization will serve as a hub of the latest information, resources and innovation in the biomedical field. 

The team at CCS includes researchers, doctors and experts with diverse backgrounds in biomedical sciences. “Our end goal is to help create a biomedical research paradigm that delivers safe and effective therapies faster and more efficiently. By doing so, we can deliver true hope to patients suffering from currently untreatable diseases, and to their families. We can heal ourselves without harming animals and do so more quickly,” shared Dr. Aysha Akhtar, President and CEO of CCS. 

One of the ways they hope to enrich the scientific field is through collaboration. CCS partners with scientists, corporations, government agencies and academia to further scientific discovery. The organization is pioneering the transition to innovative human-specific medical research and testing methods including  3D human-tissue culture, human stem-cells, organ-and body-on-a-chip methods, human spheroids and organoids, bioprinting, and more.

They are committed to creating funding opportunities by connecting investors and biotech companies as well as increasing the pipeline of biomedical students to new testing technologies.

As one of their first initiatives, the Center for Contemporary Sciences is building several databases to become the “go-to” resource for the latest innovations within the biomedical field.

“Greater than 90% of drugs and vaccines fail in human clinical trials, despite showing signs of safety and efficacy in animal and traditional laboratory tests. Human-specific research approaches are, by their nature, more predictive of human biology and disease than nonhuman methods,” added Dr. Jarrod Bailey, Director of Science and Technology at CCS. 

“We therefore need, urgently, to shift the focus of biomedical research and testing away from animals and towards hi-tech, cutting-edge human-based methods.”

Compassion fatigue in laboratory animal research: Recording available

2020-09-17

Many laboratory animal technicians enter this profession because they love animals, but this caring role may come at a cost to their own wellbeing. The NC3Rs recently held a joint webinar with the North American 3Rs Collaborative (NA3RsC), presented by NA3RsC Fellow Dr Megan LaFollette, focusing on compassion fatigue and the effect it can have on animal care staff.

Virtual SACATM meeting considers ICCVAM’s future directions

2020-09-15

The Scientific Advisory Committee on Alternative Toxicological Methods (SACATM) met virtually in a public webcast on September 2-3. Over 200 people viewed or participated in the webcast, making it one of the most broadly viewed SACATM meetings ever. SACATM meets annually to advise NICEATM, ICCVAM, and the director of the National Institute of Environmental Health Sciences regarding statutorily mandated duties of ICCVAM and activities of NICEATM.

Recognizing the occasion of ICCVAM’s 20th anniversary, SACATM members and commenters praised ICCVAM’s work to advance alternatives to animal testing and identified opportunities for further progress. Specific areas mentioned included genotoxicity and carcinogenicity and replacement of animal use for antibody production.

An entire day of the meeting was devoted to considering the data that are needed to evaluate new methods and tools that can put data to use. Presentations discussed variability in animal data, applications of machine learning, and in vitro human-based models that incorporate genetic diversity. NICEATM scientists showcased computational tools for exploring toxicity data and making toxicity predictions. Presentations from the meeting will be available soon on the NTP website at https://ntp.niehs.nih.gov/events/past/index.html?type=SACATM, and minutes will be posted following their review by the committee.

Save the date for the next ICCVAM public event: the annual ICCVAM Communities of Practice webinar is planned for Tuesday, January 26, 2021. Information will be posted on the NICEATM events webpage at https://ntp.niehs.nih.gov/go/3Rs-wksps as it becomes available.

ECHA Board of Appeal decisions concerning vertebrate animal testing on cosmetic ingredients

2020-08-22

The Board of Appeal adopted two decisions concerning compliance checks of registration dossiers for homosalate and 2-ethylhexyl salicylate, which are used exclusively as ingredients in cosmetic products (cases A-009-2018 and A-010-2018).

In the contested decisions, ECHA had required a registrant to carry out several studies on vertebrate animals on the substances to fulfil registration requirements for human health endpoints, namely a 90-day subchronic toxicity study, two PNDT and two EOGRT studies. In one of the two cases, ECHA also required the registrant to carry out a fish sexual development test.

Vertebrate animal testing on cosmetic ingredients (A-009-2018 and A-010-2018)

The registrant argued before the Board of Appeal that ECHA cannot require studies on vertebrate animals for human health endpoints because the substances are used exclusively as ingredients in cosmetic products.

The Board of Appeal found that the REACH Regulation requires registrants to perform studies on vertebrate animals even if the substance is used exclusively as an ingredient in cosmetic products. The REACH Regulation does not contain an automatic exemption from the information requirements for registration if a substance is used as an ingredient in cosmetic products. A registrant can benefit from an exemption only if it shows that the conditions for an adaptation (for example, a waiver for the studies) are fulfilled.

This conclusion is consistent with the Cosmetics Regulation. The Cosmetics Regulation contains restrictions for vertebrate animal testing on the ingredients of cosmetic products. These restrictions, however, do not prevent registrants from carrying out tests in order to comply with the information requirements of REACH.

Information requirements concerning aquatic toxicity (A-010-2018)

The registrant also argued before the Board of Appeal that ECHA cannot require a fish sexual development test because this test is not a standard information requirement for registration purposes.

The Board of Appeal held that a fish sexual development test is not a standard information requirement for registration purposes (Column 1 of Section 9.1. of Annex IX). However, ECHA has the power to require a fish sexual development test from a registrant, if necessary, as an adaptation (Column 2 of Section 9.1. of Annex IX).

In this case, ECHA had found that a fish sexual development test is necessary because existing information shows that 2-ethylhexyl salicylate may be an endocrine disruptor. As a consequence, ECHA was entitled to require the registrant to carry out a fish sexual development test.

Outcome

The Board of Appeal rejected both appeals.

Andrew Fasey, Technically Qualified Member of the Board of Appeal and rapporteur for the cases, says: “The two decisions published today are among the most important taken by the Board of Appeal to date. The relationship between the information requirements in REACH and the marketing and testing ‘bans’ in the Cosmetics Regulation have been an issue for many years with several different interpretations. The two decisions adopted today are based on a rigorous analysis of the wording and objectives of the two pieces of legislation. I don’t expect that everyone will agree entirely with these decisions. We have however tried to set out as clearly as possible how and why we have arrived at our conclusions.” 

Further information

The full text of the decisions can be found under the following links:

NAT Database on Non-Animal Technologies

2020-08-22

The NAT database (Non-Animal Technologies) recently launched by Doctors Against Animal Experiments (DAAE) gives an overview about animal-free research technologies that are developed all over the world. This database currently contains 250 entries on animal-free methods and will continuously be updated. It is freely available at www.NAT-database.org in English or German and all entries are free for download and sharing. 

Entries contain a short abstract of the respective technology as well as information on contact persons including affiliations and references such as peer-reviewed publications or press releases from universities and research institutes. Commercially available technologies and research models such as microphysiological systems or advanced human cell culture models are also included.  

The NAT database is supposed to inform scientists, regulators, and politicians, as well as the general public, about the power and the advantages of non-animal technologies. Users can run a full text search or use different filter options such as research areas (e.g., oncology, toxicology, or drug development) or research models (e.g. organ-on-a-chip, 3D bioprinting, or computer models). The NAT database also enables a specific search for validated methods, which are additionally labelled in case of regulatory acceptance for safety testing by ECVAM or OECD.

FDA accepting proposals for alternative methods webinar series

2020-08-13

The Office of the Chief Scientist of the U.S. Food and Drug Administration (FDA) is launching a webinar series on alternative methods. The webinar series supports FDA’s commitment to promote novel technologies and potentially incorporate them into its regulatory review, as applicable.

Test method developers who participate in this webinar series will have the opportunity to introduce their new technology to FDA and give individual FDA programs the option to contact them for further information. Please note, however, that participation in FDA’s webinar series does not constitute FDA’s endorsement of a new method or oblige FDA to assist the developer in qualifying a new method for regulatory use.

To be considered for the webinar series, please submit the following information to alternatives@fda.gov:

  • A description of your new method, including origin of cells or species of animal if appropriate.
  • A description of the proposed context of use of your new method.
  • A description of the regulatory issue/gap where the new method could have an impact.
  • Data from use of your method, including any publications.

FDA will respond within 60 days to your webinar submission. For more information, visit https://www.fda.gov/science-research/about-science-research-fda/fda-webinar-series-alternative-methods-showcasing-cutting-edge-technologies-disease-modeling

ICCVAM 2018-2019 Biennial Report now available

2020-08-10

The ICCVAM Biennial Progress Report 2018-2019 is now available at https://ntp.niehs.nih.gov/go/2019iccvamreport.

The ICCVAM Authorization Act of 2000 directed ICCVAM to prepare a progress report on its first anniversary and every other year thereafter. The latest ICCVAM Biennial Progress Report describes ICCVAM and ICCVAM agency activities from January 2018 through December 2019. Key ICCVAM, ICCVAM agency, and NICEATM accomplishments summarized in the report include:

  • Publication of A Strategic Roadmap for Establishing New Approaches to Evaluate the Safety of Chemicals and Medical Products in the United States.
  • Development of the Collaborative Acute Toxicity Modeling Suite, in silico models of acute oral systemic toxicity that predict five specific endpoints needed by regulatory agencies.
  • Expansion of the Integrated Chemical Environment (https://ice.ntp.niehs.nih.gov/).
  • Development of plans to replace, reduce, or refine animal use for testing by the U.S. Department of Defense, the U.S. Environmental Protection Agency (EPA) and the U.S. Food and Drug Administration.

This edition of the Biennial Report has been reorganized to make it easier for users to find content of interest. Menu items allow users to view articles by agency or find articles relevant to topics such as in vitro to in vivo extrapolation, cardiotoxicity, or mixtures toxicity. Reference pages list publications of interest as well as providing glossary terms and acronyms relevant to ICCVAM agencies and activities.

Small Business Grants available for test method development

2020-08-03

The Department of Health and Human Services (HHS) has released the 2020 Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) Omnibus Grant Solicitations. These solicitations will be used by the National Institutes of Health and other offices within HHS to fund researcher-initiated projects in health, medicine, and life sciences.

Projects being funded by the National Institute of Environmental Health Sciences (NIEHS) under this solicitation include development of toxicity screening, testing, and modeling approaches that support Tox21 and other NTP goals. Areas of high priority include development of:

  • Metabolically competent in vitro assay systems for various tissue types.
  • Computational approaches for predictive toxicology.

The first deadline for applications under this announcement is September 5. More information is available on the NICEATM website at https://ntp.niehs.nih.gov/go/alt-funding.

NIEHS has also reissued the Funding Opportunity Announcement for its Commercialization Readiness Pilot program. These grants support commercialization of previously funded SBIR and STTR Phase II and Phase IIB projects by funding activities not typically supported through Phase II or Phase IIB grants or contracts. Small businesses that have had an active National Institutes of Health SBIR or STTR Phase II or Phase IIB award within the last 36 months are eligible to apply. Awardees will receive up to $300,000. Standard SBIR/STTR application deadlines apply for these grants; the next deadline is September 5. More information is available at https://grants.nih.gov/grants/guide/pa-files/PAR-20-128.html.

ICE version 3.1 now available

2020-08-03

On July 24, NICEATM released an update of the Integrated Chemical Environment (ICE). ICE provides data and tools to help develop, assess, and interpret chemical safety tests. This update adds the following features to these ICE tools:

  • Search: query results can now be sent directly to the EPA CompTox Chemicals Dashboard.
  • In Vitro to In Vivo Extrapolation (IVIVE): assays can be selected based on mode of action; results can be filtered by mode of action or toxicity endpoint annotation.
  • Chemical Characterization: principal component analysis plots provide an additional option for visualization of chemical properties.

Other new resources in ICE 3.1 include:

  • New Chemical Quick Lists: U.S. Environmental Protection Agency (EPA) List of Active Ingredients and EPA List of Inert Ingredients Food and Nonfood Use.
  • Additional metadata provided in results downloads.
  • New tooltips and information buttons to help users set up queries.

ICE is available at https://ice.ntp.niehs.nih.gov/.

Händel Animal Welfare Prize 2020 goes to Thomas Hartung and Marcel Leist

2020-07-30

Thomas Hartung, MD, PhD, Director of the Center for Alternatives to Animal Testing (CAAT) at the Johns Hopkins Bloomberg School of Public Health, and Marcel Leist, PhD, co-director with Hartung of CAAT-Europe and Chair of the department of In Vitro Toxicology and Biomedicine at the University of Konstanz, have been selected to receive the Ursula M. Händel Animal Welfare Prize by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation). The €80,000 prize is awarded to researchers who improve research animal welfare in line with the principles known as the 3Rs of alternatives: Replacement (of animal experiments with non-animal methods), Reduction (of the numbers of animals used for a particular experiment), and Refinement (reducing pain and distress of laboratory animals).

