Population-based biobanks promise to be important resources for genetic research. However, the study of normal genomic variation across populations requires the collection of data and biological samples from individuals on a large scale. While international collaboration has become both a scientific and an ethical imperative, international sharing of data and samples poses many challenges. Significant variation persists among the legal and ethical norms governing population biobanks in different jurisdictions. Many of these norms do not clearly provide for international access. To illustrate these problems, we collected and compared applicable legislative instruments, as well as ethical guidelines issued by national, regional, and international bodies. In addition, harmonization is faced with important limitations and may not be sufficient to ensure effective international sharing. Population biobanks are therefore looking for new ways to promote sharing and improve interoperability. The formation of biobank networks and the development of common governance tools are two approaches that are setting the groundwork for international collaboration in genetic research.

Since common diseases are multi-factorial in nature, interest in ‘normal' genomic variation has spurred a revolution in genetic science. Large-scale biobanks have emerged to collect tissue and data from individuals across whole populations. These projects seek to understand the gene-environment contributions to disease risk and health [1]. The effective investigation of gene-gene, gene-disease, and gene-environment interactions over time requires large numbers of samples and data [2]. Only international collaborative efforts between population studies can achieve this statistical power [3]. For this reason, data sharing is increasingly regarded as both a scientific and ethical imperative that advances knowledge and respects the contributions of participants [3]. Interest in international data sharing also reflects a growing recognition that scientific knowledge is a common good and that the genome at the level of the species is the common heritage of humanity [4].

This paper primarily addresses population biobanks, where international sharing is not just a scientific, but an ethical imperative. In 2006, the Council of Europe defined population biobanks as ‘a collection of biological materials that has the following characteristics: (1) the collection has a population basis; (2) it is established, or has been converted, to supply biological materials or data derived therefrom for multiple future research projects; (3) it contains biological materials and associated personal data, which may include or be linked to genealogical, medical and lifestyle data and which may be regularly updated; [and] (4) it receives and supplies materials in an organized manner' [5]. The issues raised here, however, have application across the broad range of biobanks, especially where researchers seek to increase sample sizes and collaboration, and to minimize duplication of effort.

International collaboration in biobanking is hindered by widespread variability in applicable norms. At the most general level, we can differentiate between two types of biobank governance: legislative regulation and self-regulation [6]. Legislatively regulated biobanks are established by a legal instrument, which also governs their use, structure, and operation [6]. The use, structure, and operation of self-regulated biobanks are governed by internal policies and professional guidelines [6]. This article examines the specificity of legislatively and self-regulated biobanking, identifying challenges and exploring opportunities for international data sharing. Governance of access to samples and data will be our central point of comparison. Indeed, successful international sharing depends on harmonizing the rules governing the eventual availability of data and samples to researchers. Access is a touchstone for a host of ethical concerns, above all the protection of donor information. The limits of harmonizing both laws and guidelines are also discussed. Such limitations have led to a shifting away from attempts at regulatory harmonization and towards prospective collaboration between biobanks and the development of common governance tools that promote international data sharing. The laws, regulations, and guidelines described in this article are not exhaustive, but were chosen to illustrate the current state of normative diversity.

Our goal in this paper is twofold. First, we aim to illustrate different forms of biobanking regulation and the challenge these distinct frameworks pose to international harmonization. Second, we identify a recent shift towards biobank collaboration through networking and tool sharing. Relevant laws and normative guidelines were retrieved using the HumGen International Database (http://www.humgen.org), a database of international, national, and regional guidelines and policies specific to human genetic research. In particular, the PopGen Module (http://www.popgen.info) of the HumGen database was employed. This module is a specialized database composed of laws, ethical guidelines, and policies addressing issues in population biobanking. We searched for documents published between 1990 and 2013; the single keyword ‘biobanks' was used to capture the widest range of applicable norms. This search returned 31 international, 16 regional, and 91 national documents. From these results, we selected a sample of documents representative of various legal traditions (namely civil vs. common law countries) and forms of biobanking regulation (legislative vs. self-regulating). The documents we selected to analyse are listed in tables 1 (legislation) and 2 (guidelines).

