Abstract
Conference Information
The Joint Conference of ESBB & the Spanish National Biobank Network (Red Nacional de Biobancos), will be held in the Granada Conference and Exhibition Centre, in Granada, which is in the Andalucian region of southern Spain. The conference theme is: “Biobanks—Advancing Science and Serving Society in the 21st Century,” and it will feature presentations and discussions that relate to the full spectrum of biobanking activities across the clinical, biological, and environmental sciences. Particular emphasis will be given to issues relevant for Europe, the Middle East and Africa, since this is the geographic scope of ESBB.
The Programme Committee includes: Peter Doran (chair), Rita Lawlor, Maimuna Mendy, Elena Salvaterra, Christina Schroeder, Anna Bosch Comas, Maura Ferrari, Peter Riegman, Christian Chabannon, Paul Hofman, Paul Bartels, Manuel Morente, Herbert Gottweis, Ole Seberg, Tobias Schulte-in-den-Baumen, Pasquale de Blasio, Hans-Peter Deigner, Alexandre Bartsev, Christian Oste, Enrique de Álava, Erik Steinfelder, Bas de Jong, Roger Bjugn, and Robert Hewitt.
For more information please see: http://www.esbb.org.
ESBB is a chapter of the International Society for Biological and Environmental Repositories (ISBER)
ESBB is a chapter of the International Society for Biological and Environmental Repositories (ISBER)
INVITED SPEAKERS (IS)
Future Directions in Biobank Networks: The Spanish Perspective (Keynote Lecture)
Biobanking is a very heterogeneous activity. Although a global definition is desirable, more than specific definitions are necessary depending on the type of biobank activity. In any case biobank activity should be always framed by the unique final goal: PUBLIC SERVICE.
Referring to human samples biobanking oriented to biomedical research, our activity is mediated by a fourfold commitment: social, ethical, technical, and scientific. Social commitment refers to the promotion of knowledge (basic science) and health (translational/applied research). The ethical commitment refers to the guarantee of donors' rights and the chain of custody of samples and personal data to be protected. Due to these two commitments, biobanks are obliged to use the most suitable methodology in order to ensure the highest quality of service, this being their technical commitment. Finally, biobanking should be directly linked to scientific challenges, interests, and advances.
Today's excellent biomedical research is mainly seen as a global phenomenon which takes place around the study of large series of samples organized with well-defined and detailed criteria regarding the identification of patients, with the specific information required in each case. This justifies the growing interest in developing cooperative networks of biobanks to minimize biases arising from heterogeneity in the quality of biological samples by means of protocols for procedures, development of common quality assurance policies, and promotion of collaborative environments.
This lecture will try to present the Spanish vision and experience on biobank networking especially focusing on the value of attitudes, associated nodes and cooperative dimension.
Biorepositories for Future Medical Research
Sharing human samples among hospital-integrated biorepositories (HIBs) and their research groups would facilitate multi-center translational research and enable high statistically significant impact research with consequences on patient care.
Sharing samples is difficult for many investigators. Biobank networks have been set up enabling scientists to find samples. However, the enthusiasm to upload sample data is not always shared without first knowing the benefits, especially when there are language barriers, annotation problems, regulatory difficulties and quality issues to overcome.
The aim of the European project EurocanPlatform is to set up a European translational cancer research platform. In addition to bundling good existing initiatives, alternatives are developed in obstructive areas. Awareness, motivation and even influencing environments of PI's, collectors and patients have become key elements. The willingness to exchange samples, quality issues, and institutional access rules including external access, is addressed. We present a distillation of win-win situations in favor of both PI's and collectors of potential synergistic opportunities.
So far HIBs have proven to be useful for discovery of diagnostic biomarkers and molecular targets, whereas population biobanks unveil many important genomic correlations to the risk of disease acquisition and exposure due to lifestyle. The genomic correlations reveal genes and biological pathways as potential future drug targets. As both fields develop, an increase can be foreseen in the desire to use each other's samples for new research challenges. One of the most promising is to systematically study the behavior of the discovered genes and pathways unveiled in epidemiologic studies in disease progression. Study design and analyses should however involve disciplines of both worlds.
A Global Approach to Research Resource Infrastructure, the GBRCN and MIRRI
Do you speak acronym? If you consider all the initiatives, projects, societies, networks, research programs and institutions in the field of biopreservation, you can see the potential for lack of understanding, lack of cohesion and potential failure to coordinate effort to achieve an efficient mechanism for living resource delivery for research. A plethora of acronyms is before us MINE; CABRI; EBRCN; EMbaRC; GBRCN; MIRRI; ABRCN; ISBER; ESBB; BCCMTM; SBMCC; CCCCM; FCCM; CCRB; SCCCMOMB; KFCC; FORKOMIKRO; JSCC; PNCC; PNCM; TNCC; UKFCC; UKNCC; ECCO; WFCC; WDCM; ESFRI; BBMRI; EMBRC. Many have similar functions, presenting the danger of duplication of effort and fragmentation confusing the user. The microbial world has the World Federation for Culture Collections (WFCC) and its World Data Centre for Microorganisms (WDCM) to guide us through this myriad of institutions, organizations and initiatives. However, what is needed is a coordinated network with common access, strategies, policies and delivery to facilitate research and innovation, providing a conduit to make best use of their outputs. Biological Resource Centers must engage with their users and involve them in resource development and governance. The European Strategy Forum for Research Infrastructures (ESFRI) establishes pan-European structures to drive innovation and provide the resources, technologies and services necessary to underpin research, ensuring improved pathways to discovery. The Microbial Resource Research Infrastructure (MIRRI) has been established on the ESFRI roadmap. Linking MIRRI to initiatives in Asia, Africa, South America, the USA and elsewhere gives us the infrastructure for the Global Biological Resource Network (GBRCN) - networking networks.
Asian Network of Research Resource Centers (ANRRC)
Asian countries are known for a vast diversity of plants and animals due to widely varying climatic conditions and natural landscapes. The importance of developing biological resources and establishing bio-resource centers has been recognized by governments of Asian countries. Korea National Research Resource Center (KNRRC) organized an ad-hoc meeting to initiate ANRRC for cooperation and networking among Asian resource centers, culture collections and biobanks and hosted the inaugural meeting in 2009. The second annual meeting was held in Japan at RIKEN, Tsukuba and the third meeting in China at the Institute of Microbiology (IMCAS). The 4th annual ANRRC international meeting will be held in October, 2012 on Jeju Island, Korea.
At present, ANRRC has members from 85 institutes in 13 Asian countries. The network is continuing to expand its role via annual meetings, committee meetings (Bioinformatics, Regulation, Biobanking), and cross-training programs of researchers. This year, ANRRC and ISBER (International Society for Biological and Environmental Repositories) formed an affiliation partnership with the goal of maintaining maximum cooperation.
KNRRC consists of 36 RRCs that collect, preserve and distribute various specimens originated from microorganisms, plants, animals, humans etc. KNRRC is actively participating in domestic and international collaborations. One example is cooperation with Tanzania Wildlife Research Institute (TAWIRI). Since 2010, KNRRC and TAWIRI researchers have been collecting endoparasites, ectoparasites and microbes from wildlife animals in the Serengeti area. KNRRC will open the first biological resource center in Tanzania in 2013 and continue to provide support including technical training for preservation and management of biological resources.
Securing Components of Biodiversity in South Africa, for the Benefit of Society
Africa has one of the world's richest biodiversity heritages and hence a natural advantage that presents a unique opportunity to generate a strong mass of scientific evidence. Biodiversity resources are under threat from a variety of quarters, including disease, habitat destruction, population fragmentation, invading alien species and other anthropogenic causes. With the growing global market in biomaterials and biodiversity informatics, developing countries, particularly those that are recognized as ‘mega-diverse countries', face the enormous challenges of setting up systems to govern access to biodiversity and the sustainable utilization of its biodiversity heritage. Biobanking refers to the collection, processing, banking, distribution and use of biomaterials from life-forms for biodiversity conservation and biotechnology development. Biomaterials refer to tissues such as blood, serum, hair, skin, seeds, plant cultures and other bio-specimens. The purpose of the biobank is to provide a network of regional biomaterial banking services and facilities and to facilitate the co-ordination of the uses of such biomaterials on a national and global basis. Biomaterials provide the necessary vital information for a variety of interventions and developments including genetic diversity and inbreeding status of populations; DNA identification of alien invasive species and individual animals; taxonomy; forensics; as well as for studies in disease etiology and epidemiology and environmental pollution / toxicology. A network of participating stakeholders will ensure that a representative and on-going collection program is established for each bio-region. The Biobanking community in South Africa will ensure that samples are appropriately accessed, processed, secured and made available for the benefit of society.
Establishing a Biobank in a Developing Country; The Jordan Experience
King Hussein Cancer Center (KHCC) in Jordan is the only stand-alone comprehensive cancer center in the Middle East. It was established in 2002; the primary goal was to provide state of the art patient care in the diagnosis and management of cancer. It has been accredited by the Joint Commission International (JCI) and its pathology department by the College of American Pathologists (CAP).
