Announcements

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

 

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.

Apply for the EPAA 3Rs Science Prize 2020

2020-05-14

The EPAA aims to promote the development, validation and acceptance of 3Rs alternative approaches (replacement, reduction and refinement of testing on animals). The 3Rs science prize is granted every two years to a scientist with an outstanding contribution to 3Rs. We want to promote positive contributions from industry or academia and encourage more scientists to focus their research on the 3Rs goals. Scientists working on relevant methods for regulatory testing (e.g. safety, efficacy, batch testing) providing an outstanding contribution to the use of the 3Rs may apply for the prize.

A selection board (composed of EPAA members and representatives of the EPAA mirror group) evaluates the submissions and provides the EPAA steering committee with the results of the evaluation and a recommendation on the ranking of the submissions. Based on this recommendation, the steering committee then endorses the winner and grants a €10,000 prize.

The prize will be granted to the institution of the winner to be announced at the EPAA annual conference, on 10 November 2020. The winner will have the opportunity to present their work at the 2020 EPAA Annual Conference, gathering regulators, industry stakeholders, academia and civil society. Applicants should, therefore, confirm that they are available on 10 November 2020 (to present their work at the annual conference if they win). Their travel and accommodation will be paid for by EPAA.

Who should apply?

Scientists working on alternative methods for regulatory testing purposes. Applicants should be based in Europe and have up to 10 years of postgraduate experience (i.e. after obtaining their Bachelor’s or Master’s degree). Applicants should submit a written case study based on actual research (not older than 5 years and not a project on future research) where their role and involvement are shown. The application should make clear

  • how the above criteria are met (e.g. how the method or approach relates to regulatory testing)
  • for which regulatory requirements the applicant's approach can be used
  • what the applicant's postgraduate experience, role and involvement in the research are

The EPAA Secretariat will screen applications for eligibility criteria and inform the selection board of their findings. Applications that do not comply with the eligibility criteria are not eligible.

Selection criteria

The selection board, applying 6 selection criteria as shown below, will assess the eligible applications. Each member of the selection board will evaluate the submissions and assess each criterion individually with a rating from 1 (very poor) to 5 (very good). Criteria 1 and 3 will be double-weighted (i.e. a maximum of 10 points each). Every selection board member may rate applications between 0 and 40 points, thus the total ranking of an application will be between 0 and 240 points.

  1. Impact on the 3Rs (reduction, refinement, replacement of animal uses) *weighted x2*
  2. Innovation/contribution to meeting an urgent, yet unmet scientific need
  3. Possible applicability of the method/approach for regulatory testing (including for safety or potency) *weighted x2*
  4. Impact on predictive safety science (better data/science is obtained thanks to the work of the applicant compared to the current animal method)
  5. Work potentially applicable widely e.g. to other methods and endpoints and across sectors
  6. International recognition (already published work, number of publications, rankings in peer-reviewed journals etc.)

Should no application get at least 160 points, the EPAA steering committee may decide not to grant the prize.

Application process

To submit an application, send an email to grow‐epaa@ec.europa.eu by Monday 5 October at 12:00 (noon), Brussels time with the following documents

  1. CV with a list of publications
  2. Cover letter explaining why the applicant's work is relevant and how it contributes to the 3Rs
  3. A case study (max. 2500 words) introducing the applicant's selected work or project and its achievements/results. Pictures, illustrations and videos may also be attached to the case study if relevant. The case study should clearly define the targeted regulatory endpoint, the implemented method and the obtained results
  4. Letter of support/endorsement from their current organisation/employer

Enquiries should be directed to grow‐epaa@ec.europa.eu

Timeline
  • 20 April: Launch of the call for submissions
  • 5 October at noon: Deadline for submissions
  • by 23 October: Winner is notified and invited to attend the EPAA conference in Brussels (sponsored by EPAA)
  • 10 November: EPAA Annual Conference in Brussels.

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.

NCATS Funding Use of Tissue Chips to Support COVID-19 Research

2020-04-23

The National Center for Advancing Translational Sciences (NCATS) has issued two Notices of Special Interest to support research in collecting and examining data on the risks and outcomes for COVID-19 infections using microphysiological systems (MPS) or tissue chips. Such work is expected to advance the translation of research findings into diagnostics, therapeutics, and vaccines. Applications for both opportunities will be accepted on a rolling basis from May 15, 2020, through January 25, 2022.

NOT-TR-20-017 announces the availability of competitive revisions for investigators and institutions funded through existing grants of the NCATS MPS program. Proposals should address development of MPS models for COVID-19, the use of MPS for rapid detection of COVID-19 infection, or the use of MPS to evaluate potential therapeutics for COVID-19. More information is available at https://grants.nih.gov/grants/guide/notice-files/NOT-TR-20-017.html.