Table 1

Select legislation on biobanking

Select legislation on biobanking
Select legislation on biobanking
Table 2

Select international, regional and national guidelines on biobanking

Select international, regional and national guidelines on biobanking
Select international, regional and national guidelines on biobanking

This section explores the feasibility of harmonizing legal instruments regulating researcher access to population biobanks. Legislative instruments regulating biobanks cover three categories: biobanking itself, tissues, and research. The selection of legislation discussed here is presented in table 1. The choice of the regulatory approach can have important implications for access to samples and data. Personal information legislation will typically apply across all three categories, but will not be considered in detail here.

Biobanking

The Biobanks Act of Iceland of 2000 was the first European legislation relating specifically to biobanks [7]. The first article of the Act maintains that the objective of biobanking is to serve the ‘purposes of science and medicine, and is conducive to the public good'. The importance of protecting donors is then clearly stated in the second paragraph: ‘the interests of science and of the community shall never be given priority over the interests of the donor of a biological sample.' This stance is reflected in the access procedures regulated by this Act and by the country's Regulations on the Keeping and Utilization of Biological Samples in Biobanks of 2001 [8]. In order to be granted access to biological samples, scientists must first get their research protocol approved by the National Bioethics Committee or the scientific committee of the relevant health institution. If the proposed study is genetic, the informed consent of the donors must be sought if they are still alive and the data can be traced back to them. In addition, researchers must get permission from the Data Protection Authority in accordance with the Act on the Protection of Privacy as Regards the Processing of Personal Data [9]. When these criteria are satisfied, the board of the biobank can make an access agreement with the researcher. The flow of biological samples outside the country is subject to the approval of both the National Bioethics Committee and the Data Protection Authority [7]. Worthy of note also is the ‘penalty clause', which provides that any violation of the terms of the Biobanks Act or related government directives could result in revocation of the license of the biobank, and entail fines or imprisonment for up to 3 years [7].

The Swedish Biobanks in Medical Care Act of 2003 mainly pertains to biobanks created for samples collected during medical care and treatment [10]. Although research is another permitted use, approval by a research ethics committee is still required [11]. In addition, ‘if tissue samples in a biobank are to be released to a recipient in another country for research purposes, a Swedish research institution must submit an application' [11]. The Act does not specify access criteria or procedures, but mentions that the recipient has to ‘return or destroy the specimen if they are no longer needed for the purpose for which they were released' [11]. A revision of the Act is being considered in Sweden that would extend its scope of application and provide more flexible requirements for the release of tissues and samples from biobanks, as opposed to just return or release [11].

Likewise, Norway enacted the Act Relating to Biobanks in 2003 [12]. This was subsequently replaced by the 2009 Health Research Act, which regulates all medical research in the country [13]. Chapter 6 of this Act applies specifically to biobanks. It gives the person in charge of the biobank important authority with respect to access. Researchers outside Norway requesting access to samples must have prior approval from a regional ethics committee. In addition, the Health Research Act requires proof that consent and personal health information protection requirements are met. An interesting exception is made from the approval requirement for transfer that is part of ‘an ordinary international collaboration'. If the person in charge refuses a request for access, the applicant can appeal the decision to a regional ethics committee. In case of violations of the Health Research Act by the person in charge of the biobank, penalties include biobank closure, transfer of control to the Ministry of Health, fines, and/or imprisonment.

Tissue

In the biobanking context, tissue-specific legislation has limited application for genetic material and data. For example, the United Kingdom's Human Tissue Act 2004, which came into effect in September 2006, applies to material ‘which consists of or includes human cells' [14]. It governs a wide range of activities, including postmortem examinations, public display of human bodies or parts, and storage of human tissue for research [15]. Because of this law's broad application, however, many exceptions have been made for biobanking. For example, biobanks are exempt from the requirement of donor consent as long as the tissue samples are anonymized and ethics approval has been granted for the project [15]. The starting point for biobank regulation in the UK, however, remains general tissue regulation, which has resulted in a complex and incomplete ‘patchwork' of rules applying to biobanking.

Similar legislation is found in the Canadian province of Quebec: An Act Respecting Medical Laboratories, Organ, Tissue, Gamete and Embryo Conservation, and the Disposal of Human Bodies [16]. Although this law governs tissue conservation, it only regulates permits for a tissue bank, which is defined as ‘a place outside a facility maintained by an institution operating a hospital centre'. There is no specific provision for the access procedure to be followed when collaborating with outside researchers, nor on the governing body responsible for such procedures. As neither genetic material nor its tissue components are specifically highlighted in this Act, extracted DNA is not governed by these rules.