This award honors the life’s work of both scientists in making major contributions to animal welfare. Hartung was recognized for using artificial intelligence (“read-across”) to predict the toxicity of chemicals without using animals. Instead of using animals, data from a particular chemical is compared to similar chemical structures in toxicological databases to determine possible toxicity. 

The awardees were also recognized for their international networking with multiple international stakeholders (researchers, regulatory authorities, non-governmental organizations, and industry) to advance the acceptance of alternative methods.

The two winners were chosen from among nine nominees and will use the prize money of €80,000 to enable early career scientists to perform research in the 3Rs. The award ceremony is scheduled for October 1st, 2020, at the Interdisciplinary Centre for 3Rs in Animal Research (ICAR3R).

Thomas Hartung has been director of CAAT and co-director of CAAT-Europe since 2009. He has received many prizes for his research work, such as the US Society of Toxicology Enhancement of Animal Welfare Award and the Russell and Burch award of the Humane Society of the United States.

Marcel Leist has been co-director of CAAT-Europe since its foundation in 2009. Leist has received several prizes for his work, including the Animal Welfare Research Award from the German Federal Ministry of Food and Agriculture. 

The Johns Hopkins Center for Alternatives to Animal Testing (CAAT), founded in 1981, is part of the Johns Hopkins University Bloomberg School of Public Health, with a European branch (CAAT-Europe) located at the University of Kostanz, Germany. CAAT promotes humane science by supporting the creation, development, validation, and use of alternatives to animals in research, product safety testing, and education. 

The Ursula M. Händel Animal Welfare Prize goes back to the initiative of the founder of that name. A resident of Düsseldorf, Ursula M. Händel (1915–2011) championed animal welfare over several decades. Dedicated to animal welfare in science and research, Händel provided the DFG with the financial backing for the animal welfare prize. The prize is awarded every two years. 

Information about the prize, its founder Ursula M. Händel, and the prizewinners can be found a the official press release from DFG.

Press Release from the Doerenkamp-Zbinden Foundation.

ECHA issues report on animal and alternatives use

2020-07-22

The European Chemicals Agency (ECHA) has issued its fourth report on the use of alternatives to animals for testing required under the REACH regulation. Data on more than 12,000 substances show that registrants are sharing data, using adaptations to avoid animal testing, and employing alternatives to animal testing. Examples include:

  • Registrants used at least one adaptation to avoid animal testing for about 70% of substances. Read-across is the most commonly used adaptation.
  • Use of non-animal tests for evaluating potential for skin and eye irritation and skin sensitization has increased greatly since 2016.
  • Companies are reducing the numbers of animals used for repeat dose toxicity tests and reproductive screening by using the combined test described in OECD Test Guideline 422.

The report and a summary of the report can be found at https://echa.europa.eu/about-us/the-way-we-work/plans-and-reports under the subheading “Reports on Alternatives to Animal Testing.”

OECD updates and corrects eight Test Guidelines

2020-07-18

On 26 June, OECD adopted a set of updated and corrected Test Guidelines for chemicals safety testing to keep pace with scientific progress for OECD members and Mutual Acceptance of Data (MAD) adhering countries.

Eight Test Guidelines have been updated (TG 437, TG 458, TG 488, TG 491) and corrected (TG 405, TG 439, TG 442C et TG 471):

EPA releases New Approach Methods Work Plan

2020-07-03

On June 23, the U.S. Environmental Protection Agency (EPA) released its New Approach Methods Work Plan, which was created in response to the EPA Administrator’s 2019 directive to prioritize activities that will reduce the use of animal testing while continuing to protect human health and the environment. The work plan was developed by experts across the agency to set the objectives and strategies for using new approach methods to meet the ambitious goals set out in the Administrator's directive. It is available at https://www.epa.gov/chemical-research/epa-new-approach-methods-work-plan-reducing-use-animals-chemical-testing

Charité 3R Toolbox provides 3Rs related information resources for young scientists

2020-06-19

The Charité 3R Toolbox is designed to help scientists – in particular young scientists within academia – to find alternatives to animal research, use fewer laboratory animals, improve the welfare of these animals and, in doing so, enhance the quality of the scientific research.

About 60 years ago, W.M.S. Russell and R.L. Burch developed the ‘principles of the 3Rs’which they published in their book "The Principles of Humane Experimental Technique". Since then, many scholars have proposed the inclusion of additional Rs to supplement the existing three. The Charité 3R Toolbox is structured along the lines of the 6R model proposed by the BIH QUEST Center (position paper Strech & Dirnagl, 2019) which adds robustness, registration and reporting to the existing 3Rs of replacement, reduction and refinement.

Pilar Prieto wins the ALTEX Award 2020

2020-05-26

We are pleased to announce that Dr Pilar Prieto of the EU Commission Joint Research Centre (JRC) in Ispra, Italy is the winner of the ALTEX Prize 2020 as first author of the article “Investigating cell type specific mechanisms contributing to acute oral toxicity“. The article was selected by the ALTEX Editorial Board, the Board of ALTEX Edition and the ALTEX editorial office as the best article published in ALTEX during 2019. The award will be presented at the 11th World Congress on Alternatives and Animal Use in the Life Sciences in Maastricht in 2021.

The ALTEX Prize is awarded annually and is kindly sponsored by the Doerenkamp-Zbinden Foundation.

Presentations available from webinar on small business funding

2020-05-22

Presentations are now available from the April 17 town hall webinar on “Development of New Approach Methodologies to Reduce Animal Use in Toxicity Testing.” The webinar was presented by the National Institute of Environmental Health Sciences (NIEHS) Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) program in coordination with NICEATM. The presentations are available on the NTP website at https://ntp.niehs.nih.gov/go/sbir-townhall-2020. A video of the webinar is available on the NIEHS website at https://www.niehs.nih.gov/research/supported/translational/sbir/townhall/index.cfm.

A key component of the Strategic Roadmap for Establishing New Approaches to Evaluate the Safety of Chemicals and Medical Products in the United States is early interaction between developers of new approach methodologies (NAMs) and end-users, to ensure that the proposed NAMs will meet testing requirements for agency and industry stakeholders. The goal of this webinar was to facilitate improved communication between method developers, including SBIR/STTR applicants, and end-users. The webinar provided an opportunity for assay developers to hear from ICCVAM stakeholders on the desired characteristics and requirements for NAMs. Presenters included representatives from NICEATM, the U.S. Environmental Protection Agency, the U.S. Food and Drug Administration, the U.S. Department of Defense, 3M Corporation, and Novartis.

EURL ECVAM recommends use of nonanimal-derived antibodies

2020-05-22

The European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) has issued a recommendation urging end-users and other stakeholders to recognize the scientific validity of nonanimal-derived antibodies and to stop using animals for antibody development and production. The recommendation is based on the opinion of EURL ECVAM’s scientific advisory committee. It states that animals should no longer be used for the development and production of antibodies for research, regulatory, diagnostic and therapeutic applications. It also challenges misconceptions about nonanimal-derived antibodies and highlights the scientific and economic benefits of their use. The report is available at https://publications.jrc.ec.europa.eu/repository/bitstream/JRC120199/jrc120199pdf.pdf; a news release summarizing the report’s recommendations is available at https://ec.europa.eu/jrc/en/science-update/better-antibodies-without-using-animals.

Use of nonanimal-derived antibodies was the topic of the 2020 ICCVAM Communities of Practice webinar, presented in January. One of the webinar presenters, Rebecca Clewell, served on the scientific advisory committee on whose opinion the EURL ECVAM recommendation was based. Presentations from the webinar are available at https://ntp.niehs.nih.gov/go/commprac-2020.

New FDA Webpage Highlights Alternative Methods Working Group

2020-05-04

FDA has a long-standing commitment to promote the development and use of new technologies to better predict human and animal responses to substances relevant to its regulatory mission. To strengthen that commitment, FDA launched its Alternative Methods Working Group. This group facilitates interactions with global regulatory bodies interested in implementing alternative methods in toxicology. Additionally, the group examines opportunities and viable ways by which emerging methods and new technologies can support regulatory review of risk, safety, and efficacy of FDA-regulated products.

The Alternative Methods Working Group recently launched its webpage at https://www.fda.gov/science-research/about-science-research-fda/advancing-alternative-methods-fda, which will highlight FDA’s work in this area. A link to this page and to other ICCVAM agency webpages focused on alternative methods is available on the NICEATM website at https://ntp.niehs.nih.gov/go/iccvam-agencies.

WC11 postponed to August 22-26, 2021

2020-04-29

Due to the global COVID-19 developments, the Dutch authorities have decided to ban all major events taking place until 1 September 2020. After lengthy and thoughtful considerations, the WC11 organization decided to postpone the 11th World Congress on Alternatives and Animal Use in the Life Science, scheduled to take place August 23-27, 2020 in the Netherlands. The new dates for the 11th congress will be August 22-26, 2021. The venue of the congress will remain the MECC Maastricht, the Netherlands.

3Rs relevant online training material

2020-04-28

The Swiss 3RCC has compiled a dedicated webpage of organisations active in the promotion of the 3Rs who have added online training material on their websites:
 
NC3Rs – National Centre for the Replacement, Refinement and Reduction of Animals in Research offers different e-learning resources, experimental design resources and for example information on housing and husbandry.  
 
Labroots offers virtual events and webinars on a range of topics related to the 3Rs. You find keynotes on different in vitro disease models, in silico toxicology and animal models, enrichments, ways to improve reproducibility and the ARRIVE guidelines, which help you improve the design and reporting of animal research. 
 
CAAT (Johns Hopkins Center for Alternatives to Animal Testing) offers podcasts and free webinars on alternative methods. They include events on how to minimise the use of animals in toxicity testing, how to move beyond animals in the neurosciences and infectious disease research. The 7th Annual 3Rs symposium, co-hosted by the USDA Animal Welfare Information Center (AWIC), NIH Office of Laboratory Animal Welfare (OLAW), the Johns Hopkins Department of Molecular and Comparative Pathobiology, and the Johns Hopkins Center for Alternatives to Animal Testing (CAAT), will be held online on June 4-5, 2020. One of CAAT's experts has published a video where he explains how his group is using its in vitro minibrain models to study the effects of SARS-CoV-2 on brain cells.  
 
SYRCLE The SYstematic Review Center for Laboratory animal Experimentation at Radboud University Medical Centre in the Netherlands offers tools and guidelines for the conduct of systematic reviews of animal studies. 
 
Eindhoven University of Technology offers a free online statistics course. Instructor Daniel Lakens explains how to design experiments and select your sample sizes so that p-values, effect sizes, confidence intervals and likelihood ratios can answer your research questions. Participants also learn how to interpret evidence in scientific literature given the widespread publication bias, how to perform replication studies, why you should pre-register your experiment and publish it open-access.
 
The 3R Smart is an information and training platform, which addresses interested laymen as well as scientists and technical staff. The project is funded by the German Ministry of Education and Research (BMBF) and coordinated and developed by the University of Veterinary Medicine Hannover Foundation and the Philipps University Marburg. 
 
NORECOPA: Norway's National Consensus Platform for the advancement of the 3Rs suggests resources, which may be suitable for schoolchildren and undergraduate students undertaking home learning in connection with the Covid-19 pandemic. Emphasis has been placed on products which are available online, thereby avoiding the need for purchase of equipment. You may find alternatives to dissections in the NORINA database with suggestions on how to replace the use of rats or frogs.
 
RAT – Research Animal Training (formerly Flaire Learning) offer e-learning modules to support researchers applying for licences in the U.K., but that are also of interest to scientists in Switzerland. The articles and eLearning modules on the RAT site align with the learning outcomes specified for EU training modules. Some learning outcomes require practical tuition, and this should be provided in person. Further information for course attendees, a listing of the eLearning modules currently available, a website feature list, FAQ page and some example screens . 
 
BIH – Berlin Institute of Health has created a list of resources to help you make the best of this strange and challenging time and increase the quality of your research in the future. 
 
GV-SOLAS – The German Society of Laboratory Animal Science will organise two livestream events at the end of April. The 49th seminar on laboratory animals and animal research will take place on April 28th and 29th, and the 13th training event of GV-SOLAS for animal welfare officers and members of authorities will take place on April 29th and 30th. 
 
SIB – Swiss Institute of Bioinformatics experts are taking part in the global effort to develop dedicated data services, analysis tools and improve knowledge sharing to fight the COVID-19 pandemic. Find a list of tools and resources on a dedicated website of the SIB. 
 
ASCCT – American Society for Cellular and Computational Toxicology holds webinars on new animal-free testing methodologies. The webinars are available for all to attend and watch at no cost. 

Norecopa calls for contributions to Refinement Wiki

2020-04-28

Norecopa invites all members of the research animal community, regardless of their position, to add material to the Refinement Wiki which was launched last month. It can be accessed at https://wiki.norecopa.no. Please email Norecopa's secretary (adrian.smith@norecopa.no) if you would like to contribute.

Norecopa is greatful for the generous sponsorship for development of the wiki from the Research Fund of the Norwegian Animal Protection Alliance.

