How to "do" the Nagoya Protocol: common misconceptions, challenges and best practices for access and benefit-sharing compliance

Preprint v1.0 - July 21, 2025 How to “do” the Nagoya Protocol: common misconceptions, challenges and best practices for access and benefitsharing compliance Davide Faggionato * 1, Melania Mu˜ noz-Garc´ıa * 1, Tanja Kostic 2, Mariana L. Ferrari 3, 4, Pascale Vonaesch 5, Mathilde Poyet 6, 7, Perrine Portier 8, 4, Matthew J. Ryan 9, Djamila Djeddour 9, Cornelia Stumptner 10, Giovanna Cristina Varese 11, 4, Aurora Zuzuarregui 12, 4, Mathieu Groussin 13, 7, Michael Schloter 14, Robert D. Finn 15, Aylin S. Haas 1, Ian Probert 16, Gerard Verkleij 17, J ¨ org Overmann 1, Amber H. Scholz † 1 *These authors contributed equally to this work †Corresponding author; correspondence should be addressed to amber[email protected] 1Leibniz Institute DSMZ-German Collection of Microorganisms and Cell Cultures, Inhoffenstraße 7B, 381124 Braunschweig, Germany 2Center for Health & Bioresources, Bioresources Unit, AIT Austrian Institute of Technology, Konrad Lorenz Strasse 24, 3430 Tulln, Austria 3Institut Pasteur, Universit´ e Paris Cit´ e, Biological Resource Center of Institut Pasteur, F-75015, Paris, France 4Microbial Resource Research Infrastructure (MIRRI-ERIC) 5Department of Fundamental Microbiology, University of Lausanne, UNIL-Sorge, 1015, Lausanne, Switzerland 6Institute of Experimental Medicine, Kiel University, Kiel, Germany 7Global Microbiome Conservancy 8University of Angers, Institut Agro, INRAE, IRHS, SFR QUASAV, CIRM-CFBP, MIRRI-ERIC, F-49000, Angers, France 9CABI, Silwood Park, Buckhurst Road, Ascot, Berkshire, SL5 7PY, United Kingdom 10Diagnostic & Research Centre for Molecular Biomedicine, Institute of Pathology, Medical University of Graz, Neue Stiftingtalstrasse 6, 8010 Graz, Austria 11Department of Life Sciences and System Biology, Mycotheca Universitatis Taurinensis, University of Torino, 10125, Turin, Italy 12Spanish Type Culture Collection (CECT-UV), Universitat de Val` encia, Edificio 3 CUE, Parc Cient´ ıfic Universitat de Val` encia, Catedr´ atico Agust´ ın Escardino 9, 46980 Paterna (Valencia), Spain 13Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany 14Helmholtz Center Munich-German Research Center for Environmental Health, Neuherberg, Germany 15European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridge, UK 16Sorbonne Universit´ e, CNRS, FR2424, Roscoff Culture Collection, Station Biologique de Roscoff, Roscoff 29680, France 17Westerdijk Fungal Biodiversity Institute Uppsalalaan 8, 3584 CT Utrecht, Netherlands M icroorganisms are key actors for human health, biodiversity, ecosystem services, climate change mitigation, and biotechnology. Researchers seeking to untangle the role of microorganisms in these planetary processes, must navigate a wide-ranging legal landscape which includes Access and Benefit-Sharing instruments such as the Convention on Biological Diversity and its Nagoya Protocol. These United Nations instruments recognize the sovereign rights of countries over genetic resources and require sharing of benefits that arise from biodiversity utilization. We discuss the most common misconceptions and practical challenges that researchers encounter when complying with these agreements and present three case studies to showcase real-life experiences. A stepby-step guide on how to “do” the Nagoya Protocol is presented to support researchers navigating Access and Benefit-Sharing compliance in microbial research, providing best practices while fostering biodiversity conservation, equitable collaboration, and sustainable innovation. Main The days of the “wild west” approach to science – act now and ask questions later – are long over. Life sciences, including microbiology, microbiome research, and biobanking, which tap into the vast, cosmopolitan diversity of microbial life, are embedded in a number of international regulatory frameworks. This “best practices” paper serves as a high-level overview of international laws relevant to microbiologists and provides Preprint v1.0 - July 21, 2025 How to “do” the Nagoya Protocol: common misconceptions, challenges and best practices for access and benefit-sharing compliance a blueprint on how to act in the complex legal environment of Access and Benefit-Sharing (ABS) under the Convention on Biological Diversity (CBD) and its Nagoya Protocol (NP). It is intended to support practicing microbiologists (and others) with an operational understanding of these processes. To aid readers in navigating the abbreviations and acronyms used, see Table 1. It is estimated that there are between 10 6 and 10 12 bacterial and archaea taxonomic units on Earth [1, 2], of which only a small fraction has been characterized through molecular methods, and an even smaller subset has been successfully isolated in culture [3]. Geographical distribution analysis shows that prokaryotes are rarely endemic to individual countries [4,5], while playing a crucial role in global biodiversity, biogeochemical cycling, ecosystem homeostasis [6–8], and offering substantial translational potential from One Health interventions and precision agriculture to biotechnological innovations for climate resilience [9– 11]. Over the past decade, to understand complex environmental communities, many microbiologists have focused on “microbiomes” [12] to investigate the complex cross-talk between microscopic and macroscopic life. As a result, it is common practice to procure environmental samples that represent snapshots of microbial and host communities from soil, water, air, plants, and animals (including humans). Microbiologists thus need to consider the legal context regulating utilization of both the microbial components and the host organism(s) [13] (Fig. 1). In the following sections we navigate through different sources of biological samples that can be utilized by researchers and that may be subject to one or more ABS or other legal regimes. All non-human biological samples: CBD & Nagoya Protocol The 1992 CBD’s third objective requires the fair and equitable sharing of benefits arising from biodiversity utilization. The CBD recognizes each country’s sovereign rights over their biodiversity, allowing (although not requiring) them to regulate access to so-called genetic resources (GR). The CBD’s NP entered into force on October 12, 2014 and provides a binding international legal framework on access to and utilization of GR, defined as any non-human biological material containing functional units of heredity. The NP also governs derivatives, naturally occurring biochemical compounds resulting from the genetic expression or metabolism of biological or genetic resources [14], including proteins, lipids and metabolic compounds obtained from GR. Because of this broad scope, many microbial (fungi, bacteria, viruses, archaea, phages) samples need to adhere to the CBD/NP (Fig. 1). Digital Sequence Information Since 2016, CBD negotiations largely focused on benefit-sharing from the use of Digital Sequence Information (DSI) — a policy term that refers broadly to genetic sequence data and other related biomolecular information. These data are stored in open databases like the International Nucleotide Sequence Database Collaboration (INSDC) [15,16]. At the 16 th Conference of the Parties (COP16) in Cali, Colombia in 2024, countries operationalized a new multilateral benefitsharing mechanism (fundamentally different from the bilateral approach of the NP) from the use of publicly available DSI including a new global fund, the “Cali Fund” [17]. The agreement ensures that biological databases can continue providing open access to DSI and requires all users to share non-monetary benefits [18,19]. Microbial “host” samples: plants, endangered species The International Treaty on Plant Genetic Resources for Food and Agriculture (ITPGRFA), establishes a multilateral system for benefit-sharing of 64 of the world’s most important crops for food and agriculture [20]. If microbiologists use these plants for their microbial research, then they need to follow both the ITPGRFA for the plant (host) and potentially the NP for the associated microorganisms (Fig. 1). Researchers working with