Research

Laws applying generally to research have also been enacted, with implicit or explicit application to biobanking activities. The Estonian Human Genes Research Act [17],in force since 2001,is an example. Although the title of the Act implies regulation of human genes research, it is only in relation to Gene Bank, a population-based database consisting of phenotype and genotype data. The Human Genes Research Act is a legal instrument with national jurisdiction that regulates issues such as prohibition against discrimination, data protection, and the right of ownership of tissue samples, but it does not contain provisions specific to international access [2]. Researcher access to the Estonian Genome Project is not regulated by a specific legislative provision of the Human Genes Research Act, which only addresses access by donors. Instead, the Estonian Genome Project lays out its access procedures and conditions on its website. One of these conditions is that data, but not samples, may leave the country [2].

Belgium's 2008 ‘Loi relative à l'obtention et à l'utilisation de matériel corporel humain destiné à des applications médicales humaines ou à des fins de recherche scientifique' [18] is even less clear on international collaboration. Firstly, the law differentiates between biobanks and other banks containing biological material. Biobanks are defined as structures stocking biological material exclusively for research purposes. Banks are structures - managed by either a hospital or a university's faculty of medicine - that contain biological material destined for human application (e.g. medical therapy). Secondly, this law contains no selection criteria for the distribution of biological material outside the country; it explicitly forbids any exportation of biological material by anyone other than a licensed biobank and requires that any access to biological material from a biobank (with the exception of urine) be approved by an ethics committee. As with many other national laws focusing on research, the Belgian law is general in scope.

Switzerland recently adopted the ‘Loi fédérale relative à la recherche sur l'être humain' governing research involving human subjects [19]. The ‘Loi' is general in scope, mainly focusing on the general principles of research, such as consent, noncommercialization, and nondiscrimination. While there is no specific mention of biobanks, the ‘Loi' requires informed consent at the moment of collection for the secondary use of collected personal data or biological material. The donor must also be informed of the right to oppose secondary use. Likewise, any exportation of biological material or genetic data outside the country must be permitted by the donor.

Limitations of Legislation

There are both limitations to the extent that legislation can be harmonized and inherent limitations to using legislation to govern biobank activity. The major hurdle for harmonizing biobank activity through legislation is the sheer extent of variation between existing legislative regimes. This brief survey suggests that legislative regulation of biobanks is diverse and tends to treat international data sharing conservatively, if at all. Iceland, Sweden, and Norway all require research ethics board approval. Switzerland requires donor consent. Estonia's genetic research legislation makes no explicit mention of international data sharing, though data may leave the country. This variability has several causes. First, national and provincial biobanking laws emerge in distinct legal and moral traditions. Second, laws must often be tailored to the existing health research administrative structure and ethics review processes. Third, biobanking infrastructure is established at different speeds in different countries, and legislation applying to it is adopted at different times to respond to different realities. When countries first confronted the need to regulate biobanks, they may not have done so against a uniformly evolved health law framework. Indeed, in some countries ‘the necessity of regulating human tissue and biobank research in the first place triggered the legal enactment of informed consent procedures in health care and research' [20].

In addition, most of the laws cited above defer decisions about access to research ethics boards. Legislative harmonization is of little solace to a researcher applying for access to different biobanks if access is mediated by different research ethics boards with distinct procedures and requirements. The success of population biobanks may be particularly susceptible to variation in ethics review. These biobanks are built as research infrastructures for future unspecified research; many therefore rely on the use of ‘broad consent', essentially allowing the type of research carried out on samples to be defined or adapted after consent has already been obtained, albeit subject to ethics approval and monitoring. The scope of future access will depend on the ethics review body's interpretation of this broad consent [21]. This problem may be complicated by a lack of research ethics board expertise with the ethical and scientific exigencies of population biobanking. It may be compounded in situations where multiple bodies are involved in review, including personal information regulatory bodies. While some might argue that this multiplication of review has certain benefits, it does increase the bureaucracy that researchers must wade through to access data and samples.