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.

EPAA student grants for participation in 3Rs events available

2020-02-18

The EPAA has published its call for the 2020 3Rs student grants. The purpose of the grants is to sponsor students to participate in the major 3Rs events in 2020. They will award one full grant (1000 EUR) and one half grant (500 EUR) for each of the eligible events in: ESTIV2020, the 11th World Congress on Alternatives, and the EUROTOX 2020 Congress.

Every year, several high-profile international meetings bring together world-class scientists working on the development and acceptance of 3R alternatives to animal testing (Replacement, Reduction or Refinement). Costs linked to participation may prevent students with promising work or young scientists at the beginning of their career from attending these events. The EPAA partners are therefore happy to sponsor the 3Rs student grants to facilitate the participation of students and young scientists in such events.

A jury will assess the applications and propose a list of selected candidates to the EPAA steering committee. The jury will be composed of 4 members (two from the industry and two from the European Commission) who will judge.

For each of the eligible events, a lump sum of €1500 is available. Two levels of grants are offered by the EPAA partners: 1 half grant and 1 full grant.

  • A half grant covers the reimbursement of the event registration fees for the student/young scientist as well as travel and accommodation fees, based on the expense receipts up to a maximum of €500.
  • A full grant covers the reimbursement of the event registration fees for the student/young scientist as well as travel and accommodation fees, up to a maximum total amount of €1000, based on the expense receipts.

Eligibility

1) Applicants have to be based (i.e. studying) in one of the 27 EU countries or the UK. Citizenship may be from any country (i.e. also outside of the EU)
2) Applicants must be graduated (BSc / First cycle completed with at least 180 ECTS credits) when applying and should not have a doctoral degree
3) Applicants must still be considered as full-time students or young scientists (≤ 35 years old) when applying
4) Young scientists employed by industry are not eligible
5) No funding or reimbursement by another entity for the same student and event is allowed

Events

Selected high-profile scientific meetings are eligible for the EPAA 3Rs student grants. For 2020, the following events are open for application:

ESTIV - The European Society of Toxicology In Vitro (8-11 June): apply by 4 May 2020
11th World Congress on Alternatives and Animal Use in Life Sciences (23-27 August): apply by 6 July 2020
EUROTOX annual congress – Federation of European Toxicologists (6–9 September): apply by 13 July 2020

               

Application and selection process

The application process is as follows

1) Applications must be sent to EPAA functional mailbox (grow-epaa@ec.europa.eu) by midnight of the day indicated above
2) The award will be granted provided an abstract is accepted for an oral presentation. At the sole discretion of the jury, in exceptional cases work presented in a poster format will also be eligible. EPAA visibility must be guaranteed by including a clear acknowledgement of EPAA’s support in the presentation/poster.

Selection will be made by the jury based on the following documents to be provided by the applicant

  • Abstract submitted for one of the selected events
  • Detailed CV of the applicant with a list of publications (if any)
  • Cover letter describing why the work described in the abstract is important for the 3Rs and why it should be supported by the EPAA grant
  • Recommendation letter from a professor/supervisor also confirming the applicant is a full-time student
  • Proof of acceptance to the event (i.e. invitation to the event or confirmation mail)

Enquiries should be directed to grow‐epaa@ec.europa.eu

EPAA recognition

The winner of the grant will give the EPAA recognition in their presentation/poster. The winner must provide proof, clearly showing their recognition of the EPAA (i.e. a photo or a video with an oral statement). 

The winner of the grant also accepts that the EPAA may publish the abstracts of the presentation and/or the poster on its website (after the event), to promote and disseminate the research. Finally, the winner should provide a summary report of the event and how they benefitted from participation.

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

Abstract submission open for World Congress, Abstracts due March 15

2019-12-18

Abstracts are being accepted for the 11th World Congress on Alternatives and Animal Use in the Life Sciences (WC11). Abstracts should describe recent original work and reflect one of the four conference topics, “Safety”, “Innovative Technologies”, “Ethics, Welfare and Regulation”, and “Disease.” There is no abstract submission fee and registration is not required to submit an abstract, although the designated presenting author is expected to attend. Abstracts must be 300 words or less, written in English, and submitted by March 15, 2020. More information is available at http://wc11maastricht.org/abstract-submission/.

WC11 will be held August 23-27, 2020, in Maastricht, The Netherlands. The theme of the meeting is “3Rs in Transition: From Development to Application.” Registration to attend the meeting is open, with advance registration discounts available until May 15. More information, including a preliminary program, is available at http://wc11maastricht.org/.

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: RaTSRaman Transmission Spectroscopy for objective monitoring of rheumatoid arthritis progression in rodent models.
Challenge 31: MoshersMouse 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.

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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.