microbial samples from plants also need to consider and perhaps apply for phytosanitary certificates to move specimens with potential plant infectious agents between borders (Fig. 1). For microbial research performed on samples (e.g. blood, tissue, swabs) from endangered or threatened species, the UN Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) [21] applies. This is relevant for species listed in any of the CITES appendices. Here, even if the focus of the research is on the microbial community and not the host, a CITES export permit is required (Fig. 1). Marine genetic resources The Agreement under the UN Convention on the Law of the Sea on the Conservation and Sustainable Use of Marine Biological Diversity of Areas beyond National Jurisdiction (BBNJ Agreement) [22] was adopted in 2023 and is currently open for ratification. Once signed by 60 countries (expected in late 2025), it will enter into force. The BBNJ Agreement includes benefit-sharing provisions for marine genetic resources (MGR) collected from international waters (200 nautical miles offshore) and their DSI. Here, microbiologists on a research cruise into the high seas will often have samples collected both in national and international waters and therefore need to consider compliance with both BBNJ and CBD/NP. Moreover, researchers require diplomatic Page 2 of 23 Preprint v1.0 - July 21, 2025 How to “do” the Nagoya Protocol: common misconceptions, challenges and best practices for access and benefit-sharing compliance Figure 1: Regulatory landscape governing microbial GR and their derivatives. Researchers accessing GR must navigate a complex landscape of regulations and permits. Hexagons indicate various ABS frameworks. Microbial samples may also be subject to additional permits and regulations such as export controls and/or diplomatic permits; Dual-use research of concern (DURC) evaluation; or require phytosanitary certificates (indicated by blue ovals). Some strains may be subject to WIPO treaties. In addition, samples obtained or derived from humans are subject to further ethical and regulatory scrutiny (orange ovals). Finally, plant or animal-associated samples may fall under further UN multilateral frameworks and require further compliance with the access to or use of their host species. These include the ITPGRFA and CITES (blue ovals). “Microbiological samples” refer to cultures or samples that have not been isolated. permits to enter into the Exclusive Economic Zones (EEZ) and collect biological samples (Fig. 1). Pathogens and Human Health The World Health Organization (WHO)’s Pandemic Influenza Preparedness (PIP) Framework is a multilateral ABS instrument which governs pandemic influenza strains [23]. The new WHO Pandemic Agreement [24] adopted in May 2025 includes Pathogens ABS (PABS) provisions for pathogens with the potential to cause pandemics. However, the PABS procedures including which microbes will be covered, how DSI will be handled, if open access will be maintained, are to be finalized in an annex over the coming year. Once the PABS Annex is agreed, the Pandemic Agreement will be open for ratification. Pathogens are also in the scope of national and international biosecurity regulations often referred to as “dual-use research of concern” (DURC). These rules, such as European Regulation No. 2021/821 [25], aim to ensure that research on/with highly infectious or toxic agents (including, for example, proteins and toxins from non-pathogenic cyanobacteria and fungi) will not be used for malignant purposes. Here, microbiologists must consider where samples came from, their pathogenic nature or the presence of toxins (Fig. 1). Human-derived samples Research involving human-derived microbial/microbiome samples must comply with international ethical frameworks such as the Helsinki Declaration and the Oviedo Convention Regulation, and in the EU, also with the In Vitro Diagnostics Regulation (IVDR, EU Reg. 2017/746) and the Data Page 3 of 23 Preprint v1.0 - July 21, 2025 How to “do” the Nagoya Protocol: common misconceptions, challenges and best practices for access and benefit-sharing compliance Governance Act (EU Reg. 2022/868) [26–28]. One particularly ambiguous area is whether the human microbiome is or is not in scope of ABS. There is no simple answer. While human GR and derivatives (such as human chromosomal or organelle DNA, RNA, proteins, and metabolites) are excluded from the CBD and NP’s scope, microorganisms, including viruses, residing on or in the human body are not explicitly excluded. Consequently, each Party decides how to handle the utilization of GR derived from the human microbiome; some countries exclude them, some include them. These divergent interpretations by different Parties has led to a lack of clarity and confusion among biobanks and users of GR. Box 1 shares practical experience on how to deal with human microbiome under the NP. Under the EU ABS Regulation 511/2014, research on the microbiome as a whole is out of the scope, recognizing its unique composition in each person, but research on individual taxa, is within the scope [29]. Researchers must also keep in mind that the EU Regulation establishes the scope for compliance obligations, but each Member State establishes their own rules on access. World Intellectual Property Organization instruments In addition to regulations specific to the type and provenance of the samples, if research leads to intellectual property claims, researchers must deposit the corresponding strains in a collection recognized as an International Depositary Authority under the Budapest Treaty on the International Recognition of the Deposit of Microorganisms for the Purposes of Patent Procedure [30]. In addition, the May 2024 World Intellectual Property Organization (WIPO) Treaty on Intellectual Property, Genetic Resources and Associated Traditional Knowledge (WIPO GRATK) will require patent applicants to disclose the country of origin of the GR and explicitly acknowledge Indigenous Peoples and Local Communities (IPLC) who provided aTK used to develop the invention [31]. The treaty will enter into force after 15 countries ratify it; as of the time of this publication, only Malawi has done so. Principles of the Nagoya Protocol Of all of the above-mentioned international agreements, the NP is potentially the most challenging to adhere to. This stems from its bilateral nature, meaning agreements are negotiated between a provider (usually a country) and a user of GR (researchers conducting commercial or non-commercial activities). There is great variation in how countries have implemented this agreement at the national level. Due to the number of researchers impacted by the NP and the lack of clarity, we have focused this article here in an attempt to raise awareness, clarify misconceptions, describe regulatory challenges, and offer practical guidelines for microbial researchers. The main principle of the NP is that users must ask for permission to access GR and/or associated traditional knowledge (aTK) and share benefits with the country from which they were collected and/or the aTK holders (henceforth “providers”). At its core, the NP rests on three pillars: • Access: adherence to national ABS regulations on access to their GR (either in situ in country or ex situ from a collection) and/or aTK. It may be necessary to obtain Prior Informed Consent (PIC). Countries can decide whether they regulate access to GR or not. • Benefit-sharing: a commitment to share benefits back. It may imply the negotiation of Mutually Agreed Terms (MAT) with the provider(s). Benefits can be monetary (e.g., royalties) or nonmonetary (e.g. scientific collaboration [14]) which should contribute to the UN’s Sustainable Development Goals [32,33]. • Compliance: all Parties to the NP must establish measures to ensure that users within their jurisdiction comply with the ABS rules from providers. One example is the EU Regulation No. 511/2014 [29,34], which establishes obligations for users of GR within the EU and requires national authorities in Member States to implement compliance checks. Despite the requirement, many NP Parties do not have compliance measures but users should still follow national laws. Nagoya