The strategic plan for KHCC emphasized the importance of starting basic and clinical research along with continued excellence in patient care. For this reason a biobank (KHCCBIO) was planned to be established at the center to serve as a nucleus for the infrastructure of basic research.
Active networking was utilized to identify and connect with international partners, which led to a successful joint application for European Union Framework Program 7 funding to build capacities and help establish a biobank in Jordan which will be set up in compliance with ISO, EU & FDA Quality Guidelines. Our partners are The Thoracic Oncology Group at Trinity College – Dublin (TCD) under Professor Ken O'Byrne, the EU certified Tissue Establishment Biostór Ireland and Accelopment, a management company from Switzerland.
An international advisory committee of experts in the biobanking field containing members from Europe, USA and the Middle East was established to help guide the establishment of KHCCBIO.
KHCCBIO bank was conceived to create a world-class, ISO accredited Biobanking system at KHCC, Jordan and the region. The KHCCBIO mission is to advance research into diagnosis and treatment of cancer and to establish personalized medicine.
Bio-bank Setup in Saudi Arabia: A Diabetes Perspective
In the Middle East, the frequency of metabolic syndrome is higher and the numbers are increasing at a rapid pace. Currently, Saudi Arabia has a very high rate of diabetes and obesity and in coming years it will reach epidemic levels. The Saudi population is composed of various tribes which do not prefer marriages outside their tribe. Therefore, the occurrence of consanguineous marriage is very common. In addition, these metabolic diseases increased rapidly after oil was discovered. This discovery led to transformation of the living standard to a more sedentary lifestyle, when compared to the lives of the ancestors fifty years ago when hard labor prevailed. Hence, it is very intriguing to preserve specimens from these two different generations to do different types of research. At our center we have collected the blood samples (DNA and serum) from three to four generations and have linked these samples to a registry system. Consequently, the population consists of defined lineages and also detailed personal histories can be stored and analyzed. However, convincing people to participate in such research is an uneasy task as the main obstacles are ethical and cultural issues in the building of the bio-bank. Currently, we are in the process of building the setup for diabetes research and our experiences will be shared.
Biospecimens: How to Assess their Biomolecular Quality?
The progress of modern biomedicine is increasingly based on the discovery of new biomarkers for disease risk, diagnosis and prognosis, and biomaterial banks (BMB) are now their main source. The OECD sees BMB as an essential part of the infrastructure of life sciences and biotechnology integrating research and service, archiving and information technologies with respect to heredity, biochemistry and Pathobiochemistry of metabolic processes in complex functions of biological systems.
For years now, the number of biobanks has been growing rapidly. Scientific impact and downstream value of a BMB critically depends on the structural and functional integrity of the biomolecules in its samples. Specifically, biobanks featuring inferior biomolecular quality seriously compromise analytical results (garbage in - garbage out) and cause incalculable economic damage. At present, quality management exists at the levels of standardization of procedures and technologies, but provides no safeguards against preanalytical failures. Accordingly, the correct and quantitative assessment of sample age and biomolecular quality is of utmost importance and is regarded as the only way to ensure the sustainability of scientific results and/or to protect against high investment of the biomedical industry into garbage biobanks. Such systems have to be developed for different biomolecule classes (i.e. NA, proteins, metabolites, cells etc.) and need to be embedded into transparent structures that allow optimization of the value of biobanks and provide users with a clear picture of the quality level of the BMB they are using in their research and development.
Evidence-based Quality Control Tools for Biospecimens
Control of biospecimen quality, linked to processing, is one of the goals of biospecimen science. There is a lack of consensus regarding optimal sample quality control (QC) tools (markers/assays). A comprehensive and critical literature review was performed by the ISBER Biospecimen Science Working Group, in order to identify QC tools, both for fluid and solid tissue samples. The most readily applicable tools are those where a threshold for the preanalytical variation and a reference interval of the QC analyte are known. A few meaningful markers that meet these criteria were identified, such as the CD40L for assessing serum exposure at high temperatures, or VEGF for assessing serum freeze-thawing. Multiple QC markers are needed to fully assess biospecimen quality and the most promising biospecimen QC tools that were identified will be presented.
Fit for Research Purpose: Quality Control of Cells and Tissue Samples in Oncology
Human tumor cell lines and tissue samples are widely used in biomedical research in the field of oncology, as they represent a representative model system for functional studies and identification of diagnostic tools and therapeutic targets.
As far as human cell lines are concerned, the issues of misidentification and microbial contamination have been highlighted for decades, but have not yet been completely solved. Cross-contamination of human and animal cell lines is a repeated and frequent cause of scientific misrepresentation. The short tandem repeat profile international reference standard for human cell lines will be presented, as well as the Cell Line Integrated Molecular Authentication database (CLIMA) that allows linkage of available authentication data to actual cell lines distributed by cell banks. The validation of a PCR–based mycoplasma assay will also be discussed, based on European Pharmacopoeia standards.
The protocols of preservation and quality control of tumor samples in the Genoa Biological Resource Centre will also be presented.
Integrated Biobank Jena - Challenges and Solutions for High Quality Liquid Sample Storage
IBBJ is an integrated biobank at Jena University Hospital (JUH) comprising the biobank of the Competence Network “Sepsis” (SepNet), the biobank of the Center for Innovation Competence Septomics (ZIK-Septomics) and the biobank of the Center for Sepsis Control and Care (CSCC). The IBBJ combines all liquid biobanking efforts of the Jena sepsis cluster and provides comprehensive coverage of all ELSI, QM, ICT and education issues at Jena University Hospital. Embedded within the Institute of Clinical Chemistry and Laboratory Diagnostics, which is accredited according to DIN ISO 17025 and DIN ISO 15189, IBBJ provides a central biobanking resource for a number of networks (PROGRESS I, II), large-scale multicentre sepsis trials (MAXSEP, SISPCT, HYPRESS) and local clinical trials (LabALERTS). In 2010, IBBJ implemented one of the first scalable, fully automated robotic storage and retrieval systems for the automatic handling and storage of >500,000 individual tubes at −80°C. Recently this storage capacity was expanded by the implementation of LN2 storage containers with a total capacity of > 360,000 tubes for high quality long-term storage at very low temperatures. Challenges and solutions for high quality sample storage within large multicentre trials as well as local clinical trials will be discussed, with special emphasis on standardization of the preanalytical workflow and interoperability of biobanks. In addition, set up and implementation of a new liquid handling solution that allows immediate automated freezing of samples in a routine clinical laboratory environment will be presented.
Management of Biological Resource in the context of Cell Transplantation and Therapies for Cancer
Modern approaches to cancer treatment are multidisciplinary in essence, and include surgery and radiation therapy as well as a growing array of systemic therapies including cytotoxic agents, targeted therapies and biotherapies. Allogeneic hematopoietic stem cell transplantation (HSCT) is part of this armamentarium. It is one of the rare forms of cellular therapies with demonstrated immunological activity against tumors, mostly for hematological malignancies, and it provides a framework for the development of future and more extensively engineered cellular therapies. While in use now for more than 40 years, the use of allogeneic HSCT in indications other that advanced and/or poor-prognosis hematological diseases has been hampered by the difficulty to predict, prevent and cure the most prominent immunological complication called “Graft-versus Host Disease” or GVHD, while retaining the antitumor effect of the procedure. Thus understanding alloreactivity, its relation to the donor, the graft and the recipient is important. Designing research projects in this field implies the collection of samples and data from a donor (a healthy individual) and the related or unrelated patients, and thus to comply with different sets of rules that add to the complex regulations associated with cell donation for transplantation. The presentation will illustrate how to identify and address these issues practically.
Platforms Supporting Research: Bio-resources
“Biosample” science is now being redefined both in terms of quality and capacity to help researchers and clinicians to face new goals: personalized medicine guided by biomarkers and the ability to match the right treatment with the right patient at the right time. This will require the following:
• increase the quality and standardization of the collected samples and associated clinical data. • enhance the current capacity in terms of scale, geographic and disease representation. • provide an adequate ethical and legal framework to maintain public and professional trust. • ensure sustainability. • optimize the connection between potential donor sources, the biobanks and the biomedical research.
The Biobank of the Andalousian Public Health System (BB APHS) is a true network that covers the whole process of collection, processing, storage and distribution of human biological samples for research as well as giving as much as possible the services required by research groups.
The network is formed by a central node for coordination, including DNA and Stem Cell banks, plus 18 associated nodes located in seven reference hospitals, one blood transfusion and one cord blood center with capability for providing any kind of samples either from patients or normal controls. The biobank works as a decentralized but coordinated structure with common supportive areas: quality control and information system, standardized procedures, ethical and scientific committees, single window system and management with standard and uniform SOPs.
During the last 18 months the BB APHS supported 81 biomedical research projects and distributed more than 15,000 biospecimens.
Biobanking and Sample Management for Drug Discovery in Abbott
An integrated system for maintaining a collection of biological materials and the corresponding information is crucial for every pharmaceutical company and enables drug discovery efforts. The requirements for such a system are very dynamic and include more and more functions in order to capture the ever increasing complexities of drug discovery.