Norecopa makes dataset of worldwide educational resources available

2020-04-28

Norecopa has embedded a dataset of over 560 resources from 6 continents within education and training in their website. The dataset was produced by the EU Commission's Joint Research Centre (JRC). The data, collected between June and September 2018, provide a snapshot overview of education and training courses and resources on the theory and application of the 3Rs principle offered at high school, university and professional levels worldwide.
Norecopa has used the dataset's categories to make over 70 search filters, so that the number of hits can be expanded or narrowed as desired, e.g. by country, language or potential audience. Searches on the Norecopa website will automatically retrieve hits from this dataset, but the filters can be applied to remove all or some of them, depending on the user's wishes.
The work of integrating the dataset was kindly sponsored by Sanofi, to whom Norecopa is most grateful.
Some of the data will need updating, and cross-checking with data already held in the Norecopa database. This work is ongoing. The dataset complements Norecopa's International Webinar and Meetings Calendar, overview of training courses and the NORINA database of educational and training aids, all of which are updated continuously.

The dataset is described in the 2019 EURL ECVAM Status Report on the Development, Validation and Regulatory Acceptance of Alternative Methods and Approaches. A total of 569 E&T courses and resources with Three Rs relevance were identified in 52 countries worldwide, the majority located in Europe (72%) and North America (14%). In Europe, more than 80 courses were delivered in the United Kingdom, whilst Germany, Switzerland and the Netherlands provided 41, 29 and 26 courses respectively. Several E&T courses and resources combined both classroom and distance learning formats. Distance learning through, for example, webinars or interactive online resources represented 30% of the total courses and resources. The map of Europe is taken from this report.
Norecopa reminds readers that The Education & Training Platform for Laboratory Animal Science (ETPLAS) has been established to enable information sharing and communication between EU Member States, accrediting/approval bodies and training providers. The ETPLAS website contains comprehensive information about the requirements laid down by the EU Directive and associated guidance documents.

REACH Chemical Data Available Through IUCLID Database

2020-04-23

The European Union’s REACH (Registration, Evaluation, and Authorisation of Chemicals) regulation requires companies to identify and manage risks of chemicals. Data required under REACH are submitted to the European Chemicals Agency (ECHA).

On April 17, ECHA updated data from REACH studies available through the IUCLID data resource. The data contain results from studies that relate to physical-chemical properties, environmental fate and pathways, and ecotoxicology and toxicological information. These data may be helpful in the development and use of alternatives to animal testing.

More information about the April 17 data release is available at https://iuclid6.echa.europa.eu/view-article/-/journal_content/title/reach-study-results-have-been-updated.

FDA Guidance on Immunotoxicity Testing Supports Use of Alternatives

2020-04-23

In February, the U.S. Food and Drug Administration (FDA) issued draft guidance on “Nonclinical Safety Evaluation of the Immunotoxic Potential of Drugs and Biologics.” This guidance supplements previously issued recommendations on nonclinical evaluations of immunotoxic potential and is intended to assist sponsors in such evaluations. The guidance includes several specific recommendations on assessing potential for dermal sensitization:

  • FDA no longer recommends that sponsors conduct the murine local lymph node assay to assess the sensitization potential of topical drug products due to the limitations of the assay.
  • As an alternative to accepted guinea pig tests, FDA will consider a battery of in silico, in chemico, and in vitro studies that have been shown to adequately predict human skin sensitization with an accuracy similar to existing in vivo methods.

The draft FDA guidance is available at https://www.fda.gov/media/135312/download.

ASCCT webinar library now open at no cost

2020-04-01

As the impact of COVID-19 is felt around the globe, the American Society for Cellular and Computational Toxicology (ASCCT) would like to demonstrate its commitment to sharing educational resources for new non-animal approaches. The ASCCT webinar library is now open to the public at no cost. It includes over 40 expert presentations highlighting innovation in science and policy related topics. The library can be accessed at www.ascctox.org/webinars. Should you like to share your work in cellular or computational approaches through our webinar platform please email ebaker@pcrm.org.

ICE version 3.0 now available

2020-03-20

On March 11, the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods released an update of the Integrated Chemical Environment (ICE). ICE provides data and tools to help develop, assess, and interpret chemical safety tests. The update introduces a new user interface to simplify searches and new tools that will let users explore chemical properties and toxicity in more detail.

The ICE 3.0 update features improvements to the in vitro to in vivo extrapolation (IVIVE) tool. In response to customer requests, ICE now allows users to upload their own data for IVIVE analyses. A new physiologically based toxicokinetic model has been added, and the output graphics have been improved.

Other new resources in ICE 3.0 include:

  • User interface improvements
  • Organization of Tox21 assays in query setup menus based on modes of action
  • Availability of data from in vitro dermal irritation assays
  • Updated property predictions for over 800,000 chemicals from OPERA (Open Structure-activity/property Relationship App; https://ntp.niehs.nih.gov/go/opera)
  • Mapping of Tox21 assays to controlled terms from the NCI Metathesaurus

ICE is available at https://ice.ntp.niehs.nih.gov/.

NIEHS to present webinar on grant opportunities for NAM development

2020-03-18

The National Institute of Environmental Health Sciences (NIEHS) Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) program, in coordination with NICEATM, will host a webinar-based town hall meeting on “Development of New Approach Methodologies to Reduce Animal Use in Toxicity Testing.” The webinar will be held on Friday, April 17 from 1:00-3:00 p.m. EDT. Register at https://nih.webex.com/nih/onstage/g.php?MTID=e8f2aa04b3ee50db19036c52a34ef0c58.

A key component of the Strategic Roadmap for Establishing New Approaches to Evaluate the Safety of Chemicals and Medical Products in the United States is early interaction between developers of new approach methodologies (NAMs) and end-users, to ensure that the proposed NAMs will meet testing requirements for agency and industry stakeholders. This webinar will facilitate improved communication between method developers, including small business (SBIR/STTR) applicants, and end-users, providing an opportunity for assay developers to hear from ICCVAM stakeholders on the desired characteristics and requirements for NAMs. The agenda will include short presentations from experts from U.S. federal agencies and industries, including pharmaceutical developers, with time allowed for questions from method developers. Presenters include representatives from NICEATM, the U.S. Environmental Protection Agency, the U.S. Food and Drug Administration, the U.S. Department of Defense, 3M Corporation, and Novartis.

New FDA guidance available for in vitro drug interaction studies

2020-02-11

The U.S. Food and Drug Administration (FDA) published “In Vitro Drug Interaction Studies – Cytochrome P450 Enzyme- and Transporter-mediated Drug Interactions Guidance for Industry” in January. The guidance is available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/vitro-drug-interaction-studies-cytochrome-p450-enzyme-and-transporter-mediated-drug-interactions.

This guidance is intended to help drug developers plan and evaluate studies to determine the drug-drug interaction (DDI) potential of an investigational drug product. It focuses on in vitro approaches to evaluate the interaction potential between investigational drugs with cytochrome P450 enzymes and transporters, as well as how in vitro results can inform future clinical DDI studies. The appendices of this guidance include factors to consider when choosing in vitro experimental systems, key issues regarding in vitro experimental conditions, and more detailed explanations regarding model-based DDI prediction strategies.

New version of OECD's eChemPortal now available

2020-02-11

The Organisation for Economic Co-operation and Development (OECD) has released eChemPortal v3.0, available at https://www.echemportal.org/echemportal/. The new version includes a modernized user interface architecture, a refreshed design, improved navigation, and the alignment of eChemPortal to OECD Harmonised Template 2018. The user experience is now more fluid, and the user can search for chemical information more efficiently. New features include quick search functionality from the homepage, filtering and sorting on results tables, and a preliminary indication of the number of results expected in a search by chemical properties.

EU statistics on animal use for scientific purposes in 2015-2017 published

2020-02-07

The European Commission has published its 2019 report on animal use for scientific purposes in the EU in 2015-2017. This is the first report compiled according to changed reporting requirements and covers areas of animal use that were not included previously, limiting comparison with previous reports. The report identifies issues with severity reporting as well as consistency of reporting animal use for the maintenance of genetically altered animals. The report also voices concern with the use of animals in areas where alternative methods have reached regulatory acceptance (e.g. skin irritation/corrosion, serious eye damage/eye irritation and pyrogenicity testing) and calls for further attention by the authorities authorizing projects for these use purposes.

The numbers of animals used for the first time for research and testing were 9.59 million (2015), 9.82 million (2016) and 9.39 million (2017) in comparison to almost 11.5 million reported in 2011 (see caveats above). The numbers of procedures (including reuse of animals) were higher by 2% than the number of animals used for the first time in each reported year. The numbers of animals used for the first time for the creation and maintenance of genetically altered (GA) animal lines were 1.59 million (2015), 1.19 million (2016) and 1.28 million (2017).

In 2017, of the animals used for research and testing for the first time, mice, fish, rats and birds together represented 92%. Species of particular public concern (dogs, cats and non-human primates) represented less than 0.3%. No Great Apes were used. While between 2015 and 2017 there was a decrease in the number of amphibians, cephalopods and reptiles (-42%), hamsters (-37%), horses, donkeys and cross-breeds (-25%), and birds (-11%), there was an increase in the numbers of sheep and goats (+9%), cattle (+14%) and non-human primates (NHP) (15%).

2% of the animals used were born outside of the EU; 90% were born in the EU at a registered breeder. However, of the NHPs, only 14% were born in the EU at a registered breeder; most were imported from Africa or Asia. 30% of all NHPs came from self-sustained colonies and 53% were second or higher generation purpose-bred. No NHP used for the first time was captured from the wild in 2017.

In 2017, the main purpose of animal use was research (69%). Subcategories are basic research (45%), translational and applied research (23%), regulatory use (23%) and routine production (5%). Other main purposes were protection of the natural environment in the interest of the health or welfare of human beings or animals, preservation of species, higher education or training for the acquisition, maintenance or improvement or vocational skills and forensic enquiries.

In 2017, severity was categorized as mild (51%), moderate (32%), severe (11%) and non-recovery (6%). Severe uses increased from 2015 to 2016 from 8 to 11%. Batch potency testing resulted in the highest number of severe uses (> 264k). Within a sub-category, the proportion of severity was highest (70%) for production of monoclonal antibodies by the ascites method, followed by diagnosis of diseases (54%) and acute toxicity studies in the area of ecotoxicity (37%).

39% of regulatory uses in 2017 were for toxicity and other safety testing: this amounts to 8% of all animal use. 79% of quality control related uses were for batch potency testing purposes in 2017.

Of GA animals, 17% exhibited a harmful phenotypic alternation. Zebra fish (64%) and mice (38%) were the most common GA species. In 2017, 658K animal uses were carried out to create new GA animal lines. The use of GA NHPs was reported for the first time in the EU in 2017. The use of animals for maintaining colonies of established GA animal lines decreased between 2015 and 2017 from 1 million to 0.6 million.

Video available from webinar on acute toxicity modeling tool

2020-02-07

A video recording and slides are available from a January 22 webinar titled “CATMoS: Development and Use of the Collaborative Acute Toxicity Modeling Suite,” presented by the PETA International Science Consortium (PETA-ISC). Links to recordings of all webinars in the PETA-ISC series on “Use of New Approach Methodologies in Risk Assessment” are available at https://www.piscltd.org.uk/nam-webinars/.

In this webinar, NICEATM Acting Director Nicole Kleinstreuer and Kamel Mansouri, ILS (contractor supporting NICEATM), discussed development of CATMoS, a free resource for screening organic chemicals for acute oral toxicity. Predictions generated by CATMoS compare favorably with performance characteristics of the in vivo acute oral toxicity test. Kleinstreuer and Mansouri also demonstrated how to use the modeling suite to generate acute oral toxicity predictions.

Nicole Kleinstreuer assumes leadership of NICEATM

2020-01-23

As of January 1, Nicole Kleinstreuer has assumed the role of Acting NICEATM Director. Kleinstreuer has been NICEATM Deputy Director since 2016. Before that she worked for ILS, the NICEATM support contractor. In both roles, she has contributed significantly to the development of NICEATM’s capabilities in computational toxicology.

Kleinstreuer received her Ph.D. in bioengineering from the University of Canterbury in Christchurch, New Zealand, and B.S. degrees in mathematics and biomedical engineering from the University of North Carolina at Chapel Hill (UNC-CH). Prior to joining ILS, she completed postdoctoral training at the U.S. Environmental Protection Agency’s National Center for Computational Toxicology. In addition to her work with NICEATM, Kleinstreuer holds a secondary appointment in the Biostatistics and Computational Biology Branch at the National Institute of Environmental Health Sciences (NIEHS) and adjunct faculty appointments at Yale University School of Public Health and Eshelman School of Pharmacy at UNC-CH. Her research focuses on mathematical and computational modeling of biological systems and their susceptibility to perturbations that result in adverse health outcomes. Her achievements have been recognized with awards from a number of organizations, including the Society of Toxicology, Society for Birth Defects Research and Prevention, Australian Mathematical Society, and American Society for Cellular and Computational Toxicology.