Protocol and microbial biobanking Legal ABS obligations fall on the user who conducts research and development on the GR, storage of GR or environmental samples without conducting research is outside the scope of the NP. Nevertheless, biobanks should fulfill international obligations when distributing such materials. It is good practice to store NPrelevant information, such as the country and date of collection and any associated ABS permits, and to transfer it to the user alongside the biological material. Such practices facilitate future legal utilization because it would be difficult for the final user to obtain relevant NP information from the original depositor without the collection or biobank facilitating it. Page 4 of 23 Preprint v1.0 - July 21, 2025 How to “do” the Nagoya Protocol: common misconceptions, challenges and best practices for access and benefit-sharing compliance Correcting frequent misconceptions about the Nagoya Protocol, the “DOs” While the principles of ABS and the importance of the NP are straightforward, the requirements are often written in complex legal terms and often only in the local language, making them difficult to understand and follow. Consequently, several misconceptions have emerged within the scientific community over the past decade. In this section, we address common misconceptions and provide clarity on the language of the NP. 1. Non-commercial academic research is subject to ABS obligations It is often incorrectly assumed that non-commercial or academic research is exempt from the NP. However, the NP defines the term “utilization” as conducting research and development on the genetic and/or biochemical and molecular components of GR (derivatives), regardless of the purpose of the research. This misunderstanding can inadvertently lead to noncompliance, potentially resulting in legal consequences, reputational damage, or retraction of scientific articles for researchers unaware of the full scope of the NP’s requirements [35,36]. 2. Researchers must follow ABS laws of the country where the genetic resource was originally collected – not where it was cultivated or stored! Defining the provider country of a microbial GR is often a source of confusion because of the various ways of accessing microbial GR in practice. The provider country is the one where the material (in situ sample) was originally collected. It is not the country where the microbial strain was ultimately cultivated or isolated in the laboratory, nor the country of storage (i.e. ex situ collection or biobank). 3. ABS legislations often apply to national researchers Whether ABS regulations apply to domestic researchers varies by country, but often they too must obtain an ABS permit to access and utilize GR within their own country, whether on private property or in protected areas. For example, Brazilian researchers need to follow Brazilian ABS laws and so do foreign researchers. Some countries offer facilitated procedures for such access and use, while others apply the same set of rules that apply to researchers working for foreign research institutions. 4. Researches from countries that are not a Party to the CBD... should still “do Nagoya” Scientists carrying out research in countries that are non-Parties to the NP, such as the United States of America (USA) [37], must still comply with the ABS rules established in provider countries and obtain the necessary ABS permits. The key difference is that researchers within the USA will not be checked for compliance by a USA federal authority. But they can damage their reputation and international collaborations if they willfully ignore national laws. Additionally, as the EU is a Party to the NP and its ABS law on compliance [29, 34] applies to all Member States, all researchers based in the EU have compliance obligations, including those based in non-NP-Parties – such as Italy and Poland. 5. Utilizing commodities for research purposes changes their intended use and can trigger ABS obligations Trade and exchange of commodities, whether for direct consumption or as ingredients, e.g. microbial starters in food and drink products, falls outside the scope of NP. However, if research and development are carried out on commodities, the intended use has changed. The user is expected to determine and contact the provider country to determine if ABS permits are needed. However, microorganisms introduced unintentionally in the EU (e.g. pathogens or food contaminants) and the isolation and identification of microorganisms from commodities for quality control purposes are out of the scope of the EU ABS Regulation. Challenges in applying the Nagoya Protocol in noncommercial research The Nagoya Protocol presents several challenges that may delay or hinder research. 1. Legal complexity Obtaining ABS permits often implies understanding multiple legal documents, completing forms (usually in the local language) and, in many cases, long benefitsharing negotiations with providers. Often, simply being able to confirm whether or not a country regulates access to GR/aTK can be a challenging task, as many Parties have not shared clear guidelines in the ABS Clearing-House (ABS-CH) [38], an online platform established under the CBD to facilitate the ABS information sharing, and sometimes do not respond efficiently to enquiries. Once a determination is made, obtaining the necessary ABS permits can take several Page 5 of 23 Preprint v1.0 - July 21, 2025 How to “do” the Nagoya Protocol: common misconceptions, challenges and best practices for access and benefit-sharing compliance months or even years, causing significant delays. Box 2 highlights the legal complexity arising from a real case on biological control of non-native invasive species. 2. Diversity of regulatory frameworks and liability fragmentation The CBD and the NP recognize the sovereign rights of countries over their GR, which enables Parties to define their own ABS rules. Consequently, many aspects differ among ABS legislation, including scope, definitions, requirements, procedures, and even terms used to name ABS permits (such as declaration, notification, registration, Mutually Agreed Terms (MAT), Material Transfer Agreement (MTA)). Varying administrative procedures, legal interpretations and wording may cause misunderstandings, making it difficult for researchers to engage with provider countries, further disrupting project timelines [39–41]. In some countries, several Competent National Authorities (CNA) (e.g. ministries, agencies, and local entities) are designated to implement ABS procedures under local legislation, creating challenges in identifying a clear point of contact for users seeking ABS compliance. Temporary rules add to the uncertainty, making it difficult for researchers to navigate regulations efficiently [42] (Box 3). 3. Governance and legal complexities affecting Indigenous Peoples and Local Communities involvement in ABS The scientific community supports the rights of IPLCs as custodians of GR and aTK and their role as providers and beneficiaries of ABS systems. However, lack of official recognition by the provider country and unclear governance frameworks, can add further complexity to the process of obtaining ABS permits. Although some national ABS frameworks clearly define the role of IPLCs, in many cases they are not formally recognized as beneficiaries, requiring them to appeal to human rights courts to assert their rights to fair and equitable benefit-sharing and prior informed consent [43]. This lack of recognition complicates the identification of authorized representatives, particularly in countries without legal frameworks to uphold collective community rights. This puts researchers between a rock and a hard place and makes full compliance difficult. 4. Retroactive ex situ access and utilization rules Researchers may also face challenges with ABS regulations that cover new utilization of GR collected before the implementation of the NP. While international law is generally not retroactive, some countries’ legislation is retroactive de facto because utilization (not access) triggers ABS, causing confusion and administrative challenges [44,45]. This particularly affects research on microorganisms from ex-situ collections and biobanks, where the legal status of these samples varies according to the ABS legislation in the provider country. 