At Abbott Neuroscience Discovery in Ludwigshafen, the first biobank was introduced in 2003 to cope with local biobanking needs. The implementation called GEOS3, supplied useful features to handle plasmids, cell lines and genetically modified cell lines, and provided a rich dataset to annotate these biological samples. Although very useful, this system needed improvements to increase the user base and the general utilization of the system, providing the best possible user-friendly interface. To address these requirements, GEOS4, a new version of the database was implemented in 2007. As a result of the improvements, this system had high acceptance from the users and had an improved quality of the registration and inventory. In 2011, the system was extended to accommodate the needs of other departments in Abbott Ludwigshafen handling clinical samples used in biomarker development.
Potential future improvement of the local biobanking database includes the increased capacity to handle global needs among different sites within Abbott. Another necessary feature is the implementation of sample tracking capabilities in a global system. Only such a globally integrated biobanking system can cope with the cumulative rise of biological samples from animal and clinical studies.
Bio Banking in Populations of Large Effective Size
Bio Banking is currently responding to growing demands of the human species in fields of regenerative and transplantation medicine, which are among the most expanding fields in biomedicine. Although the future seems to promise solution to questions of matching through autologous stem cell implants, there are aspects of demand that will continue to require tissue and genetic information from other human sources. This is probably where Africa and other populations with increased effective size may be especially valuable.
Bio banking in populations of pronounced genetic variation like Africans, however, poses unique and interesting challenges as much as promise and opportunities for medical application and translation. On one side there is the challenge of implementing genomic applications now increasingly perceived as individualized in population context and vice versa; challenges also include the practicality of profiling, storage and processing of a large number of tissue samples representative of a population, and the economics of maintaining large repositories in underdeveloped countries that lack the necessary financial resources and are entrenched in outdated cultures of nation states and sovereignty that impede sharing resources, flow of information and benefits.
On the other hand there are the immense opportunities of: matching tissues to a wide repertoire of genetic backgrounds of genomes at the root of the human evolutionary tree, identifying novel and unique expression profiles, genetic mechanisms, fitness and adaptation measures and characterizing and defining the “normal biological ranges” of the human species, given evidence that humans evolved recently in east Africa for a considerable period before undergoing subsequent expansion that carried part of the human group to other continents.
Biobanking in Low Resource Settings – A Pathologist's View
Cancer in Africa has high mortality rates and has become a serious health problem. Knowledge about epidemiology, pathogenesis and genetics of many kinds of cancer in the African population is scarce. Pathology plays an important role not only in diagnostics, but also in cancer research. However, especially in sub-Saharan Africa there are only a few laboratories which can provide regular service for surgical pathology. Formalin fixed paraffin embedded (FFPE) sections which are widely used for pathology diagnostics may be a great source for tissue based research. One of the most crucial issues, though, is the quality of the specimens. Current existing infrastructure allows diagnostic standard staining. Application of further molecular analysis, however, is hampered by the lack of standardization of pre-analytic tissue handling (variable fixation times, unclear fixation agents etc.). A basic approach for building up biobanking structures in low resource settings, e.g. in sub-Saharan Africa should encompass: A) Structuring and standardization of tissue processing that would allow even for FFPE tissue to serve as a firm base for scientific projects. Recently developed alternative fixation agents show certain advantages over FFPE in terms of usage for molecular analysis and may offer alternatives for robust tissue preservation. B) Complementary to tissue collection, the establishment of clinical data banks is of high relevance in order to document corresponding relevant clinical information. C) Consideration of ethical issues for the usage of tissue (informed consent, respect of cultural aspects, etc.) is of high importance. Tight collaboration with ethics commissions should be regarded as mandatory.
Establishing a Biorepository to Support Ecological/Environmental Studies in Southern Africa
The purpose of this project is to establish a longitudinal repository of annotated genomic nucleic acids from impacted ecosystems in Southern Africa. Collection sites were selected where documentable major ecological, environmental and socio-economic changes are currently on-going and projected to intensify. Specifically, ecosystems rapidly losing biodiversity due to climate change and human activities will be studied. This project is not simply to collect DNA and related biological material. Taxonomic [classification and physical description of the donor individual] and functional [exact collection location and climatic, behavioral, ecological and human socioeconomic conditions] information associated with each specimen will be preserved. Longitudinally collected genetic material, fully annotated with respect to taxonomy and functional characteristics, will provide international scientists unique opportunities to study multiple dimensions of biodiversity. Annotated materials will be distributed to multi-disciplinary, multi-national investigators. Both currently active investigators and new investigators, especially those among under-represented groups that may lack adequate resources, will be able to participate. Data assessing changes in gene expression and population genetic diversity, in the context of documented ecological change, are predicted to significantly expand our understanding of the bilateral interplay between ecological and evolutionary processes. Such new knowledge will have long term, local and global impacts on human society at large.
Privacy, Reciprocity, and Biobanks
In the context of biobanking, there has been a shift toward conception of research donations as “conditional gifts,” in which participants are understood to attach varying conditions to their donations. Such perspectives highlight the ongoing interests of the donors in their donation, and emphasize interaction, engagement, and collaboration between participants, researchers, and society.
By focusing on ongoing returns of favors between participants and researchers, this conditional-gift model can incorporate both participants' collective interests in how samples are used or what research is pursued with them, and also their individual conditions of acceptance, and enables participants to retain some degree of control throughout the research process. This process of biobanks “returning something,” however, is complex and subject to different interpretations and understandings. As such, it then becomes salient to ask what forms of reciprocity or “favors” are offered to potential biobank participants?
Based on focus-group research with participants of the UK Biobank and the KORA study, together with other biobank participants and wider lay publics in the United Kingdom and Germany, we empirically examine how potential and actual participants in population biobanks negotiate the complex relationship between concerns in privacy protection, reciprocity and benefit sharing. We then discuss the broad strategies of recruitment of the UK Biobank and KORA to explore the need for flexible modes of reciprocity in future population biobanking strategies.
Privacy as a Matter of Concern in Responsibly Governing Biobanks
Informed by a triennial interdisciplinary cooperation with lawyers, sociologists, and political scientists (cf. www.private-gen.eu), ethical judgment (analysis and recommendations) is provided on how to cope with the on-going variations, adaptations and transformations of privacy in an era of (post-)genomics. As one of the results of the Private-Gen consortium it emerged that biobanks are run in an ethically responsible way if concerns on privacy are taken seriously and at the same time are balanced against partly complementary, partly conflicting norms, values and interests. Surveys carried out within the Private-Gen consortium showed that, for many people, privacy is a value of major but not of preeminent concern. Many are willing to make decisions on providing samples and data to biobanks in line with their daily experiences with other technologies and data streams. In order to meet these attitudes, within existing legal frameworks and ethical criteria, a twofold strategy is essential for biobanking enterprises: On the one hand, they are recommended to build robust trust in their regimens of confidentiality by providing technical and communication means, respectively. On the other hand, these technical and communication strategies must be set up in such a flexible way that they can manage a diversity of interests and attitudes in terms of privacy.
Maintaining Confidentiality of Donor Data: Tools and Procedures
Access to data and biological material stored in biobanks has to satisfy pertinent international, national, institutional and individual requirements, constraints and proscriptions for information access and exchange. Specifically: (1) Legislation imposes data minimization, purpose limitations, data subjects rights, notification and security of processing. (2) Institutional (Biobank) policies typically impose procedural and substantive requirements for access. (3) Data subjects (donors of data and/or biological material) may impose restrictions on type of users or types of use.
We present and discuss approaches to support researchers in their search for and use of available data/material for their research projects, taking into account the characteristics of the requestor and his/her project and the requirements, constraints and proscriptions pertaining to the individual biobank.
We will present strategies to balance these seemingly conflicting requirements of research needs and the above mentioned limitations. We will show that the consideration of different phases of project planning, project approval, and project execution, allows maintenance of the rights and dignity of donors without jeopardizing the legitimate information needs of researchers. For each of these phases, we discuss its genuine duties and tasks together with the constraints and goals, and analyze which tools and techniques can be applied.
The Frozen Ark Project
Despite conservation efforts, the United Nations Environment Program and the International Union for the Conservation of Nature conclude that 30% of all wild animals will go extinct within 50 years. This is due to increasing human population leading to climate change, habitat destruction, agricultural land needs, over-fishing and acidification of oceans. The Frozen Ark Project is a global strategy to conserve genetic resources of the world's endangered species for the long term before they go extinct. The project is analogous to the preservation of the world's plants, such as Kew Garden's ‘Millennium Seed Bank’. Its global Consortium consists of a growing number of 22 zoos, aquaria, natural history museums and research laboratories dedicated to collecting and storing undegraded material for the long term. The material provides knowledge of great value to both wild animals and humans.
