Use Of Animals In Research Research Articles

A4Development and evaluation of a chest cavity simulation model for teaching surgical chest drain insertion

Surgical chest drain insertion is indicated in pneumothorax or haemothorax secondary to thoracic trauma. It is a mandatory emergency procedure that is incorporated as a part of the core medical training curriculum [1]. However, sparse training opportunities result in low clinician competency and increased risk of complications. While simulation training can offer a solution, the affordability of commercial models and hygiene and ethical implications of animal carcasses are significant limiting factors. The aim of this project is to build a reusable, high-fidelity, low-cost human chest cavity model excluding animal use for simulation-based teaching of surgical chest drain insertion. To construct the model, plaster gauze, metal wires and u-channel rubber trims were used to build a ribcage. Soy-protein-based sausage casing was used to create the pleural layers, and the muscles and subcutaneous fat were represented with ADAMgel (Aqueous Dietary fibre Antifreeze Mix gel), a novel material with tactility and dissection sensation similar to human soft tissue [2]. Synthetic chamois leather was used to represent skin. The resulting model allowed locating the safe triangle using anatomical landmarks, blunt dissection of muscles, pleural puncturing and advancement and suturing of the chest tube. The model cost less than £130, and it could be repaired after over 20 uses with less than £15. Verbal consent on study participation was obtained from all participants who performed chest drain insertion on the model and evaluated its fidelity and educational value using an anonymized Likert scale questionnaire. All questionnaire responses were converted to numerical values for data quantification, as shown in Median and range of questionnaire responses collected from study participants Sixteen senior clinicians with multiple experience on chest drain insertion and 11 junior clinicians with limited experience took part in the study. Anatomical and haptic fidelity of the model was evaluated very highly amongst experienced clinicians. Junior doctors stated increased confidence in performing the procedure, overall assessing the model as an appropriate learning tool. Twenty participants with previous training experience compared the quality of this model to other commercial or animal-based models, and 18 rated this model to be of the same or superior quality. This chest cavity model is suitable for simulation training of chest drain insertion. Importantly, the model excluded the use of animals under the principle of replacing, refining and reducing animal use in research [3]. Further training opportunities that utilize this model can increase clinician competence in the procedure, which can improve clinical practice and reduce patient mortality. Authors confirm that all relevant ethical standards for research conduct and dissemination have been met. The submitting author confirms that relevant ethical approval was granted, if applicable.

Alternative Non-Mammalian Animal and Cellular Methods for the Study of Host-Fungal Interactions.

In the study of fungal pathogenesis, alternative methods have gained prominence due to recent global legislation restricting the use of mammalian animals in research. The principle of the 3 Rs (replacement, reduction, and refinement) is integrated into regulations and guidelines governing animal experimentation in nearly all countries. This principle advocates substituting vertebrate animals with other invertebrate organisms, embryos, microorganisms, or cell cultures. This review addresses host-fungus interactions by employing three-dimensional (3D) cultures, which offer more faithful replication of the in vivo environment, and by utilizing alternative animal models to replace traditional mammals. Among these alternative models, species like Caenorhabditis elegans and Danio rerio share approximately 75% of their genes with humans. Furthermore, models such as Galleria mellonella and Tenebrio molitor demonstrate similarities in their innate immune systems as well as anatomical and physiological barriers, resembling those found in mammalian organisms.

Attitudes to the use of animals in biomedical research: Effects of stigma and selected research project summaries.

Three groups of participants (largely recruited from the UK) completed a survey to examine attitudes to the use of animals in biomedical research, after reading the lay (N = 182) or technical (N = 201) summary of a research project, or no summary (N = 215). They then completed a survey comprising the animal attitude (AAS), animal purpose (APQ), belief in animal mind (BAM) and empathy quotient (EQ) scales. The APQ was adapted to assess attitudes towards the use of animals for research into disorders selected to be perceived as controllable and so 'blameworthy' and potentially stigmatised (addiction and obesity) and 'psychological' (schizophrenia and addiction) versus 'physical' (cardiovascular disease and obesity), across selected species (rats, mice, fish pigs and monkeys). Thus, the APQ was used to examine how the effects of perceived controllability and the nature of the disorder affected attitudes to animal use, in different species and in the three summary groups. As expected, attitudes to animal use as measured by the AAS and the APQ (total) correlated positively with BAM and EQ scores, consistent with the assumption that the scales all measured pro-welfare attitudes. Participants in the two research summary groups did not differentiate the use of rats, mice and fish (or fish and pigs in the technical summary group), whereas all species were differentiated in the no summary group. Participants given the lay summary were as concerned about the use of animals for schizophrenia as for addiction research. APQ ratings otherwise indicated more concern for animals used for addiction research (and for obesity compared to cardiovascular disease in all summary groups). Therefore, the information provided by a research project summary influenced attitudes to use of animals in biomedical research. However, there was no overall increase in agreement with animal use in either of the summary groups.

