Biobanking Legislation in Spain: Advancing or Undermining Its Ethical Values?

Abstract

Biobanks are important resources for improving public health and individual care. Some legal frameworks can be more or less conducive to advancing the potential benefits of biobanks. The purpose of this article is to assess biobanking legislation and practices in Spain to determine how well they fare in such a regard. We focus here on some of the primary ethical values that ground relevant legislation and that we believe are consistent with promoting biobanking benefits: the value of scientific research; efficient use of scarce resources; and respect for the dignity of donors. We argue that although Spanish regulations advance these values in important ways, they also have provisions that undermine them and thus risk limiting the potential benefits of biobanks. We offer some suggestions for improvement.

Introduction

Few today would question the value of biobanks. They open new routes of knowledge production, create additional options for public health research, and permit greater possibilities for understanding the progression, prognosis, and treatment of complex human diseases.¹ Indeed, successful clinical and translational biomedical research is currently dependent on biobanks that provide high-quality specimens in large numbers.¹ The number and quality of specimens have a direct impact on the questions addressed, the diseases studied, the treatments evaluated, or the generalizations of results that one can make across patient populations. Because of the importance of these resources, numerous national and international biobanking initiatives have been developed,^2,3 and both academia and industry researchers are increasingly dependent on biobanks.⁴

The potential benefits that biobanks offer for improving public health and individual care can only be realized if people donate samples and provide relevant health-related data, researchers use these resources appropriately, and relevant authorities safeguard their sustainability. Countries and institutions use various regulatory frameworks to govern biobank operations, access to samples, donation practices, etc. Some of these frameworks can be more or less conducive to promoting donations, facilitating access, optimizing use, and ensuring sustainability, and thus more or less successful enabling the potential benefits of biobanks.^5–7

The purpose of this article is to assess biobanking legislation and practices in Spain to determine how well they fare in such a regard. We focus here on some of the primary ethical values that ground relevant legislation and that we believe are consistent with promoting biobanking benefits: the value of scientific research; efficient use of scarce resources; and respect for the dignity of donors. We argue that although Spanish regulations advance these values in important ways, they also have provisions that undermine them and thus risk limiting the potential benefits of biobanks. We offer some suggestions for improvement. Before proceeding, we present an overview of relevant biobanking regulations and practices in Spain.

Biobanking Legislation and Practices in Spain

Regulatory approaches to biobanking in European countries are strongly influenced by their ethical, legal, and research traditions. Unsurprisingly, there are significant differences regarding the regulation of biobanks across Europe.⁸ While some countries use a combination of various legal and policy mechanisms to regulate the management of biological materials, Spain has enacted specific legislation.

Regulations in Spain related to the collection, storage, and use of human samples for research are found primarily in two legislative acts: Act 14/2007 of July 3 on Biomedical Research⁹ and the Royal Decree 1716/2011 of November 18.¹⁰ The Biomedical Research Act provides the main framework for regulating biomedical research in general. It lays down rules in areas that were unregulated before 2007, or where existing regulations had not kept pace with advances in the biomedical sciences. It thus incorporates regulations on various areas, including invasive research involving human beings, the donation and use of embryos and fetuses, and their cells, tissues, or organs, advances in regenerative medicine and cell therapy, as well as genetic testing and investigations with human biological samples.

Title V of the Biomedical Research Act focuses on requirements for the use of biological samples and for the creation of biobanks. The Royal Decree 1716/2011, which pertains exclusively to the handling of human samples, develops the provisions included in Chapter III and IV of Title V of the Biomedical Research Act. Together, these regulatory mechanisms establish the basic requirements for the management of human biological samples and the authorization and functioning of biobanks for biomedical research and regulate the operation and organization of the National Biobank Registry for biomedical research.

The Spanish legislation accounts for three possible ways of storing and handling biological materials for research purposes: a specific project; a collection; and a biobank (Table 1). Each of these systems of storage and use has its own set of norms. Samples collected for a specific project are time-restricted and can be used only for that project. If after project completion, a new use of the samples arises for the surplus materials, and with donors' consent, the samples can be integrated into a collection or a biobank.

Table 1.

Management Regimens for the Use of Human Samples for Research

	Project	Collection	Biobank
Use of samples	Only for a specific project	Only for a particular research line	Any research
Storage of samples	Time-restricted	Long-term	Long-term
Transfer to third parties	Noa	Noa	Yes
Responsibility for samples	Principal investigator	Principal investigator	Biobank (legal entity)
Ethical assessment	Institutional REC	Institutional REC	Institutional REC and Biobank Ethics Committee
National registry	Not required	Required	Required
Administrative authorization	Not required	Not required	Required • By the Ministry of Science and Innovation for national biobanks • By the Autonomous Community for regional biobanks

^a Surplus samples can be transferred to biobanks or collections for other uses only if donors provide a new consent. Regulations also contemplate some exceptions to the reconsent requirement.