The NICEATM leadership change occurs as former Director Warren Casey has accepted the position of Acting Chief of the Biomolecular Screening Branch in the National Toxicology Program Division at NIEHS. Casey will continue as ICCVAM Executive Director, where his responsibilities will focus primarily on administrative and strategic duties.

ALTEX Proceedings gets a facelift

2020-01-22

The website of the journal ALTEX Proceedings, which publishes Abstract books and Proceedings of scientific conferences in cooperation with the respective organizers has been upgraded to offer a more user-friendly experience well in time for the upcoming publication of the Abstract book for the 11th World Conference on Alternatives and Animal Use in the Life Sciences in August 2020.

Like ALTEX, ALTEX Proceedings is published with open access to allow scientists from anywhere in the world to stay up to date on current topics in the field of alternative methods.

We are grateful to the Doerenkamp Zbinden Foundation for supporting the website upgrade and to Ixodes Webservices for its design and implementation.

Presentations Available from EPA Conference on NAMs

2020-01-20

Presentation slides are available from the First Annual Conference on the State of the Science on Development and Use of New Approach Methods (NAMs) for Chemical Safety Testing, presented by the U.S. Environmental Protection Agency (EPA) on December 17. Presentations and other meeting materials are available at https://www.epa.gov/chemical-research/first-annual-conference-state-science-development-and-use-new-approach-methods-0.

This conference was one of EPA’s commitments in the "Directive to Prioritize Efforts to Reduce Animal Testing" signed by Administrator Andrew Wheeler on September 10, 2019, calling for EPA to reduce use of mammalian studies. Presentations discuss both animal and non-animal tests used to satisfy testing requirements and establishing baselines for animal use. Presenters included Acting NTP Biomolecular Screening Branch Chief Warren Casey, Acting NICEATM Director Nicole Kleinstreuer, and ICCVAM Co-chair Anna Lowit, EPA.

A breathing lung-on-a-chip and women’s reproductive organs on-a-chip join the 2020 Lush Prize shortlist

2020-01-07

Lush Prize announced its 2020 shortlist on January 6th.  Among the projects shortlisted were:

- a team from Brunel University in London working on organ-on-a-chip platforms using human cells to replicate female organs (vagina, ovaries, placenta and breast) to better understand the causes and treatment of women’s diseases.

- a Swiss start-up company called AlveoliX who have created a lung-on-a-chip with a moving ‘microdiaphragm’ connected to a soft porous membrane where human cells are cultured.

Both these projects were thought to offer promising routes to replace the use of animals in chemical safety testing with more human-relevant scientific data.  In total, 58 projects from 21 countries were shortlisted for the £250,000 prize fund. The full shortlist is available on the Lush Prize website at www.lushprize.org.

               For the first time this year, Lush Prize were pleased to announce that the shortlist contained a group from Turkey, where awareness-raising of animal welfare issues is just beginning to take off.  As before, it also contained nominations from as far afield as China, New Zealand, Chile and Slovakia.

We have reproduced the full 2020 shortlist for the Science Prize below.  Computational toxicology projects were most frequently shortlisted in this category, with six of the 14 shortlisted groups working in this area.  This will partly be a consequence of Lush Prize altering its criteria in 2019 to focus on computational solutions, and may be a consequence of an upsurge in interest in this area too. 

The next most frequently shortlisted projects were organs-on-chips, where four projects made it through to the final cut, including the two mentioned above.  The Science Prize winner in 2018 was the blinking eye-on-a-chip from the BIOLines Research Group at the University of Pennsylvania.

The winners of the 2020 Lush Prize will be chosen by an expert panel of judges on January 24th in London but will not be publicly announced until the Lush Prize Awards Ceremony in May.

2020_LushPrize_Tab2.png

Free online course on 3Rs and animal use in science

2019-12-18

Young scientists are needed to help meet the European Union’s commitment to replace animal use in science. The European Commission's Joint Research Centre is funding a Massive Open Online Course (MOOC) on the 3Rs (replacement, reduction, and refinement of animal use in science) to provide ideas and examples on how to address the 3Rs in the classroom and develop students’ critical thinking and understanding of science.

The course begins on January 13, 2020, and lasts for five weeks with an estimated workload of four hours per week. It is tailored to secondary school teachers but anyone can register. More information is available at https://www.europeanschoolnetacademy.eu/courses/course-v1:3Rs+AnimalsInScience+2020/about#about

EPA updates List of Alternative Test Methods and Strategies (or New Approach Methodologies [NAMs])

2019-12-10

The U.S. has EPA released an updated version of its List of Alternative Test Methods and Strategies (or New Approach Methodologies [NAMs]). The document can be viewed here:

https://www.epa.gov/sites/production/files/2019-12/documents/alternative_testing_nams_list_first_update_final.pdf

The list contains links to test guidelines, method protocols, computational tools and databases, and guidances and policies from EPA  that "do not use vertebrate animals to develop new data/information," and additional guidance or other documents that are considered "tools and approaches which may enhance the use of NAMs for regulatory use under TSCA."

New additions to the list include:

  • The ToxCast Estrogen Receptor Agonist Pathway Model
  • In vitro BALB/c 3T3 Cell Transformation Assay
  • Determination of in vitro intrinsic clearance using rainbow trout hepatocytes (OECD TG NO. 319A)
  • Determination of in vitro intrinsic clearance using rainbow trout liver S9 sub-cellular fraction (RT-S9) (OECD TG NO. 319B)
  • Several guidance documents related to waiving or bridging or alternative approaches for acute systemic toxicity, eye irritation, skin sensitization, and endocrine disruption
  • FIFRA SAP reports on endocrine disruption, respiratory toxicity, and the EPA CompTox Chemicals Dashboard

 

 

 

Egon Naef Foundation for In Vitro Research awards its 3R Prize to Carole Bourquin of the University of Geneva

2019-11-25

Professor Carole Bourquin receives the Egon Naef Foundation 3R Prize 2019 in recognition for the development of a new in vitro technique that reduces by 20% the number of mice needed for nanoparticle research in immunotherapy.

Nanoparticles allow drugs to be transported to selected sites in our bodies. By targeting the lymph nodes, it is possible to specifically stimulate the immune system, a promising approach to fight cancer. To choose appropriate nanoparticles, researchers test their behavior in animals. Carole Bourquin’s team from the University of Geneva (UNIGE) has developed a technique that makes it possible to perform a first in vitro screening of the nanoparticles. Only the best performers are then tested in animals. This method, which has been awarded the 2019 Egon Naef Foundation Prize for In Vitro Research, reduces the number of mice used in nanoparticle research for immunotherapy.

Immunotherapy research aims to stimulate the immune system to recognize and destroy cancer cells. Nanoparticles can improve treatment effectiveness by delivering the drug in the human body to the exact site where it will trigger the immune response, in the lymph nodes. The most efficient nanoparticles for transporting and releasing drugs into the lymph nodes must be captured by immune cells to be transported to the lymph nodes; they must not be toxic to cells; and they must not activate the immune system against themselves. Until now, nanoparticles were systematically tested in mice to ensure that they meet these three criteria.

The team in Geneva incubated the nanoparticles with immune cells grown in the laboratory. Then it was assessed by flow cytometry whether they had captured nanoparticles and whether or not the cells were in a state of activation. To date there is no non-animal method to predict whether the nanoparticles are transported to the lymph nodes, but the screening method can select the most promising particles before animal testing commences and so reduce the number of animals required for testing.

EPA actions to reduce animal testing

2019-11-02

In a September 17 news release, the U.S. Environmental Protection Agency (EPA) announced a draft science policy to reduce testing of pesticides on birds when registering conventional outdoor pesticides. The draft science policy is based on a retrospective study by EPA and People for the Ethical Treatment of Animals that explored the quantitative and qualitative contributions of risk assessment methods using single oral dose and subacute dietary toxicity endpoints to the overall conclusions of acute avian risk. The analysis indicated that, in most cases, the subacute dietary results had little impact on risk conclusions arrived upon by use of acute oral data alone. This finding is expected to reduce the number of animals tested by a total of 60 birds per test, for a total projected animal savings of over 700 animals per year. The news release is available at https://www.epa.gov/newsreleases/epa-releases-draft-policy-reduce-pesticide-testing-birds. The draft policy can be found at https://www.epa.gov/sites/production/files/2019-09/documents/draft-waiver-guidance-avian-sub-acute-dietary.pdf.

An article in Regulatory Toxicology and Pharmacology co-authored by ICCVAM co-chair Anna Lowit summarizes the activities of EPA’s Hazard and Science Policy Council (HASPOC). HASPOC was established in 2012 by the EPA Office of Pesticide Programs to consider requests for waiving animal study requirements for human health risk assessments. Since its inception, HASPOC has evaluated over 1,000 requests to waive animal studies and granted waivers in response to nearly 90% of requests. These waivers have saved over 200,000 animals, $300 million in study costs, and $6 million in study review costs. The article is available at https://doi.org/10.1016/j.yrtph.2019.104481

FDA presents update on Predictive Toxicology Roadmap; video available

2019-11-02

At a September 18 public meeting, the U.S. Food and Drug Administration (FDA) presented an update on activities to implement its Predictive Toxicology Roadmap. Speakers from seven FDA centers described how predictive toxicology methods are being advanced towards application to safety and risk assessments. Recordings of the meeting webcast are available on the FDA website at https://www.fda.gov/science-research/about-science-research-fda/fdas-predictive-toxicology-roadmap.

Presentations available from September 19-20 SACATM meeting

2019-11-02

Presentations from the September 19-20 meeting of the Scientific Advisory Committee on Alternative Toxicological Methods (SACATM) are available on the NTP website at https://ntp.niehs.nih.gov/events/past/index.html?type=SACATM (click “Presentations” in far right column under “Meetings”).

In presentations at the meeting, scientists from NICEATM, ICCVAM member agencies, and collaborators described advances in alternatives to animal use. SACATM members expressed support for the current activities and direction of ICCVAM and noted the progress that has been made in advancing alternatives to animal testing.

Discussions on the use of computational methods focused on the limitations and applications of machine learning models in predicting toxicology. Considering the potential uses of microphysiological systems (also known as “tissue chips”) in predicting human toxicity, committee members suggested these might be most useful for early-stage toxicity screening, evaluating effects on diverse populations, and providing models for applications lacking established animal models. They cautioned, however, that the context of use for these platforms need to be clearly defined, and expressed support for developing a roadmap to build confidence in specific applications.

SACATM meets annually to advise NICEATM, ICCVAM, and the director of the National Institute of Environmental Health Sciences regarding statutorily mandated duties of ICCVAM and activities of NICEATM.

NTP web update changes location of NICEATM webpages

2019-11-02

An October 2 update to the NTP website implemented a new navigation structure that affects the location and addresses of NICEATM webpages.

Please contact the NICEATM webmaster at spranklec@niehs.nih.gov if you need any help finding specific content within the NICEATM webpages.

ALTEX supports replacement of research materials associated with pain and suffering in animals

2019-10-24

Methods developed to replace animal use for scientific purposes often still make use of a variety of animal-derived materials whose production causes the animals pain and suffering. For example, fetal bovine/calf serum (FBS/FCS), which is used as a universal supplement in cell culture media, is derived from blood drawn from bovine fetuses discovered in pregnant cows during the slaughtering process. If this procedure is performed before the death of the fetus, it may cause the fetus pain and distress.

The journal ALTEX wishes to raise awareness of these issues and of the availability of alternative materials or production methods by recommending to authors to use or develop such approaches, which are also considered to offer better-defined and quality-controlled reagents than the animal-derived materials. While papers submitted for review will not be penalized for using such materials, authors will be asked to consider whether alternative materials might be tested for use in their system in future or would need to be developed from scratch. For example, the FCS-free database maintained by Utrecht University informs on alternative medium supplements to FBS/FCS. Reviewers of scientific papers in ALTEX already often suggest the replacement of FBS/FCS where applicable.

A further animal-derived material is Matrigel, commonly used as a cell scaffold for three-dimensional cell culture, which is produced from Engelbreth-Holm-Swarm (EHS) mouse sarcoma, a tumor grown and propagated in mice. Synthetic hydrogels have been developed as alternatives to Matrigel and some are commercially available.

Monoclonal antibodies, used to mark or bind molecules or to influence their activity, may still be purified from ascites fluid in mice in some countries. This involves inducing an inflammatory reaction in the peritoneal cavity of the mouse, injecting hybridoma (cancer) cells that produce the antibody into the peritoneum and later drawing out (tapping) the ascites fluid. Instead, antibodies can now be produced recombinantly and synthetic aptamers are also used as non-animal affinity reagents.

