Guidelines for the establishment and functioning of Animal Ethics Commitees (Institutional Animal Care and Use Committees) in Africa

Animals are used for scientific purposes across Africa to benefit humans, animals or the environment. Nonetheless, ethical and regulatory oversight remains limited in many parts of the continent. To strengthen this governance framework, the Pan-African Network for Laboratory Animal Science and Ethics brought together experts from 12 African countries to create an Africa-centric practical guide to facilitate the establishment and appropriate functioning of Institutional Animal Ethics Committees across Africa. The Guidelines are based on universal principles for the care and use of sentient animals for scientific purposes, with consideration of the cultural, religious, political and socio-economic diversity in Africa. They focus on 11 key elements, including responsibilities of institutions and of the Institutional Official; composition of the Committee; its responsibilities, functioning and authority; ethical application and review processes; oversight and monitoring of animal care and use and of training and competence; quality assurance; and the roles of other responsible parties. The intent is for African institutions to adopt and adapt the guidelines, aligning with existing national legislation and standards where relevant, thus ensuring incorporation into practice. More broadly, the Guidelines form an essential component of the growing discourse in Africa regarding moral considerations of, and appropriate standards for, the care and use of animals for scientific purposes. The increased establishment of appropriately functioning animal ethics committees and robust ethical review procedures across Africa will enhance research quality and culture, strengthen societal awareness of animals as sentient beings, improve animal well-being, bolster standards of animal care and use, and contribute to sustainable socio-economic development.


Introduction
The African Union Commission's 'Agenda 2063 -the Africa we want' aspiration envisions 'a prosperous Africa based on inclusive growth and sustainable development'. 1Research animals are seen to play a critical role in this sustainable economic development, particularly in improving human and animal health and wellbeing (UN Sustainable Development Goal (SDG) 3), 2 sustainable food and agriculture (SDGs 2 and 12) and economic growth (SDGs 8 and 9).
Whilst some African countries have legislation and systems for the ethical and regulatory oversight of the use of animals for scientific purposes, these remain limited in many parts of the continent. 3Recognising this call for change, the African Union's Animal Welfare Strategy in Africa 4 articulates a vision of 'an Africa where animals are treated as sentient beings, as a leading continent in implementation of good animal welfare practices for a competitive and sustainable animal resource sector', with the goal 'to transform the animal resources sector through adoption of good animal welfare practices for human well-being, sustainable livelihoods, poverty reduction and economic growth'.
Africa faces challenges in implementing this vision.In addition to legal and regulatory constraints, there are limited resources and expertise to develop human capacity in animal research ethics.There is a need to promote animal welfare better, enhance research quality and culture, and harmonise good practice across the continent through co-operation and collaboration.
The Pan-African Network for Laboratory Animal Sciences and Ethics (PAN-LASE) 5 was created in 2017 as a forum to develop human resources and capacity for the humane and ethical care and use of research animals across Africa.In addition to providing professional educational opportunities, it resolved to create guidelines for the establishment and functioning of Animal Ethics Committees (AECs), otherwise known as Institutional Animal Care and Use Committees (IACUCs), in Africa.
Whilst several global guidelines are recognised for AECs, Africa is unique regarding its cultural, religious, political and socio-economic diversity.Hence, there was a need to create Guidelines that were Africacentric, which drew on existing good practice and expertise from across Africa [6][7][8][9] and which reflected the continent's diversity, resources and balances.
While several African countries have guidelines, policies and resources for Human Research Ethics Committees, 10 the same is often not true for AECs, thus the need for AEC Guidelines.

Rationale for development of the Guidelines
Humans have a moral obligation and ethical responsibility to promote the well-being of sentient animals and to recognise the intrinsic value of animal life.The humane care and use of animals creates awareness of animal welfare, and individual (personal) and institutional cultures of care. 11Africa aspires to be a continent with 'strong cultural identity, common heritage, values and ethics'. 1 Ethical review is a critical component of the oversight of the care and use of animals for scientific purposes to ensure humane care and use standards.Ethical review of animal research is critical to ensure that research results are reproducible and that research is conducted with due regard to the well-being and sentience of animals.Appropriate ethical and scientific standards for animal research enhances research quality and therefore global acceptance of the science, 12,13 in turn enhancing international collaboration, international rankings of educational institutions, career progression and promotion of scientists, and the mitigation of reputational and legal risk.It also promotes public confidence.Robust ethical review is a requirement for publication in international journals, for the welfare accreditation of animal care and use programmes, and as a requirement of funding bodies.
From a national and regional perspective, appropriate ethical standards encourage the national and African advancement of science and technology, improvements to human and animal health, and wellbeing and realisation of other UN SDGs. 2

