Basic principles of biobanking: from biological samples to precision medicine for patients.

The term "biobanking" is often misapplied to any collection of human biological materials (biospecimens) regardless of requirements related to ethical and legal issues or the standardization of different processes involved in tissue collection. A proper definition of biobanks is large collections of biospecimens linked to relevant personal and health information (health records, family history, lifestyle, genetic information) that are held predominantly for use in health and medical research. In addition, the International Organization for Standardization, in illustrating the requirements for biobanking (ISO 20387:2018), stresses the concept of biobanks being legal entities driving the process of acquisition and storage together with some or all of the activities related to collection, preparation, preservation, testing, analysing and distributing defined biological material as well as related information and data. In this review article, we aim to discuss the basic principles of biobanking, spanning from definitions to classification systems, standardization processes and documents, sustainability and ethical and legal requirements. We also deal with emerging specimens that are currently being generated and shaping the so-called next-generation biobanking, and we provide pragmatic examples of cancer-associated biobanking by discussing the process behind the construction of a biobank and the infrastructures supporting the implementation of biobanking in scientific research.

Mini-gut feelings: perspectives of people with cystic fibrosis on the ethics and governance of organoid biobanking.

Aim: Organoid technology has enormous potential for precision medicine, such as has recently been demonstrated in the field of cystic fibrosis. However, storage and use of organoids has been associated with ethical challenges and there is currently a lack of harmony in regulation and guidelines to govern the rapid emergence of 'organoid medicine'. Developing sound governance demands incorporation of the perspectives of patients as key stakeholders. Materials & methods: We conducted 17 semi-structured interviews with people with cystic fibrosis to explore their perspectives on the ethics and governance of organoid biobanking. Results: We identified three themes: prioritization of research and trust, ambivalent views on commercial involvement and transparency and control. Conclusion: Our study offers important insights for ethically robust governance of 'organoid medicine'.

Lay abstract Organoids are living tissues that can be grown in a lab out of stem cells, which can replicate some features of actual organs in the body. They can be used to study diseases or develop drugs, but also to test the effectiveness of therapy for a specific patient (which is called precision medicine). Organoid technology is promising for the treatment of cystic fibrosis. At the same, storing and using organoids raises ethical and practical challenges. In order to ensure that the interests of those who provide the cells are respected, we interviewed people with cystic fibrosis. Their motivation to participate in organoid research was high, but at the same time they wanted to know how their organoids are used. In addition, while they did not feel the need to be directly involved in decisions about how their tissue is used, they valued ongoing communication from biobanks about its activities.

Pediatric biobanks and parents of disabled children associations opinions on establishing children repositories in developing countries.

Pediatric biobanks are an indispensable resource for the research needed to bring advances in personalized medicine into pediatric medical care. It is unclear how or when these advances in medical care may reach children, but it is unlikely that research in adults will be adequate. We conducted the screening for a hypothetic problem in various European and American pediatric biobanks based on online surveys through e-mail distribution based on the Biobank Economic Modeling Tool (BEMT) questionnaire model. Participants in the survey had work experience in biobanking for at least 3 years or more. Contact information about the survey participants was confirmed on the social networks profiles (LinkedIn), as well as on generally available websites. First, we tried creating a model which can show the pediatric preclinical and basic clinical phase relationship and demonstrate how pediatric biobanking is linked to this process. Furthermore, we tried to look for new trends, and the final goal is to put the acquired knowledge into practice, so medical experts and patients could gain usable benefit from it. We concluded that leading positions must take into account ethical and legal aspects when considering the decision to include children in the biobank collection. However, communication with parents and children is essential. The biobank characteristics influence the biobank's motives to include children in the consent procedure. Moreover, the motives to include children influence how the children are involved in the consent procedure and the extent to which children are able to make voluntary decisions as part of the consent procedure.