5. Incompatibility of some ABS laws and the International Code of Nomenclature of Prokaryotes According to the International Code of Nomenclature of Prokaryotes (ICNP), for the valid publication of names of new prokaryotic taxa, scientists must deposit voucher specimens of type strains in publicly accessible ex situ culture collections in two different countries that must be made available without restrictions [46]. However, if the ABS permit imposes restrictions on sharing them with third parties or requires new ABS permits, the conditions for valid publication under the ICNP cannot be met. As a result, researchers may still describe new taxa, but their names cannot be validated according to the ICNP and therefore will not be internationally recognized. Consequently, some culture collections now refuse deposits of strains originally collected in certain provider countries [47]. 6. Insufficient legal and regulatory training in scientific education Despite over a decade of international NP implementation, training on ABS and other international legal and regulatory frameworks remains largely absent from microbiology education, leaving researchers unprepared [48]. Researchers often learn informally through experience or colleagues, increasing the risk of institutional non-compliance. Integrating legal and regulatory topics into life sciences education is essential to equip future researchers for NP compliance. Similarly, there is a lack of structured ABS-related training and capacity building for biobank managers. Biobanks and collections need to be aware of their obligations and of best practices for NP compliance, in order to manage and transfer NP-relevant information. How to comply with the Nagoya Protocol: a step-by-step guide Whether you are collecting new samples in the field or working with previously gathered materials, this section highlights five key stages of the ABS procedure and provides an overview of the main steps (Fig. 2). Complying with the NP can be complex, as each country has its own ABS rules. Not all Parties to the Protocol regulate access (e.g. Germany), while some non-Parties (e.g. Colombia) do. In some cases, ABS Page 6 of 23 Preprint v1.0 - July 21, 2025 How to “do” the Nagoya Protocol: common misconceptions, challenges and best practices for access and benefit-sharing compliance Figure 2: Step by step guide to comply with the Nagoya Protocol. Visual guide outlining the main steps for navigating ABS obligations. laws may only relate to compliance, not access. Therefore, it is critical to review each country’s profile on the ABS-CH [38] and, when needed, follow up directly with national authorities. Partnering with local collaborators can also help navigate procedures and cultural contexts. Understanding how provider countries regulate ex situ access is especially important. Some countries consider “access” any new utilization of GR, even if those resources were collected long ago. The ABS World interactive infographic [49] can help determine whether ABS laws apply to your project. When information is insufficient, contact the ABS National Focal Points or Competent National Authorities listed on the ABS-CH [38]. Provide detailed information about your research, including taxonomic focus, sampling locations, and project objectives. You may also request documentation about forms and procedures and seek confirmation of your understanding of the ABS measures. Before requesting permits or signing agreements, make sure your planned use–such as transfer to thirdparty or publishing genetic sequences in open access databases–is covered. Use the ABS Strategy Checklist [50] to prepare effectively to deal with ABS in provider countries. Once permits are issued, ensure your use of the material strictly follows the authorized terms. Don’t forget to check compliance obligations in your user country. For researchers in the EU, this may include seeking, keeping, and transferring relevant ABS documentation and submitting a due diligence declaration via DECLARE [51]. Reading the EU ABS Guidance Document [29] is highly recommended–it includes clear explanations and practical examples. For more details, tools, and examples, explore the full guide: How to “do” the Nagoya Protocol (see Supplementary Information). Outlook The regulatory frameworks established by the NP and CBD can appear complex and daunting for microbiologists and other life sciences researchers (Fig. 1). However, adherence to these guidelines not only facilitates equitable research aligned with biodiversity conservation and sustainable use objectives, but also opens new opportunities for international collaboration and capacity building. In this context, scientists and institutions working with genetic resources–microbial or otherwise–benefit from collaborating, sharing knowledge, experience and best practices to address ABS regulatory challenges effectively. Closer engagement between the scientific community, policymakers, and local authorities can facilitate the development of a more effective ABS framework [52]. Such partnerships are particularly important for guiding biological research on biodiversity and environmental sustainability. The implementation of NP compliance in noncommercial research involving GR from provider countries requires dedication, patience, and, occasionally, a readiness to make compromises (Fig. 2, Box 1,2, and 3). Nevertheless, these efforts contribute to the development of more ethical research practices that align scientific advancement with respect for the rights and interests of provider communities and nations. Page 7 of 23 Preprint v1.0 - July 21, 2025 How to “do” the Nagoya Protocol: common misconceptions, challenges and best practices for access and benefit-sharing compliance Box 1. Navigating the NP and ABS compliance in human microbiome research - case studies for best practices Figure 3: Navigating human-derived microbiome utilization and sample (re)use. The body of every single human being is home to a variety of different microbiomes (A). Geographically distant human communities may have patterns in their associated microbiomes, which can help understand how lifestyle, diet, environment, and other differences alter human microbiomes and may be related to health or disease. International initiatives such as the Global Microbiome Conservancy (GMbC) and Afribiota have developed collaborations in diverse geographical areas to address this type of research questions (B). However, in addition to the imperative to utilize human samples ethically and fairly, the lack of legislative uniformity in regulating ABS for human microbiomes and microorganisms makes it difficult for researchers to navigate the path to legally accessing these microbiological GR (C). Furthermore, (re)use of ex situ samples originally collected for other projects, shared by collaborators, or obtained from biobanks may also prove intricate and lead to a complex ABS journey (C). Despite the difficulties in navigating this fragmented regulatory landscape, research consortia like the GMbC and Afribiota demonstrate that human microbiome research can be both NP-compliant and scalable, serving as models for global collaboration (B). The globalization of human microbiome research has drawn new attention to the complexities of the NP and associated ABS regulations. While the NP clearly does not apply to human GR, the status of human-associated microorganisms and/or their genetic material and derivatives remains ambiguous. Page 8 of 23 Preprint v1.0 - July 21, 2025 How to “do” the Nagoya Protocol: common misconceptions, challenges and best practices for access and benefit-sharing compliance Challenge 1: Does human microbiome fall under NP regulations? National interpretations vary widely: some countries classify human microbiota as within the scope of the NP, others explicitly exclude them, and some offer no official guidance at all. This uncertainty creates an unpredictable landscape for microbiome researchers. Scientists who are not trained in international policy may unknowingly fall into