Obtaining primary animal cells from sentient animals will usually involve some level of pain for the donor animals and should be avoided where possible; models designed to reflect human physiological processes should preferably use human cell-based testing systems to avoid species-specific differences. Proteins and enzymes purified from animal tissue obtained by invasive sampling are often available in recombinant form, e.g. bovine serum albumin.

 

German Animal Welfare Research Prize 2019 goes to IfADo toxicologist

2019-10-22

The Federal Ministry of Food and Agriculture, Germany will award the Animal Welfare Research Prize 2019 to Wiebke Albrecht, a PhD student at the Leibniz Research Centre for Working Environment and Human Factors (IfADo), Dortmund in the group of Jan G. Hengstler, on October 23rd. The prize, which is awarded each year, entails €25,000.

The multi-author publication that was recognized introduces novel test performance metrics to systematically assess and optimize in vitro systems to predict drug-induced liver injury (DILI) and to define the acceptable daily intake of drugs. In the development of in vitro tests to replace animal models, one major challenge is the extrapolation of in vitro cytoxicity results to drug doses that can cause liver toxicity in humans upon oral intake. The performance metrics developed in the study quantify how well a test differentiates between hepatotoxic and non-hepatoxic compounds and how well in vivo hepatotoxic blood concentrations can be estimated. These metrics were employed to optimize test performance on a training set of compounds such that the in vitro concentrations could be extrapolated to in vivo blood concentrations in humans that would be associated with a specific probability of hepatotoxicity, and corresponding oral doses were obtained by reverse modeling. The method also allows the estimation of acceptable daily intake for food additives.

 

 

 

Germany to reform Animal Protection Law following complaint by EC

2019-10-07

Following a complaint from the European Commission, the Federal Government of Germany has announced to the Commission that it will reform the German Animal Protection Law, according to an article in the newspaper "Neue Osnabrücker Zeitung". This action is necessary to avert referral to the European Court of Justice. The Commission had initiated treaty violation procedures by sending a letter of formal notice in July 2018. It had critisized that more than 20 Articles and also Annexes of Directive 2010/63 on the protection of animals used for scientific purposes had not been fully translated into national law. For example, the Directive requires that only primates born in capitivity can be used for experiments. This was not transposed fully into German law according to Brussels. Although Berlin had initially rejected the criticism, it has now conceded that some of the stipulations had not been transposed in sufficiently clear language. First drafts of a reformed law and by-law were included in the letter to Brussels according to the report.

The Commission has also sent a letter of formal notice to Poland in July 2019 with regard to shortcomings in the enactment of 19 articles and three Annexes to the Directive 2010/63.

EPA releases draft guidance for waiving in vivo avian toxicity studies

2019-09-25

In a September 17 news release, the U.S. Environmental Protection Agency (EPA) announced a draft science policy to reduce testing of pesticides on birds when registering conventional outdoor pesticides. The draft policy is open for public comment until November 1. The news release is available at https://www.epa.gov/newsreleases/epa-releases-draft-policy-reduce-pesticide-testing-birds. The draft policy can be found at https://www.epa.gov/sites/production/files/2019-09/documents/draft-waiver-guidance-avian-sub-acute-dietary.pdf; email comments to OPPeco@epa.gov.

This document describes the results and implications of a retrospective study conducted by EPA and People for the Ethical Treatment of Animals. The study explored the quantitative and qualitative contributions of risk assessment methods using single oral dose and subacute dietary toxicity endpoints to the overall conclusions of acute avian risk. The analysis indicated that, in most cases, the subacute dietary results had little impact on risk conclusions arrived upon by use of acute oral data alone. This finding is expected to reduce the number of animals tested by a total of 60 birds per test, for a total projected animal savings of over 700 animals per year.

Herbert-Stiller-Prize for Animalfree Research awarded by Doctors Against Animal Experimentation

2019-09-18

The Herbert-Stiller-Prize 2019 was awarded by the society Doctors Against Animal Experimentation on occasion of the society's 40th anniversary in Frankfurt am Main, Germany on September 14, 2019. The prize aims to support the winners to realize a planned research project in the field of medicine or life science. Prof. Jens Kurreck and Dr Johanna Berg of the TU Berlin won first prize. Their project aims to optimize animal product-free 3D bioprinting. The second prize went to Dr Mario Rothbauer of the TU Vienna, who plans to develop a human-based cell culture model of the synovium as an organ-on-a-chip model for rheumatoid arthritis research. Both projects will be supported with €20.000.

EPA directed to phase out animal testing by 2035

2019-09-12

In a memorandum published September 10, 2019, Administrator Andrew R. Wheeler has directed the United States Environmental Protection Agency (US EPA) to "aggressively pursue a reduction in animal testing" by prioritizing ongoing efforts and directing existing resources towards new activities to reduce animal testing while ensuring protection of human health and the environment. He also indicated that additional agency resources may be activated to support new cross-office activities.
The memo states that more than 200,00 laboratory animals and $300 million have been saved in recent years as a result of collective efforts to reduce animal testing and that new approach methods (NAMs) have extensive benefits, which, apart from reducing the use of animals, allow the evaluation of more chemicals across a broader range of potential biological effects in a shorter timeframe and using fewer resources "while often achieving equal or greater biological predictivity than current animal models".
Specific commitments formulated in the memo are that EPA will reduce its requests for and funding of live mammal studies by 30% by 2025 and eliminate all live mammal study requests by 2035. Any mammal studies requested or funded after this date will require Administrator approval on a case-by-case basis. The EPA will further strive to exclude any reliance of mammal studies from third parties in its approval processes after January 1, 2035, subject to legal requirements.
The Administrator further requests a joint annual conference on NAMs to be held from 2019 forward organized by the Office of Chemial Safety and Pollution Prevention (OCSPP) and the Office of Research and Development (ORD) as a resource on NAM developments to scientists and policy makers.

NICEATM and ICCVAM workshop reports available

2019-07-26

NICEATM and ICCVAM scientists were coauthors on three recently published workshop reports.

  • NICEATM Deputy Director Nicole Kleinstreuer is a coauthor of the report on the Ninth Berlin Workshop on Developmental Toxicity held in September 2018. Attendees at this workshop considered the future of in vitro methods for developmental and reproductive toxicology, the potential relevance of alternative species in testing of developmental effects, and risk and hazard assessment of developmental and endocrine effects. Recommendations included the need for a harmonized terminology for classification of anomalies in laboratory animals in developmental toxicity studies for human health risk assessment. The report is available at https://www.ncbi.nlm.nih.gov/pubmed/31288076.
  • The October 2018 workshop “Implementing Nonanimal Approaches to Human and Veterinary Vaccine Testing: Achieving Scientific and Regulatory Success for Rabies and Beyond” explored how to advance alternative methods for human and veterinary rabies virus vaccine potency testing. NICEATM Director Warren Casey and David Allen, ILS (contractor supporting NICEATM), workshop participants, coauthored the report, which is available at https://www.sciencedirect.com/science/article/pii/S1045105619300545. The workshop was co-sponsored by NICEATM and the International Alliance for Biological Standardization-North America.
  • A report from the October 2018 “Summit on Artificial Intelligence in Environmental Health Science and Decision Making” is available at http://environmentalhealthcollaborative.org/wp-content/uploads/2019/07/RTEHC-2018-Summit-Report.pdf. The goal of the summit was to identify and prioritize environmental health sciences research questions that might be investigated with artificial intelligence and machine learning techniques. Kleinstreuer and Lyle Burgoon, U.S. Department of Defense, co-chair of the ICCVAM Ecotoxicology Workgroup, were among the presenters at the summit.

European Organ-on-Chip Society open for active membership

2019-07-10

The founding phase is complete: the European Organ-on-Chip Society (EUROoCS) is now welcoming members to join. The annual conference, held this year in Graz (Austria), saw the launch of the community website and the start of its availability as an information resource. “We invite scientists, engineers, as well as regulators and patient representatives interested in these new laboratory models to become active members of the society and contribute to efforts of the Organ-on-Chip community in promoting recognition and implementation of  this exciting research field,” says Christine Mummery, chair of EUROoCS and professor of Developmental Biology at Leiden University Medical Center, the Netherlands 

Organ-on-Chip (OoC) systems are among the latest emerging technologies for healthcare research. It is believed they will accelerate drug discovery, advance drug efficacy and toxicology testing and open new opportunities for personalized medicine. “Organ-on-Chip systems can reduce and perhaps eventually replace animal experiments and provide predictive human data before expensive and lengthy clinical trials actually start,” vice-chair Peter Loskill says. The biophysicist heads the Organ-on-Chip research group at the Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB in Germany.  

OECD issues new and updated in vitro and in chemico Test Guidelines

2019-07-10

The Organisation for Economic Co-operation and Development (OECD) issued three new and six updated Test Guidelines on June 18. Included among the new documents are tests relevant to replacing or reducing animal use for common acute toxicity endpoints. Links to the new Test Guidelines are available at  http://www.oecd.org/env/ehs/testing/oecdguidelinesforthetestingofchemicals.htm

  • Test Guideline 494 (new) describes the in vitro Vitrigel-Eye Irritancy Test (EIT) to identify chemicals not requiring classification and labelling for eye irritation or serious eye damage.
  • Test Guideline 442C (updated) describes in chemico assays that measure covalent binding of a test chemical to skin proteins, a key event in the adverse outcome pathway for skin sensitization. The previous TG 442C described the direct peptide reactivity assay. The updated Test Guideline also describes a similar method, the amino acid derivative reactivity assay (ADRA), and discusses how in chemico protein binding assays could be used within integrated approaches to testing and assessment for skin sensitization.
  • Test Guideline 492 (updated) describes in vitro reconstructed human corneal epithelium test methods to identify chemicals not requiring classification and labelling for eye irritation or serious eye damage. The Test Guideline is based on four commercial methods of this type. It includes descriptions of essential test method components and a list of chemicals to be used to demonstrate proficiency with the assays.
  • Test Guidelines 431 and 439 (updated) describe in vitro reconstructed human epidermis test methods to identify chemicals that may cause skin corrosion (TG 431) or irritation (TG 439). The test guidelines were revised to include a greater number of commercial methods of this type. Both Test Guidelines include lists of chemicals to be used to demonstrate proficiency with the assays.

ECHA to scrutinise all REACH registrations by 2027

2019-06-27

The European Chemicals Agency ECHA has announced that the European Commission will propose an amendment to REACH, requiring that compliance checks of registration dossiers are performed on 20% of dossiers in each tonnage band instead of currently 5%. This means that around 30% of all dossiers of registered substances will be checked. This amendment is a result of a joint action plan of ECHA and the Commission to improve compliance of registration dossiers and thus ensure that safety data on chemicals is complete.

ECHA further states that it aims to screen all registration dossiers that were submitted by the 2018 deadline - for substances in the > 100 tonnage band by 2023; for substances in lower tonnage bands by 2027. Similar substances will be assessed in groups and substances will be categorized by the end of 2020 as a priority for risk management, data generation or of low priority for further action.

ECHA Press release: ECHA/NR/19/09

Use of cell-based assay for botulinum toxin products approved

2019-06-18

Ipsen Pharma has received approvals from U.S. and Canadian regulatory authorities for use of their in vitro Cell-Based Assay to establish stability and potency of its botulinum toxin products. This follows prior approval received in the European Union and Switzerland for this application of the Cell-Based Assay.

The basis of the Cell-Based Assay is the BoCell® technology platform, developed by BioSentinel Inc., a Madison, Wisconsin-based company that specializes in developing platforms for the detection and measurement of botulinum toxins. BioSentinel and Ipsen collaborated closely in development of the Cell-Based Assay, which achieves a level of precision comparable to the mouse-based LD50 assay.

The announcement of the approval is available at https://www.ipsen.com/websites/Ipsen_Online/wp-content/uploads/2019/02/01155324/00-IAW-POSITION-STATEMENT-US-and-CN-approvals-01-02-2019.pdf.

ICE version 2.0 now available

2019-06-04

On May 20, NICEATM released a major update of the Integrated Chemical Environment (ICE), available at https://ice.ntp.niehs.nih.gov/. ICE provides data and tools to help develop, assess, and interpret chemical safety tests. The ICE update introduces a new user interface to simplify searches and new tools that will let users explore chemical properties and toxicity in more detail.

The new ICE home page delivers users easy access to all the tools within ICE, as well as user guides and related information. The updated ICE search tool includes a new module that simplifies assay selection. Another new feature allows users to add chemicals with the same core structure, such as different salt forms and stereochemistry, to their search, which expands the relevant toxicity data returned from the search.

In addition to the search tool, ICE includes in vitro to in vivo extrapolation (IVIVE), machine learning, and chemical characterization tools. The updated IVIVE tool provides more complex models, including those from the U.S. Environmental Protection Agency’s httk package, to improve prediction accuracy.