Collaborative co-creation of the Guidelines
Fourteen African researchers, veterinarians and animal welfare experts from across Africa, all with experience and expertise in the ethics of animal research (i.e. the authors of this paper), convened at the Ecole Nationale de M edecine V et erinaire de Sidi Thabet, Tunisia, in 2019 and engaged in collaborative discussions to cocreate these Guidelines.
The objective was to create a practical guide which would facilitate the establishment and functioning of AECs (i.e.IACUCs) in Africa as fundamental instruments for the responsible oversight of animal care and use for scientific purposes (including for research, testing and teaching).
The Guidelines are aligned with universal principles for the care and use of animals for research and education, 14,15 that animals should only be used when there are no valid non-animal alternatives, with consideration of animal sentience, the application of the principals of humane experimental technique (3Rs), 16 the five freedoms, 17 the five domains, 18 the requirement for robust ethical review (with a harm/benefit analysis), and formal approval before studies may commence. 14,15heir content was informed by existing good practice, legal frameworks, standards and policies relating to the care and use of animals for scientific purposes across Africa, [6][7][8][9][19][20][21][22][23][24][25] as well as established international codes and guidelines, 14,15 with due regard to the rich cultural, religious, political and socio-economic diversity across Africa.
The draft Guidelines were discussed with an additional 20 delegates from 13 African countries attending the PAN-LASE train-the-trainer workshop for animal research professionals, which was run in parallel at the Ecole Nationale de M edecine V et erinaire, for debate, comments and modifications.
The final set of democratic Guidelines, reported here, was approved by all 34 delegates.

Scope of the Guidelines
• The Guidelines are intended to be used in conjunction with applicable national legislation.In cases of inconsistencies, national legislation takes precedence over the Guidelines; • The Guidelines apply to all live non-human vertebrates (i.e.fish, amphibians, reptiles, birds and mammals) and higher invertebrates (i.e.cephalopods and decapods), of all life stages from half of gestation or being capable of independent feeding (whichever comes first), including but not limited to laboratory animals, farm animals, wildlife, freeliving animals, domestic animals, feral animals and genetically altered animals; • The Guidelines apply to all circumstances involving the care and use of animals for scientific purposes, including for research, education (teaching and training), testing, safety and efficacy studies, the use of animals for diagnostic purposes, production of biological products or substances, field trials, conservation studies, observation, environmental studies and regulatory studies to register a product, including animals that are produced for use in scientific purposes; • AECs may choose to extend the scope of these Guidelines to include other species (e.g.other invertebrate animals), uses of animals (e.g.non-scientific uses) or other aspects (e.g. the use of animal tissues) to meet their specific situational needs.

Key elements of the Guidelines
The guidelines describe 11 key elements for implementation by AECs, to ensure the appropriate functioning and standards of the committee (Table 1).
Institutional responsibilities and the Institutional Official

Composition of the Animal Ethics Committee
• The composition of the committee should ensure competent animal ethics review and oversight; • The impartiality and independence of members should be appropriately considered, including consideration that at least one member should be independent of the institution; • The chairperson of the committee should report regularly (usually annually) to the Institutional Official; • The committee's composition should have fair representation in terms of gender; • The membership of the committee should enable the committee to fulfil its functions and meet its responsibilities as outlined in these guidelines; • Membership of the committee should consist of the following: • at least one veterinarian with the relevant expertise and knowledge; • at least one scientist with relevant experience in animal research and use; • at least one public member to represent general community interests, who is independent of the science and care of the animals in the institution and who is not involved in the care or use of animals for scientific purposes; • Additional members may be included as committee members in order to meet the needs of the committee (e.g.animal care staff, people with knowledge of animal welfare, statisticians, ethicists, people with knowledge of biosafety, people with legal training, etc.).Additional people may be co-opted as required.• The overall membership of the committee, including additional members, should be representative of the institutional environment, considering the needs of relevant stakeholders.An institutional analysis of animal care and use, including identification of relevant parties, can be beneficial to identify key stakeholders.