Collections of human biological samples are understood as an organized and permanent set of human biological samples stored outside of a biobank regimen (although they might be physically housed in biobanks, which act only as custodians). Samples in collections can be used for specified research lines or goals, and only by the research group that collected them; they cannot be transferred to third parties. They must be entered in the National Registry.

Finally, biobanks serve as platforms to provide researchers with high-quality biological samples. They thus incorporate samples that can be used for multiple projects and many researchers. They have a defined structure and must fulfill various complex organizational requirements, including having a scientific director, a written operating regulation, and two external committees—an ethics and a scientific external committee—that advise the director and evaluate requests to transfer samples to approved research projects. Biobanks must also be registered in the National Registry.

Promoting and Hindering the Potential Benefits of Biobanks

The general framework of biobanking legislation in Spain follows the Spanish Constitution,¹¹ which entrusts public authorities with promoting scientific and technical research for the benefit of society. One of the primary ethical values underlying the biobanking legislation is thus the recognition of the importance of science to further health and societal well-being. Such value is certainly consistent with advancing the benefits that biobanks can provide, and various aspects of the legislation attempt to encourage this value. For example, the legislation safeguards freedom of research and scientific production, which are necessary for knowledge development.¹² It also promotes biobanks as institutions where biological material necessary for research can be maintained in optimal conditions, hence enabling high-quality research.¹³

It mandates that samples be shared with the scientific community without profit, thus facilitating access to investigators from a variety of institutions and with diverse research interests, which also contributes to promoting research lines of relevance to the public.¹⁴

Despite the various factors that foster the potential benefits of biobanks, some of the Spanish legislation's provisions and practices undermine the promotion of such benefits. Particularly salient in this regard are aspects of the legislation related to private collections and projects. Permission to collect biological samples for collections or projects promotes the underutilization of such samples. This is so because the legislation limits the use of these samples exclusively to the collection's research line or to a specific project, respectively. If surplus samples exist, they cannot be used for other relevant studies but must be destroyed or, in the case of collections, can be left unused indefinitely. Long-term storage increases the risks imposed by preanalytical variables.^15–17 Even when the legislation allows—with donors' consent—the transferring of leftover samples from specific projects to collections or to a biobank, this still fails to promote appropriate use of such samples. Because different groups follow various procedures for the collection, processing, and storage of samples, the lack of standardization reduces their worth to other researchers.

Furthermore, because the legislation aims primarily at regulating biological materials used for research purposes, it fails to consider other valuable uses. Specifically, the Spanish legislation does not account for the importance of samples in educational practices. The law indicates explicitly that biobank samples can be transferred only for use in research projects that have been scientifically approved. Hence, even if surplus samples exist that are not useful for other purposes, because of, for example, low-quality or lack of associated data, such samples cannot be used for educational activities. However, biological samples are of immense value in the educational context. They provide students or trainees with substantial learning experiences, support practical skill development, and facilitate a better understanding of various biological processes. When used by younger students, working with biological samples can promote curiosity, foster interest in scientific inquiry, and contribute to the growth of future scientists.

To be clear, the Spanish legislation does not explicitly prohibit the use of biological materials for educational purposes, but it has no provisions for such use. The lack of such provisions, together with the fact that the legislation explicitly indicates that biobank samples can only be transferred for use in research projects, thus limits the usability of samples and ultimately the benefits that can be obtained from biobanks.

The Spanish legislation also calls for an efficient use of scarce resources, a value also conducive to advancing the potential benefits of biobanks. Biobanks involve two types of scarce resources: financial and biological. That these scarce resources must be used efficiently is justified on ethical grounds. First, funding for biobanks comes primarily from public money, and governments have an obligation to ensure their effective and efficient use. Clearly, funding for biobanks creates opportunity costs and thus money used in this regard cannot be used for other worthy purposes. Second, efficient use of resources—whether funding or samples—is necessary for biobanks to be able to fulfill their promise of advancing knowledge and promoting well-being. Third, donors of biological materials have reasonable expectations that their samples will be used in appropriate ways.¹⁸ Fourth, an efficient way of using biobank resources is needed to ensure warranted trust from taxpayers and donors. Similar to any other social institution, without such trust biobanks cannot function.^19,20

The underutilization of biobank resources is a well-known problem.²¹ Some of the reasons for such underutilization are restrictive policies that limit access to specimens, collection of samples for research projects that lack well-defined goals, or investigators' unawareness of the existence of sample availability.^21–23 Given these concerns, it is important that the Spanish legislation explicitly calls for the efficient use of biological materials.

