Why Is It Important To Follow Proper Procedures In Animal Research?

Abstract

Animal care and use play a pivotal role in the inquiry process. Upstanding concerns on the use of animals in inquiry have promoted the cosmos of a legal framework in many geographical areas that researchers must comply with, and professional organizations continuously develop recommendations on specific areas of laboratory animal science. Scientific evidence demonstrates that many aspects of brute care and use which are beyond the legal requirements take straight impact on enquiry results. Therefore, the review and oversight of animal intendance and use programs are essential to identify, define, control, and improve all of these aspects to promote the reproducibility, validity, and translatability of beast-based research outcomes. In this chapter, we summarize the ethical principles driving legislation and recommendations on creature care and utilize, likewise as some of these laws and international recommendations. Examples of the touch on of specific animal care and use aspects on inquiry, too as systems of internal and external oversight of animal intendance and use programs, are described.

Keywords

• Beast intendance and utilise
• Beast studies
• Interplay
• Preclinical information quality
• Reliability

1 Ethical and Legal Framework

The use of animals for research purposes has been a subject of debate for a long time. The increment of societal concerns on this affair has been and is being reflected in the development and implementation of guidelines and strict legislation on the protection of animals used in research across the world (Guillen 2017). Although international legislation may differ between countries in some practical aspects, they are all based on the same upstanding principles, mainly the Three Rs of Replacement, Reduction, and Refinement (Russell and Burch 1959) and, at a lesser extent, the 5 Freedoms (Brambell 1965). The Iii Rs are explicitly mentioned in most important international guidelines and regulations:

• Replacement refers to the avoidance or replacement of the utilize of animals in experiments where otherwise they would have been used. However, the concept of "relative replacement" based on strategies focused on reduction of animals and refinement of procedures performed on animals is besides valid.

• Reduction refers to minimizing the number of animals needed to obtain the desired research objectives. Reduction strategies are normally based on improvements of the experimental pattern and/or the implementation of new techniques (e.thousand., imaging). An important concept is not only using less number of animals, but the right number, equally using too depression numbers could invalidate the inquiry results.

• Refinement refers to the implementation of housing (e.1000., micro- and macroenvironment), intendance (e.g., husbandry practices and veterinary care), and use (experimental techniques) procedures that minimize creature hurting and distress.

The V Freedoms (from hunger and thirst; from discomfort; from pain, injury, or affliction; from fear and distress; and from the ability to express normal behavior), although initially proposed for the farm animal surroundings, are also referred to in some legislation on research animals, especially in Asia, just also have been recently considered for other related purposes, such as a recent proposal for the harm-benefit analysis to be performed as function of the ethical evaluation of research projects (Brønstad et al. 2016; Laber et al. 2016).

1.ane Recommendations for the Care and Utilize of Laboratory Animals

The common aspects of the ethical framework described above help with the harmonization of animal care and use in scientific discipline, and of science itself through the implementation of international guidelines and recommendations, likewise as uniform pieces of legislation (Guillen and Vergara 2017). Based on the current ethical concepts, the International Quango for Laboratory Animal Science (ICLAS) collaborated with the Council for International Organizations for Medical Sciences (CIOMS) to update the International Guiding Principles for Biomedical Research Involving Animals, with the intention to guide emerging countries in developing a framework of responsibility and oversight on the use of animals in research and to serve as an international benchmark also in countries with well-developed brute-based enquiry programs (Council for International Organizations for Medical Sciences and International Council for Laboratory Creature Science 2012). The Three Rs correspond a significant aspect of this certificate. Also, the World Organization for Animal Health (OIE), with 180 member countries, recognizes the Five Freedoms as valuable guidance in fauna welfare and more specifically describes the Three Rs and highlights their key role in the utilize of animals in science in Chap. 7.viii of the Terrestrial Animal Health Code (Globe Organization for Animal Health 2012).