illegality. In this complex regulatory context, the Global Microbiome Conservancy (GMbC) [53] provides a practical example of how an international consortium can advance scientific goals while navigating legal complexity. Aiming to promote diversity in available human-microbiome datasets to better understand the impact of lifestyle on microbiomes and health, GMbC consortium members collect and sequence human microbiome samples worldwide (Fig. 3A, B), which are then stored in a biobank for downstream analysis and distribution of isolated microorganisms. Since 2016, the GMbC has encountered several NP interpretations, including working with countries that consider human-associated microbiomes within scope and require a formal ABS-permit process (e.g., Pakistan, 2021), countries who consider these materials outside the scope of the NP and provided a waiver (e.g., Rwanda, 2018), and non-NP Party countries that also provided a waiver (e.g., Paraguay, 2024). Despite this variability, the GMbC has adopted a policy of full ABS compliance. Standardized documents are used in all participating countries, including Collaboration and Collection Agreements, and, when applicable, ABS permits or waivers. They include commitments to equitable scientific collaboration, such as co-authorship of publications, capacity-building, and long-term partnerships. Working closely with national focal points, the GMbC consortium constantly strives to ensure ongoing ABS compliance even if the road to this goal can often be winding (Fig. 3C). Its experience highlights the importance of vigilance: regulations can be modified, countries may become NP Parties, their interpretations of whether human microbiomes fall within scope may change, retroactivity may become an issue, and additional ABS permits or waivers may have to be obtained. Challenge 2: How to handle subsequent sharing of bio-material stored in already existing biobanks As culturing techniques develop, laboratories are building their own microbial repositories. Initially created to address their own research objectives, collected human-derived microorganisms are sometimes requested by others. However, in most cases, original participant consent forms and ABS permits were obtained before such distribution was anticipated. Consequently, this new utilisation requires new permits and renegotiated benefitsharing terms (Fig. 3C). The Afribiota Consortium [54] has collected human-microbiome samples from children to better understand the physiology of stunted childhood development and its link to gut microbial communities (Fig. 3B). The corresponding ABS approvals or waivers were obtained for these specific research objectives and subsequent sharing of resources was not included in the initial ABS agreement. Therefore, new ABS contracts were needed for that purpose. Retroactive ABS permits or waivers have been crucial to ensure the legally compliant dissemination of biobanked GR. In this case, retroactive permits were granted only because the original consent forms specifically mentioned both long - term biobanking and the possibility of third-party distribution. Had those clauses been absent, the consortium would have had to either re-consent participants or refrain from sharing the material. The experiences of the GMbC and the Afribiota consortiums highlight that NP-compliant human microbiome research is not only possible but also scalable worldwide. Collaboration with research groups in each provider country should be the norm: it facilitates navigation of local regulations and promotes capacity-building. As microbiome science evolves, the need for clear ABS frameworks for humanmicrobiomes becomes urgent. International ABS compliance could be strengthened through global guidelines clarifying the scope of the NP with respect to human-associated microbes, and through toolkits to help researchers navigate often complex ABS requirements (Fig. 3C). Page 9 of 23 Preprint v1.0 - July 21, 2025 How to “do” the Nagoya Protocol: common misconceptions, challenges and best practices for access and benefit-sharing compliance Bibliography 1. Lennon, J. T. & Locey, K. J. More support for Earth’s massive microbiome. Biology Direct 15, 5. issn: 1745-6150. https://biologydirect. biomedcentral . com / articles / 10 . 1186 / s13062-020-00261-8 (Dec. 2020). 2. Louca, S., Mazel, F., Doebeli, M. & Parfrey, L. W. A census-based estimate of Earth’s bacterial and archaeal diversity. PLOS Biology 17 (ed Jansson, J. K.) e3000106. issn: 1545-7885. https://dx. plos.org/10.1371/journal.pbio.3000106 (Feb. 4, 2019). 3. Lewis, W. H., Tahon, G., Geesink, P., Sousa, D. Z. & Ettema, T. J. G. Innovations to culturing the uncultured microbial majority. Nature Reviews Microbiology 19, 225–240. issn: 1740-1526, 17401534. https://www.nature.com/articles/ s41579-020-00458-8 (Apr. 2021). 4. Louca, S. The rates of global bacterial and archaeal dispersal. The ISME Journal 16, 159– 167. issn: 1751-7362, 1751-7370. https : / / academic.oup.com/ismej/article/16/1/159167/7474160 (Jan. 1, 2022). 5. Overmann, J. & Scholz, A. H. Microbiological Research Under the Nagoya Protocol: Facts and Fiction. Trends in Microbiology 25, 85–88. issn: 0966842X. https : / / linkinghub . elsevier . com/retrieve/pii/S0966842X16301640 (Feb. 2017). 6. Anantharaman, K. et al. Thousands of microbial genomes shed light on interconnected biogeochemical processes in an aquifer system. Nature Communications 7, 13219. issn: 20411723. https://www.nature.com/articles/ ncomms13219 (Oct. 24, 2016). 7. Loreau, M. et al. Biodiversity and Ecosystem Functioning: Current Knowledge and Future Challenges. Science 294, 804–808. issn: 0036-8075, 1095-9203. https://www.science.org/doi/ 10.1126/science.1064088 (Oct. 26, 2001). 8. Voolstra, C. R. et al. The coral microbiome in sickness, in health and in a changing world. Nature Reviews Microbiology 22, 460–475. issn: 17401526, 1740-1534. https://www.nature.com/ articles/s41579-024-01015-3 (Aug. 2024). 9. Callens, K. et al. Microbiome-based solutions to address new and existing threats to food security, nutrition, health and agrifood systems’ sustainability. Frontiers in Sustainable Food Systems 6, 1047765. issn: 2571-581X. https://www. frontiersin.org/articles/10.3389/fsufs. 2022.1047765/full (Dec. 7, 2022). 10. D’Hondt, K. et al. Microbiome innovations for a sustainable future. Nature Microbiology 6, 138– 142. issn: 2058-5276. https://www.nature. com/articles/s41564-020-00857-w (Jan. 28, 2021). 11. Ibáñez, A., Garrido-Chamorro, S. & Barreiro, C. Microorganisms and Climate Change: A Not so Invisible Effect. Microbiology Research 14, 918– 947. issn: 2036-7481. https://www.mdpi.com/ 2036-7481/14/3/64 (July 25, 2023). 12. Berg, G. et al. Microbiome definition revisited: old concepts and new challenges. Microbiome 8, 103. issn: 2049-2618. https : / / microbiomejournal . biomedcentral . com / articles / 10 . 1186 / s40168 - 020 - 00875 - 0 (Dec. 2020). 13. Salem, H. & Kaltenpoth, M. The Nagoya Protocol and its implications for microbiology. Nature Microbiology 8, 2234–2237. issn: 2058-5276. https://www.nature.com/articles/s41564023-01532-6 (Nov. 29, 2023). 14. Conference of the Parties to the Convention on Biological Diversity. Nagoya Protocol on Access to Genetic Resources and the Fair and Equitable Sharing of Benefits Arising from their Utilization to the Convention on Biological Diversity: Text and Annex 2011. https://wedocs.unep.org/20. 500.11822/27555. 15. International Nucleotide Sequence Database Collaboration https://www.insdc.org/. 16. Karsch-Mizrachi, I. et al. The international nucleotide sequence database collaboration (INSDC): enhancing global participation. Nucleic Acids Research. Publisher: Oxford University Press (OUP). issn: 1362-4962. https://academic. oup.com/nar/article/53/D1/D62/7899524 (Nov. 13, 2024). 17. CBD/COP/DEC/16/2. Digital sequence information on genetic resources. https://www.cbd. int/doc/decisions/cop-16/cop-16-dec-02en.pdf (2024). 18. Orozco, P. & Scholz, A. H. The Cali Fund promises conservation benefits, but only if countries and businesses take action. Nature Reviews Biodiversity 1, 276–278. issn: 3005-0677. https : / / www . nature.com/articles/s44358-025-00050-z (May 16, 2025). 