Regulating biobanks: an ethical analysis of the Spanish law and the new challenges of the bigdata-driven biomedical research / Regulando los biobancos: un análisis ético de la ley española y los nuevos retos de la investigación biomédica con datos masivos

In the European landscape, Spain represents a positive reference point when it comes to biobank regulation. Indeed, at the beginning of XXI century, the Spanish legislation has promptly responded to challenges posed by new biotechnologies and advances in genomics in the field of biomedical research by enacting in 2007 the Ley de Investigación Biomédica in order to keep up with the paradigm shift. Over the past 10 years, this Spanish framework along with the Real Decreto 1716/2011 has hold the merit to tackle the most controversial ethical issues related to use of human samples and personal data in biomedical research and biobanking (e.g. broad consent, secondary uses, governance, etc.). However, today the regulation of biomedical research and biobanks has to deal with big data, artificial intelligence and data-intensive research which have brought a number of challenges and controversies. The aim of this paper is two-fold. First, I will analyse from an ethical point of view the merits of Spanish regulation on biobanking in order to draw some lessons for the still unregulated situation in other Member States. Secondly, I will discuss the big data paradigm shift in biomedical research and question if the ethical and legal framework introduced the Spanish law at the beginning of the century is still able to hold the ground with the new contextual and societal challenges. In this respect, I will identify some opportunities for implementation and suggest strategies to achieve them in the specific context of biobanks (AU)

En el panorama europeo, España representa un punto de referencia positivo en lo que respecta a la regulación de los biobancos. De hecho, a principios del siglo XXI, la legislación española ha respondido rápidamente a los retos planteados por los avances de la biotecnología y la genómica en el campo de la investigación biomédica mediante la promulgación en 2007 de la Ley de Investigación Biomédica para mantenerse al día con el cambio de paradigma. Durante los últimos 10 años, este marco español junto con el Real Decreto 1716/2011 ha tenido el mérito de abordar las cuestiones éticas más controvertidas relacionadas con los biobancos. Sin embargo, hoy la regulación de la investigación biomédica y los biobancos tiene que lidiar con la inteligencia artificial e investigaciones con gran cantidad de datos que han planteado una serie de desafíos y controversias. El objetivo de este artículo es doble. En primer lugar, analizaré desde un punto de vista ético los méritos de la regulación española sobre biobancos con el fin de extraer algunas lecciones de la situación aún no regulada en otros Estados miembros. En segundo lugar, trataré el cambio de paradigma en la investigación biomédica y me preguntaré si el marco ético y legal que introdujo la ley española a principios de siglo todavía es capaz de mantenerse firmeante los nuevos desafíos contextuales y sociales. En este sentido, identificaré algunas oportunidades de implementación y sugeriré estrategias para lograrlas en el contexto específico de los biobancos (AU)

En el panorama europeu, Espanya representa un punt de referència positiu pel que fa a la regulació dels biobancs. De fet, a principis del segle XXI, la legislació espanyola ha respost ràpidament als reptes plantejats pels avanços de la biotecnologia i la genòmica en el camp de la recerca biomèdica mitjançant la promulgació en 2007 de la Llei de Recerca Biomèdica per a mantenir-se al dia amb el canvi de paradigma. Durant els últims 10 anys, aquest marc espanyol juntament amb el Reial decret 1716/2011 ha tingut el mèrit d'abordar les qüestions ètiques més controvertides relacionades amb els biobancs. No obstant això, avui la regulació de la recerca biomèdica i els biobancs ha de bregar amb la intel·ligència artificial i recerques amb gran quantitat de dades que han plantejat una sèrie de desafiaments i controvèrsies. L'objectiu d'aquest article és doble. En primer lloc, analitzaré des d'un punt de vista ètic els mèrits de la regulació espanyola sobre biobancs amb la finalitat d'extreure algunes lliçons de la situació encara no regulada en altres Estats membres. En segon lloc, tractaré el canvi de paradigma en la recerca biomèdica i em preguntaré si el marc ètic i legal que va introduir la llei espanyola a principis de segle encara és capaç de mantenir-se ferm davant els nous desafiaments contextuals i socials. En aquest sentit, identificaré algunes oportunitats d'implementació i suggeriré estratègies per a aconseguir-les en el context específic dels biobancs (AU)

Report from the GHPP-BloodTrain inspection workshop in Harare the 20th to the 24th of May 2019.