Origins of US Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training.

The US Government Principles for the use of animals in research are a landmark statement of ethical values and guidance for the biomedical research community. However, when The Principles were introduced, a context was not provided for their source or foundation. The US Government Principles were formulated with input from the Council of Europe, World Health Organization, and US Interagency Research Animal Committee. The Principles continue to provide an ethical foundation for the biomedical research community.

Why Animal Experiments Are Still Indispensable in Bone Research: A Statement by the European Calcified Tissue Society.

Major achievements in bone research have always relied on animal models and in vitro systems derived from patient and animal material. However, the use of animals in research has drawn intense ethical debate and the complete abolition of animal experimentation is demanded by fractions of the population. This phenomenon is enhanced by the reproducibility crisis in science and the advance of in vitro and in silico techniques. 3D culture, organ-on-a-chip, and computer models have improved enormously over the last few years. Nevertheless, the overall complexity of bone tissue cross-talk and the systemic and local regulation of bone physiology can often only be addressed in entire vertebrates. Powerful genetic methods such as conditional mutagenesis, lineage tracing, and modeling of the diseases enhanced the understanding of the entire skeletal system. In this review endorsed by the European Calcified Tissue Society (ECTS), a working group of investigators from Europe and the US provides an overview of the strengths and limitations of experimental animal models, including rodents, fish, and large animals, as well the potential and shortcomings of in vitro and in silico technologies in skeletal research. We propose that the proper combination of the right animal model for a specific hypothesis and state-of-the-art in vitro and/or in silico technology is essential to solving remaining important questions in bone research. This is crucial for executing most efficiently the 3R principles to reduce, refine, and replace animal experimentation, for enhancing our knowledge of skeletal biology, and for the treatment of bone diseases that affect a large part of society. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Tendon-Derived Mesenchymal Stem Cells (TDSCs) as an In Vitro Model for Virological Studies in Wild Birds.

The use of wild animals in research is complicated due to the capture and housing conditions, as well as to legal aspects, making it difficult to develop in vivo and in vitro models for the study of pathologies that affect these species. Here we validate an in vitro model of tendon-derived mesenchymal cells (TDSC) from Eurasian blackbird (Turdus merula) cadaveric samples. Through the expression of surface markers and the ability to differentiate into multiple lineages, the nature of the cells was confirmed. We then evaluated Mesenchymal Stem Cells (MSCs) as an infection model for the Usutu Flavivirus. To this aim, blackbird TDSCs were compared to Vero E6 cells, commonly used in Flavivirus studies. Both cells showed permissiveness to USUV infection as confirmed by immunocytochemistry. Moreover, TDSCs exhibited replication kinetics similar to, although slightly lower than, Vero E6, confirming these cells as a pertinent study model for the study of the pathogenesis of USUV. In this work, we isolated and characterized tendon-derived mesenchymal stem cells, which represent an interesting and convenient in vitro model for the study of wildlife species in laboratories.

Current overview of induced pluripotent stem cell-based blood-brain barrier-on-a-chip.