Separate legal regimes may also apply to samples as physical specimens and data as purely informational [22]. Not only that, but regulation may differ according to the purpose for which physical specimens are used or the type of physical specimens. In the UK, for example, licenses are required to store tissues or cells, but not DNA [22]. Estonia's legal regime is relatively unique in that the Human Genes Act does away with the distinction between the two, referring to ‘biosamples and personal data' in combination.

There are also inherent limitations to the legislative regulation of biobanks. Legal regulation is not sufficient in and of itself to generate the transparency and public trust needed to ensure citizen support for population biobanks. Iceland, even with a dedicated legislative regime to govern its population biobank, was confronted with a strong negative response from the public for its ‘automatic opt-in' for patient records (under a different law than the Biobanks Act) and its arrangement with a private company to run the biobank [23]. This proposed legislation seeking to establish the countrywide health record database was in fact ruled unconstitutional by the Icelandic Supreme Court [24]. On the other hand, UK Biobank, which is to a large extent self-regulating, has been identified as a leader in ‘promoting trust, confidence, credibility and participation' even in the absence of direct legal regulation [22].

Legislation can also struggle to effectively distinguish various types of biobanks. In Britain, the Human Tissue Act requires a license from the Human Tissue Authority. Population biobanks in particular have different exigencies than smaller types of biobanks. One solution has been to establish and regulate a national biobank through legislation, as is the case in Estonia. However, in cases where population biobanking has developed by combining smaller biobanks from different jurisdictions, a generalizable regulatory approach might be difficult. Another weakness of legislation is it tends to be inflexible and reactive. Estonia's biobank, for example, grants extensive rights to donors, including the right to access their data stored in the biobank [17]. It is unclear how this right would affect the obligations of international researchers looking to access the biobank or to biobank operators when managing the return of research results. Legislative regulation in general is static by nature and cannot easily keep pace with the rapid development in genetic research. This situation has opened the door for soft law - recommendations and guidelines - to fill legislative gaps and address the practical needs of population biobanks.

Regulation of research today is achieved in large part by the development of practice guidelines that establish standards for the research community. Guidelines are not in themselves binding, but they can be an ‘authoritative reference point' codifying good practice [25]. Over the past decade, population genetics research studies and collections have emerged around the globe. This development has challenged the adequacy of traditional ethical norms pertaining to research involving human subjects, namely their relatively exclusive focus on protecting the individual participant [1]. However, it is not possible to examine issues of access to large-scale human population biobanks without exploring intellectual property and confidentiality issues, especially those relating not just to individuals, but to communities and populations. This section examines soft law at the international, regional, and national levels (table 2).

International Level

The issue of access to genomic materials and collaboration has been widely examined in international instruments, and has often been prospective in nature. As early as 1996, the Human Genome Organisation's (HUGO) Bermuda Principles recommended that all human genomic sequence information be freely available in the public domain ‘in order to encourage research and development and to maximize its benefit to society' [26]. In 1998, the HUGO Ethics Committee's Statement on DNA Sampling: Control and Access stated that research samples obtained with consent may be used for other research if ‘there is general notification of such a policy, the participant has not objected, and the sample to be used by the researcher has been coded or anonymized' [27]. In 2002, the HUGO Ethics Committee's Statement on Human Genomic Databases proposed that ‘the free flow of data and the fair and equitable distribution of benefits from research using databases should be encouraged' [4]. In 2003, the Bermuda Principles were revisited in the Fort Lauderdale Rules, which recognized that ‘the scientific community will best be served if the results of community resource projects are made immediately available to free and unrestricted use by the scientific community to engage in the full range of opportunities for creative science' [28]. Community projects were defined as research projects ‘specifically devised and implemented to create a set of data, reagents or other material whose primary utility will be as a resource for the broad scientific community'. Some international guidelines encourage a stronger initiative from states, such as the United Nations Educational, Scientific, and Cultural Organization's International Declaration on Human Genetic Data, which upheld the need to regulate, ‘in accordance with their domestic law and international agreements, the crossborder flow of human genetic data, human proteomic data and biological samples so as to foster international medical and scientific cooperation and ensure fair access to these data' [29].