One of the most widely followed sets of recommendations on fauna care and use can be constitute in the Guide for the Intendance and Use of Laboratory Animals (Guide; National Inquiry Council of the National Academy of Sciences 2011). The Guide, issued in the USA by the Found for Laboratory Brute Research (ILAR) of the National Inquiry Council (NRC), is the primary nonregulatory reference in the USA, also serves as the basis for regulations and recommendations in other areas of the world (Guillen 2017), and is one of the primary standards for the accreditation of animal intendance and employ programs beyond the globe performed past the nonprofit organization AAALAC International (run across below). The Guide refers to the Three Rs and to the Us Government Principles for the Utilization and Intendance of Vertebrate Animals Used in Testing, Research, and Preparation (United States Government 1985), which already incorporate these aforementioned basic ethical principles. It offers recommendations on all areas of an animate being care and use plan, such as the institutional responsibilities (including the oversight procedure, the training of personnel, and the occupational health and safe plan); the animal environment, housing, and management; the veterinary care; and the concrete constitute. The Guide states that information technology "is created by scientists and veterinarians for scientists and veterinarians to uphold the scientific rigor and integrity of biomedical research with laboratory animals as expected by their colleagues and social club at large" and "establishes the minimum upstanding, practice, and intendance standards for researchers and their institutions."

Many professional organizations publish more than specific recommendations on item areas of an fauna intendance and utilise programme, such as ethical review, wellness monitoring, or education and training. Specially noteworthy are the Federation of European Laboratory Animal Science Associations (FELASA; www.felasa.eu), the American Association for Laboratory Animal Science (AALAS; www.aalas.org), and the Canadian Council on Animal Care (CCAC; world wide web.ccac.ca). Other organizations focus exclusively on the evolution and broadcasting of Three Rs initiatives, like the NC3Rs in the Great britain (www.nc3rs.org.united kingdom), the North American 3Rs Collaborative in the U.s. (http://www.na3rsc.org/home.html), or Norecopa in Norway (https://norecopa.no/).

1.2 Legislation in the USA

In the USA, legislation on the care and employ of animals comes from the U.s. Department of Agriculture (USDA) and the Public Wellness Service (Bradfield et al. 2017). The Guide details the requirements of the Public Health Service Policy (PHS Policy) on Humane Intendance and Use of Laboratory Animals (Public Health Service 2002) and is used by institutions to comply with the PHS Policy. Therefore, although the Guide is non a slice of legislation, its standards are considered as minimum requirements past the PHS. On the USDA side, the Animal Welfare Human activity and related Animal Welfare Regulations represent the only federal law in the U.s.a. that regulates the handling of animals in research, with the particularity that rats, mice, and birds are not considered regulated species (United States Government 1966). However, the Guide standards are applied to all vertebrate species. The US system gives a lot of autonomy to the institutions and is based on the Institutional Creature Care and Utilise Committees (IACUCs), where participation of researchers is mandatory. The IACUC is the body responsible for the evaluation and authorization of the inquiry protocols, and the oversight of the unabridged institutional animal intendance and use program, including the advisable training of personnel to perform the assigned tasks.

one.3 Legislation in the European union

Legislation in the European union is based on Directive 2010/63/Eu (European Parliament and the Council of the European union 2010), which has been transposed into the legislation of all European member states (Guillen et al. 2017). The Directive addresses explicitly the Iii Rs and distributes the main responsibilities betwixt the public competent government and the users. Authorized establishments must have an Animal Welfare Torso (AWB) with an advisory role on ethical matters, while the (upstanding) project evaluation is assigned to the public competent authorities. However, the Directive allows member states to designate other bodies than public competent authorities for the implementation of certain tasks, and at nowadays the project evaluation is performed in a variety of manners across the European union, either by institutional ideals committees, external bodies, public competent authorities at regional or national level, or a combination of them (Guillen et al. 2015). Annex III of the Directive dictates the requirements for care and accommodation of animals, based on the minimum cage sizes of the Appendix A of the European Convention ETS 123, which, although not a slice of legislation, was the first pan-European document addressing in detail the protection of animals in science and was signed and ratified by a majority of the members of the Council of Europe (Council of Europe 1986, 2006). These minimum cage sizes are generally bigger than the ones recommended in the Guide and represent one of the nigh visible differences betwixt the United states of america and European research programs. In terms of grooming of personnel, the Directive requires that staff shall be adequately educated and trained before they perform certain functions including carrying out procedures on animals and designing procedures and projects and that competence is demonstrated. However, it is a competence of the member states to plant the minimum training requirements.