Induced pluripotent stem cells (iPSCs) show great ability to differentiate into any tissue, making them attractive candidates for pathophysiological investigations. The rise of organ-on-a-chip technology in the past century has introduced a novel way to make in vitro cell cultures that more closely resemble their in vivo environments, both structural and functionally. The literature still lacks consensus on the best conditions to mimic the blood-brain barrier (BBB) for drug screening and other personalized therapies. The development of models based on BBB-on-a-chip using iPSCs is promising and is a potential alternative to the use of animals in research. To analyze the literature for BBB models on-a-chip involving iPSCs, describe the microdevices, the BBB in vitro construction, and applications. We searched for original articles indexed in PubMed and Scopus that used iPSCs to mimic the BBB and its microenvironment in microfluidic devices. Thirty articles were identified, wherein only 14 articles were finally selected according to the inclusion and exclusion criteria. Data compiled from the selected articles were organized into four topics: (1) Microfluidic devices design and fabrication; (2) characteristics of the iPSCs used in the BBB model and their differentiation conditions; (3) BBB-on-a-chip reconstruction process; and (4) applications of BBB microfluidic three-dimensional models using iPSCs. This study showed that BBB models with iPSCs in microdevices are quite novel in scientific research. Important technological advances in this area regarding the use of commercial BBB-on-a-chip were identified in the most recent articles by different research groups. Conventional polydimethylsiloxane was the most used material to fabricate in-house chips (57%), whereas few studies (14.3%) adopted polymethylmethacrylate. Half the models were constructed using a porous membrane made of diverse materials to separate the channels. iPSC sources were divergent among the studies, but the main line used was IMR90-C4 from human fetal lung fibroblast (41.2%). The cells were differentiated through diverse and complex processes either to endothelial or neural cells, wherein only one study promoted differentiation inside the chip. The construction process of the BBB-on-a-chip involved previous coating mostly with fibronectin/collagen IV (39.3%), followed by cell seeding in single cultures (36%) or co-cultures (64%) under controlled conditions, aimed at developing an in vitro BBB that mimics the human BBB for future applications. This review evidenced technological advances in the construction of BBB models using iPSCs. Nonetheless, a definitive BBB-on-a-chip has not yet been achieved, hindering the applicability of the models.

Animal Research in Spain: A Study of Public Perception and Attitudes

Since the time of Hippocrates in the 4th century BC, animal research has been extensively used for various purposes up to the present day. However, the use of animals for research has also been controversial for a long time. We report the findings of a public, online questionnaire-based survey designed to assess the opinions of a sample of Spanish society regarding animal research. Demographic data and opinions were obtained from 806 respondents. The results indicated a high level of acceptance of animal research (73.1%). However, certain factors, such as completing the questionnaire immediately after a reading negative media report (OR = 2.41; 95%CI: 1.64–3.54; p < 0.001), being a woman (OR = 1.77; 95%CI: 1.24–2.53; p = 0.002) or having a non-scientific background (OR = 2.47; 95%CI: 1.76–3.47; p < 0.001), were associated with a tendency towards a more negative opinion. The opinions seemed to be influenced by gender, education level and by protest incidents reported in the media. Our results also indicate that a lot of information regarding animal welfare, such as care and handling protocols, along with legislation was unknown to individuals. Further, a growing popularity of companion species and opposition to animal experimentation for non-biomedical purposes were reflected in the responses obtained. The use of animals for research purposes emerged as a sensitive social issue in terms of concerns about animal ethics and welfare.

Animal ethics in biology teaching and research in selected Asian countries

Governance and regulation of the use of live animals in research and teaching is examined in Australia, Malaysia, Indonesia, the Philippines, Singapore, Thailand, China, Japan and India. A comparison of the systems in different countries will enable the determination of best practice and fit-for-purpose regulation. The most comprehensive government regulation of animal welfare in institutions covers a broad range of animals and institutions are required to have an Institutional Animal Care and Use Committee, whose membership is specified in guidelines or regulations. The work of the Committees is rigorously overseen by government and facilities that use live animals are audited externally. All countries examined have legislation governing the use of live animals in research, although only Australia and Malaysia have a fully equivalent mandated oversight of teaching. Teaching that uses live animals is partly covered in the Philippines, Japan, Singapore and Thailand This paper thus aims to review the regulation of animal use in different Asian jurisdictions in order to determine best practices that are appropriate to those settings. The most comprehensive oversight is provided in Australia and Malaysia that essentially use the same regulatory framework.

Advancing the 3Rs: innovation, implementation, ethics and society.

The 3Rs principle of replacing, reducing and refining the use of animals in science has been gaining widespread support in the international research community and appears in transnational legislation such as the European Directive 2010/63/EU, a number of national legislative frameworks like in Switzerland and the UK, and other rules and guidance in place in countries around the world. At the same time, progress in technical and biomedical research, along with the changing status of animals in many societies, challenges the view of the 3Rs principle as a sufficient and effective approach to the moral challenges set by animal use in research. Given this growing awareness of our moral responsibilities to animals, the aim of this paper is to address the question: Can the 3Rs, as a policy instrument for science and research, still guide the morally acceptable use of animals for scientific purposes, and if so, how? The fact that the increased availability of alternatives to animal models has not correlated inversely with a decrease in the number of animals used in research has led to public and political calls for more radical action. However, a focus on the simple measure of total animal numbers distracts from the need for a more nuanced understanding of how the 3Rs principle can have a genuine influence as a guiding instrument in research and testing. Hence, we focus on three core dimensions of the 3Rs in contemporary research: (1) What scientific innovations are needed to advance the goals of the 3Rs? (2) What can be done to facilitate the implementation of existing and new 3R methods? (3) Do the 3Rs still offer an adequate ethical framework given the increasing social awareness of animal needs and human moral responsibilities? By answering these questions, we will identify core perspectives in the debate over the advancement of the 3Rs.