Functioning of the Animal Ethics Committee
• AECs should establish formal documentation and standard operating procedures to describe all relevant aspects of their functioning, including decisionmaking processes;

Applications for animal ethics review
• Applications for the use of animals for scientific purposes should be submitted and approved by the AEC before any of the animals are used for the specified purposes; • Applications for animal use should be by completion of the relevant AEC protocol application form; • The minimum details to be included in the protocol application form should enable the AEC to conduct the ethical review as outlined in the section 'The Ethical Review Process'; • Applications should provide the rationale for animal use in lay language (i.e.non-specialised terms) so that it is understandable by people who are not subject experts; • The Principal Investigator (PI; i.e. the person who takes primary responsibility for compliance with the approved conditions of the protocol) should be clearly specified.
The ethical review process ; the clinical progression of the animal's condition over time; welfare monitoring (i.e.frequency, signs to be monitored, the people responsible); humane end points (i.e. the maximum level of suffering that will be permitted) and the actions to be taken when these are reached; methods for euthanasia and confirming death; appropriate disposal of biological materials; the availability of appropriate facilities; and acceptance by the PI of full primary responsibility for the protocol; • The AEC should perform a harm/benefit assessment in order to ensure that the likely benefits of the study will outweigh the total cumulative lifetime harms to the animals; 26 • The AEC may use a checklist for reviewers to harmonise the ethical review process; • The AEC should ensure that appropriate scientific review of all protocols, including the pedagogical justification where animals are being used for education and training, is conducted, as well as appropriate review of biosafety and occupational health and safety.

Oversight and monitoring of animal care and use
• Post-approval monitoring of approved protocols to ensure compliance with the conditions of the approval, including the competence of personnel in procedures performed on animals; • Inspection of facilities or areas where animals are kept and used; • Progress reports from PIs (annual and final) -issues identified can help improve institutional practice; • Review and approval of standard operating procedures for animal care and use.

Oversight of training and competence
• All AEC members should be appropriately trained in relevant animal ethics review processes; Quality assurance of the Animal Ethics Committee's functioning • Oversight of the AEC's functioning is an essential quality-assurance mechanism; • The chairperson of the AEC should report regularly (usually annually) to the Institutional Official; • Internal oversight should include institutional assessment of AEC functioning.This can increase the efficiency and performance of the AEC and may contribute to recognition of the AEC and its authority within the institution; • External (to the institution) oversight may include auditing and/or registration of AECs by noninstitutional bodies to confirm appropriate composition and functioning of the committees.This may include national and/or regional oversight mechanisms and may include the compilation of national statistics of animal use for scientific purposes.National Competent Authorities may also play a role in terms of external oversight of facility standards and competence in procedures.

Other responsible parties
• Veterinarians: In addition to membership of the AEC, the role of veterinarians should include evaluation of animal health and welfare (including preventative care, health monitoring, diagnosis, treatment and post-mortem examination), sharing and promoting activities or approaches which enhance both physiological and psychological aspects of animal welfare, training and evaluation of competence of personnel in animal procedures, evaluation of standards of animal facilities and consultation during the design of protocols.The veterinarian should liaise with the AEC chairperson and the institutional official; • Researchers, teachers, students, staff and other people with responsibility for the humane care and use of animals for scientific purposes; • Institutional bodies with oversight of biosafety and occupational health and safety; • Institutional bodies responsible for the scientific review of proposals for animal use; • National Competent Authorities may regulate standards of facilities and competence; • National bodies may regulate standards of animal ethics review and oversight.