19. Muñoz-García, M. et al. Navigating COP16’s digital sequence information outcomes: What researchers need to do in practice. Patterns 6, 101208. issn: 26663899. https : / / linkinghub . elsevier . com / retrieve / pii / S266638992500056X (Mar. 2025). Page 16 of 23 Preprint v1.0 - July 21, 2025 How to “do” the Nagoya Protocol: common misconceptions, challenges and best practices for access and benefit-sharing compliance 20. Food and Agriculture Organization of the United Nations. International Treaty on Plant Genetic Resources for Food and Agriculture 2001. https : / / www . fao . org / plant - treaty / overview / texts-treaty/en/. 21. Convention on International Trade in Endangered Species of Wild Fauna and Flora | CITES https: //cites.org/eng/disc/text.php. 22. BBNJ Agreement | Agreement on Marine Biological Diversity of Areas beyond National Jurisdiction https://www.un.org/bbnjagreement/en. 23. Pandemic Influenza Preparedness (PIP) Framework https : / / www . who . int / initiatives / pandemic - influenza - preparedness - framework. 24. World Health Assembly adopts historic Pandemic Agreement to make the world more equitable and safer from future pandemics https : / / www . who . int / news / item / 20 - 05 - 2025 - worldhealthassemblyadoptshistoricpandemicagreementtomaketheworldmoreequitableandsaferfromfuturepandemics. 25. Regulation - 2021/821 - EN - EUR-Lex Doc ID: 32021R0821 Doc Sector: 3 Doc Title: Regulation (EU) 2021/821 of the European Parliament and of the Council of 20 May 2021 setting up a Union regime for the control of exports, brokering, technical assistance, transit and transfer of dual-use items (recast) Doc Type: R Usr_lan: en. https://eur-lex.europa.eu/eli/reg/2021/ 821/oj/eng. 26. The Oviedo Convention and human rights principles regarding health - Human Rights and Biomedicine - www.coe.int Human Rights and Biomedicine. https : / / www . coe . int / en / web/human - rights - andbiomedicine/the - oviedo - convention - and - human - rights - principles-regarding-health. 27. Regulation - 2017/746 - EN - Medical Device Regulation - EUR-Lex Doc ID: 32017R0746 Doc Sector: 3 Doc Title: Regulation (EU) 2017/746 of the European Parliament and of the Council of 5 April 2017 on in vitro diagnostic medical devices and repealing Directive 98/79/EC and Commission Decision 2010/227/EU (Text with EEA relevance. ) Doc Type: R Usr_lan: en. https://eurlex.europa.eu/eli/reg/2017/746/oj/eng. 28. Regulation - 2022/868 - EN - EUR-Lex Doc ID: 32022R0868 Doc Sector: 3 Doc Title: Regulation (EU) 2022/868 of the European Parliament and of the Council of 30 May 2022 on European data governance and amending Regulation (EU) 2018/1724 (Data Governance Act) (Text with EEA relevance) Doc Type: R Usr_lan: en. https://eur-lex.europa.eu/eli/reg/2022/ 868/oj/eng. 29. Guidance document on the scope of application and core obligations of Regulation (EU) No 511/2014 of the European Parliament and of the Council on the compliance measures for users from the Nagoya Protocol on Access to Genetic Resources and the Fair and Equitable Sharing of Benefits Arising from their Utilisation in the Union 2021/C 13/01 https:// eur-lex.europa.eu/legal-content/EN/TXT/ ?uri=uriserv%3AOJ.C_.2021.013.01.0001. 01.ENG&toc=OJ%3AC%3A2021%3A013%3ATOC. 30. Budapest Treaty on the International Recognition of the Deposit of Microorganisms for the Purposes of Patent Procedure https://www.wipo.int/ treaties/en/registration/budapest/index. html. 31. WIPO Treaty on Intellectual Property, Genetic Resources and Associated Traditional Knowledge https:/ / www.wipo. int / treaties/en / ip / gratk/index.html. 32. Crowther, T. W. et al. Scientists’ call to action: Microbes, planetary health, and the Sustainable Development Goals. Cell 187, 5195–5216. issn: 00928674. https : / / linkinghub . elsevier . com/retrieve/pii/S0092867424008456 (Sept. 2024). 33. THE 17 GOALS | Sustainable Development https: //sdgs.un.org/goals. 34. Regulation - 511/2014 - EN - EUR-Lex Doc ID: 32014R0511 Doc Sector: 3 Doc Title: Regulation (EU) No 511/2014 of the European Parliament and of the Council of 16 April 2014 on compliance measures for users from the Nagoya Protocol on Access to Genetic Resources and the Fair and Equitable Sharing of Benefits Arising from their Utilization in the Union Text with EEA relevance Doc Type: R Usr_lan: en. https://eurlex. europa.eu/eli/reg/2014/511/oj/eng. 35. Kim, E., An, S. L., Choi, J. B. & Park, J. K. RETRACTED: Taxonomic study on the montanellus species group of the genus Cyclommatus (Coleoptera: Lucanidae) from Borneo Island, Malaysia, and Indonesia. Journal of AsiaPacific Biodiversity 13, 372–379. issn: 2287884X. https : / / linkinghub . elsevier . com / retrieve / pii / S2287884X20300789 (Sept. 2020). 36. Statement of Retraction: Additional new species of Grouvellinus Champion 1923 (Insecta, Coleoptera, Elmidae) discovered by citizen scientists and DNA barcoded in the field applying a novel MinION-based workflow. Journal of Natural History 54, 1697–1697. issn: 0022-2933, 1464-5262. https://www.tandfonline.com/ doi/full/10.1080/00222933.2020.1851935 (July 17, 2020). Page 17 of 23 Preprint v1.0 - July 21, 2025 How to “do” the Nagoya Protocol: common misconceptions, challenges and best practices for access and benefit-sharing compliance 37. Unit, B. Parties to the Nagoya Protocol Publisher: Secretariat of the Convention on Biological Diversity. https://www.cbd.int/abs/nagoyaprotocol/signatories. 38. ABSCH | Access and Benefit-Sharing ClearingHouse https://absch.cbd.int/en/. 39. Ebert, A. W., Engels, J. M. M., Schafleitner, R., Hintum, T. v. & Mwila, G. Critical Review of the Increasing Complexity of Access and Benefit-Sharing Policies of Genetic Resources for Genebank Curators and Plant Breeders–A Public and Private Sector Perspective. Plants 12. Publisher: MDPI AG, 2992. issn: 2223-7747 (Aug. 2023). 40. Morgera, E. Fair and equitable benefit-sharing in international law isbn: 978-0-19-886213-0 (Oxford University Press, New York, 2024). 41. Heinrich, M. et al. Access and Benefit Sharing Under the Nagoya Protocol—Quo Vadis? Six Latin American Case Studies Assessing Opportunities and Risk. Frontiers in Pharmacology 11. Publisher: Frontiers Media SA. issn: 1663-9812 (June 2020). 42. Ferrari, M. L. et al. Clarification on the implementation of the Nagoya Protocol in France for the access and sharing of benefits arising from the utilization of microbial genetic resources. International Journal of Systematic and Evolutionary Microbiology 74. issn: 1466-5026, 1466-5034. https : / / www . microbiologyresearch . org / content/journal/ijsem/10.1099/ijsem.0. 006262 (Mar. 6, 2024). 43. Zheng, X. Empowering indigenous peoples and local communities: A human rights-based appraisal of the compliance mechanism of the Nagoya Protocol. Review of European, Comparative & International Environmental Law 30, 61–72. issn: 20500386, 2050-0394. https : / / onlinelibrary . wiley.com / doi/10. 1111 /reel.12343 (Apr. 2021). 44. Margo A. Bagley, Arti K. Rai. The Nagoya Protocol and Synthetic Biology Research: A Look at the Potential Impacts. Virginia Public Law and Legal Theory Research Paper, Emory Legal Studies Research Paper. https://papers.ssrn.com/sol3/ papers.cfm?abstract_id=2388794 (2014). 45. Rabitz, F. Biopiracy after the Nagoya Protocol: Problem Structure, Regime Design and Implementation Challenges. Brazilian Political Science Review 9, 30–53. issn: 1981-3821. http : / / www . scielo . br / scielo . php ? script = sci _ arttext & pid = S1981 - 38212015000200030 & lng=en&tlng=en (Aug. 2015). 46. Rahi, P. Regulating access can restrict participation in reporting new species and taxa. Nature Microbiology 6, 1469–1470. issn: 2058-5276. https://www.nature.com/articles/s41564021-01002-x (Nov. 17, 2021). 47. Leibniz Institute DSMZ: Strain Deposit https:// www.dsmz.de/collection/nagoya-protocol/ strain-deposit. 48. Smith, D., Da Silva, M., Jackson, J. & Lyal, C. Explanation of the Nagoya Protocol on Access and Benefit Sharing and its implication for microbiology. Microbiology 163, 289– 296. issn: 1350-0872, 1465-2080. https : / / www . microbiologyresearch . org / content / journal / micro / 10 . 1099 / mic . 0 . 000425 (Mar. 1, 2017). 