Many institutions store genetic material but often in a manner that does not allow preservation of undamaged material and seldom in coordination with other essential institutions. Few are exclusively for endangered species and none is designed for invertebrates on which all larger animals, including mankind, depend. The Frozen Ark is not a substitute for the conservation of the animals themselves, but an essential back-up to the conservation movement. International collaboration with the world's biobanks will be essential to the success of this project.
Trials and Tribulations of a Biodiversity Biobank: Tales from Natural History Museum London UK
The NHM is the UK's national museum of natural history, a world center of scientific excellence in taxonomy and biodiversity with 70 million specimens in its collections. An average of 25K new specimens are received each year, from focused collections by researchers, opportunistic collecting, donations and bequests by scientists and public, and confiscations by Customs; all sources of genetic material for analysis.
The NHM Molecular Collections Facility (MCF), a centralized biorepository for collections destined for or created by molecular research internally and externally, built in 2011 was launched in February 2012. During this time, the facility set up, operations, and implementation of policy and procedures, have tackled various obstacles in order to meet the imperative to bank genetic resource information in a race against time in the face of the current biodiversity crisis. The talk will share some experiences and challenges faced:
• Organizational and culture change; centralization vs. local laboratories, museum research and curation conflicts. • Infrastructure considerations: essential environmental requirements, disaster planning, running costs/overheads. • Access to local archival collections for centralization (ownership issues). Marketing facility benefits for museum researcher/curator buy in. • Harmonization of internal/external data management and record systems (Botany, Entomology, Zoology databases): BIMS, new data capture, loan systems. • Cold chain establishment: logistical difficulties in many biodiversity-rich areas transporting genome quality samples from field to repository. • Cost recovery business models for non-human biobanks. • Future proofing ultra-long term (museum timescale) storage, extraction methods, and future compliance issues (policy and procedure).
“Frozen Dumbo Project”: How Biobanking Allowed Creation of a Link Between Wild and Captive African Elephant (Loxodonta africana) Populations
Long term sustainability of the African elephant population in captivity is jeopardized by the low number of breeding bulls. The success of artificial insemination techniques developed to face this problem relies heavily on access to good quality semen samples. In order to establish a reliable semen bank available to the international zoo community, the Frozen Dumbo Project was launched in 2009 by an international team of experts. The aim of this project was first to collect and store frozen semen from wild African elephant bulls from South Africa and then to import the cryo-preserved samples to Europe and United States to be used for future breeding programs. Skin, hair and blood samples were also collected for biobanking in South Africa. Numerous technical and legal issues have been raised in the process. Collection and optimal processing of the semen samples under field conditions, as well as definition and compliance with specific health requirements were two of the main concerns. Importing and banking wild animals' gametes, instead of live animals, for captive breeding programs is an interesting tool for long-term management of natural resources and conservation of endangered species. Health risk assessment of such imports is very challenging for the health authorities of importing countries due to the specificity of wild animal sample collection. The small number of specimens involved in such a project as well as the close health monitoring of the animals who benefit from assisted reproductive technologies should be taken into account when designing the health certificate.
Converting Biospecimens into Secure Information: Cryptographic Assurance for Biobank-Derived Data
With ongoing progress in analytical and sequencing technologies, secure and privacy-preserving distributed access to and use of biospecimen-derived data has become the bottleneck of collaborative work in personalized medicine and beyond. First attempts - for instance during the BBMRI Preparatory Phase with their “Expert Centers” model - rely on traditional legal and organizational approaches to ensure privacy, confidentiality, and security. We present here a framework of secure multi-party computation; in particular, tailor-made for bioinformatic analysis by statistical modeling as common in, e.g., genetic association studies. This system implements the privacy-by-design-paradigm and allows geographically and/or institutionally heterogeneous collaborations, while ensuring the non-distribution and non-accessibility of sensitive information (either privacy related or intellectual property related) to participants, but still allowing them to use the data.
This work is pursued in collaboration with Prof. S. Katzenbeisser, Security Engineering, TU Darmstadt.
Trans-Institutional e-Infrastructures for the Secure Management of Biosamples: National and International Perspectives
Based on discussions and developments in national and international projects, challenges and possible solutions for the sharing of data and biomaterials are presented. First, on the database level, decisions between virtual and materialized integration concepts have to be made, i.e. between federated systems vs. conventional warehouses or hybrid solutions. Secondly, semantic interoperability raises questions at the levels of data, metadata, and ontologies. Necessary steps are harmonization and/or standardization. More recent developments are ontological integration and the use of semantic web technologies, including RDF and SPARQL. Thirdly, security and privacy concepts are of central relevance in any case. They comprise the choice of pseudonymity and anonymity models, as well as models for role-based access. They may vary for the different project phases, which are mainly collection/ management and the use/sharing of data and samples. For all phases, risks and threads need to be considered, to guide decisions concerning the release of data or meta-data; e.g. statistical vs. micro data release. Management and verification of informed consent is essential, especially when data and samples are shared and re-used. Finally, there are determining factors such as regulations, but also IT skills and staffing. They are influential for local autonomy and for the definition/implementation of services.
Where are My Samples? Knowledge Management in Pre-competitive Translational Research
In this talk, we will explore the challenges in transparently providing a view of bio-specimens from large disease-research networks, where multiple organizations collaborate to investigate the biological mechanisms that underlie complex disease. These challenges include the traceability of samples across the research network and the selection of samples appropriate for a disease. We will also show examples of knowledge management technology such as the TranSMART platform that have been used to help overcome these challenges.
DNA Barcoding: A Valuable Sample Source for Biobanking
Species identification is usually the necessary first step in biological research and many related life science disciplines. Among other factors, inexpensiveness, speed, automation, parallelization, ease of application, and increased availability are causing molecular markers in taxonomy to evolve into a very widely used tool for species identification. Within a worldwide initiative, ‘DNA barcoding’ standardizes this approach regarding marker choice, data and data collection, etc. Currently, a multitude of institutions in around 50 countries are compiling large barcode reference libraries that merge into a central online database. In my presentation I want to show how these barcoding projects, often organized as national campaigns, qualify as one of the most valuable sources for biobank specimens of wild organisms. This applies to the speed with which samples are obtained, to the quality of the underlying data (taxonomic determinations, etc.), to vouchering requirements, to the diversity and taxonomic coverage of samples, to collecting permits, and to molecular subsampling. Non-human biobanks should be highly aware of this source and should plead for and guarantee the longevity and high-quality storage of the molecular (sub)samples of DNA barcoding, thus consolidating their role as a key infrastructure not only for biodiversity-centered research but also for the many disciplines dependent on it.
Ownership, Property Rights and Commercialization in Relation to Biobanking
Ownership rights regarding biobanks and genetic material stored in them are controversial. Advances in biotechnology and progress in genetic research have accentuated the existing debate on ownership and commercialization of body parts. Biobanks pose particular questions when it comes to ownership of samples and data. The economic value of the material itself, in general DNA derived from blood samples and data stored in computers, is often negligible. However, collections of samples may acquire significant scientific and economic value if the biological material and associated data come from unique and well documented donor cohorts and promise interesting results that give rise to patents and other sources of possible profit. Various solutions have been proposed to settle debates about ownership rights in biobanking. Although some biobanks refer to the idea of donation of samples and data and imply that full ownership is transferred to the biobank, other stakeholders have claimed that donors continue to own their samples. It is generally admitted that donors retain some rights related to their samples and data, for example the right to opt out of a biobank, understood as the right to ask for destruction or unlinked anonymization of samples and data. Uncertainty as regards ownership rights may impose risks for those who engage in biobanking activities and hamper future research. In this presentation, different schemes of ownership and property rights will be described and ethical and legal arguments in favor and against them will be discussed, based on the framework of international human rights implemented in Europe.
Electronic Consent
The case has been well made that “informed consent” for donating biospecimens, particularly paper based consent conducted face to face, is an imperfect system. Is the consent “free”? Is the donor informed? How can he be informed of uses as yet unknown? Does the donor really have time to weigh up the pros and cons? Is this not primarily a mechanism to protect the investigator? The imperfections are well established; but this is the system we have.
Traditional IC is also expensive. Letters sent to potential donors, call centers, face to face IC, wet signatures, paperwork, manual data capture all add to the expense.
Many organizations are now moving towards electronic consent and building evidence that it works. Donors better informed, improved confidentiality, less risk of data capture errors, lower costs and higher donor involvement are immediate improvements.
Further, this is an opportunity not to treat population cohorts in particular as isolated constructs, but as rich assets embedded in the health system, providing a platform for those benefitting from the pooled resources of the health system to contribute continuously, altruistically and transparently to the research that feeds back into better treatment.
This presentation will give examples of current practice, and road blocks, and describe the approach being taken for the Luxembourg National Cohort.
Biobanking and the Tree of Life
Biodiversity is of immense importance for human welfare. The Convention of Biological Diversity estimates that at least 40 per cent of the world's economy and 80 per cent of the needs of the poor are derived from biological resources.
The richer the diversity of life, the greater the opportunity for medical discoveries, economic development, and adaptive responses to climate change. The variety of life is our insurance policy.