Slides and video available from ICCVAM Public Forum

2019-06-04

Slides and a video recording from the May 23 ICCVAM Public Forum are available on the NICEATM website at https://ntp.niehs.nih.gov/go/iccvamforum-2019. ICCVAM holds annual public forums to share information and facilitate direct communication of ideas and suggestions from stakeholders. The May 23 meeting was held at the Natcher Conference Center, National Institutes of Health, Bethesda, Maryland.

Over 40 attendees and more than 200 webcast viewers heard presentations by ICCVAM members representing eight U.S. agencies on current activities related to the development and validation of alternative test methods and approaches. Presenters described member agency activities to implement the strategic roadmap for establishing new approaches to evaluate the safety of chemicals and medical products in the United States. A key focus was progress made towards reduction and replacement of animal use for acute toxicity tests required by regulatory agencies: acute systemic toxicity, skin and eye irritation, and skin sensitization testing. Public comments submitted to the meeting praised specific actions agencies have taken in the past year to advance the strategic roadmap goals, and suggested additional activities that could support further progress.

ICCVAM activities will also be discussed at the September 19-20 meeting of the Scientific Advisory Committee on Alternative Toxicological Methods, to be held at the U.S. Food and Drug Administration Center for Food Safety and Applied Nutrition in College Park, Maryland. Information about that and other upcoming NICEATM events is available on the NICEATM 3Rs Meetings and Workshops page at https://ntp.niehs.nih.gov/go/3Rs-wksps.

Jan van der Valk receives Björn Ekwall Award

2019-05-17

Dr. Jan van der Valk, director of the 3Rs-Centre ULS, has been selected as the recipient of the Björn Ekwall Memorial Award for the year 2019. The annual award recognizes scientists who have substantially contributed to the field of cell toxicology, e.g. by developing new in vitro tests, or via mechanistic or validation studies.
Dr van der Valk was recognized for his work to make scientists aware of the issues regarding the use of fetal calf serum (FCS), which is harvested from bovine foetuses taken from pregnant cows during slaughter. In the past 20 years, Dr van der Valk has organized workshops, given lectures and published several papers on this topic, including recently in ALTEX (doi:10.14573/altex.1705101). The 3Rs-Centre Utrecht Life Sciences and Animal Free Research UK launched the FCS-free Database in 2017, where researchers can find FCS-free media for specific cell-types.

China accepts nine non-animal testing methods for the regulation of cosmetics

2019-04-08

China’s National Medical Products Administration (NMPA) has accepted certain non-animal test methods for the regulation of cosmetics as reported by the Institute for In Vitro Sciences. In a March 22 notice, NMPA announced acceptance of nine test methods, including the direct peptide reactivity assay for skin sensitization and the short time exposure test assay for eye irritation. These new regulations will go into effect January 1, 2020 and will be the preferred toxicological tests for the registration and pre-market approval of cosmetic ingredients. 

New book available: Animal Experimentation: Working Towards a Paradigm Change

2019-04-01

There is growing recognition that a focus on human-relevant data is needed for the understanding and possible treatment of chronic, complex diseases, many of which are not well understood and, thus, cannot be readily modeled in non-human animals. The technology revolution has greatly changed the field of life sciences and now provides us with tools enabling a shift away from animal experimentation. The 51 experts who have contributed to Animal Experimentation: Working Towards a Paradigm Change (Brill open access) review current animal use in science, and they discuss innovative, human-relevant approaches to advance the life sciences and to accelerate the shift towards the replacement of animals in research, testing and education.
 
Background: The book was initiated by Kathrin Herrmann, Director of CAAT’s Evidence-based Refinement Program. Besides co-editing the book with Kimberley Jayne, Kathrin wrote the introductory chapter.

You can read the open access book online or purchase a physical copy here.

Read CAAT Director Thomas Hartung's article, Research and Testing Without Animals: Where are We Now and Where Are We Heading? and Refinement on the Way Towards Replacement: Are We Doing What We Can? by CAAT's Director of Evidence-based Refinement program, Kathrin Herrmann. 

Felix Wankel Animal-Welfare-Research-Award for Dorothea Döring

2019-03-29

On March 14, 2019 the Felix Wankel Animal-Welfare-Research-Award 2019 was bestowed at the Ludwig Maximilians University in Munich on Dr Dorothea Döring for her work on the behaviour of laboratory dogs and aspects of animal protection in dog husbandry. Prof. Dr Christian Klimmt gave a keynote lecture on public acceptance of animal experiments from the perspective of a communications scientist.

Dr Döring has published an article in ALTEX on the behaviour of dogs before and after rehoming to private homes: https://doi.org/10.14573/altex.1608171

The prize of €30.000 is awarded every two years.

 

NICEATM SOT presentations available

2019-03-27

A webpage summarizing NICEATM and ICCVAM activities at the March 10-14 Society of Toxicology (SOT) annual meeting is available at https://ntp.niehs.nih.gov/go/niceatm-sot19. The page includes links to presentations from the ICCVAM exhibitor-hosted session, “ICCVAM Update on Implementing New Approaches to Evaluate the Safety of Chemicals and Medical Products in the United States.” Six NICEATM poster presentations are also available on the webpage.

Australian cosmetic animal test ban bill passes Senate

2019-03-04

The Industrial Chemicals Bill passed by the Australian Senate on February 14, 2019 includes measures to prohibit reliance on new animal test data for chemicals introduced into Australia for use as ingredients in cosmetics. The Government reached an agreement with the Humane Society International to commit to reinforcing measures that ensure that all cosmetic ingredients are included in the ban and to fund and support the development and uptake of non-animal test methods.
To date there are nearly 40 national bans and further national bans are under discussion in numerous states. The Humane Society International with its global campaign #BeCrueltyFree and its partners have played a leading role in raising awareness in the countries and negotiating with the governments on the issue of banning animal testing for cosmetics ingredients.

SOT honors scientists working on alternative methods

2019-02-21

The recipients of the 2019 SOT Awards have been announced, among them the following scientists working in the field of alternatives to animal experiments:

Nicole Kleinstreuer, NIEHS/NICEATM will receive the SOT Achievement Award to recognize her leadership and distinction in contributing to the field of toxicology, particularly in the areas of alternative toxicological methods and computational toxicology.
Suzie Fitzpatric, US FDA, wins the SOT Enhancement of Animal Welfare Award for her expertise in alternative toxicological methods and work to improve animal welfare within the field of toxicology.
Yvonne Chang, Oregon State University, will receive the Colgate-Palmolive Award for Student Resaerch Training in Alternative Methods.
Helena Hogberg, Johns Hopkins University, and Hao Zhu, Rutgers, both win the Colgate-Palmolive Grant for Alternative Research.

EURL ECVAM issues status report on alternatives

2019-02-13

The European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) has issued its 2018 “Status Report on the Development, Validation and Regulatory Acceptance of Alternative Methods and Approaches.” The status report describes research, development, and validation activities, as well as initiatives that promote the regulatory and international adoption and use of alternative approaches and their dissemination. Key findings include:

  • Significant progress has been made in combining in vitro and computational methods to 'read-across' toxicological properties between similar chemicals to avoid unnecessary animal testing.
  • There is increased use of alternatives to identify endocrine disruptors and assess chemical mixtures.
  • Challenges still prevent the use of alternatives alone to fully characterize complex toxicological properties of chemicals that cause chronic systemic health effects.

EURL ECVAM, which is part of the European Commission's Joint Research Centre, coordinates research and validation studies on alternatives to animal testing within the European Union. EURL ECVAM also shares knowledge about and promotes use of alternative methods.

A link to the report and an interview with two of its authors are available at https://ec.europa.eu/jrc/en/news/finding-alternatives-animal-testing-going-win-win-win. More information about EURL ECVAM is available at https://ec.europa.eu/jrc/en/eurl/ecvam.

ICCVAM members recognized by SOT

2019-01-17

The Society of Toxicology will present awards to two ICCVAM members at its annual meeting in March.

Suzanne Fitzpatrick of the U.S. Food and Drug Administration (FDA) Center for Food Safety and Applied Nutrition (CFSAN) will receive the 2019 SOT Enhancement of Animal Welfare Award. This award recognizes contributions that advance toxicological science through development and application of methods that replace, refine, or reduce the need for experimental animals. This marks the fourth consecutive year that an ICCVAM or NICEATM affiliated scientist has been honored with this award. Fitzpatrick, who is principal FDA representative on ICCVAM, is a Senior Science Advisor for Toxicology at CFSAN. She is the FDA lead for Tox21 and chair of the FDA Predictive Toxicology Roadmap Committee. She also plays a leading role in FDA evaluations of organs-on-chips technology.

NICEATM Deputy Director Nicole Kleinstreuer will receive the 2019 SOT Achievement Award. This award is presented to an SOT member who, within 15 years since obtaining their highest degree, has made significant contributions to toxicology. Kleinstreuer’s research focuses on mathematical and computational modeling of biological systems and perturbations that result in adverse health outcomes. She has made key contributions to strategies that combine in vitro high throughput assay data with computational models to predict the likelihood of toxicity. She also represents the National Institute of Environmental Health Sciences on ICCVAM.

Collaborative Acute Toxicity Modeling Suite (CATMoS) now available

2018-12-20

NICEATM has released the Collaborative Acute Toxicity Modeling Suite (CATMoS), a free resource for screening organic chemicals for acute oral toxicity. CATMoS is implemented in v2.0 of the Open Structure-Activity/Property Relationship App (OPERA), a free and open-source quantitative structure-activity relationship (QSAR) tool. OPERA v2.0 can be downloaded from the NIEHS Github repository at https://github.com/NIEHS/OPERA/releases.
CATMoS is the result of a global collaboration to develop in silico models to predict acute oral toxicity. It is a suite of consensus models developed by combining the results of individual models contributed by participants in the April 2018 Workshop on Predictive Models for Acute Oral Systemic Toxicity (see https://ntp.niehs.nih.gov/go/atwksp-2018 and https://doi.org/10.1016/j.comtox.2018.08.002). The individual models were built using information on chemical structures and rat oral acute toxicity data for nearly 9000 chemicals, and tested using approximately 3000 chemicals.
CATMoS includes models for predicting five acute oral toxicity endpoints: very toxic, non-toxic, U.S. Environmental Protection Agency hazard classification, United Nations Globally Harmonized System of Classification and Labelling of Chemical (GHS) hazard classification, and LD50. Predictions generated by CATMoS may be useful to those developing or triaging new chemicals or for prioritizing existing chemicals for more detailed and rigorous toxicity assessments.

NICEATM Integrated Chemical Environment updated

2018-12-13

Updates to the NICEATM Integrated Chemical Environment (ICE) resource were launched in September and November. ICE is available at https://ice.ntp.niehs.nih.gov/.

Successful computational toxicology projects depend on freely available, high-quality data that are formatted for use in computational workflows. ICE provides data from NICEATM and its partners, as well as other resources and tools, in an environment designed to support chemical safety assessment and new method development.

Recent ICE updates have:

  • Expanded physicochemical property predictions to include over 720,000 chemicals using an updated set of predictive models (described in Mansouri et al. 2018, https://jcheminf.biomedcentral.com/articles/10.1186/s13321-018-0263-1)
  • Updated the curated high-throughput screening data from the Tox21 initiative to include increased curation and the most up-to-date data release
  • Added new workflows to enable:
    • In vitro to in vivo extrapolation (method described in Casey et al. 2018, https://ehp.niehs.nih.gov/doi/10.1289/ehp1655)
    • Construction of machine-learning models to predict chemical hazard
    • Characterization of chemical lists using physicochemical properties to relate chemicals

Future updates will allow users to get physicochemical property predictions on their own data sets, add chemical use descriptions to chemical characterizations, and provide a three-compartment generalized physiologically based pharmacokinetic model for in vitro to in vivo extrapolation.

The History of Alternative Test Methods in Toxicology published

2018-12-01

The History of Alternative Test Methods in Toxicology uses a chronological approach to demonstrate how the use of alternative methods has evolved from their conception as adjuncts to traditional animal toxicity tests to replacements for them. This volume in the History of Toxicology and Environmental Health series explores the history of alternative test development, validation, and use, with an emphasis on humanity and good science, in line with the Three Rs (Replacement,Reduction, Refinement) concept expounded by William Russell and Rex Burch in 1959 in their now classic volume, The Principles of Humane Experimental Technique.

The book describes the historical development of technologies that have influenced the application of alternatives in toxicology and safety testing. These range from single cell monocultures to sophisticated, miniaturised and microfluidic organism-on-a-chip devices, and also include molecular modelling, chemoinformatics and QSAR analysis, and the use of stem cells, tissue engineering and hollow fibre bioreactors. This has been facilitated by the wider availability of human tissues, advances in tissue culture, analytical and diagnostic methods, increases in computational processing, capabilities, and a greater understanding of cell biology and molecular mechanisms of toxicity.