Specific recommendations regarding access can be found in the Council for International Organizations of Medical Sciences' International Ethical Guidelines for Epidemiological Studies [30]. They highlight the importance of access as a way to expand genetics and epidemiological research while emphasizing the need for restricting access in order to safeguard donor privacy, confidentiality, and security. In October 2009, the Organization for Economic Co-operation and Development (OECD) published their Guidelines on Human Biobanks and Genetic Research Databases(HBGRD), which addresses access issues [31]. They state that the ‘operators of the HBGRD should strive to make data and materials widely available to researchers so as to advance knowledge and understanding'. In regards to access, the HBGRD propose mechanisms to ensure the validity of the access procedures and of applications for access. In fact, they insist that access to human biological materials and data should be based on ‘objective and clearly articulated criteria […] consistent with the participants' informed consent'. Most importantly, they recommend that access policies be fair, transparent, and not inhibit research. Access requests should include a ‘scientifically and ethically appropriate research plan'. The Guidelines also state the importance for HBGRD to make publicly available their access policies and ‘procedures as well as a catalogue of the resources accessible for research purposes'. Moreover, the OECD recommends that ‘the operators of the HBGRD should have in place mechanisms to review applications for access to human biological materials and/or data' and that ‘the operators of the HBGRD should have in place mechanisms to review the envisaged uses of the human biological materials and/or data for consistency with the types of research uses agreed to by a participant'. Finally, the OECD proposes that the terms of access be set out in a contract, namely a material transfer agreement (discussed in more detail below).

Regional Level

At the regional level, access to materials and terms of collaboration has been addressed by the European Society of Human Genetics. Its recommendations in ‘Data storage and DNA banking for biomedical research: technical, social and ethical issues' [3] state that, provided confidentiality is protected, there is an ethical imperative to promote access and exchange of information. Indeed, ‘the value of a collection is proportional to the amount and quality of the information attached to it. The full benefits for which the subjects gave their samples will be realized through maximizing collaborative high-quality research'. Moreover, this recommendation emphasizes the need that agreements on access to biological materials and information be determined by multiparty contracts and not by legislation, so as to allow more flexibility in the process. On a similar note, the Council of Europe's Recommendation Rec(2006)4of the Committee of Ministers to Member States on Research on Biological Materials of Human Origin [5] encourages the cross-border flow of biological material and associated data if the recipient state can ensure an adequate level of protection. The Council of Europe's Recommendation reserves an entire chapter to population biobanks (chapter V). As concerns access, it simply affirms that member states ‘should take appropriate measures to facilitate access by researchers to biological materials and associated datastored in population biobanks'.

National Level

The National Cancer Institute's Best Practices for Biospecimen Resources provides principles and guidelines to promote respect for ethical and legal requirements and to ensure the quality of biospecimens and data in US biobanks [32]. One of the aims of this revision was to harmonize recommendations from international biospecimen organizations. While this effort is promising, the scope of the document is still limited to research within the United States and does not address international sharing of data and samples. The Government of Western Australia's Guidelines for Human Biobanks, Genetic Research Databases and Associated Data is more expressive about international research, recommending that biobanks comply with international instruments. In addition, international collaborations must be ‘clearly articulated' and communicated to participants. Participants must also be informed of and consent to international release of data or samples. Access by international researchers to samples and data ‘should be contingent on recipients being subject to law or other binding requirements which are substantially similar' to those governing the biobank in question. Much uncertainty remains, however, as to what qualifies as a sufficiently similar normative framework.