Human activity has reduced natural habitats dramatically and continues to do so at an alarmingly high rate, simultaneously driving a steadily increasing extinction.
Conservatively estimated there are 10–14 million species on earth, only 1.75 million of which are known. To preserve just a synoptic, global collection of the entire genome of these 1.75 million species is a formidable task. Acknowledging this, an international consortium of some of the world's leading natural history museums are in the process of creating a global organization, the Global Genome Biodiversity Network (GGBN), to develop a common research agenda and to promote a network of biodiversity biorepositories to preserve and study genomic biodiversity. The challenges are immense, as these collections do not share a common IT-platform and their collection activities have been uncoordinated. Thus, what already exists or what constitute genome-quality samples are unknown. Once these are determined, we need to identify gaps in the collections, both geographic and taxonomic, and to develop a stratified collection strategy for further collection, viz. is the aim to collect exemplars of all known genera? Overlaying everything is compliance with access and benefit sharing.
Biobanking the Tree-of-Life for Evolutionary and Conservation Studies of Biological Diversity
The DNA Bank at the Royal Botanic Gardens, Kew is the largest of its kind in the world, with more than 40,000 accessions, representing ca. 35,000 species of angiosperms, gymnosperms and pteridophytes, and growing by several thousand every year. This collection has exemplified, through the two decades since its establishment, the crucial importance of this type of collection for scientific research, particularly phylogenetics. The DNA samples housed at Kew served as basis for hundreds of studies examining phylogenetic relationships among plants, which have contributed to the better understanding of plant classification and evolution and, ultimately, to the development of the Angiosperm Phylogeny Group classification. I will discuss the growing value of such collections in light of the colossal advances in sequencing technologies of the genomics era and how they are essential resources in our understanding of the intricacies of the Tree-of-Life, the conservation of biodiversity and much more.
The Tissue and DNA Collection of the National Museum of Natural History (CSIC) and Our Efforts to Assemble the Tree of Life
The National Museum of Natural History is part of The Spanish National Research Council (CSIC) and maintains scientific collections. Among its tasks is to maintain and house the scientific collections that have generated and continue to generate research in the area of natural resources.
The tissue and DNA collection (MNCN) began its activity in 2000. Today it includes 52,100 specimens in its catalogue with over 80,000 samples already classified and available to the scientific community. Approximately 250,000 samples more are also deposited and are currently in the process of being classified. The popularity of this collection is growing and the number of users requiring tissues or extracted DNA is steadily increasing. Until the present 10,500 samples have been lent to national and international researchers, all of them with the required permits, as they belong to species included in annexes of CITES. The catalogue number of the samples in our collection is a voucher number, which appears in Genebank, where currently more than 7,000 sequences belonging to our frozen samples can be localized. More than 12,000 records have been uploaded in the GBIF data base during recent years.
Currently, the tissue collection or the molecular samples have 3 preservation methods; frozen at 80 degrees, liquid-preserved (in ethanol or DMSO buffer), and dried material (non-invasive samples) in silica or freeze-dried material.
Biobanking, Tumor Heterogeneity, and the Molecular Diagnosis of Cancer
Our limited knowledge of the genetic basis of cancer diseases based on candidate gene approaches has now been expanded by the use of massive parallel sequencing (MPS). This approach has helped to uncover the genomic landscape of cancers showing that, beyond high frequency mutations, a plethora of different molecular features are identified at low frequency and define cancer molecular subgroups of clinical interest. Recent works exploring the molecular variations' landscape of different cancers have also highlighted a high degree of genetic heterogeneity in metastatic deposits, which substantially reflects the presence of different subclones within the primary disease. When ignored, molecular heterogeneity can lead to failure in therapeutic treatments, as drugs that may have efficacy in subgroups of patients with specific molecular phenotypes may show marginal response when tested in a large group of unselected patients. This calls for revisitation of the classical pathological diagnosis of cancer where the description of intra-tumor heterogeneity at both morphological and molecular levels is taken into account for a diagnostic report to be clinically useful and contribute to decisions on first, second and additional therapeutic choices.
BIOBANK MANAGEMENT (BM)
caTissue Suite - An Open Source Biobanking Software Solution
caTissue Suite developed by the National Cancer Institute under the aegis of caBIG® program is a web-based software solution for biospecimen inventory management, tracking and annotation. This tool permits users to enter and retrieve data concerning the collection, storage, quality assurance, and distribution of biospecimens. caTissue has been successfully adopted across the globe in various biospecimen banks of varying size and function, and that manage multiple types of biospecimens (tissue, biofluids, nucleic acid). For example, caTissue at Washington University, St. Louis holds more than 100k participants and 1M specimens.
caTissue supports specimen collection for simple to complex longitudinal protocols, shipping and tracking, ordering and distribution, and bulk upload using spreadsheets. It also provides search functionality for both the biorepository staff and research scientist, who may be interested in searching and requesting biospecimens for correlative science studies. caTissue also provides interfaces to capture specimen and study participant annotations which include informed consent status, clinical data (e.g. treatment, follow-up events), pathology data (based on College of American Pathologists organ site checklists), and textual pathology reports.
The team at Krishagni has been involved in development of caTissue since 2005 along with Washington University at St. Louis, and has been a pioneer in helping various centers adopt caTissue.
IMM-Biobank - The First Year
Biobanks are increasingly recognized as crucial resources for health research. The Instituto de Medicina Molecular (IMM) Biobank is based in Lisbon, Portugal and is integrated into the Academic Medical Center of Lisbon, which brings together on the same campus a research institute (IMM), the university medical school and a teaching hospital.
Since the creation of the IMM Biobank in May 2011, a great effort has been made to offer high-quality services. The implementation process was to optimize laboratory facilities and to standardize operational procedures, as well as legal and ethical aspects. The IMM Biobank has already collected more than 10,000 samples from 1050 individuals. Our Biobank involves signed collaborations with research groups, hospitals and scientific societies, such as the Portuguese Rheumatology Society. The samples are structured into 5 different collections: the rheumatology collection (6790 samples), the neurotumors collection (56 samples), the neurosciences collection (1203 samples), the cardiovascular collection (324 samples) and the endocrinology collection (1680 samples). In addition, the IMM Biobank has also a service for DNA and RNA extraction from tissue and body fluids and general support for research projects.
The IMM Biobank works in accordance with European and Portuguese regulations and allows studies of the pathogenesis of multiple diseases with high impact on human health, improving the identification of new prognostic and diagnostic tests and new therapeutic targets.
Our vision is that the IMM Biobank will be an important tool for promoting health, and new opportunities for cooperation between academic researchers and the pharmaceutical industry.
Uppsala Biobank- Uppsala University and Uppsala County Council Come Together to Found a Common Biobank Infrastructure
When the Biobanks in Medical Care Act was taken into force in Sweden, research and healthcare principals started biobank organizations. In Uppsala, a vast majority of the samples was collected and stored within healthcare at Uppsala County Council while Uppsala University usually was the principal source of research publications. We have seen that vagueness around rights to samples can give rise to conflicts.
The principals represented by Uppsala University hospital and Uppsala University Faculty of Medicine decided to found a common biobank infrastructure in 2008 by initiating and investing in Uppsala Biobank. The principals believed that benefits gained from a united organization for all sample collections would facilitate tracing, security and quality assurance and promote collaborations.
Uppsala Biobank represents the only biobank of the principals and includes all sample collections with biobank samples both for research and health care. The mission of Uppsala Biobank is to administrate, establish, support and maintain stable biobank structure, obtain and supply high competence and tools to fulfill laws and regulations, and perform services in relation to sample management and processing. The head of Uppsala Biobank is the biobank custodian and every sample collection has a responsible person. The principals are represented in the Biobank council that meets four times per year.
Uppsala Biobank as a center of competence for biobanking and as an infrastructure for medical research has so far been a success. This is an example of how a research and a health care principal with common interest in biobanks can collaborate in a successful manner.
Molecular Medicine for Care Program, Department of Experimental Oncology IEO, European Oncology Institute, Milan, Italy
The IEO Biobank and Biomolecular Resource Infrastructure (IBBRI) is one of the pillars of a “program” of complete integration between clinical and research activities. The purpose of IBBRI is to provide a resource of biological samples for research, with the aim of improving the prevention, diagnosis and, above all, cure of cancer, in the broader perspective of “personalized biomedicine”. IBBRI is currently using the Thermo Scientific Nautilus LIMS software for the accurate management and analysis of biospecimens. The system is specifically designed to manage biosamples and biospecimen collection, localization, and patient demographics. Nautilus is integrated with the systems in use at the European Oncology Institute (IEO) to collect and manage all the patients' clinical data, as well as with other patient information systems to retrieve pathology results. IBBRI also collects electronically the patient informed consent. The IBBRI project and the new informed consent document were created to ensure that the donation of biological materials is done properly and that this legacy is used in the best way, adhering to ethical and legal standards. Patients' donation of their tissue and/or their body fluids implies a strong sense of responsibility towards the community and is an act of altruism that can lead to benefits for others that suffer. A key aspect of the informed consent procedure (and a prerequisite for its success) is the strong relationship that has to be established between the patient and the researcher/interviewer who provides information about the study. Generating trust in researchers and institutions and supporting their credibility at the time of the request of consent plays a key role in decision-making processes of potential participants to the study. The involvement of patients in decisions that affect their lives and their health should occur in a personal and totally transparent manner, respecting both privacy and confidentiality. This would favor a tight, two-way relationship between researcher and donor, where one can be of help and support to the other, with obvious benefit to both for the individual research project and for research in general.
arktic - Automated −20/−800C Biobanking for Every Laboratory
Since the early 1990s biobanking has been evolving as a key resource, increasing the availability and use of biological materials, such as DNA, RNA, tissues and cells, across biomedical research.
