Dear readers,

Recent news from the United States on new policies toward reducing the reliance on animal testing and implementing new approach methodologies signals a major advance for the recognition of the NAMs field. While the US Food and Drug Agency (FDA) announced plans to phase out the requirement for animal testing for monoclonal antibodies and other drugs such as other biological molecules, new chemical entities and medical countermeasures, the National Institutes of Health (NIH) announced an initiative to prioritize human-based research technologies by establishing a new Office to coordinate NIH-wide efforts on NAM development, validation and regulatory translation. The initiative’s aims include reducing funding for animal studies and increasing funding for human-based approaches. Nicole Kleinstreuer, Acting NIH Deputy Director, stated in July that NIH would no longer be funding proposals based solely on animal experiments (see the Announcements on the ALTEX website and the Comment by Thomas Hartung in this issue for details).

Following on from Good Cell Culture Practices, Ronit Mohapatra et al. have drafted Good In Vitro Reporting Standards as a complementary guidance to improve the reproducibility of cell culture work in their Food for Thought … contribution and call on stakeholders to join the discussion.

Genome-wide gene expression analysis of human liver cells exposed to drugs can predict their ability to cause liver damage. Wiebke Albrecht et al. assess how the many data points obtained from such studies can best be consolidated into a single, predictive value that can help eliminate liver-damaging drug candidates from development.

While traditional risk assessment based on animal tests labels chemicals as safe or unsafe, probabilistic risk assessment uses computational tools and in vitro toxicological data to estimate the likelihood of harm in different scenarios. The t⁴ Workshop Report by Alexandra Maertens et al. describes the advances and the challenges faced in the implementation of this approach.

Laurence Walder and colleagues report on a roundtable held by animal protection organizations to support the EU Roadmap for Phasing Out Animal Testing for Chemical Safety Assessments by identifying important elements and organizational structures to shape the roadmap and practical steps towards a transition to a regulatory system that does not rely on animal testing.

Patrick J. Devine and collaborators summarize the outcomes of a joint workshop of the IQ MPS Affiliate, comprised of pharmaceutical companies, with the FDA and other regulatory agencies on the potential use of animal cell-based microphysiological systems in drug discovery.

The CRISPR-Cas9 system can correct DNA mutations, however there are concerns about its safety, which is difficult to assess in classical testing models. Emanuele Celauro and colleagues argue that combing CRISPR technology with microphysiological systems can benefit both fields and lead to safer, effective gene therapies.

Modern statistical methods can optimize the accuracy of in vitro toxicological tests in classifying chemicals. Christian Tobias Willenbockel et al. revisit two sets of historical data on eye irritation testing to determine whether the cut-off values applied to the in vitro data can be improved using uncertainty quantification, out-of-sample error estimation, and bootstrapping.

Inhalation of chemicals that interfere with surfactant in the lung can cause severe breathing issues. Sreyoshee Roy Sengupta and colleagues characterize the effects of chemicals found in spray products on surfactant in vitro. Combined with other in vitro methods their results can be used to assess chemicals without using animals.

Motivated by the evaluation of a commonly used UV filter for potential interference with the hormone system, Maria T. Baltazar and colleagues performed a comprehensive safety evaluation to compare this non-animal approach with the traditional safety assessment that had been based on historical animal data. They show that the next generation risk assessment effectively addresses safety concerns for the intended use of the substance.

When animal studies are performed, they should be designed to use the lowest number of animals necessary to generate a conclusive result. Alexander D. Bird and colleagues demonstrate mathematically that performing a pilot study to estimate the number of animals required is not useful when the effect size is unknown and will not contribute to minimizing the number of animals used.

The logistics of sending cell- and tissue-based test systems from one laboratory to another, possibly in another country, are often underestimated, which may lead to wasted resources and the generation of invalid or discordant data. Hans A. Raabe and colleagues share their experience and insights to support other laboratories in transferring models in their BenchMarks contribution.

Wishing you an inspiring experience at the 13^th World Congress on Alternatives and Animal Use in the Life Science,

Sonja von Aulock

Editor-in-chief

We have lost a special friend who cared for experimental animals

Manfred Liebsch, the former head of ZEBET (National Center for the Registration and Evaluation of Alternative Methods to Animal Experiments) at the BGA/BfR in Berlin, died in Bremen after a long illness. Everyone who had the privilege of working with Manfred enjoyed his warm charisma.

He coordinated validation studies of toxicity tests in close cooperation with colleagues from the EU Reference Laboratory for alterna­tives to animal testing (EURL ECVAM), the Japanese health authority NIEHS, and the US Environmental Protection Agency (EPA), in which human cells and tissues were used for local toxicity tests on the eye and skin in order to replace animal testing with animal-free methods for the compatibility testing of cosmetics. After successfully completing the validation studies, Manfred worked at the OECD in Paris to replace legally required animal testing with new OECD test guidelines using human cells and tissues. Manfred’s contributions were crucial to the ban on animal testing for cosmetics in the European Union, which came into force in 2013. He rendered outstanding services to both scientific animal welfare and consumer health protection for cosmetics.

Our condolences go to his wife Ingrid, his two children, and his family.

Horst Spielmann, Barbara Grune, Axel Hahn, Helena Kandarova and Michael Oelgeschlaeger as colleagues from ZEBET at the BGA/BfR, Berlin, Germany, and the following international colleagues: Sonja von Aulock, Germany; Michael Balls, United Kingdom; Joao Barroso, Italy; Jose V. Castell, Spain; Samuel Constant, Switzerland; Rodger Curren, United States; David Es­dale, United Kingdom; Chantra Eskes, Italy; Julia Fentem, United Kingdom; Alan Goldberg, United States; Allison Gray, United Kingdom; John Harbell, United States; Thomas Hartung, United States; Erin Hill, United States; Sebastian Hoffmann, Germany; Koichi Imai, Japan; Brigitte Jenner, Germany; Dagmar Jírová, Czech Republic; Hajime Kojima, Japan; Robert Landsiedel, Germany; Claus-Michael-Lehr, Germany; Sue Leary, United States; Marcel Leist, Germany; Susanna Louhimies, Belgium; Judith Madden, United Kingdom; Uwe Marx, Germany; Gavin Maxwell, United Kingdom; Emily McIvor, United Kingdom; Winfried Neuhaus, Austria; Vicky Robinson, United Kingdom; Vera Rogiers, Belgium; Brigitte Rusche, Germany; Ulrich Schäfer, Germany; Lena Smirnova, United States; Kristie Sullivan, United States; Susan Trigwell, United Kingdom; Kristina Wagner, Germany; Sherry Ward, United States; Carl Westmoreland, United Kingdom; Maurice Whelan, Italy; Andrew Worth, Italy