49. Understanding the ABS world – infographic – Nagoyaprotocol-hub https : / / www . nagoyaprotocol - hub . de / abs - world - infographic/. 50. Build your ABS Strategy – checklist – Nagoyaprotocol-hub https : / / www . nagoyaprotocol-hub.de/abs-strategy/. 51. EC AV PORTAL https : / / audiovisual . ec . europa.eu/en/video/I-193088. 52. New ´fast track´Access and Benefit-Sharing Agreement for Costa Rican microbes https : / / www . dsmz . de / press / press - releases / singleview/newfasttrackaccessandbenefit - sharing - agreement - for - costa - rican-microbes. 53. Global Microbiome Conservancy https : / / microbiomeconservancy.org/. 54. Afribiota project: Childhood malnutrition Institut Pasteur. https : / / www . pasteur . fr / en / international / international - programs / afribiota - project - childhood - malnutrition. 55. Arrêté du 3 septembre 2019 relatif aux espèces modèles - Légifrance https://www.legifrance. gouv.fr/jorf/id/JORFTEXT000039180351. 56. Ressources génétiques : l’application du protocole de Nagoya en France | Ministère de l’Agriculture et de la Souveraineté alimentaire https://agriculture.gouv.fr/ressourcesgenetiques - lapplication - du - protocole - de-nagoya-en-france. 57. TITLE V ACCESS TO GENETIC RESOURCES, FAIR AND EQUITABLE BENEFIT - SHARING Courtesy translation (We identified a translation error in Article 47 paragraph 7, “Domestic or cultivated species” should be “Domesticated or cultivated species” instead). https: //absch.cbd .int/ api/v2013/documents/728A5D5D-21BB-30580A10 - D752E62C3F25 / attachments / 211500 / Page 18 of 23 Preprint v1.0 - July 21, 2025 How to “do” the Nagoya Protocol: common misconceptions, challenges and best practices for access and benefit-sharing compliance Title % 20V _ Law % 20on % 20biodiversity % 20dated % 208th % 20of % 20August % 202016 _ French%20%20ABS%20legislation.pdf. 58. Declaration regarding access to genetic resources and benefit-sharing arising from their utilisation (Formulaire 15786*02) | Entreprendre.ServicePublic.fr https : / / entreprendre . service - public.fr/vosdroits/R57747. 59. Access to genetic resources and associated traditional knowledge and sharing of the benefits arising from their utilization (ABS) https://www. ecologie.gouv . fr / sites/default/ files / documents/Accesstogeneticresourcesand-associated.pdf. Page 19 of 23 Preprint v1.0 - July 21, 2025 How to “do” the Nagoya Protocol: common misconceptions, challenges and best practices for access and benefit-sharing compliance Supplementary Information How to “do” the Nagoya Protocol: a step-by-step guide Have you heard of the Nagoya Protocol but don’t know where to start? This guide is for you! This guide highlights the main steps researchers need to follow to comply with the Nagoya Protocol (NP) [1]. It includes important clarifications and practical recommendations. Step 1: Determine whether the provider country regulates access. Identify the provider countries. Before starting the research project, it is essential to identify the countries where the genetic resources (GR) originate from. If you are planning to collect samples in the field (in situ), the provider countries are those you or your collaborators will directly collect the samples from. If you will utilize “old” material (previously collected) from a collection or another source (known as ex situ access) the provider country is the one in which the material was originally collected, not the country where it is currently cultivated or stored. If you plan to utilize “old” material the basic information you should compile is where and when each sample was originally collected and whether they have an associated ABS permit. Once you have identified the relevant provider countries, consult the Access and Benefit-sharing Clearing House (ABS-CH) [2], the official Nagoya Protocol platform managed by the Convention on Biological Diversity (CBD) [3]. It compiles ABS relevant information published by national authorities in their country profiles, including national ABS legislation, procedural guidelines, contact information for national authorities, among others. Keep in mind that not all the Parties to the NP regulate access to GR and/or associated traditional knowledge (aTK), furthermore, some non-Party countries do. Unfortunately, this information is not always easy to find in the ABS-CH. For instance, Germany does not regulate access to GR and while it has published ABS measures on the ABS-CH, these refer to compliance rather than access. In such cases, to understand how access is regulated, it is necessary to examine the profile of the country on the ABS-CH carefully. For instance, for some countries like Germany, this information is available under question 11 of the interim report [4]. However, these reports were published in 2018, and new decisions may have been made since. Updated national reports are expected by 2026. It is also possible to indirectly confirm if a country regulates access if it has issued permits (Internationally Recognized Certification of Compliance or IRCCs), published ABS procedures, or if its legal measures have elements related to access. In some cases, the information available in the ABS-CH is not sufficient to determine whether a country regulates access. For example, the presence of “zero” ABS measures on the ABS-CH does not necessarily mean that GR/aTK can be freely accessed. It may simply indicate that the country has not published its national laws on the platform. The absence of published ABS measures on the ABS-CH is not sufficient proof of legal compliance in the event of a dispute. If the ABS-CH does not provide enough information, consider consulting other sources. These may include national government websites, local partners, colleagues who have experience in the country in question, institutional ABS contact person and documents such as academic papers or fact sheets. Step 2: Verify whether the ABS rules in the provider country apply to your project Analyze legal definitions, scope, and exemptions to check if your specific material and type of research are under the scope of national ABS laws. Some laws only cover certain types of organisms or organisms collected in certain areas. Some countries include exemptions or simplified procedures for basic research. In microbiological research, the applicability of ABS laws may be unclear, especially in cases of access to human microbiome, which is covered by some countries and not by others, therefore direct clarification from authorities is often necessary. For more detailed guidance on this you can check the ABS world interactive infographic [5]. Page 20 of 23 Preprint v1.0 - July 21, 2025 How to “do” the Nagoya Protocol: common misconceptions, challenges and best practices for access and benefit-sharing compliance Understand how the provider country regulates ex situ access and check whether and how the ex situ samples you want to utilize are covered. This is relevant if your research involves utilizing previously collected samples. Start by determining when the country’s ABS laws entered into force. If the material was collected after that date, you may have legal obligations to utilize it. Some countries have ABS rules before the NP came into force that may apply to your ex situ samples. Besides that, some countries define access to include new utilization of GR and in these cases, you may require an ABS permit even if the material was collected and left the country long ago, even before the CBD and the NP came into force. Moreover, if samples housed in a collection are linked to an ABS permit, it is important to carefully review that permit to understand any conditions related to transfer and use. National ABS measures sometimes include specific sections on ex situ access, which offer guidance on how to proceed. Contact the national authorities to request information or confirm your interpretations. After reviewing available documentation in the ABS-CH and other sources, you may need additional clarification. In such cases, contact the ABS National Focal Points and Competent National Authorities, whose contact information is listed on the ABS-CH. When communicating with authorities, provide as much detail as possible about your research. This includes information about the