Aside from large biobanking schemes set up by national and institutional biobanks (e.g. the genome project and the NCI), there are a growing number of smaller research groups and companies needing low cost, compact, automated secure biobanking facilities as their sample library increases.
At present, these smaller research groups employ traditional storage methods, using freezers and liquid nitrogen Dewars, which require manual labeling, rack organization, logging and placement. With vast numbers of biological samples, this process becomes time consuming, labor intensive and open to error.
In addition, sample placement and retrieval can result in significant temperature fluctuations as a result of freezer doors being opened, lids being removed and racks being removed. These activities can result in the unnecessary partial thawing of unpicked samples within the freezer and selected racks, potentially affecting sample stability and quality.
Small pharma companies and research groups are unable to commit both the space and the finances to invest in the large automated −80°C storage platforms currently available on the market. It would therefore be advantageous to have an efficient, small, robust automated −80°C biobanking store providing secure tube placement and sample tracking. In addition the ability to retrieve or “cherry-pick” individual samples, minimizing disturbance to other samples also would be beneficial.
Serumbank@UZA: A Hospital-Integrated Oncological Serumbank
Reorganization of Biobanks at Uppsala County Council and Uppsala University-140 biobanks in Uppsala Become One
Uppsala Biobank was founded in September 2008 as a collaboration between Uppsala County Council and Uppsala University. The purpose was to become a centre of competence for biobank issues and the only biobank of the two principals. However, there were already 140 biobanks registered by individual researchers when the Uppsala Biobank was initiated. These former biobanks had to be reorganized into sample collections.
The head of Uppsala Biobank is the biobank custodian of all sample collections. Every sample collection also will have a person responsible for that sample collection. . Responsibilities and rights to samples donated for research had to be regulated and clarified between these two parties. A legally approved model contract was therefore prepared. The contract gives the sample-collection-responsible person the sole right to use samples for research at the two principal organizations, given informed consent and ethical approval.
All former biobanks have been invited to individual meetings with Uppsala Biobank. The purpose of the meeting is to identify the responsible person and sign a contract. Information about the sample collection such as what kind of samples, how personal data is handled and what kind of research is performed is registered. In autumn 2012 110 contracts were signed.
The process of reorganizing biobanks in Uppsala has been very positively received. Both researchers and principals appreciate that responsibilities and rights are clarified. The reorganization is expected to be completed by the end of 2012. A registry describing all sample collections in Uppsala Biobank will thereafter be compiled, published and reported.
LPCE Biobank and PACA Biobank, University of Nice, Nice, France
Thyroid cancers are infrequent, but their incidence is increasing in France, largely through the optimization of radio-imagistic investigation methods allowing their detection. A significant feature is that some thyroid cancers are linked to medical exposure by ionizing radiations in childhood or to accidental exposure, which makes it a model of ionizing-radiation-induced human carcinoma. A number of differentiated thyroid cancers are difficult to diagnose and may be under- or overestimated. Some thyroid tumors are impossible to categorize on histological criteria and have been called, thyroid tumors of uncertain malignant potential. The BIOTHYBASE was set up in order to create a national centralized base of epidemiological, clinical and biological data in patients with malignant tumor of the thyroid gland or tumor of uncertain malignant potential. The objective was to connect an epidemiological and clinical database to a biological database, based on criteria of high quality and to associate specific items of thyroid pathology within the items in the repository of French INCa biobanks. All collected data will facilitate co-operative studies among different centers participating in the BIOTHYBASE project; these studies may involve a field of epidemiological or clinical-biological research. The participation of 15 centers highly specialized in the management of thyroid tumors ensures recruitment potential, quality criteria and follow-up of patients. A Charter of functioning was established to ensure compliance with the INCa Biobank Code of Ethics. Each participating center will be the sole proprietor of various data exported in the database, and biological samples collected locally in the biological resource center.
Biobanking in an Integrative Biopathology System Model: Fact or Fancy?
The discovery of oncology biomarkers that are clinically relevant for diagnostics, therapy, and prognosis, together with the development of consistent and reliable molecular techniques, led to the incorporation of biobanks and molecular testing as source of strength to surgical pathology laboratories. Biobanking, particularly in the field of oncology, is strongly integrated within both clinical practice and molecular pathology, but also in translational research programs, including the next-generation sequencing approaches. Pathologists often conduct research for identification of novel biomarkers, an area of research which is at the intersection of histology, molecular biology and cell biology. The acquisition of tissue samples and biological fluids is best facilitated in centers where physicians, biologists, pathologists, and biobankers interact as a multidisciplinary team and can closely coordinate their efforts. The challenge is the sampling of the tissue for histology, molecular pathology and research. Another challenge is the selection of the proper preservation technique for the tissue or biological fluid samples. Preservation is an irreversible step that will determine the usefulness of the specimen for histopathological diagnosis, molecular testing and research. In this regard, we strongly believe that an integrative biopathology laboratory which associates in a single location, the surgical pathology, the molecular pathology and the biobank activities can be of great value to improve both the quality of clinical diagnosis and biological research. We have set up such an integrative biopathology laboratory (LPCE, Nice, France) and we described in particular the workflow of samples from the clinical and surgical departments to the biobank area.
Implementation and Monitoring of a Quality Management System Based on Accreditation According to the ISO/EN 15189 Referential in a Biobank Unit: Is it Necessary ?
The rapid emergence of several targeted therapies and the concept of personalized medicine underlie the strong necessity to develop a well-organized molecular biology (or molecular pathology) unit of high quality dedicated to clinical care, in order to seek tissue and cellular biomarkers. These biomarkers can be searched from formalin fixed biospecimens, and also from frozen samples which can be stored in biobanks. The management of frozen specimens dedicated to clinical care for hospitalized patients needs to be optimal. Quality measures of biobanks in Europe can be evidenced by ISO 9001 and S96–900 certification or an ISO 17025 certification. However, these certifications have been set up to certify only the management system, in particular for human samples used for research. In France, using tissues stored in a biobank for patient health care will be available soon, as it is in the surgical pathology laboratory, under conditions defined under accreditation according to the ISO 15189 norm. The present work aims to describe the main steps required for an ISO 15189 accreditation in a biobank. The different chapters of this norm will be described. We will explain the potential difficulties of this initiative and the pros and cons for the ISO15189 in the biobanking field. We describe our experience through the set-up procedure in the LPCE Biobank of Nice (University of Nice Sophia Antipolis, France), in particular, for the management of lung carcinoma.
The BMBF Initiative to Build up Centralized Biomaterial Banks in Germany: Concept of the Interdisciplinary Bank of Biomaterials and Data Würzburg (ibdw)
The build-up process is split into four partly overlapping phases:
(1) build up organization including patient consent and standard operating procedures (SOP) (2) build up liquid biobank (3) build up tissue biobank (4) implement unified IT infrastructure and interface to the clinical database.
All data within the IBDW will be stored pseudonymized and are protected by an independent gatekeeper.
Together with the local ethics committee, a patient and a proband open consent have been developed. The individual subject donates BM to the IBDW for future research for an unlimited time period. The consent allows collection of specified amounts of BM from an individual subject once within a pre-specified time period. Processing of liquid BM samples is highly automated to ensure a high quality pre-analytic phase (SPREC). All BM is managed by a Biobank Management System which tracks all handling and processing steps of a sample starting with its acquisition until storage of the sample or its aliquots in the cryo-repository.
Applied Accreditation in Tissue Banking, the Benefits and Drawbacks
The Swedish Biobank Sample Handling and Storage Process for Human Liquid Based Cervical Cell Specimens
The Swedish National Cervical Cytology Biobank is the first prospective repository of a large-scale biobank for liquid-based gynecological cell samples from women participating in an organized cervical cancer screening program. Sharing successful strategies for the development of standardized methods for sample handling and long-term storage has been one of the driving forces for The BioBanking and Molecular Resource Infrastructure of Sweden, BBMRI.se, www.bbmri.se. Protocols were developed through a review of the literature on biobanking processes, wide consultation within the academic communities and various verification assays with collaboration of the clinical laboratories of cytology. The biobank excellence has been assured by the Quality Management System (QMS) of laboratory accreditation procedures, which includes Quality Assurance (QA) and Quality Control (QC) programs and related SOPs that covered the full spectrum of biobanking operations. The Swedish Cervical Cytology Biobank now has been established into the seven different Swedish county councils. During 2011 and 2012 more than 100,000 liquid-based gynecological cell samples will be processed for biopreservation.