Going forward
These Guidelines provide the basis for the establishment of AECs and of associated robust ethical review implementation at institutions across Africa.We have attempted to reduce the Guidelines to minimum requirements, which should be practically implementable, to encourage institutions to adhere to good practice when establishing AECs.The intent is for African institutions and national councils to adopt and adapt the Guidelines, in line with existing national legislation or standards, [19][20][21][22][23][24][25] other relevant legislation (e.g. for medicines development, wildlife, etc.), taking into account local cultural and religious diversity, and the ownership of animals, to ensure incorporation into practice, that is, the establishment of appropriately functioning institutional AECs that formally review and approve all proposals for animal use before studies are initiated.On a broader level, the Guidelines are intended to encourage the growing discourse in Africa regarding the moral principles and standards for the care and use of animals.The Guidelines provide guidance for institutions seeking to strengthen their existing procedures, harmonised with universal good practice and the African context.It is an opportunity to harmonise practice across the continent for the benefit of all.The Guidelines may be modified and expanded as AECs are introduced across Africa, and the animal care and use community learn from their experiences.There is a need for ongoing discussions and engagement with stakeholders, including scientific organisations, regulators and institutions across Africa, to encourage the awareness, uptake and implementation of the Guidelines.The Pan-African Network for Laboratory Animal Science and Ethics (PAN-LASE), 5 in collaboration with key local, national and regional stakeholders, aims to drive this vision forward.
The purpose or aim of developing these Guidelines was to empower and support Institutions and individuals in establishing and operationalising AECs across Africa.The Guidelines are very much the first step.Going forward, as AECs become more commonplace and embedded across the continent, these Guidelines can be revised and refined, incorporating additional elements or good practice from elsewhere in the world.This could include broadening the recommended membership of the committee; the requirement that all those involved in the care and use of research animals have an education and understanding of the 3Rs; consideration of who (e.g.veterinarian, AEC chair, etc.) should have 24/7 access to research animals; inclusion and guidance on undertaking harm-benefit analyses; and recommendations for reporting of progress to Competent Authorities.These suggestions, and others, could be a starting point for the working party creating version 2 to focus on.
The establishment of more AECs and robust ethical review systems across Africa will strengthen the societal awareness of animals as sentient beings, improve animal well-being, strengthen the humane care and use of animals for scientific purposes, enhance research quality and culture, and contribute to sustainable socio-economic development.

Lignes directrices pour la cr eation et le fonctionnement des comit es institutionnels de protection et d'utilisation des animaux en Afrique R esum e
Bien que les animaux soient utilis es a `des fins scientifiques dans toute l'Afrique pour profiter aux humains, aux animaux ou a `l'environnement, le contro ˆle ethique et r eglementaire reste limit e dans de nombreuses r egions du continent.Pour renforcer ce cadre de gouvernance, le R eseau panafricain pour la science et l' ethique des animaux de laboratoire a r euni des experts issus de 12 pays africains afin de cr eer un guide pratique centr e sur l'Afrique pour faciliter la cr eation et le fonctionnement appropri e des comit es institutionnels d' ethique des animaux a `travers l'Afrique.Les lignes directrices sont fond ees sur des principes universels de soin et d'utilisation des animaux sensibles a `des fins scientifiques, en tenant compte de la diversit e culturelle, religieuse, politique et socio-economique en Afrique.Directrices para la creaci on y el funcionamiento de comit es institucionales para el cuidado y uso de animales en Africa Resumen

Table 1 .
The 11 key elements (fundamental principles) for implementation by Animal Ethics Committees (AECs) to ensure the appropriate functioning and standards of the Committee.Inspection of animal facilities and areas to advise on changes needed to improve or ensure animal welfare.• Report all needs and deficiencies in the animal care and use programme to the Institutional Official.• Ensure that appropriate mechanisms are created for reporting and investigation of concerns regarding animal welfare or non-compliance; • Ensure appropriate veterinary care of all animals; • Keep records of the use of animals for scientific purposes in the institution; • Provide a forum of discussion to promote a culture of care in the institution; Elles se concentrent sur les 11 el ements cl es: Responsabilit es des institutions et du fonctionnaire institutionnel; composition du Comit e; ses responsabilit es, son fonctionnement et son autorit e; processus d'application et d'examen ethique; supervision et surveillance des soins et de l'utilisation des animaux, formation et comp etences; assurance de la qualit e; ro ˆles des autres parties responsables.L'intention est que les institutions africaines adoptent et adaptent ces lignes directrices, en s'alignant sur la l egislation et les normes nationales existantes, le cas ech eant, et en assurant ainsi leur incorporation dans la pratique.Plus largement, elles constituent une composante essentielle du discours croissant en Afrique concernant les consid erations morales et les normes appropri ees concernant le soin et l'utilisation des animaux a `des fins scientifiques.La mise en place accrue de comit es d' ethique animale fonctionnant de mani ere appropri ee et de proc edures d'examen ethique solides en Afrique permettra d'am eliorer la culture et la qualit e de la recherche, de renforcer la conscience soci etale des animaux comme e ˆtres sensibles, d'am eliorer le bien-e ˆtre des animaux, de renforcer les normes de soin et d'utilisation des animaux et de contribuer au d eveloppement socioeconomique durable.