The European Commission has published a number of consensus documents on the implementation of the Directive, which tin be found at: http://ec.europa.eu/environment/chemicals/lab_animals/interpretation_en.htm. Similar legal requirements are enforced in other European countries exterior of the European Union, due east.g., in Switzerland and Norway (Guillen et al. 2017; NORECOPA 2016).

1.4 Legislation in Other Countries

Other areas of the earth have also developed legislation which have been extensively described elsewhere (Guillen 2017). In addition to countries such every bit Canada, Australia, New Zealand, or Israel having similar frameworks to those developed in the United states or the Eu, many Asian countries accept adult specific legislation, too as several countries in Latin America (i.east., Brazil, Mexico, and Uruguay). Africa is the region where there is less legislation, although there are already professional associations or scientific events in some countries.

The well-nigh important aspect of the legislative initiatives is that all of them are based on the aforementioned ethical principles and try to achieve the aforementioned objectives (Guillen and Vergara 2017): Improving animal welfare standards in science is an objective per se, but this objective brings forth some other very important one which is the comeback of scientific quality.

Legislation that reflects international, common ethical questions is a key element in achieving these objectives. Also, legal documents unremarkably address the same master topics: a process for the upstanding evaluation (and authorization) of enquiry protocols or projects; the need for appropriate training and competence of all personnel involved in the care and use of animals (caretakers, researchers, veterinarians, etc.); the animal environment and management (housing conditions, daily care, etc.); the need of effective veterinarian care; and general requirements for facilities. Fifty-fifty in countries lacking specific legislation, researchers, veterinarians, and research institutions and associations work to follow these general instructions and the establishment of oversight systems, and the beingness of active IACUCs or institutional ethics committees to review and improve the research protocols involving the use of animals is mutual as well in these areas.

2 Implications for Preclinical Information Quality

ii.one Oversight Bodies Impact on Preclinical Data Quality

Thus, there is an extensive legal framework in many countries that regulates animate being care and apply, only how does animal care and utilise bear on the quality of the preclinical data generated in fauna experiments? Showtime, the legal framework and its interpretation past oversight bodies (i.e., IACUCs/AWBs/ethics committees) can have a significant affect on data quality, both positive and negative.

As mentioned above, a reduction in the number of animals used according to the Three Rs is an of import concept for the ethical evaluation of an brute written report. Only overemphasizing the need to minimize the number of animals in an experiment, without consideration of the appropriate number of animals needed to reliably answer the research question, tin lead to underpowered studies with spurious results. As well, an uncritical refusal of study replications equally unnecessary duplication of previous experiments by oversight bodies would violate the principles of practiced scientific methods required to gain confidence in an experimental finding (Pritt and Hammer 2017). A more than balanced view by oversight bodies, on the other paw, helping with experimental design and statistical input to, eastward.thou., decide the required sample size for the proposed studies at time of project application, can be an important step to ensure the advisable number of animals is used and to facilitate the generation of reliable data. Clearly, this is what IACUCs/AWBs/ethical committees should strive for.

2.2 Animal Care and Use Programs Affect Preclinical Data Quality

Second, it is important to recognize that, despite the legal framework, animate being facilities and their institutional animal intendance and use programs can differ in many aspects, even within the aforementioned country or the aforementioned organisation (e.m., university). For example, there could be different barrier, hygiene, and sanitation levels to protect the wellness and well-being of the animals and the people working in the facility; animals could differ in microbiological status and receive different levels of veterinary care; there could be differences in the macroenvironmental (temperature, relative humidity, lite intensity and duration, noise level, air circulation) and/or in the microenvironmental conditions (e.g., caging arrangement, bedding, physical or social enrichment); there could exist variations in food supplied and in water quality and as well in a number of procedures, east.grand., in animal acclimation, handling, transport, or surgery, to proper name a few, all of which could touch experimental outcome (Table 1).