taxonomic group you intend to study (if known in advance), the exact geographic location(s) of sampling, and the objectives and methods of your project. In some fields, such as microbiology, it may be difficult to specify species or taxonomic groups in advance. If this is the case, explain that identifications will be made during the research and commit to submitting a species list once the data are available. You may also ask for relevant forms, clarification of procedures, or confirmation of your interpretation of the ABS laws. Be aware of potential language barriers and cultural differences during these communications. Authorities may take time to respond, so patience and follow-up reminders are often necessary. If no response is received, consider reaching out to the CBD National Focal Point or other officials in the Ministry of Environment or its equivalent. Collaborating with a local partner is often extremely helpful, as they can assist with communications, help navigate the national context, and facilitate the permitting process. Step 3: Understand each country’s specific ABS requirements and procedures Each country determines its own access rules, which can differ significantly. This includes differences in terminology, definitions, and required documentation. It is important to have clarity on each country’s specific requirements and procedures. To do so, you should first check the ABS procedures section on the ABS-CH [2]. However, only a limited number of countries have published their ABS procedures. In most cases, it will be necessary to request additional information from national authorities. Determine the type of permit needed, the required documents, and the submission procedures. Some countries have online application platforms, although for some countries these may require national ID credentials or the submission of physical documents with original signatures. Other requirements might include legal authentication of signatures, translations, and payment of permit fees. Verify if you need other types of permits. In addition to ABS permits, you may also need research, collection or export permits, depending on the country. Step 4: Request the necessary permits Ensure that your permit application covers everything you need for your project, such as all samples, access to aTK, planned methods, physical access to the sampling site, publishing genetic sequences in open access databases, project collaborators who will receive and utilize the material or be co-authors in publications, any intended deposits in ex situ collections, no restrictions to transfer to third parties (it may be particularly relevant in case of description of new species). If you plan to store samples in a collection or biobank for future use or distribution, it is a good practice to compile all relevant ABS documentation and confirm under what conditions you are allowed to share the material or what requirements recipients must meet. Page 21 of 23 Preprint v1.0 - July 21, 2025 How to “do” the Nagoya Protocol: common misconceptions, challenges and best practices for access and benefit-sharing compliance Check the ABS strategy checklist [6] for more detailed guidance. Most countries require an agreement on benefits-sharing. In academic research, this often involves non-monetary benefits such as scientific publications, joint research outputs with local scientists, conservation recommendations, or capacity building and technology transfer. In some countries, you may need to negotiate benefit-sharing terms with national authorities, Indigenous Peoples and Local Communities (IPLCs), or other designated providers, such as research institutions, national parks, or landowners. In others, simplified mechanisms are available, such as standardized model agreements or declarations outlining intended benefits. Before agreeing to benefit-sharing terms, clearly define what benefits you can offer, considering grant agreements and institutional policies. These agreements are legally binding, and you must comply with and report on them. Seek legal advice within your institution for help with contracts and to determine who is authorized to sign them. After receiving your permits, verify that they are valid and sufficient. The issuing authority should match the Competent National Authority in the ABS-CH. If there is any discrepancy, follow up with the ABS National Focal Point. In general, the national permit or its equivalent is sufficient to ensure compliance, but you may also request an IRCC, which provides a globally recognized certificate published on the ABS-CH and has a standardized global code. Step 5: Check for compliance obligations Throughout your research, make sure that your use of the material aligns with the terms authorized in your permit. This includes publishing genetic sequences in public databases, transferring materials to partners, or depositing samples in collections. Ensure that all research partners using the material are covered under the permit. If the scope of your project changes, if you intend to reuse samples for a new purpose, or if your permit is set to expire before the research concludes, you may need to request a permit modification or extension. Check for compliance rules in the user country. Finally, remember that compliance obligations may also exist in the country where your research is conducted. For example, users of genetic resources in the European Union are required to seek, keep, and transfer all relevant NP documentation, including permits. They may also need to submit due diligence declarations and cooperate with compliance checks conducted by national authorities. Ensure that you are familiar with and adhere to any user-country requirements that apply to your research activities. For more details on the implementation of the EU ABS Regulation check the guidance document [7], it includes very clear explanations and practical examples. Upon completing your research, share benefits as agreed and report back to the authorities in the provider country on the benefits you shared with local scientists, IPLCs, protected areas and any other entity or person considered a provider within the country. When publishing your findings, include your IRCC number or national permit number in all scientific publications, as this enhances the visibility of research results as a form of non-monetary benefit-sharing and supports reporting under the Kunming-Montreal Global Biodiversity Framework [8]. Page 22 of 23 Preprint v1.0 - July 21, 2025 How to “do” the Nagoya Protocol: common misconceptions, challenges and best practices for access and benefit-sharing compliance Supplementary Information - Bibliography 1. Conference of the Parties to the Convention on Biological Diversity. Nagoya Protocol on Access to Genetic Resources and the Fair and Equitable Sharing of Benefits Arising from their Utilization to the Convention on Biological Diversity: Text and Annex 2011. https://wedocs.unep.org/20.500.11822/27555. 2. ABSCH | Access and Benefit-Sharing Clearing-House https://absch.cbd.int/en/. 3. United Nations Environment Programme. Convention on biological diversity June 1992. https://wedocs.unep.org/20.500.11822/8340. 4. Germany | ABSCH-NR-DE-238614 | Interim National Reports on the Implementation of the Nagoya Protocol | Access and Benefit-Sharing Clearing-House https://absch.cbd. int/en/database/ABSCH-NR-DE-238614-2. 5. Understanding the ABS world – infographic – Nagoyaprotocol-hub https : / / www . nagoyaprotocol-hub.de/abs-world-infographic/. 6. Build your ABS Strategy – checklist – Nagoyaprotocol-hub https://www.nagoyaprotocolhub.de/abs-strategy/. 7. Guidance document on the scope of application and core obligations of Regulation (EU) No 511/2014 of the European Parliament and of the Council on the compliance measures for users from the Nagoya Protocol on Access to Genetic Resources and the Fair and Equitable Sharing of Benefits Arising from their Utilisation in the Union 2021/C 13/01 https://eurlex.europa.eu/legal-content/EN/TXT/?uri=uriserv%3AOJ.C_.2021.013.01. 0001.01.ENG&toc=OJ%3AC%3A2021%3A013%3ATOC. 8. Kunming-Montreal Global Biodiversity Framework - Target 13 https://www.cbd.int/ gbf/targets/13. Page 23 of 23