OECD releases revised GD 150 on evaluating chemicals for endocrine disruption

2018-11-23

The revised edition of Guidance Document (GD) 150 includes new and updated test guidelines that have been validated, or are currently in the validation process. Updates to the test guidelines concern all levels in the OECD Conceptual Framework for Testing and Assessment of Endocrine Disrupting Chemicals, and the Conceptual Framework itself has been updated. The revised GD includes various cross-cutting issues and a summary of some experiences gained from using the guidance in the first edition.

Of the five levels of the Conceptual Framework, Level 1 considers existing data and existing or new non-test information and Level 2 considers in vitro assays providing data about selected endocrine mechanism(s)/pathway(s). Levels 3-5 consider in vivo assays on endocrine mechanism(s)/pathway(s), on adverse effects on endocrine-relevant endpoints, and more comprehensive data on adverse effects on endocrine-relevant endpoints over move extensive parts of the life cycle or the organism.

The tests included in Level 2 are:
– Estrogen (OECD TG 493) or androgen receptor binding affinity (US EPA TG OPPTS 890.1150)
– Estrogen receptor transactivation (OECD TG 455, ISO 19040-3), yeast estrogen screen (ISO 19040-1 & 2)
– Androgen receptor transactivation (OECD TG 458)
– Steroidogenesis in vitro (OECD TG 456)
– Aromatase assay (US EPA TG OPPTS 890.1200)
– Thyroid disruption assays (e.g. thyroperoxidase inhibition, transthyretin binding)
– Retinoid receptor transactivation assays
– Other hormone receptors assays as appropriate
– High throughput screens

Use of NAMs in risk assessment webinar series started

2018-11-19

A new webinar series on the use of new approach methodologies (NAMs) in risk assessment is being organized by the Physicians Committee for Responsible Medicine, the U.S. Environmental Protection Agency (EPA), and the PETA International Science Consortium Ltd. The first webinar in this series was presented on November 7 and can be viewed at https://www.piscltd.org.uk/nam-webinars/. The next webinar in the series is planned for January 2019, and details of the webinar will be posted on the PISC webpage.

The November 7 webinar focused on the two testing strategies included in EPA’s “Policy on the Use of Alternative Approaches for Skin Sensitization Testing” (available at https://www.epa.gov/pesticides/epa-releases-draft-policy-reduce-animal-testing-skin-sensitization). Susanne Kolle described BASF’s “2 out of 3 approach” and Taku Nishijou discussed Kao Corporation’s sequential testing strategy for in vitro skin sensitization testing.

LUSH Prize 2018 awarded

2018-11-17

The winners of the LUSH Prize in the categories science, public awareness, training, lobbying and young researchers were announced at a gala dinner in Berlin on November 16. The Andrew Tyler Award was presented to Prof. Dr Horst Spielmann for his lifetime achievements. The dinner followed a conference titled: Is there an end in sight for animal testing? Can Organ-on-a-Chip replace animal use in safety testing with advanced human focused approaches?

NC3Rs launches Tech3Rs newsletter

2018-11-14

The NC3Rs has launched a new newsletter aimed at animal technicians, focusing on refinements and animal welfare. Tech3Rs will feature updates on the most relevant resources, research and events, supporting technicians to identify opportunities to embed the 3Rs in practice.

Issues will be published quarterly on the NC3Rs website in a downloadable PDF format. Facilities in the UK can also order hard copies for display.

NICEATM, PISC workshop explores alternatives to animal use for pyrogen testing

2018-10-23

A workshop on September 18-19 at NIH explored challenges to acceptance of a human cell-based assay for pyrogen testing of medical devices. The workshop was organized by NICEATM and the PETA International Science Consortium.
Pyrogens are substances that can produce fever when present as contaminants in a drug or medical device. Most pyrogens are biological substances derived from bacteria, fungi, and viruses; material-mediated pyrogens (MMPs), while less common, may also be present. Drugs for injection and medical device products for implantation or other systemic exposure should meet pyrogen limit specifications before they are marketed. Animal-based pyrogen tests are often conducted to investigate the presence of pyrogens. Non-animal monocyte activation tests (MAT) are widely available but infrequently used for pyrogen testing.
At the September workshop, regulators, test developers, medical device manufacturers, and other experts explored how the U.S. Food and Drug Administration Medical Device Development Tools Program could be used to qualify the use of MAT as a standalone pyrogen test for specific medical device contexts-of-use. There was general agreement that the MAT could be qualified as acceptable for batch-release testing for microbial-based pyrogens. However, additional studies were recommended to demonstrate its ability to detect known MMPs. This testing would determine whether the assay can be used for both biocompatibility and sterility or if other information on MMPs would be needed to address biocompatibility.
More information about NICEATM and ICCVAM evaluation of pyrogen test methods is available at https://ntp.niehs.nih.gov/go/iccvam-pyrogen. An agenda, presentations, and other materials from the meeting are available at https://www.piscltd.org.uk/medical-device-pyrogen/.

NICEATM and IABS hold rabies vaccine workshop

2018-10-23

NICEATM and the International Alliance for Biological Standardization co-organized an October 16-17 workshop “Implementing Non-animal Approaches to Human and Veterinary Vaccine Testing: Achieving Scientific and Regulatory Success for Rabies and Beyond” at the National Institutes of Health (NIH) in Bethesda, Maryland. Over 60 scientists from government, academia and industry gathered to develop recommendations to advance alternative methods for human and veterinary rabies vaccine testing.
Presentations on the first day of the workshop detailed the current state of the science of non-animal alternatives to traditional rabies vaccine potency and safety tests. On day two, separate breakout group discussions focused on the steps necessary for implementing alternatives for veterinary and human rabies vaccine potency testing. Participants identified actions and data still needed to achieve this, and laid the foundation for a roadmap towards successful implementation. Meeting outcomes and associated recommendations will be summarized in a report in the journal Biologicals.

Postdoctoral opportunities available at NTP

2018-10-23

The U.S. Food and Drug Administration is accepting applications for postdoctoral fellows to develop human cell- and protein-based assays for assessing cardiotoxicity of new drugs. These projects are part of an initiative to design, build, and test new non-animal approaches to assess cardiotoxicity hazard. The initiative is supported jointly by the National Toxicology Program (NTP; Biomolecular Screening Branch and NICEATM), the U.S. Food and Drug Administration Center for Drug Evaluation and Research, and the Health and Environment Sciences Institute.
Candidates for these two postdoctoral positions should have received Ph.D. or equivalent degrees in computer sciences or life/health/medical sciences within the last five years. Work will be done at National Institute of Environmental Health Sciences (NIEHS) in Research Triangle Park, NC. More information about the projects and instructions for applying are available at https://ntp.niehs.nih.gov/go/cardio.

SACATM meeting focuses on key issues in replacing animal testing

2018-10-23

At its September 5-6 meeting, members of the Scientific Advisory Committee on Alternative Toxicological Methods (SACATM) and other experts advised U.S. government scientists on issues to be addressed to replace animal use for safety testing. About 60 participants met at NIEHS for the annual advisory committee meeting. Participants discussed actions needed to advance goals outlined in a strategic roadmap for new approaches to evaluating the safety of chemicals and medical products.
At the meeting, industry representatives indicated a need for regulators to clearly communicate both their information requirements and willingness to accept data from new approach methodologies to fulfill those requirements. Participants also discussed the need for high-quality reference data from past animal tests to evaluate the performance of new methods, and considered issues involved in sharing and using those data.
SACATM, the advisory committee for ICCVAM, is a panel of experts drawn from industry, academia, and animal welfare organizations. SACATM meets annually to advise ICCVAM, NICEATM, and the NIEHS director on activities related to ICCVAM’s mission.
Materials from the SACATM meeting are available at https://ntp.niehs.nih.gov/events/past/index.html?type=SACATM, and a longer summary is available in an article in the October issue of the NIEHS Environmental Factor newsletter at https://factor.niehs.nih.gov/2018/10/science-highlights/toxicity_testing/index.htm.

UK Home Office publishes 2017 statistics on animal experiments

2018-10-14

The ‘Annual Statistics of Scientific Procedures on Living Animals, Great Britain’ was published by the UK Home Office on the 19th of July 2018.
The figures show that 3.79 million animal experiments took place in Great Britain in 2017, a slight decrease of 4% compared to the previous year. Of these, 1.90 million (50%) related to the creation or breeding of genetically altered animals who were not used in further procedures, while the remaining 1.89 million experiments (50%) were experiments on animals for various purposes. These purposes were basic research (55%); translational/applied research (17%), regulatory tests (27%), and others (1%).
In 2017, there were increases in the number of experiments conducted on horses (up 18% to 10,600) and cats (up 4% to 198 experiments) in Great Britain. However, there were decreases in the use of other species, including mice (down 10% to 1.1 million), rats (down 2% to 234,000), non-human primates (down 17% to 2,960) and dogs (down 22% to 3,847).
Almost 700,000 experiments (32%) carried out in Great Britain in 2017 were deemed to have caused moderate or severe suffering to the animals involved; moderate or severe suffering was alse experienced by 5% of the genetically altered animals not used for further procedures. Moderate suffering is described by Directive 2010/63/EU as causing short term moderate pain or distress or long-lasting mild pain or distress to animals while severe suffering is described as causing severe pain or distress or long-lasting moderate pain or distress to animals.

German Federal Animal Protection Research Prize awarded for secondary nanobodies

2018-10-11

Dirk Görlich and Tino Pleiner of the Max-Planck-Institute for Biophysical Chemistry in Göttingen today receive the Animal Protection Research Prize of the German Federal Ministry of Nutrition and Agriculture (Bundesministerium für Ernährung und Landwirtschaft). The scientists have developed secondary nanobodies as a new form of secondary antibody for use in medicine and research. Secondary nanobodies are based on very small antibodies of Alpakas and are multiplied in bacteria. This approach can reduce the number of animals used for secondary antibody production.

Biomed21 launches newsletter

2018-10-04

The Biomedical Research for the 21st Century (BioMed21) Collaboration brings together scientists and institutions from across Europe, Asia and the Americas who share a vision of a human-focused paradigm in health research. This unique mix of biomedical stakeholders provides both a broad, global outlook as well as deep ties at regional and national levels. BioMed21 welcomes new collaboration opportunities with like-minded organizations and individuals.
The Biomed21 website is designed to be a hub for information related to innovative, human-specific approaches in health research, including relevant publications, funding opportunities, workshops, training opportunities, and other events.
The newsletter delivers top highlights to your inbox every quarter.

NIH to build cell map of human body

2018-10-02

The National Institutes of Health has issued its first set of research funding awards for the Human BioMolecular Atlas Program (HuBMAP). HuBMAP is an open, global framework that will support research community efforts to map the adult human body at the level of individual cells. The project is planning to award $54 million over the next four years to support:

  • Generating, standardizing, and validating data sets on cell organization and variability
  • Development of new tools and techniques to construct high-resolution tissue maps
  • Coordinating program activities, managing HuBMAP data, and building an atlas of tissue maps

An announcement of the grant awards is available at https://www.nih.gov/news-events/news-releases/nih-build-detailed-map-cells-within-human-body. The project website is located at https://commonfund.nih.gov/hubmap

ALTEX Prize 2018 awarded to Martin Paparella

2018-09-28

The ALTEX Prize 2018 for the best paper published in ALTEX in the previous year was awarded to Dr Martin Paparella, Medical University Innsbruck, as first author of "Uncertainties of testing methods: What do we (want to) know about carcinogenicity" at the social evening of the EUSAAT Congress in Linz on September 25 by Dr Sonja von Aulock. Martin Paparella is a regulatory toxicologist; he is coordinator of the Austrian OECD WNT (Working Group of National Coordinators of the Testing Guidelines programme) and of the PARERE (Preliminary Analysis of Regulatory Relevance) network.
The ALTEX Prize is awarded annually and was again kindly sponsored by the Doerenkamp-Zbinden Foundation.

Input Requested on Scientific Program for 11th World Congress

2018-09-11

The 11th World Congress on Alternatives and Animal Use in the Life Sciences (WC11) will be held in Maastricht, the Netherlands, on 23-27 August 2020. Visit the congress website http://wc11maastricht.org/ for the latest updates.

The general theme of the congress, “3Rs in Transition: From Development to Application”, emphasizes the increasing focus on the use of better, more human-relevant models for personalized and preventive health care, safer products and innovative research. A scientific committee is currently being established and the first meeting will take place before the end of this year. The scientific committee will set up the scientific program of the congress around four main themes: safety, disease, innovative technologies, and ethics and welfare. Input on topics for the scientific program is welcomed; please visit the congress website for details.

Guidance Document on Good In Vitro Method Practices (GIVIMP) now online

2018-09-11

The Guidance Document on Good In Vitro Methods Practices (GIVIMP) is a project led by the European Commission’s Joint Research Centre. The aim of this document is to provide guidance in order to reduce the uncertainties in cell and tissue-based in vitro method derived predictions by applying all necessary good scientific, technical and quality practices from method development to implementation for regulatory use. The document is targeted towards test method developers and test guideline users and provides best practices for designing guideline in vitro methods, carrying out safety tests and assuring quality and scientific integrity of the resulting data. The GIVIMP is intended to be an important resource that can help to avoid a scientific reproducibility crisis in in vitro toxicological sciences.