During the training workshop on Inspection of Blood Establishments, which was hosted by the PEI GHPP BloodTrain in Harare from the 20th to the 24th of May 2019, participants from the National Regulatory Authorities from seven Sub-Sahara African countries presented their current experiences related to regulation and inspection of blood establishments in their respective countries. While in all seven countries regulation and inspection of conventional medicinal products manufacturer is performed, the regulatory situation of blood and blood components as well as inspection of blood establishments is still heterogeneous.

The ethicolegal framework relevant to human faecal microbiota transplants in South Africa: Part 3. Stool as a 'drug' or medicine.

The purpose of this article, the last in a series of three exploring the legal framework for the regulation of faecal microbiota transplantation (FMT) in South Africa (SA), is to determine the regulatory framework that applies to microbial-based treatments involving a level of manipulation that exceeds that of basic stool transplantation, e.g. processed FMT-derived products in capsule form. The article highlights the legal requirements for the registration of these products as biological medicines in SA law. Although human stool banks are not regulated in terms of the National Health Act 61 of 2003 (NHA) and regulations, the earlier articles point out that human stool fits the definition of human tissue and human biological material as defined by the NHA. For this reason, stool banks should be considered tissue banks in terms of the NHA and regulations. Healthcare practitioners and researchers involved in FMT banking and transplantation should strive to comply with these regulations in the absence of clear legal direction at present.

The ethicolegal framework relevant to human faecal microbiota transplants in South Africa: Part 2. Human stool as tissue?

Faecal microbiota transplantation (FMT) has been shown to be an effective treatment for recurrent Clostridioides difficile infection. The purpose of this article, the second of a series of three articles, is to explore the legal framework governing human FMT in South Africa (SA). FMT involves different modes of administration that require different regulatory considerations. The focus of this article is to explore the legal classification of human stool as tissue in terms of the National Health Act 61 of 2003, as well as the regulation of human stool banks as tissue banks. The article concludes with specific recommendations aimed at improving the current regulatory vacuum relating to the regulation of FMT in SA.

The ethicolegal framework relevant to human faecal microbiota transplants in South Africa: Part 1. A legal vacuum.

The legal regulation of faecal microbiota transplantation (FMT) in South Africa (SA) is currently unclear. The purpose of this article, the first of three in a series, is to explore the nature, role and clinical application of FMT in SA in order to determine, from a legal perspective, the appropriate regulatory pathways governing FMT as a procedure that may combine approaches for the treatment of drugs, human tissue for transplantation, or clinical treatment as part of the practice of medicine. FMT has been shown to be a novel, safe and effective treatment for recurrent Clostridioides difficile infection (CDI). Stool banks are instrumental in enabling access to FMT for patients and clinicians and help to catalyse research in the microbiome. However, the regulatory landscape in SA remains unclear. Microbial therapies such as FMT are necessary, especially in a time of rising microbiome-associated inflammatory diseases and increasing resistance to traditional antibiotics. FMT is now considered as part of the standard of care for recurrent CDI overseas, but is currently only being used for research purposes in a minority of clinical cases of CDI in SA. This article, which lays the foundation for consideration of this question in three parts, suggests that the relevant regulatory system would depend on the categorisation of human stool as tissue, the exact composition of the FMT, how it is administered to patients, and the relevant levels of manipulation of the stool for FMT-derived products.

Consent and Privacy in the Era of Precision Medicine and Biobanking Genomic Data.

"Big Data represents a challenge that points to the need for collective and political approaches to self-protection rather than solely individual, atomistic approaches."- Anita Allen, "Protecting One's Own Privacy in a Big Data Economy".

[Ethical, legal and social issues publications on biobanks 2011-2018. A scoping review.] / Publicaciones sobre los aspectos éticos, legales y sociales de los biobancos entre 2011-2018. Una revisión panorámica.