Table 1 Aspects of an animal care and use program that tin touch on the quality of preclinical data from animal studies

Full size tabular array

2.3 Health Status Influencing Preclinical Information

Play a joke on and colleagues, for instance, reported on a study designed to determine whether long-term oral supplementation with creatine, used past athletes in training, would cause histologic organ lesions in mice. Animals treated with creatine developed hepatitis merely and so did the control mice. Notably, Helicobacter bilis (H. bilis) was isolated from these mice and associated with hepatotoxicity seen in that study, thus misreckoning the experiment (Play a joke on et al. 2004). A related Helicobacter species, H. hepaticus, has also been associated with hepatitis, inflammatory bowel affliction, and cancer (Zenner 1999) and tin can promote drug-induced tumorigenesis in mice (Diwan et al. 1997; Nagamine et al. 2008; Stout et al. 2008). Of annotation, mouse Helicobacter infections often remain subclinical, and the animals appear healthy only can become symptomatic. The occurrence of clinical signs depends on various factors, such as strain, immunocompetency, and the gastrointestinal microbiome (Ihrig et al. 1999; Staley et al. 2009; Yang et al. 2013) and hence can atomic number 82 to unexpected confounds of creature studies.

There are several other opportunistic and obligatory pathological microorganisms that tin interfere with experimental outcome. It is therefore important that animals are regularly screened for the presence of these microorganisms (cf. FELASA recommendations for health monitoring in rodents, last revision: Mähler et al. 2014), either to exclude infected animals from the experiment, to initiate treatment if required (and possible), or at to the lowest degree to have clarity about the presence or absence of microorganisms.

Yet, the importance of microorganisms goes beyond agents causing clinical or subclinical disease. The gut microbiota also plays a critical role in animal and human health and affliction, and its impact on animal physiology and, therefore, on how animals react in certain studies has been extensively studied in recent years (Franklin and Ericsson 2017; Hansen et al. 2015). Both the potential bear upon of infectious agents and natural microbiota can be modified past routine housing and husbandry conditions.

2.4 The Bear on of Housing and Husbandry

Housing conditions and husbandry can also have substantial furnishings on experimental rodent information, still oft researchers are not fully aware of all the ecology factors in an animal facility that can influence data quality in their experiments (Jain and Baldwin 2003; Toth 2015). These factors include cage size, positioning of the belongings cage in the rack, cage textile, type of bedding, ambient cage temperature, humidity, noise levels, low-cal intensity, duration of the calorie-free/dark cycle, number of animals per muzzle (individual vs. social housing), food access (continuous or restricted), blazon of nutrient, physical enrichment provided, cage changing practices, transporting cages with animals within a room or betwixt rooms, and sanitation cycle of the holding room (reviewed in Castelhano-Carlos and Baumans 2009; Everitt and Foster 2004; Nevalainen 2014; Toth 2015), and this listing is far from complete.

Social housing, for instance, increased dopamine D2 receptor expression in dominant monkeys, but not in subordinate monkeys, when compared to individual housing, and as well affected the reinforcing properties of cocaine (Morgan et al. 2002). The stability of baseline cardiovascular parameters was affected past the arrangements of pens and the social setting in dogs implanted with telemetry devices (Klumpp et al. 2006). Similarly, social enrichment has been reported to impact cardiovascular function at resting land in monkeys (Xing et al. 2015). Housing temperature affects the growth rate of tumors in mice (Hylander and Repasky 2016; Kokolus et al. 2013). These examples highlight the importance of housing weather on preclinical data beyond a variety of species.