Various provisions in the legislation attempt to advance this ethical value. For example, the law requires that samples stored in biobanks be transferred without profit to third parties who require them to conduct biomedical research. This facilitates the use of collected samples and gives access to all researchers with approved scientific projects. The law says that biobanks cannot charge for the samples and make a profit from them. However, biobanks can charge researchers or institutions the cost of obtaining, handling, maintaining, managing, and shipping of samples. This permits biobanks to recover at least some of their associated costs and contribute to ensuring their sustainability, an important aspect of biobanking success.^23,24 Likewise, the legislation allows biobanks to transfer samples only to researchers with projects that have been approved by an external Scientific and an Ethics Committee associated with the biobank as well as by an Ethics Committee from the institution where the research will be done. These committees evaluate research projects to ensure that they will be carried in accordance with relevant methodological, ethical, and legal aspects. Such evaluations minimize the possibility that biological samples will be wasted in scientifically or ethically invalid projects.

However, the legislation leads also to wastefulness by promoting underutilization of resources. It does so in at least three ways. First, it supports sample use for projects and private collections. The utilization of samples for projects is limited to the duration of the project. Thus, even if there are leftover materials from these projects, they cannot be automatically used. In some cases—and if donors' consent—these samples can revert to a biobank. However, because of the lack of standardization and traceability problems mentioned above, these samples are unlikely to be of much utility. The storage of samples in collections similarly limits the use of scarce biological materials. Samples in collections cannot be shared with third parties even when they are no longer used for the original research goals.

Second, because the law mandates that biobanks transfer samples only when requested to conduct approved research projects, it deters the option that samples be used for educational goals. However, the educational uses of samples are essential to an effective and efficient use of resources. As mentioned earlier, it is certainly a way to facilitate training of future researchers, and thus, samples and other biobank resources are not utilized in ways that optimize their value. This is even worse when existent samples cannot be utilized for other purposes because of low-quality, insufficient numbers, or lack of associated data.

Third, financial resources are also wasted because of long-term storage of biological materials in collections or biobanks even when such materials might not be useful. The Spanish legislation does not provide for a maximum number of years of storage. Space and energy are necessary to house and manage samples. Low-temperature storage freezers, for example, need a significant amount of energy to operate, and freezers must also be placed in temperature-controlled rooms, which also consume large amounts of energy.²⁵

Similarly, because of problems related to quality and traceability, when samples from projects are sent to biobanks for storage, this also imposes financial costs that are unlikely to result in significant benefits. Although, as mentioned, the Spanish legislation allows biobanks to recover costs when samples are shared with researchers, this is usually insufficient to maintain biobanking infrastructures in healthy conditions.²⁴ Lack of adequate attention to the need for sustainability has led many biobanks to close their doors.^3,26 Insufficient consideration to sustainability issues is a problem from the point of view of the appropriate use of scarce resources on several grounds. If biobanks fail, the public resources used to create them are wasted. Moreover, because biobanks might need to close despite having valuable samples and data, lack of attention to sustainability also contributes to wasting biomedical materials.

Another ethical value grounding the Spanish legislation on biobanks that also promotes their potential benefits is respect for the dignity of the donor. Dignity is attributed to people simply in virtue of the fact of their humanity; it is accorded to all people equally; and it is inalienable.²⁷ Respecting people's dignity requires recognition that human beings' moral values and goals deserve attention and that they have a right to make their own decisions and to privacy and confidentiality.²⁸

In recognition of the importance of this value, the Spanish legislation mandates that biobanks ensure the free and informed consent of donors, protect their right to withdraw their samples or data, and safeguard their privacy and confidentiality. Moreover, to the degree that the legislation promotes research that can reduce suffering and advance human flourishing, it also respects human dignity. In addition, as mentioned earlier, the Spanish legislation decrees that the Scientific and Ethics Committees evaluate research projects requesting access to biological materials to ensure that they meet relevant scientific, ethical, and legal standards. Of course, these various mechanisms implemented to safeguard peoples' dignity also contribute to nurturing public trust in biobanks.

Likewise, the legislation acknowledges donors' interest in obtaining information regarding the use of their samples and calls for responsible individuals to share such information when requested by the donors. It also contemplates the return of unexpected results that might be germane to a donor's health and charges the relevant Ethics committee with determining when and what individualized information to convey to the donor.

However, the legislation fails to respect people's dignity in various ways and thus can detract from advancing biobank benefits. First, some donors who give their samples for specific projects agree to have their samples sent to biobanks after finalization of the project. Nonetheless, there is no established way to determine whether samples are indeed sent to biobanks as donors have requested. Second, the Spanish legislation is inattentive to the ways in which the waste of resources discussed above constitutes an affront to people's dignity. Donation is a morally significant act. Donors of biological materials, whether they are healthy or sick, whether their samples are excess material or specifically obtained for research purposes, usually think of their donation as contributing to an important social good.¹⁸ Given that tissue donors rarely benefit directly from their donation, attention to the moral significance of their actions is all the more important. But, donors' moral action is demeaned when their samples are underused. Furthermore, to the extent that donors put their health or well-being at risk when donating—for some donors through the physical risks involved with some donations, for all of them through the risks to their privacy and confidentiality—the underuse of samples constitutes a devaluing of their effort and of the potential harms they can incur. Moreover, researchers and biobanks make an implicit promise to donors that their samples will be utilized appropriately rather than wasted.⁹ When biological materials are thus squandered, the promissory obligation generated by the donation goes unfulfilled, the expectation of donors unmet, and their trust betrayed.