Use of laboratory animals and issues regarding the procurement of animals for research in Korea

BackgroundLaboratory animals remain critical to biomedical research, despite the increasing availability of alternative approaches. Indeed, scientists strive to reduce and refine and replace the use of laboratory animals, even in the face of public calls for ever-more stringent regulation for the protection and care of animals in research. This report outlines the current status and legal regulatory issues with regard to the procurement and use of animals for research in Korea.ResultsThe number of animals used for education and research purposes was increased nationwide, from 2.5 to 4.9 million in 2015 and 2021, respectively. When compared with figures from the UK, institutions in Korea were found to use more mammals such as mice and dogs. In our research, we identified three major issues concerning recent animal supply in Korea, particularly: (1) Purchase of dogs from unregistered animal supplier for a dog cloning project; (2) Purchase of dogs from an unclear source for veterinary education and training; (3) Illegal cat experiments using cats obtained from unauthorized routes.ConclusionsOur findings support the notion that alternatives to laboratory animal research should be implemented. We conclude that improvements in the regulations and guidelines for animal suppliers, together with the recent introduction of legislation will improve animal safety and wellbeing of animals in laboratory research in Korea.

First report of Eimeria myoxi in the garden dormouse (Eliomys quercinus Linnaeus, 1766) from Doñana Natural Area (Andalusia, SW Spain).

This work reports for the first time the presence and molecular characterization of Eimeria myoxi in the garden dormouse (Eliomys quercinus) from the Doñana Natural Area (Andalusia, SW Spain). Fresh faecal samples were collected from a total of 28 garden dormice, which were caught following current guidelines for the ethical use of animals in research, and processing by a standard flotation technique with saturated saline solution. Then, wet drops were examined microscopically, and the number of oocysts was semi-quantified. Eimeria oocysts were observed in 16 of the 28 (57.1%) faecal samples, showing most of them a very low number of oocysts (≤1 oocyst per microscopic field × 400). The unsporulated oocysts visualized in 16 faecal samples were subspherical and of length 19.2±1.2μm and width 17.4±1.1μm, being morphologically compatible with E. myoxi. This finding was supported by molecular analysis of the small subunit ribosomal RNA (SSU-rRNA) gene, identifying the same species in 22 of the 28 (78.6%) dormice, including 15 samples in which oocyst size was compatible with E. myoxi. Moreover, the subsequent analyses of the apicoplast open reading frame 470 (ORF470) and the mitochondrial cytochrome c oxidase subunit I (COI) genes confirmed the molecular identification of the isolates as E. myoxi. The phylogeny analyses were consistent with previous phylogenetic studies and support the existence of three lineages of rodent-infecting Eimeria species.

New horizons of microphysiological systems: India forging its path in human-relevant research

The past decade has seen expeditious developments in our ability to grow and maintain a variety of human cells and tissues, with properties closely mimicking those in the human body. Prominent researchers and entrepreneurs from all over the world assembled in Hyderabad, India to discuss developments in this field that have not only aided fundamental understanding of organ development and disease processes but have served as good physiological models for toxicity testing and drug development. The speakers presented ingenious, cutting-edge technology and forward-thinking ideas. This report presents the salient aspects of their discussions, highlights the importance of identifying unmet needs, and discusses setting of standards that will help regulatory approvals as we move into a new era, with nominal animal use in research and effective drug discovery.

Partition of variation for predicting experimental power with a broiler chicken example