The Swedish Cervical Cytology Biobank uses state-of-the art methods that emphasize trust and privacy protections. This large-scale cytology biobank that was established as a hospital-integrated biobank provides for the exchange of data across national and international boundaries and a structural and economic model to reduce patient costs. The national cervical cytology biobank will afford infrastructure for disease advocacy organizations to pursue sophisticated, novel research collaborations with academia and industry to develop new diagnostics and therapeutics to better understand and treat disease.
Global Biobanking Automation. Markets Automation - The Next Big Leap for Biorepositories
The goal of this presentation is to analyze the dynamics and trends of automation in the biobanking market and project a future outlook for the various market segments and the opportunities it offers to the OEMs and other members of the value chain. Key questions this presentation can answer include:
- Is automation within biobanks growing, how long will it continue to grow and at what rate? - Who are the existing competitors competing within several segments of automating biobanks? - What are the demands of the biobanks? - Are the competitors offering what the customer needs? - How will the structure of the market change over time? Is it ripe for acquisitions? - Are the products/services offered today meeting customer needs or is additional development needed? - Are the vendors in the space ready to go it alone, or do they need partnerships to take their business to the next level?
Improving Targeted Sample Management at Roche Diagnostics
To improve global collaboration, address the increasing number of studies and a growing stored sample collection, with attention to the cost and value of stored samples and evolving global regulatory requirements, Roche Diagnostics has undertaken a process improvement initiative for global sample management. The objectives include developing a reusable Sample Management Health Check process and enhancing Sample Management Controls for both operational and regulatory purposes to address the following:
• Sample storage space management • Sample cost, value and reusability • Global business collaboration requirements • Emerging global regulatory requirements
This quality improvement initiative will improve global sample management controls, provide more complete sample information shared across the global enterprise, better control costs, and improve the reusability of stored samples as follows:
• Improve sample storage capacity by removing samples that do not have sufficient annotated data • Require sample owners to provide a scientific, regulatory or operational rationale to store targeted blood specimens, • Improve prospective sample collection processes and protocols to collect targeted samples simultaneously for multiple new indications • Explore commercial options for acquisition of targeted blood specimens • Build an abbreviated Quality Management System (QMS) specifically for Sample Management processes to improve global standards and regulatory compliance • Improve access to clinical data elements associated with each sample (sample panel in EDC) • Improve access to constraints of informed consent.
Preparation of EBV Cell Lines
Since its creation in 1990, the goal of the Genethon DNA and Cell Bank has been to encourage advances in research in genetics by placing the high quality services of a cell and human material bank at the disposal of the scientific community. It now functions as a service provider for the scientific and medical community as a whole. Since October 1990, we have collected more than 81,459 blood specimens from 38,530 families afflicted with 420 different pathologies. We have extracted DNA from 65,942 of them, and established 36,226 lymphoblastoid B cell lines. The methodology employed by Genethon's Bank for B-lymphocyte immortalization uses standard EBV “Epstein Barr Virus” produced in the DNA Bank by B95–8 cells. The protocols include cell separation by gradient centrifugation “Ficoll” and lymphocyte growth enhancement by Cyclosporine A. As a result of having processed thousands of blood samples (more than 35,000), Genethon's Bank has been able to examine in detail the many variables which may affect transformation success: the anticoagulant used, time and volume between sample collection and processing, type of diseases, and to develop a protocol to guarantee almost complete success with transformation. This presentation will examine these variables and, by manipulating them, suggest ways to improve the success rate.
Biobanking: Why Now?
Modern medicine is trending toward early detection of disorders and personalized medicine for better diagnostics, therapy and prognosis. Innovation under this scope is mainly addressing the identification, validation and application of biomarkers with better differential power. Based on rapid technological development, biomarker research has changed tremendously. On one hand, technologies like sequencing, single cell detection, and high sensitivity mass spectrometry combined with globally accessible databases and bioinformatics offer huge opportunities. On the other hand, international cooperations disclose an urgent need for standardization and harmonization. One of the evident major challenges now, related to sample and data quality, is the increasing number of study participants required to set up sufficiently powered studies. A systematic approach is necessary for availability of bioresources. A biobanking Infrastructure usually aims to sustain an efficient and purposeful platform specifically designed to support system biology approaches, biomarker and drug discovery, and public health. To apply the currently few binding regulations on common standards, to juggle partial and individual interests, to meet requirements of quality standards in an ethical, legal environment is a big challenge. Thus, effort is required to enable modern epidemiology and biomarker pipelines. Further, a biobank should explore an economic justification, effective reporting and quantify economic and often even non-profit performance. Biobanking is now heavily relied on internationally for advancing research into a vast variety of health problems and to develop new ideas, technology and knowledge. Access to biorepositories and associated data is nowadays crucial to ongoing biomedical research.
Data Protection and Security in Support of the National Institutes of Health Genotype Tissue Expression Project (GTEx)
The NIH Genotype Tissue Expression Project (GTEx) is a 2 year pilot study to evaluate human gene expression and regulation in multiple tissues. GTEx aims to provide valuable insights into the mechanisms of gene regulation. The cancer Human Biobank (caHUB) provides the underlying infrastructural support to procure, process and distribute tissues and the associated data for the GTEx project. A critical aspect of this biobanking collaboration involves the protection of donor privacy through the security of Protected Health Information (PHI) and donor-related information. caHUB's strategy in development of a model to address these areas is multi-pronged in its approach. Discussed are the various tools and strategies utilized by caHUB in order to ensure donors and donor families that their data will be protected and shared in accordance with their wishes as represented in the relevant Informed Consent Document and study agreements.
IMIM (Hospital del Mar Medical Research Institute). MARBiobanc. Barcelona, Spain
One of the main current challenges of BioBanks in the management of surplus tissue samples obtained at hospitals during routine diagnostic workup studies is the ability to transfer this material for research purposes.
These samples were traditionally preserved in the repositories of Departments of Pathology and researchers from the hospital could use these samples without restriction. At the present time, however, ethical and legal constraints have changed this scenario and a number of requirements should be met before transfer of these samples for research.
1. ANALYSIS: To assess the functioning of the Pathology Service to be able to share surplus tissue samples repositories between the service of Pathology and the BioBank. 2. ORGANIZATION: To develop a systematic process for the request of samples to the BioBank including assessment of research protocols by the BioBank ethical and scientific committees. 3. COMMUNICATION: To develop an informative campaign in the hospital to make physicians aware of the need to obtain routinely the informed consent for research purposes. On the other hand, to inform patients attending the hospital about the structure of the BioBank and its goals, and to raise awareness on the importance of providing consent for the use of clinical data and surplus samples for research.
Analysis of results will allow assessment of the impact of the BioBank project on dynamics of patient care and research.
Information/Communication with Study Participants: the Experience of Institut Pasteur's Biobank
Since the mid 20th century, the impact of ethics on clinical research has radically increased, resulting in strict regulation of medical and research experiments on human subjects (Nuremberg Codex (1947) and the Declaration of Helsinki (8 versions from 1964 to 2008)).
Taking advantage of the experience of scientific and medical research led at Institut Pasteur, the biobanking platform ICAReB is involved in the ethical debate about information to research participants, whether healthy volunteers or patients. Here, we review the issues raised by this central concern.
In accordance with French regulation, the study organizers must give precise information to participants before obtaining their consent. The Kouchner law (March 2002) also requires the communication to the subjects (initially the patients) of all information of medical interest for them. Last, diffusion of the global scientific results at the end of a clinical study is obligatory. Most participants agree that communication of personal as well as global results is a clear benefit of their participation. However, the appropriateness of diffusing the different sorts of information and reports must be carefully examined beforehand, and not only in genomic studies.
Here we expose the various tools we have applied (mailing, web-based information, focus group…) to better inform and communicate with research participants, and give some insights on how to fulfill the societal mission of biobanks.
This communication should go beyond the passive dissemination of basic data but instead develop a mutual trust between society and research organizers.
Department of Pathology (UZG)
For several years, the Department of Pathology of the University Hospital Ghent (UZG) has been storing leftover material from tumors at −80°C. This snap-frozen tumor material allows the possibility to perform crucial molecular genetic profiling, as these analyses can often not be performed otherwise due to sample impairment from formalin fixation and paraffin embedding. The additional collection of (rare) tumor samples is the cornerstone for translational research as it opens the way for research regarding tumor development and characterization, leading to improved diagnosis and treatment. In 2007, a joint Belgian Tumor biobanking network between different partners was established. This resulted, in 2008, in the launch of the “Virtual Belgian Tumor Database”, which has as its primary goal to make tumor samples and their related (clinical) data available in order to expedite cancer research in academic, medical and industrial settings. These last 5 years, the repository of the UZG TumorBiobank has been keeping up with changing quality regulations. Only material that is handled by the UZG Pathology lab, that works according to standardized and accredited quality procedures, is accepted into the UZG TumorBiobank. Additionally, the TumorBiobank organized its own quality procedures and database with guarantied sample traceability and anonymity. Over 8000 samples have been collected. Soon, the TumorBiobank will be integrated into the Central UZG Biobank Platform, under coordination of Bimetra, the local Clinical Research Center of the University Gent and the UZG. This Central UZG Biobank Platform will institute a facility with elaborate quality management procedures, a clear ethic-legal framework and powerful data management solutions.