Publicly funded research in Canada is governed by the second edition of the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans (TCPS 2) [33]. This document, while not legislative, has a binding effect on the institutions and its researchers financed by the three largest funding agencies in Canada. The TCPS 2 covers all research on humans, and includes provisions relating to identifiable information (chapter 5), human biological materials (chapter 12), and genetic research and biobanking of genetic materials (chapter 13). The TCPS 2 does not make a distinction between national and international sharing of data and samples, i.e. it does not impose specific restrictions for international sharing. Indeed, one condition for access to genetic material under the TCPS 2 is that prospective participants are provided information on ‘confidentiality, privacy, storage, use of the data and results, possibility of commercialization of research findings, and withdrawal by participants'. Another condition is implementing administrative and technical safeguards to protect samples and data from unauthorized handling. The TCPS 2 addresses numerous other issues, such as the conditions that researchers have to satisfy in order to seek a waiver of consent for secondary use of identifiable material. In the Canadian province of Quebec, the Network of Applied Genetic Medicine's 2003 statement of principles on the ethical conduct of human genetic research involving populations promotes open access to biobanks under the principle of freedom of research subject to certain conditions [34]. This provincial statement also promotes collaboration between foreign researchers and the dissemination of research results. France's Comité consultatif national d'éthique pour les sciences de la Vie et de la Santé's Avis (No. 77). Pro blèmes éthiques posés pas les collections de matériel biologique et les données d'information associées: ‘biobanques' ‘biothèques' acknowledges the importance of maximizing the benefits from donors' samples by collaborating with other researchers [35]. For its part, the Italian Society of Human Genetics, in its 2004 Guidelines for Genetic Biobanks, provides guidance on what it calls the ‘distribution of samples stored in a genetic biobank' [36]. The Guidelines insist that this distribution process be limited to valid reasons and be free and reserved for donors and researchers working in a qualified institution. The applicants must sign a request form that encompasses certain conditions, mainly the fact that the material cannot be used for commercial purposes and that the biobank where the samples originated must be acknowledged in any subsequent publication.

Limitations of Soft Law

The proliferation of biobanking guidelines has not meant a steady march towards consensus. At each level - national, regional, and international - there are multiple bodies generating frameworks for biobanking research. In part because of a lack of coordination, in part because of the many different moral and legal traditions behind these guidelines, and in part because of the complex ethical issues posed by population biobanking, variation in terminology and substantive rules are commonplace [37].

To some extent, soft law may be self-harmonizing. Despite the multiplicity of generating bodies, these organisations often draw substance, or at least inspiration, from each other. Broad international policies can be fleshed out and refined by national documents. This process, however, is far from systematic. An important limitation to the harmonization of soft law is that many of the issuing bodies were instituted to oversee research more generally, not biobanking in particular [23]. It may be unclear to researchers which of these documents or their sections apply. Even the most basic definition of ‘population biobank' is inconsistent between supranational documents. Compare, for example, the detailed definition from the Council of Europe (above), with the Human Genome Organisation's definition of ‘human genomic databases' as ‘a collection of data arranged in a systematic way so as to be searchable' [38]. The traditional divides between the international, regional, and national levels are in many ways less important than the divide between the types of biobanks and types of research. Useful guidelines must be set up by ‘a team of experts that are not only aware of the variety of biobanks, but are also well informed on the specific differences' between them [39]. As we discuss in the next section, a participatory model where similar biobanks actively network and collaborate to generate policies and tools that balance access with participant protection may be a preferable solution.

An inherent limitation of soft law, or at least certain provisions of soft law applying to population biobanking, is that it tends to lack the normative force to influence biobank practice. For example, many of the international and regional guidelines described above promote international data sharing. But what is the power of such recommendations? Influence on research practices may be limited, especially if the supranational guidelines conflict with restrictive local laws and policies. This is especially true given that genomic science and infrastructure are evolving so rapidly that it is often difficult to see guidelines crystallizing into a standard of practice. One incentive is that researchers have to follow guidelines when there are conditions of funding. This incentive structure, however, poses other problems. Guidelines, even those limited to a national scope, may conflict with applicable laws, leaving researchers with the choice of breaching one or the other [40].

Laws and ethical guidelines share some related deficits, tending to respond reactively to control risks, and to apply restrictively. While the aspirations of many guidelines are to promote research and data sharing and while they are more flexible and adaptable then legislation, the individual stipulations tend to focus on controlling certain behaviours that threaten participant autonomy or confidentiality. There is no doubt that laws and ethical guidelines have an important role to play in governing biobanks, especially in establishing adequate donor protections. However, biobanks themselves are increasingly being asked to play a central role in the generation of biobanking norms and harmonization, through networked collaboration and the generation of shared tools.

In order to facilitate accessibility to genetic materials and encourage international collaboration, there is a movement towards harmonization - not of the regulations, but of the methods, approaches, and tools used in operating biobanks.

The Canadian Tumour Repository Network (CTRNet), for example, aims to streamline research access to tissue and tumour samples and to provide standards to ensure sample quality. To streamline access, CTRNet has created an electronic portal for access to all its member biobanks. CTRNet has also strived to establish standard ethical and scientific protocols across its member tumour biobanks [41]. The creation of the CTRNet provides both normative guidelines and scientific infrastructure to promote ethical and effective access.