A 1932 editorial in Poultry Science stated that sampling theory, or experimental power, could be useful for "the investigator to know how many … birds to put into each experimental pen." Nevertheless, in the past 90 yr, appropriate experimental power estimates have rarely been applied to research with poultry. To estimate the overall variation and appropriate use of resources with animals in pens, a nested analysis should be conducted. Bird-to-bird and separate pen-to-pen variances were separated for 2 datasets, one from Australia and one from North America. The implications of using variances for birds per pen and pens per treatments are detailed. With 5 pens per treatment, increasing birds per pen from 2 to 4 decreased the SD from 183 to 154, but increasing birds/pen from 100 to 200 only decreased the SD from 70 to 60. With 15 birds per treatment, increasing pens/treatment from 2 to 3 decreased SD from 140 to 126, but increasing pens/treatment from 11 to 12 only decreased the SD from 91 to 89. Choosing the number of birds to include in any study should be based on expectations from historical data and the amount of risk investigators are prepared to accept. Too little replication will not allow relatively small differences to be detected. On the other hand, too much replication is wasteful in terms of birds and resources, and violates the fundamental principles of the ethical use of animals in research. Two general conclusions can be made from this analysis. First, it is very difficult to detect 1% to 3% differences in broiler chicken body weight with only one experiment consistently because of inherent genetic variability. Second, increasing either birds per pen or pens per treatment decreased the SD in a diminishing returns fashion. The example presented here is body weight, of primary importance to production agriculture, but it is applicable whenever a nested design is used (multiple samples from the same bird or tissue, etc.).

Individualized Housing Modifies the Immune-Endocrine System in CD1 Adult Male Mice.

In the last years, different research groups have made considerable efforts to improve the care and use of animals in research. Mice (Mus musculus) are the most widely used animal species in research in the European Union and are sociable and hierarchical creatures. During experiments, researchers tend to individualize males, but no consideration is given to whether this social isolation causes them stress. The aim of this study was, therefore, to explore whether 4 weeks of social isolation could induce changes in different physiological parameters in adult Crl:CD1(ICR) (CD1) males, which may interfere with experimental results. Body weight, blood cells, and fecal corticosterone metabolites levels were the analyzed parameters. Blood and fecal samples were collected at weeks 1 and 4 of the experimental procedure. Four weeks of single housing produced a significant time-dependent decrease in monocytes and granulocytes. Fecal corticosterone metabolite levels were higher in single-housed mice after 1 week and then normalized after 4 weeks of isolation. Body weight, red blood cells, and platelets remained unchanged in both groups during this period. We can, therefore, conclude that social isolation affects some immune and endocrine parameters, and that this should be taken into account in the interpretation of research data.

Preclinical research performed on reanimated/perfused swine kidneys: The Visible Kidney™ methodologies.

Preclinical research remains the essential platform in the development and optimization of medical therapies and advancements in translational medicines. However, specifically to animal research, federal laws, and institutional policies require investigators to apply the principles of the 3R's (replacement, reduction, and refinement). The concept of benchtop models utilizing isolated organs, in which multiple variables can be controlled to recreate human function, has been innovative advancements in preclinical research models that adhere to these principles. More specifically, isolated perfused kidney (IPK) models have been invaluable preclinical tools that have led to numerous advancements over the decades, including understanding renal physiology, pharmacologic therapies, and improvements in renal transplantation. However, pre-existing IPK models are not without their own limitations, leaving areas for improvement. An isolated perfused kidney apparatus was designed to best recreate human use conditions as a preclinical tool. Porcine renal blocks were chosen over the more commonly used rodent models, due to their greater similarities to human anatomies. Sixteen porcine kidney pairs obtained en bloc were extracted and placed onto an apparatus where aortic flows, pressures, and overall systemic temperatures were controlled. Organ viability was assessed in 10 renal blocks (n= 8 fresh and n= 2 previously frozen specimens) via both urinary flows and compositions at timepoints up to 180 min. Multimodality imaging, which included fluoroscopy, ultrasound, optical coherence tomography (OCT), and video scopes, was also employed to capture internal and external images to determine renal artery orientations and dimensions. Anatomical measurements and viability assessments of porcine renal blocks were successfully achieved in our perfusion model. Renal main artery diameters averaged smaller in our sample size than in human anatomy while also having more superior takeoff angles. Yet, the average lengths of each main segment were comparable to human anatomy: 32.09 ± 7.97 mm and 42.23 ± 7.33 mm in the left and right renal main artery, respectively. Urine production and urine composition of the fresh renal blocks, when compared to the frozen blocks and baseline perfusate, showed kidney viabilities of up to 3h via excretion and retention of various metabolites. In this paper, we described a protocol for an isolated perfused kidney apparatus using large mammalian renal blocks. We believe this protocol to be an improvement from similar pre-existing models in better representing human physiologic function while allowing for multimodal imaging. The resulting Visible Kidney™ preclinical model, which has shown viability after isolation and reperfusion, can be a fast and reliable tool for the development of medical devices while also reducing the unnecessary use of animals for research.

In Vivo Longitudinal Monitoring of Disease Progression in Inflammatory Arthritis Animal Models Using Raman Spectroscopy.