ICCVAM publishes 2016-2017 Biennial Report

2018-08-09

The Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) has published a report summarizing activities of member agencies during 2016 and 2017.
The 2016-2017 ICCVAM Biennial Report is available at https://ntp.niehs.nih.gov/go/2017iccvamreport

The report highlights member agency activities supporting toxicology innovation, as well as regulatory agency initiatives to promote the 3Rs (replace, reduce, or refine animal use) and to provide information about the use of in vitro methods.
Key ICCVAM, ICCVAM agency, and NICEATM accomplishments summarized in the report include:

- Publication of A Strategic Roadmap for Establishing New Approaches to Evaluate the Safety of Chemicals and Medical Products in the United States.

- Guidance documents published by the U.S. Environmental Protection Agency describing approaches to reduce animal use in testing required for pesticide registration.

- Notices published by the U.S. Department of Agriculture describing approaches to reduce animal use for vaccine testing.

- A Predictive Toxicology Roadmap published by the U.S. Food and Drug Administration.

- A non-animal defined approach developed by NICEATM and EPA that identifies substances that may interact with the androgen receptor.

- A non-animal defined approach developed by NICEATM and ICCVAM to predict skin sensitization risk.

- A proposed method developed in collaboration with international partners to evaluate non-animal approaches to identify skin sensitizers.

- Launch of the NICEATM Integrated Chemical Environment (ICE), an online resource that provides high-quality curated data and computational workflows for chemical safety assessment.

Ellen Fritsche and Hamid Reza Noori to receive Ursula M. Händel Animal Protection Prize 2018

2018-07-26

The Ursula M. Händel Animal Protection Prize 2018 of the German Research Council (DFG) will be shared between the toxicologist Prof. Dr Ellen Fritsche of the Leibniz Research Institute for Environmental Medicine at the Heinrich-Heine-University in Düsseldorf and the mathematician, physicist and physician Dr Dr Hamid Reza Noori of the Max-Planck-Institute for Biological Cybernetics in Tübingen. This is the seventh time the prize will be awarded to scientists who improve animal protection in science in accordance with the 3R principle (Reduce, Replace and Refine).

2018 CRACK IT Challenges announced

2018-07-24

This year’s CRACK IT Challenges competition consists of three Challenges identified jointly by the NC3Rs and sponsors:
Challenge 29: ImmuLiver – An immunologically-competent liver model to assess attenuation of yellow fever vaccines.
Challenge 30: RaTS – Raman Transmission Spectroscopy for objective monitoring of rheumatoid arthritis progression in rodent models.
Challenge 31: Moshers – Mouse Smart Hoppers.

This year the competition is funded by the NC3Rs, with co‑funding provided by EPSRC (RaTS) and in-kind contributions from the sponsors.

Improving peer review of in vivo research proposals - videos online

2018-07-24

The NC3Rs recently hosted a workshop on experimental design for funding panel members of the NC3Rs, BBSRC, CRUK, MRC and Wellcome Trust. Videos of the workshop presentations are now available to watch online. As well as supporting funding panel members to assess in vivo research proposals, the videos can help applicants to ensure their proposals provide quality information on experimental design.

NC3Rs announce 2019 highlight notice

2018-07-24

To encourage funding applications relating to areas of strategic importance to the NC3Rs, regular highlight notices are issued that apply across all funding schemes. The 2019 highlight notice will support the development or transfer of innovative applications of non-mammalian organisms by facilitating new partnerships between rodent and non‑mammalian model organism users. A highlight notice launch event will take place on September 4, 2018 in Central London; attendance is free but registration by August 21, 2018 is essential.

 

3Rs-Centre ULS launches e-learning on humane endpoints in animal research and veterinary practice

2018-07-05

The 3Rs-Centre Utrecht Life Sciences has developed an E-learning module on humane endpoints in animal research and veterinary practice. This module is available free of charge, for everyone who works with animals, on www.humane-endpoints.info. It provides both a solid basic training on humane endpoints, and practice opportunities with case studies. This E-learning will contribute to refinement by preparing the users to make well-balanced decisions regarding animal welfare and science.

3Rs-Centre ULS Newsletter July 2018

Experiments on primates to be reduced by 40% in The Netherlands

2018-06-29

Ingrid van Engelshoven, Minister for Education, Culture and Science has called on the Second Chamber to phase out experiments on primates in the Netherlands. The first step will be a 40% reduction of experiments on primates in the Biomedical Primate Research Centre (BPRC) in Rijswijk and a reduction of the colony size by introducing birth control. The letter to the Chamber is a response to the commissioned report "Van Aap na Beter" (from ape to better) of the Rathenau Institute.

With around 1500 primates, the BPRC is Europe's largest primate center.

HESI workgroup surveying use of thyroid assays

2018-06-29

The Health and Environmental Sciences Institute (HESI) Developmental and Reproductive Toxicology Technical Committee Thyroid Hormone Workgroup and the European Teratology Society Thyroid Hormone Task Force have initiated a survey to collect historical data for thyroid hormone measurements from nonclinical studies. This effort aims to provide clarification and guidance regarding the collection, assessment, and interpretation of thyroid hormone data for regulatory toxicology and risk assessment. The data collected will be anonymously archived in a database that will ultimately be available for public use and incorporated into a workshop planned for spring 2019. The ultimate goals of this effort are to improve data interpretation, establish biologically relevant ranges for each assessment, and develop recommendations for best practices for thyroid assessment.

If your organization conducts or has conducted these assays and you are interested in participating in the survey and contributing to the data collection effort, please contact Connie Chen at cchen@hesiglobal.org for more information.

 

3R relevant OECD Test Guidelines and updates released

2018-06-29

On June 25, OECD adopted a set of new and updated Test Guidelines for chemicals safety testing.

Those include two new Test Guidelines on in vitro methods for fish hepatic clearance, TG 319A and TG 319B that can be used to improve in silico predictions of the test chemical bioaccumulation in fish.

Important updates to existing Test Guidelines encompass the inclusion of endocrine-related endpoints in TG 408 (90-d repeated dose toxicity study) and TG 414 (Developmental toxicity study); also Test Guidelines in the area of eye irritation and skin sensitisation have been revised to either improve predictivity of the existing method (TG 438, isolated chicken eye method) or include similar methods to those already existing (me-too methods in TG 442B, TG 442D, TG 492) ensuring more readily usable practical matter by members and Mutual Acceptance of Data (MAD) adhering countries.

A few other Test Guidelines have been slightly amended as well and can be accessed from the sections mentioned below:

A set of supporting documents and Guidance Documents associated to these Test Guidelines will soon be published.

http://www.oecd.org/chemicalsafety/testing/oecdguidelinesforthetestingofchemicals.htm

US EPA releases strategic plan to reduce animal testing for TSCA

2018-06-27

The U.S. Environmental Protection Agency (EPA) has published its Strategic Plan to Promote the Development and Implementation of Alternative Test Methods Within the TSCA Program. The document describes how EPA will promote development and implementation of methods and strategies that reduce, refine, or replace vertebrate animal testing to provide chemical safety information required under the Toxic Substances Control Act (TSCA).
The core components of the plan are (1) identifying, developing, and integrating new approach methodologies (NAMs) for TSCA decisions; (2) building confidence that the NAMs are scientific reliable and relevant for TSCA decisions; and (3) implementing the reliable and relevant NAMs for TSCA decisions.
The strategic plan and related documents are available at https://www.epa.gov/assessing-and-managing-chemicals-under-tsca/strategic-plan-reduce-use-vertebrate-animals-chemical

NICEATM News June 27, 2018

NC3Rs publish strategy to update ARRIVE guidelines

2018-06-22

In 2010 the NC3Rs developed the ARRIVE guidelines, a 20-item checklist covering the key information that should be included in scientific publications describing animal studies to ensure transparency and reproducibility. Despite widespread endorsement of the guidelines, there is mixed evidence of their impact on the quality of reporting. The NC3Rs have published a strategy for the revision of the ARRIVE guidelines, developed with an international working group of experts, in BMJ Open Science.

Report Available from BioMed21 Workshop

2018-06-22

The June 2017 BioMed21 workshop, co-organized by NICEATM and the Human Toxicology Project Consortium, examined actions needed to implement a human systems-biology approach to understanding disease and improving interventions. The report from the workshop has been published in the journal Drug Discovery Today and is available at https://www.ncbi.nlm.nih.gov/pubmed/29870792.

Catherine Sprankle (NIH/NIEHS)

US Government Accountability Office assesses animal use in federal research

2018-06-14

The U.S. Government Accountability Office (GAO) has published a report on the submission of data from agencies to the ANimal and Plant Health Inspection Service (APHIS) and the National Institutes of Health. The report finds that agencies publicly report some data on animal use but do not report other data unless asked. Some data may not be reported accurately because of inadequate instructions, i.e. research with birds, activities outside the United States, and field studies outside a typical laboratory. The GAO recommends that APHIS improve its instructions.
USDA stated that APHIS will take steps to implement GAO's recommendations, with the exception of clarifying reporting instructions for activities outside the United States.

HighlightsFull report

India approves non-animal alternatives to the pyrogen and the abnormal toxicity test

2018-06-05

The Indian Pharmacopoeia Commission has replaced the rabbit pyrogen test and the guinea pig abnormal toxicity test with non-animal alternative methods for drugs manufactured and marketed in India according to The Hindu. The new guidelines will come into effect on July 1, 2018.
The pyrogen test, which is used to test drug batches for fever-inducing contaminations, will be replaced by the bacterial endotoxin test or a monocyte activation test. The abnormal toxicity test, a batch test done for vaccines, which has already been stricken from the U.S. and European pharmacopoeia, can be waived if a compliance certificate is obtained from the National Control Laboratory.

California to ban cosmetics and cosmetic ingredients tested on animals

2018-06-05

Californian senators have voted for a piece of legislation to ban the sale of cosmetic products tested on animals or cosmetic products containing ingredients tested on animals from January 1, 2020. The bill, authored by Senator Cathleen Galgiani, was supported by the Physicians Committee for Responsible Medicine (PCRM) and Social Compassion in Legislation (SCIL). The state's assembly will make a final decision on the bill by the end of September.

Utrecht Advanced In Vitro Models (U-AIM) HUB inaugurated

2018-05-25

The Utrecht Advanced In Vitro Models (U-AIM) was officially launched on May 16, 2018. The goal of U-AIM is to become a “one-stop shop” where high potential in vitro models are being developed, validated and transitioned to stakeholders. Through a strong cooperation between scientists, students, regulators and industry, U-AIM aims to strongly reduce animal experimentation and increase market potential of innovative models. The 3Rs-Centre ULS is directly involved in the U-AIM activities.

FDA final guidance on toxicokinetics studies reduces numbers of animals needed

2018-05-24

In a May 10 Federal Register notice, the U.S. Food and Drug Administration (FDA) announced availability of final guidance on the benefits and limitations of the use of microsampling techniques in toxicokinetics studies. Benefits of these techniques include reducing the numbers of animals needed for these studies.

The Federal Register notice is available at https://www.gpo.gov/fdsys/pkg/FR-2018-05-10/pdf/2018-09930.pdf. All FDA guidance documents are available at https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm

BfR awards fellowship to Malcolm Macleod

2018-04-17

The German Federal Institute for Risk Assessment (BfR) has awarded the first Maria Sibylla Merian Fellowship to Malcolm Macleod for his contribution to improving animal welfare.

EPA requests comments on draft policy on skin sensitization testing

2018-04-13

The U.S. Environmental Protection Agency has released a draft science policy to reduce the use of animals in testing chemicals to evaluate whether they cause an allergic reaction, inflammation or sensitization of the skin. The draft policy is open for public comment until June 9, 2018.

NC3Rs awards 2017 International 3Rs Prize

2018-03-27

The prize was awarded to Dr Elisa Passini and colleagues from the University of Oxford and Janssen Pharmaceutica for developing an in silico model to predict the potential of drugs to cause heart arrhythmia.

OECD launches QSAR Toolbox version 4.2.

2018-02-07

The Toolbox is a software application intended to the use of governments, chemical industry and other stakeholders in filling gaps in (eco)toxicity data needed for assessing the hazards of chemicals. 

SOT announces award winners

2018-01-31

Among the prizes to be awarded at the SOT this March, numerous prizes will be awarded for 3Rs related activities.

CERST to become state institute

2018-01-22

The parliament of North Rhine Westphalia in Germany has increased the budget of the Centrum für Ersatzmethoden zum Tierversuch (CERST) and will make it a state institute.

Norecopa turns 10

2018-01-08

Norway's 3R center and National Consensus Platform for the Replacement, Reduction and Refinement of animal experiments celebrates its anniversary.