BACKGROUND: Human-based biobanks have been presented as intermediary agents between donors/participants, the scientific community, the healthcare system, and patients. The objective of this systematic review was to contribute with an updated thematic synthesis in Spanish of the international literature (2011-2018) regarding ethical, legal, and social issues on contemporary biobanks. METHODS: A scoping review and thematic analysis were carried out on biobanks' ethical, legal, and social issues. The following databases were searched: Web of Science, SciELO, and Dialnet. The review included 2011-2018 publications with the term "biobank" or "biobanco" in English, Spanish, Portuguese, and French. RESULTS: A total of 153 publications were analyzed. The most published themes were: informed consent, biobanks as a scientific tool, other ethical issues, public engagement, and regulation. While documents published in English provide studies with a broader anthropologic approach and display the participatory turn, in Spanish a technical approach is more common. Aportar datos y cifras principales. CONCLUSIONS: Publications confirm and support biobanks' relevance in current and future biomedical research, but also illustrate the entanglement of a diverse range of healthcare institutions and relations. Biobanks' techno-scientific issues cannot be split from the ethical, legal, and social ones or place them as secondary; all of them are co-produced. This review points to current topics and challenges which need to be addressed to establish transparent, accountable, dynamic, and trust-worthy biobanks.

OBJETIVO: Los biobancos, con muestras de origen humano, han sido definidos como agentes intermedios entre los donantes/participantes, la comunidad científica, el sistema sanitario y los pacientes. El objetivo de esta revisión fue aportar una revisión de la literatura internacional actualizada (2011-2018), que incluyera publicaciones en español y sintetizara los temas más publicados sobre los aspectos éticos, legales y sociales de los biobancos. METODOS: Se llevó a cabo una revisión panorámica y un análisis temático de las publicaciones que abordaban los aspectos éticos, legales y sociales de los biobancos. Se realizaron búsquedas en las bases de datos Web of Science, SciELO y Dialnet. Se incorporaron publicaciones entre 2011-2018 con el término "biobank" o "biobanco" en inglés, español, portugués y francés. RESULTADOS: Se incluyeron 153 publicaciones. Los temas con más publicaciones fueron: consentimiento informado, el biobanco como herramienta científica, otras cuestiones éticas, participación ciudadana y regulación. Se encontró una clara diferencia entre las publicaciones en inglés y español. Las primeras se centraron en el giro participativo, mientras que las segundas se situaron más en una esfera técnica. CONCLUSIONES: Las publicaciones señalan la relevancia de los biobancos en la investigación biomédica contemporánea y futura, así como el entramado de instituciones y relaciones que los componen. Las cuestiones científico-técnicas de los biobancos no pueden separarse de las éticas, legales y sociales, ni relegarlas a un segundo plano, ya que se coproducen. La revisión sintetizó los temas y retos existentes para establecer unos biobancos transparentes, responsables, dinámicos y que fomenten la confianza ciudadana.

Ethical publication of research on genetics and genomics of biological material: guidelines and recommendations.

Forensic Science International: Genetics and Forensic Science International: Reports communicate research on a variety of biological materials using genetics and genomic methods. Numerous guidelines have been produced to secure standardization and quality of results of scientific investigations. Yet, no specific guidelines have been produced for the ethical acquisition of such data. These guidelines summarize universally adopted principles for conducting ethical research on biological materials, and provide details of the general procedures for conducting ethical research on materials of human, animal, plant and environmental origin. Finally, the minimal ethics requirements for submission of research material are presented.

Future-proofing biobanks' governance.

Good biobank governance implies-at a minimum-transparency and accountability and the implementation of oversight mechanisms. While the biobanking community is in general committed to such principles, little is known about precisely which governance strategies biobanks adopt to meet those objectives. We conducted an exploratory analysis of governance mechanisms adopted by research biobanks, including genetic biobanks, located in Europe and Canada. We reviewed information available on the websites of 69 biobanks, and directly contacted them for additional information. Our study identified six types of commonly adopted governance strategies: communication, compliance, expert advice, external review, internal procedures, and partnerships. Each strategy is implemented through different mechanisms including, independent ethics assessment, informed consent processes, quality management, data access control, legal compliance, standard operating procedures and external certification. Such mechanisms rely on a wide range of bodies, committees and actors from both within and outside the biobanks themselves. We found that most biobanks aim to be transparent about their governance mechanisms, but could do more to provide more complete and detailed information about them. In particular, the retrievable information, while showing efforts to ensure biobanks operate in a legitimate way, does not specify in sufficient detail how governance mechanisms support accountability, nor how they ensure oversight of research operations. This state of affairs can potentially undermine biobanks' trustworthiness to stakeholders and the public in a long-term perspective. Given the ever-increasing reliance of biomedical research on large biological repositories and their associated databases, we recommend that biobanks increase their efforts to future-proof their governance.