Suggestions for Improvement

Various legislative changes could be implemented to enhance the value of scientific research, maximize the efficient use of scarce resources, and respect the dignity of people who participate in biobanking research so as to enhance the benefits of biobanks. First, the use of biological samples for collections outside of biobanks should be eliminated given that they contribute to wasted resources and preclude scientific research. Biobanks would thus be the primary source of biological materials, best able to keep this scarce resource and its associated data in conditions that can ensure long-term quality. Biobanks could contribute to research promotion by recruiting cohorts for studies with a clear research aim. They could also act as catalyzers for collaborations among various national and international research groups. Access to samples from biobanks in different jurisdictions increases the number and types of samples as well as the data available for research, which can result in greater individual and public health benefits.

Second, a registry should be established to facilitate the tracking of projects with surplus samples and that receive consent from participants to have the samples deposited in biobanks after project completion. Article 28 of the Royal Decree 1716/2011 of November 18 requires that researchers communicate data from samples to the institution where they work. Institutions could then set up an automatic system that, once the project is finalized and in those cases where the donors have agreed, would notify the associated biobank. This would facilitate the fulfillment of donor's wishes as well as ensure that available surplus samples can be used to enable worthy research.

Third, the Spanish legislation should offer guidance on quality requirements for samples stored in projects. Particularly important would be the standardization and harmonization of procedures to process and store biological materials following CEN Technical Specifications and ISO standards. Such requirements would promote scientific research in at least two ways. They would improve reproducibility of analytical research data as samples from various projects could be compared. It would also promote the incorporation of quality samples into biobanks, which in turn would further allow the use of these samples in other research studies.²⁹

Finally, explicitly allowing the use of samples for educational purposes as well as for validation of methods would advance the ethical values underlining Spanish regulation on biobanks by promoting the training of future scientists and the development of new methods. As indicated, these activities can contribute to enhancing the training of future scientists and facilitate the development of new techniques. Moreover, it would maximize the usefulness of low-quality samples, hence enhancing the worth of donation.

These various suggestions are not incompatible among them and thus can all be applied. Nonetheless, even if only some of them are implemented, this would contribute to promoting the values the Spanish legislation aims to foster and advancing the potential benefits of biobanks.

Summary and Conclusions

The collection and storage of human biological samples have become an essential aspect of biomedical research. Biobanks thus constitute mechanisms that can help advance knowledge and the development of interventions that can ultimately contribute to improving public health and individual care. Biobanking regulatory frameworks can be more or less conducive to promoting these benefits. In this article, we have argued that the Spanish legislation on biobanking is grounded on ethical values likely to contribute to advancing the potential benefits of biobanks: the value of scientific research, efficient use of scarce resources, and respect for the dignity of donors. Crucially, although many of the provisions in the Spanish regulations advance these values in important ways, others can also undermine them.

We have shown that the legislation upholds freedom of research, furthers high-quality research with biological materials, facilitates access by mandating that samples be put at the disposal of the scientific community free of charge, promotes appropriate use by ensuring that research projects have been ethically evaluated, and protects the dignity of donors by ensuring that consent is obtained for the collection and use of samples and by requiring assessment of scientific proposals to safeguard their scientific validity and ethical soundness. On the other hand, some of the legislative provisions undermine the ethical values grounding the legislation and thus can limit the potential benefits of biobanks. By permitting the collection of samples for private collections and deterring the use of biological samples for educational purposes, the legislation encourages wastefulness and constrains scientific development. In doing so, it fails to uphold the dignity of persons, as the donors' moral action is lessened when their samples are underutilized.

We believe that the Spanish legislation has much to offer in advancing the ethical values more likely to promote the potential benefits of biobanks. We have offered some suggestions that we believe can contribute to such a goal. In particular, eliminating the use of biological samples for private collections can have a significant effect on the promotion of scientific research, the appropriate use of scarce resources, and the respect that donors are owed.

Authors' Contributions

Both authors have made substantial contributions to the conception the work; have drafted and reviewed it critically for important intellectual content; have approved the final version to be published; and agree to be accountable for all aspects of the work.

Author Disclosure Statement

No conflicting financial interests exist.

Funding Information

Inmaculada de Melo-Martin's work for this project was supported by NIH/NCATS under award UL1TR002384.