Thus, the health condition of the brute, environs factors in the beast facility, daily brute care routines and experimental manipulations (e.g., recovery surgery), as well as the feel, skills, and qualifications of the people performing these activities in the animal facility (animal care staff, veterinarians, researchers) contribute to the variability of preclinical data generated in animals (Howard 2002). A reduction in the variability of experimental data generated in laboratory animals has been coupled to refinements in microbial quality monitoring and husbandry, likewise as college professional expertise (Quimby 1993), and there is boosted evidence suggesting that this tendency continues with boosted refinements, due east.g., the introduction of environmental enrichment, even though this was initially much debated (Bayne and Würbel 2014). This is important, not just for the quality of the preclinical data generated but as well from an upstanding perspective as high data variability requires a college number of test animals for a written report to be conclusive. Also, the scientific utility of a highly variable and non-reproducible report can be questioned, with the associated risk that animals are wasted. As has been pointed out, "laboratory animal husbandry issues are an integral but [unfortunately still] underappreciated part of investigator's experimental design" (Nevalainen 2014, p. 392). Thus, there is a plea for even more than reduction of variability in further refined animal care and use programs and for more detailed reporting of brute holding conditions in publications in order to enhance transparency and consequently reproducibility of preclinical data.

With this aim in mind, guidelines have been proposed for the items to be considered when planning and reporting animal experiments (see also chapter "Minimum Data in In Vivo Enquiry"). The Ready Guidelines aim to aid researchers to consider all relevant items when planning animal experiments "to reduce the risk of issues, artefacts or misunderstandings arising once studies accept begun" (Smith et al. 2018). The Make it Guidelines were developed "to maximize the output from enquiry using animals past optimizing the information that is provided in publications on the design, acquit, and assay of the experiments" (Kilkenny et al. 2010). Many scientific journals have already adhered to the ARRIVE Guidelines (although their impact is debatable, cf. Hair et al. 2019) and more than recently an update of the guidelines has been published (Percie du Sert et al. 2019a, b), while the impact of the Set up Guidelines is still to be evaluated.

iii Assessment of Fauna Care and Use Programs

3.1 Internal Oversight

Internal oversight bodies, i.e., IACUCs/AWBs/ethics committees, tin can have a significant impact on data quality. Outset, they are tasked with the review of the ethical protocols, in accordance with national and international legislation and institutional policies. As part of this review process, the internal oversight trunk too plays an important role in advising on the experimental design of the proposed studies, including statistical considerations, and assures pain, discomfort, and distress are reduced to a minimum (Everitt and Berridge 2017; Silverman et al. 2017). Every bit mentioned higher up, those factors can significantly touch on on preclinical data quality. 2d, the internal oversight body should conduct inspections of its ain animal program and facility, at least annually or preferentially more oft, also depending on legislation and policies. Also assurance of the ethical and humane use of animals in research, this will besides ensure that all aspects of an beast care and use program that can bear on the quality of preclinical information from animal studies are well controlled, and it will create opportunities for further improvements of the quality of research, east.chiliad., by assuring that surgical facilities are state of the art and that investigators conducting surgical procedures are properly trained. Third, post-approval monitoring conducted by the oversight body, primarily serving to ensure that fauna use is occurring as described in the canonical protocol, may also contribute to data quality. There are interdependencies betwixt compliance, consistency, and reproducibility, and failure to reproduce an experiment has been considered equally an unintended effect of noncompliance with approved procedures (Silverman et al. 2017). Thus, the internal oversight body plays a pivotal function in the assurance of information quality in animal studies.

iii.2 External Oversight

Depending on national legislation, ethical evaluation and/or authorization for animate being studies may also be provided by external ethics committees, e.one thousand. past bodies at the regional or national competent authority level, or other bodies authorized by the competent authorities to perform the ethical evaluation on their behalf. Their role in the balls of data quality during project review is comparable to the function of an internal oversight body. In addition, many countries accept a mandatory requirement for regular, announced or unannounced, inspections of animal facilities by a competent authorisation to monitor compliance with legal obligations. Naturally, experienced inspectors will also have an bear on on preclinical data quality through assurance of a compliant animal intendance and use program. Still, frequently these inspections are gamble-based and may not cover all aspects of an creature care and use program that could affect preclinical data quality, and whether advice relevant to data quality is given may besides depend on the profile, skills, and feel of the individual inspector. The internal oversight body is much better positioned to ensure full coverage of the aspects relevant to the quality of information from studies involving animals, to promote consistency and timely activeness, if required, and should have primary responsibility.