The International Society for Biological and Environmental Repositories (ISBER) [42] has taken a similar approach as CTRNet on the international stage. ISBER's focus is providing training and governance resources for human specimen repositories. The society has developed a Standard Preanalytical Code to identify and document factors that affect the quality of samples during collection, processing, and storage. The ISBER Best Practices also provides standardized terminology describing the level of identifiability of samples [43]. This is essential for encouraging international collaboration, as many countries impose their own set of constraints on access to samples depending on the types of personal information they are linked with.

The Public Population Project in Genomics and Society (P3G) is an international consortium made up of not-for-profit organizations that ‘conduct, use or collaborate' with health studies, biobanks, and research databases [44]. P3G's services are structured around 6 modules. The ‘Toolkit' module provides existing health infrastructure projects with epidemiological, ethical, statistical, and information technology tools. The ‘Lifespan' module offers guidance for the development and maintenance of biobanks. The remaining modules provide related information, training, discussion forums, and evaluation tools. Research tools and other results yielded by the six modules are shared with P3G members and the larger scientific community. P3G encourages international data sharing through projects such as the Data Schema and Harmonization Platform for Epidemiological Research (DataSHaPer) Project. DataSHaPer fosters harmonization of emerging biobanks by providing a template for retrospective pooling and support for the development of questionnaires and information collection [45]. This is achieved in part by providing a common lexicon, tools for matching variables in questionnaires, and generic consent and access templates.

A common means relied on by biobanks to promote ethical access is a ‘material access agreement' (MTA). An MTA is a bilateral agreement between a biobank and a researcher who wants to access samples or data. The agreement lays out the rights, obligations, and limitations on intellectual property of the two parties [46]. It may include private law remedies, oversight provisions, or dispute resolution mechanisms to ensure that researchers respect donor consent and confidentiality. Standardized versions of MTAs are an important tool to promote sharing between researchers. Standardized agreements reduce the costs of drafting and negotiation, and also serve to articulate and reinforce research norms. In 1995, the Uniform Biological Material Transfer Agreement (UBMTA), a model agreement for the exchange of biological materials, was introduced by the National Institutes of Health [47]. The goal of the UBMTA was to encourage open access to research materials needed to replicate or build on the results of publicly funded studies. In a similar vein, P3G has recently published a generic MTA, updated for the biobanking age [48]. This generic MTA lays out core elements for MTAs, thus providing a level of predictability for researchers accessing multiple biobanks. It also includes a list of optional elements so as to allow individual studies the flexibility to conform to their national laws, policies, ethical norms, and cultural context. In a similar vein, P3G recently helped to launch the International Policy Interoperability and Data Access Clearinghouse (IPAC), which offers services supporting international research collaborations [49]. IPAC can help researchers prospectively or retrospectively craft harmonized strategies and policies for recruitment, data access, participant re-contact, and data security. For data access in particular, IPAC specializes in the creation and management of offices to ensure compliance with access conditions.

Another ambitious example of international collaboration is the formation of the Global Alliance for Genomics and Health [50]. The alliance is developing technical and ethical standards as a basis for interoperability, and also aims to develop shared technology platforms that support open data sharing (e.g. cloud computing). Such an approach is likely to ensure that international networking is both ethically and technologically feasible. This proactive networking will be bolstered by engagement with governments and the public. In short, the Global Alliance combines a comprehensive approach: harmonization of existing norms, generation of research networks and tools, public relations, and government lobbying.

Both hard law and soft law have important roles to play in biobank regulation. Three categories of legislation apply to biobanks: biobanking-specific laws, tissue laws, and research laws. While these binding laws provide strong protections for the rights of donors, they may not meet the needs of modern biobanking. They are often inflexible, limited in application, or extend to types of research far from the reality of biobanking. National and reactive in nature, few provide adequate encouragement for international access. Three levels of guidelines also regulate biobanking: international, regional, and national. While soft law is able to provide practical and flexible guidance, it exhibits much variability, even between overlapping norms applying to the same projects. Given these limits, population biobanks should actively participate in prospective harmonization of their access procedures to the extent possible under existing regulations. Such collaboration will encourage access for researchers - who will be relieved to encounter similar procedures across studies - and will establish international data sharing as a priority.

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