Current techniques for monitoring disease progression and testing drug efficacy in animal models of inflammatory arthritis are either destructive, time-consuming, subjective, or require ionizing radiation. To accommodate this, we have developed a non-invasive and label-free optical system based on Raman spectroscopy for monitoring tissue alterations in rodent models of arthritis at the biomolecular level. To test different sampling geometries, the system was designed to collect both transmission and reflection mode spectra. Mice with collagen antibody-induced arthritis and controls were subject to in vivo Raman spectroscopy at the tibiotarsal joint every 3 days for 14 days. Raman-derived measures of bone content correlated well with micro-computed tomography bone mineral densities. This allowed for time-resolved quantitation of bone densities, which indicated gradual bone erosion in mice with arthritis. Inflammatory pannus formation, bone erosion, and bone marrow inflammation were confirmed by histological analysis. In addition, using library-based spectral decomposition, we quantified the progression of bone and soft tissue components. In general, the tissue components followed significantly different tendencies in mice developing arthritis compared to the control group in line with the histological analysis. In total, this demonstrates Raman spectroscopy as a versatile technique for monitoring alterations to both mineralized and soft tissues simultaneously in rodent models of musculoskeletal disorders. Furthermore, the technique presented herein allows for objective repeated within-animal measurements potentially refining and reducing the use of animals in research while improving the development of novel antiarthritic therapeutics.

Norecopa: A global knowledge base of resources for improving animal research and testing.

There are good ethical, legal and scientific reasons for ensuring that our use of animals in research and testing is limited to the lowest number of animals, and that those which are used are treated as humanely as possible, while at the same time providing reliable, reproducible and translatable data which is adequately reported. Unfortunately, there is widespread evidence that there is room for improvement in all these areas. This paper describes the Norecopa website, which offers links to global resources which can be used to resolve these issues. Much of the website content is linked to the PREPARE guidelines for planning any research or testing which appears to need animals. Attention to detail on all steps of the pathway from early planning to manuscript submission should lead to better science, improved animal welfare, and fewer health and safety accidents. This will also minimize the chances of manuscript rejection due to inadequate planning, avoiding a waste of human resources and animal lives.

Spontaneous Epileptic Recordings from hiPSC-Derived Cortical Neurons Cultured with a Human Epileptic Brain Biopsy on a Multi Electrode Array

A growing societal awareness is calling upon scientists to reconsider the use of animals in research, which stimulates the development of translational in vitro models. The physiological and architectural interactions between different cell types within an organ present a challenge to these models, particularly for a complex organ such as the brain. Thus far, in vitro brain models mostly consist of a single cell type and demonstrate little predictive value. Here, we present a co-culture of an epileptic human neocortical biopsy on a layer of human induced pluripotent stem cell (hiPSC)-derived cortical neurons. The activity of the cortical neurons was recorded by a 120-electrode multi-electrode array. Recordings were obtained at 0, 3, and 6 days after assembly and compared to those obtained from cortical neurons without a biopsy. On all three recording days, the hybrid model displayed a firing rate, burst behavior, number of isolated spikes, inter-spike interval, and network bursting pattern that aligns with the characteristics of an epileptic network as reported by others. Thus, this novel model may be a non-animal, translational alternative for testing new therapies up to six days after resection.

The use of recovery animals in nonclinical safety assessment studies with monoclonal antibodies: further 3Rs opportunities remain

Assessment of reversibility from nonclinical toxicity findings in animals with potential adverse clinical impact is required during pharmaceutical development, but there is flexibility around how and when this is performed and if recovery animals are necessary. For monoclonal antibodies (mAbs) and in accordance with ICH S6(R1) if inclusion of recovery animals is warranted, this need only occur in one study. Data on study designs for first-in-human (FIH)-enabling and later-development toxicity studies were shared from a recent collaboration between the NC3Rs, EPAA, Netherlands Medicines Evaluation Board (MEB) and 14 pharmaceutical companies. This enabled a review of practices on recovery animal use during mAb development and identification of opportunities to reduce research animal use. Recovery animals were included in 68% of FIH-enabling and 69% of later-development studies, often in multiple studies in the same program. Recovery groups were commonly in control plus one test article-dosed group or in all dose groups (45% of studies, each design). Based on the shared data review and conclusions, limiting inclusion of recovery to a single nonclinical toxicology study and species, study design optimisation and use of existing knowledge instead of additional recovery groups provide opportunities to further reduce animal use within mAb development programs.