3.3 The AAALAC International Accreditation Process

AAALAC International (AAALAC) (www.aaalac.org) is a voluntary accrediting organization that enhances the quality of research, testing, and education by promoting humane and responsible inquiry animal care and employ through provision of communication and independent assessments to participating institutions and accreditation of those that encounter or exceed applicative standards. More than ane,000 institutions including companies, universities, hospitals, government agencies, and other research institutions in 47 countries have earned AAALAC accreditation, demonstrating their commitment to responsible animal care and apply. These institutions volunteer to participate in AAALAC's programme, in addition to complying with the implementing laws that regulate animate being enquiry.

AAALAC was established in 1965 in the USA and is governed by approximately 70 scientific organizations from all around the world. The assessment and accreditation activities are performed by contained professionals with expertise in the field, who form the Council on Accreditation. The Council has 3 North American sections, two in the Pacific Rim, and one in Europe, each taking care of the activities in their respective geographical areas. The principal standards used by the Council are the Guide, the ETS 123, and the Guide for the Care and Use of Agricultural Animals in Research and Teaching (Federation of Animal Science Societies 2010). The Council may too apply other scientific publications on different topics called Reference Resources (https://world wide web.aaalac.org/accreditation/resources.cfm) and has to ensure that accredited programs comply with the implementing legislation in the specific location of the evaluated program. Quango members are helped by ad hoc consultants/specialists, who are the same type of professionals, normally selected based on the item expertise needed for each evaluation process.

When one institution voluntarily applies for the accreditation, it has to complete and submit the Program Description (https://www.aaalac.org/accreditation/apply.cfm), a document where all areas of the beast care and employ program take to be thoroughly described. This includes the institutional responsibilities (key responsible personnel, oversight and upstanding review procedure, competence of personnel, and occupational health and safety plan), the brute environment, housing and direction, the veterinary care programme, and the physical plant. The Programme Clarification is and so reviewed past a Council member and the collaborating advertising hoc(s), and a site visit to the establishment is scheduled to evaluate the quality of the program on site. The report coming from this site visit is reviewed by and discussed with the other Council members of the same section and a decision on the accreditation status taken. Depending on the severity of the issues (if any) identified during the process, at that place may be mandatory bug that the institution must correct before obtaining full accreditation, and/or suggestions for improvement, which are strong recommendations for the improvement of the plan that the institution can voluntarily address.

The evaluation procedure is based on performance standards rather than on engineering standards, which is peculiarly of import when because the global scope of AAALAC (Guillen 2012). While applied science standards are rigidly defined, hands measurable (east.g., minimum cage sizes), performance standards are upshot oriented, focused on goals or expected results rather than the process used to achieve the results, and have the flexibility needed in the various enquiry environment. AAALAC has to brand certain that institutions comply with the engineering standards which are normally function of legislation, but on top of that also apply the operation standards as described in the AAALAC Principal Standards. For example, AAALAC may have different ethical review processes if they, in add-on to be legally compliant, are effective and at that place is evidence of a practiced outcome.

The AAALAC accreditation process is uniform with quality systems similar GLP or ISO. In fact, many institutions who implement GLP or ISO considering they perform regulated enquiry or have general quality systems in place (e.g., contract research organizations, pharmaceutical companies) also implement the AAALAC accreditation as this is the only global organization specifically focused on animate being care and apply programs and carried out by independent professionals in the field. This peer-review process has been extremely successful and continues to expand in institutions around the world.

3.4 Assessments by Manufacture

Animal studies course an integral office of the drug development process. Those studies are either conducted within the research facilities of a company or are outsourced and performed past external service providers. To ensure external partners comply with technical requirements and upstanding standards, more and more pharmaceutical companies started to formally appraise the brute care and use programs of their collaborators on a regular ground, including contract research organizations (CROs), academic groups, and breeders (Mikkelsen et al. 2007; Underwood 2007). A more recent evolution is the joint cess of breeders and CROs past consortia of pharmaceutical companies, which facilitates harmonization of processes across companies and enhances capacity and expertise (Interpharma 2018). In general, these animal intendance and use program assessments cover the aspects highlighted in Table i, plus boosted topics, such as documentation, occupational wellness, and safety, and often are closely oriented on the AAALAC procedure.