Disruptive and avoidable: GDPR challenges to secondary research uses of data.

The advent of the European Union's General Data Protection Regulation (GDPR) has posed several significant difficulties for the secondary research uses of data and associated biospecimens and has led to widespread unease within the international biobanking and databanking community. This disruption of research using personal data and associated biospecimens has gone largely unremarked in the professional literature, including in a recent account of GDPR's relationship to biobanking practices published in this journal, which instead advocated even more stringent, and in our view, unnecessary restrictions on research uses of banked data and materials. In this article, we describe challenges that GDPR has posed for biobanks and databanks and for researchers who use those banked resources for secondary research. We discuss the limitations inherent in the few pathways that GDPR makes available for secondary research, given that such pathways rely upon complex and varied laws of individual European Union member states. We advocate mitigation of these difficulties through regulatory guidance in order to allow important scientific research to continue.

Governing Commercial Access to Health Data for Public Benefit: Charity Law Solutions.

There is a growing body of evidence that supports the view that research participants and the public are concerned about commercial access to health data. Evidence also suggests that attitudes are ameliorated when charity organisations are involved and where research promises to deliver 'public benefit'. To a significant extent, therefore, mechanisms that ensure the public benefit are key to sustaining public and participant support for research access to health data. As a regime founded on the concept of public benefit, charity law provides regulatory and governance mechanisms through which the public benefit of a charity is protected and promoted. This article examines the merits of charity law mechanisms and analyses their significance for governance of commercial access to health data for public benefit, using UK Biobank Ltd, a charitable company limited by guarantee, as an example. The article critically analyses three charity law mechanisms that operate to ensure that an organization providing access to data meets its public benefit requirements: charitable purposes; members' and directors' powers and duties; and accountability via the oversight powers of the Charity Commission and charity proceedings in court. The article concludes that there is potential for the charity model to be the benchmark for governing commercial access to health data for public benefit research, but notes the limitations of the model and recommends the appointment of independent data governance committees to further bolster the charity law framework.

Legacy samples in Finnish biobanks: social and legal issues related to the transfer of old sample collections into biobanks.

Biobank operations started officially in Finland in 2013 when the Biobank Act defining and regulating biobank operations came into force. Since then, ten biobanks have been established and they have started to collect new prospective samples with broad consent. The main corpus of biobank samples, however, consists of approximately 10 million "legacy samples". These are old diagnostic or research samples that were transferred to biobanks in accordance with the Biobank Act. The focus of this article is on ambiguities concerning these legacy samples and their transfer in terms of legality, human rights, autonomy, and social sustainability. We analyse the Finnish biobank operations in the context of international regulation, such as the European Convention of Human Rights, the Oviedo Convention, European Charter of Fundamental Rights, the GDPR, and EU Clinical Trials Regulation, and show that the practice of using legacy samples is at times problematic in relation to this regulatory framework. We argue that the prevailing interpretations of these regulations as translated into the Finnish biobank practices undermine the autonomy of individuals by not giving individuals a right to consent or an actionable right to opt-out of the transfer of these legacy samples to the biobank. This is due to the fact that individuals are not given effective notification of such transfers. Thus, issues regarding the legal status of the biobank samples and the social sustainability of biobank operations remain a challenge for biobanks in Finland despite governmental efforts to create pioneering, comprehensive, and enabling legislation.

Considering "clonality": A regulatory perspective on the importance of the clonal derivation of mammalian cell banks in biopharmaceutical development.

There has been much recent focus on the regulatory emphasis and the relative importance surrounding clonal derivation of mammalian production cell lines used in the manufacture of recombinant DNA-derived biopharmaceuticals. This interest has led to an ongoing discussion between regulators and industry on how this topic is evaluated and the role it plays in the development of a new biopharmaceutical. Herein the authors describe that the clonal derivation of the production cell line is a factor with potential impact on product quality, and thus should not be considered separately from, but rather in the context of all elements comprising the control strategy necessary to support approval of a regulatory application. Considerations for how clonal derivation of cell banks and clonal variation thereof may be viewed during the lifecycle of a biopharmaceutical product is provided.