4 Decision

There are multiple evidences of the influence of beast care and utilize conditions and practices on beast-based inquiry outcomes. The existing legislation on the employ of animals in research, established upon internationally accepted upstanding principles, helps creating a more than common enquiry surround that facilitates extrapolation of research results obtained in particular institutions. Still, animate being care and utilise practices may differ significantly across institutions, with potentially significant and oft unknown effects on enquiry results. Professional person science-based recommendations endeavor to complement legislation by creating standards on a number of areas, including upstanding review, health monitoring, beast environment, husbandry practices, grooming of personnel, and others. Just the implementation of the standards past research institutions still varies significantly and is very often depending on institutional or even individual delivery.

What can nosotros learn for Good Inquiry Do? First and foremost, it should exist clear now that the quality of animal intendance and use directly impacts on the quality of preclinical information. In addition, the field of brute care and employ has established a framework that could be seen as a part model for Expert Inquiry Practice: Minimum requirements every bit defined by guidelines and legislation such equally the Guide or the Directive 2010/63/EU set the standards for animal care and use programs in the USA and in EU member states, and both internal and external oversight bodies have been created to ensure proper implementation and adherence to these standards. The review and oversight of animal care and use programs is a cardinal tool to not only ensure compliance with legal requirements just also to institute a well-divers inquiry environment that considers all aspects of animal intendance and use that can impact research outcomes. This oversight may be internal, already mandated by legislation in many countries, and external by peers. A combination of the solar day-to-mean solar day internal oversight with a periodic independent external review seems to exist the most efficient way to ensure the implementation of a high-quality animal intendance and utilize program where, in add-on to addressing animal ethical and welfare problems, researchers tin can produce meliorate quality science.

Neither the Guide nor the Directive 2010/63/Eu is overtly prescriptive (except for a few conspicuously defined and nonnegotiable engineering standards), and also accrediting organizations such as AAALAC International strongly adhere to the principle of performance standards, which allows flexibility in the implementation of these standards.

These principles of minimum requirements, performance standards, and internal and external oversight could be implemented in other areas of enquiry in a mode that is fit for the intended purpose. I may envision Good Research Practice that is guided by lean, easy to apply minimal requirements defined by a quality organisation, based on the specific needs of the research group and working on operation standards, with day-to-mean solar day internal oversight and periodic external assessments, non to police simply to better daily research practice, maybe in combination with an accreditation procedure. The European Quality in Preclinical Data (EQIPD) IMI consortium (https://quality-preclinical-data.eu/) is in fact following these aforementioned principles, with the added advantage to look at animal care and utilise and Good Research Exercise holistically, every bit not only does beast care and use affect the quality of preclinical information, only the demand for preclinical data quality will impact on fauna care and use.

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Authors and Affiliations

1. AAALAC International, Pamplona, Kingdom of spain

   Javier Guillén

2. Janssen Pharmaceutica NV, Beerse, Kingdom of belgium

   Thomas Steckler

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Correspondence to Thomas Steckler .

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Editors and Affiliations

1. Partnership for Assessment & Accreditation of Scientific Practise, Heidelberg, Baden-Württemberg, Germany

   Dr. Anton Bespalov

2. Department of Pharmacology, Johannes Gutenberg University, Mainz, Rheinland-Pfalz, Germany

   Prof. Martin C. Michel

3. Janssen Pharmaceutica N.V., Beerse, Kingdom of belgium

   Dr. Thomas Steckler

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Guillén, J., Steckler, T. (2019). Good Inquiry Practice: Lessons from Animal Care and Use. In: Bespalov, A., Michel, M., Steckler, T. (eds) Good Research Practise in Not-Clinical Pharmacology and Biomedicine. Handbook of Experimental Pharmacology, vol 257. Springer, Cham. https://doi.org/10.1007/164_2019_292

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