MolMeth - The Social Network Solution to Biobank Harmonization and Development
The Molecular Methods database (MolMeth) combines open access publishing with social networking features to create efficient workflows in the development and publishing of methods in biobanking.
In its simplest form the website can be used as an online repository for lab protocols and standard operating procedures (SOPs)., Protocols are searchable by the public and, by adding detailed technical information on MolMeth, improvements can be made without invalidating published articles describing the biobank. Readers accessing MolMeth can themselves decide if they want to read the most current version or the document used at the time of publication.
MolMeth is however more than a simple repository for information. It also offers an interface that uses social networking features to provide feedback on published documents as well as promoting collaboration and harmonization among biobanks. By inviting researchers to workgroups, scientists are able to create expert communities on matters relevant to biobanking or general research. These groups can then be used as news groups, support groups or fully fledged harmonization projects dedicated to enhance inter-biobank compatibility of samples, storage procedures or even legal requirements.
When creating such standards, the users are greatly helped by MolMeth's workbench. MolMeth's workbench provides an archiving system where each version of a draft is saved and fitted with a tool to compare different editions of the draft. Upon finalization of a project these documents can be published by normal means or turned into living documents available on the MolMeth website.
Biobanking for Research at the CHUAC: Interaction with Tissue Banking
• Possible contamination: from donor, from tissue processing, etc. • Expiration of the sample, under the provisions of applicable law.
Given these considerations, the usual practice is to thaw and discard those samples/specimens. However, these discarded samples/specimens could be a valuable source to include in biobanks for potential use in research rather than transplantation.
Different Legal Framework for Biomedical Research Conducted Only with Clinical Data or Both Clinical Data and Human Biological Samples
• Biomedical research using samples and clinical data is specifically regulated by Law 14/2007, Biomedical Research (LIBM) and Royal Decree 1716/2011, which implements part of the LIBM, and all the rules that these laws dictate. • Biomedical research only with personal and clinical data is governed essentially by the Organic Law 15/1999, Protection of Personal Data, which refers to the health legislation, i.e. Law 14/1986, General Health and law 41/2002, of patient autonomy.
In both cases it is necessary to obtain:
• Written informed consent of participants, with different content for each situation. • Authorization from the center that stores the material for research.
Large-scale Biobanking of Blood — The Importance of High-density Sample Processing Procedures
Basque Biobank for Research, Bizkaia, Spain
Biobanks are well-organized sample collections that combine genetic, clinical and lifestyle information with the mission of providing resources to understand the balance between disease and health. In this respect, the Basque Government created in 2004 the Basque Biobank for Research-OEHUN www.basquebiobank.com which was recently the first biobank in Spain to receive national operating authorization.
The Basque Biobank forms a network of 7 main hospitals of the Public Health System that covers a 2.1 million population, and has collected almost half million of samples of 300 different diagnoses. What differentiates the Basque biobank is the focus on promoting translational clinical research: “from the bench to the bedside”: To do that, the Basque Biobank:
- is a bridge between clinical and basic research, identifying needs found in the clinical setting that could be answer by basic research. - collaborates in clinical trials - ensures the highest quality of the samples though strict quality control - has a biobanking research department to improve sample processing methods and develop new tools to offer new services to the scientific community, such as BIOPOOL software: a meeting point of biobanks in the network and a search tool for sample images all over the world.
As a result, Basque Biobank in 2011 has transferred more than 4.000 samples to 26 research centers to carry out 42 projects for translational research, including development of a new patent for diagnosis in colon cancer and testing of new medical devices for prognosis and treatment.
Basque Biobank for Research, Bizkaia, Spain
Obtaining RNA from human specimens is of great interest for basic research, diagnosis, prognosis and treatment of human diseases. However RNA is a very labile molecule and therefore, the extraction and conservation procedure in the surgical room can have a profound impact on the quality of the purified nucleic acid. The objective of this study was to define a protocol that would fit the routine of surgical practice and at the same time preserve the tissue for molecular studies. For this study, we used sheep necropsy tissue and the preservative RNA stabilizer RNA later (Qiagen). We considered the following variables as important factors for the preservation of the RNA: Temperature and length of preservation in RNA later and processing of the tissue after embedding it in the preservative. First, we tried to find out if washing the tissue (2 washes of 15 minutes with PBS 1X) after retrieving it from RNA later and prior to the RNA purification step provided better RNA yields, as a user-developed protocol of Qiagen recommends. Our results revealed that this washing step resulted in the degradation of the nucleic acids. Based on this new protocol, we also established that fresh tissues preserved in RNA later for up to two weeks, either at room temperature or at 4°C, show similar quality to fresh snap-frozen tissue in the two sheep tissues tried. Our studies show that fresh samples can easily be preserved in the surgical room without compromising RNA quality or the routine of the surgical team.
Basque Biobank for Research-O+Ehun Fundación Vasca De Innovación E Investigación Sanitarias (BIOEF), Bizkaia, Spain
BIOBANC-MUR, Fundación para la Formación e Investigación Sanitarias de la Región de Murcia (FFIS), Edificio Unidad AECC-Murcia, Hospital Universitario Virgen de la Arrixaca (HUVA), Murcia, Spain
Biobanks are an essential tool for development and advancement of biomedical research. Quality research requires excellent biobanks that are established according to quality criteria. In Spain, a recently established legal norm (Real Decreto 1716/2011) provides for the implementation of a Quality Management System (QMS) as a legal requirement for a biobank. However, this rule does not establish any specific QMS, so the design of the Quality Plan for each biobank will depend on its activities, resources and above all, the involvement of biobank human resources. The implementation of a Quality Management System allows optimization of the biobank activities, making the organization function effectively, and enhancing customer satisfaction. Nowadays there is no specific standard for the management of biobanks, so that those who decide to implement a Quality Management System are choosing the international standard ISO 9001:2008, which is applicable to any organization that focuses its processes to the users' satisfaction and to achieve continuous improvement. Establishing a Quality Management System specific for biobanks is necessary to ensure excellence of these institutions and make them competitive both nationally and internationally. Evidences of concern for QMS are found in the publications and documents of significant national and international biobanks, working for the establishment of quality criteria to be fulfilled by a biobank in the technical, ethical, economic, human resources and public service areas.
Arizona Biospecimen Locator
Acquiring quality biospecimens is one of the largest obstacles researchers face as they strive to advance medical science and improve patient care. The Arizona Biomedical Research Commission (ABRC), under the direction of the Arizona Department of Health Services (ADHS), has established an innovative approach working with a newly formed Arizona Biospecimen Consortium, comprised of scientific, legal and research representatives from healthcare institutions with biospecimen banks. This consortium worked with an IT vendor, 5AM Solutions, to develop the Arizona Biospecimen Locator (ABL), a centralized, web-based biospecimen database which allows researchers worldwide to browse, query and request biospecimens stored in physical repositories at member Arizona hospitals and research facilities. The ABL system displays information for researchers to locate biospecimens suitable for their research, including disease, type of specimen, preservation type, anatomic source, and demographics of participants.
Underpinning the ABL system is the goal of creating approaches that encourage state-wide collaboration across tissue banks. These approaches address key aspects of managing and ensuring quality of biospecimens for the research community, including a common annotated dataset, a standardized material transfer agreement, a collaborative scientific review process, and shared standards on collection and storage protocols. Benefiting from the diverse population in and around Phoenix, which includes children, the elderly, Hispanic Americans, and Native Americans, the ABL expands the visibility, quality, quantity, and population coverage of biospecimens to the research community, increasing research collaborations and accelerating the progress of research.
Center for Medical Innovation, Heverlee, Belgium
Translational biomedical innovation refers to the research and development of new preventive, diagnostic or therapeutic applications in a patient-centered environment. Through this kind of research, strategic basic research is linked to clinical research, from bench to bedside and vice-versa. The Flemish government initiated the Center for Medical Innovation (CMI) in order to integrate and facilitate harmonization between all stakeholders in Flanders. The mission of CMI is to support a faster and more efficient translation of research findings. It was conceived as a single virtual platform, linking Flemish Clinical Research Centers (CRC - Antwerp-Brussels-Ghent-Hasselt-Leuven), and functioning as an interface with international translational biomedical research. The establishment of a relevant ethical and legal framework is a known challenge especially at the international level but also at national, regional and even institutional levels. Moreover, the implementation of existing guidelines and instruments for data and samples, such as the EU Data Protection Directive (Directive 95/46/EC), varies, thereby hampering collaboration and exchange of information and samples. Therefore, the coordinators of the Flemish CRCs prepared an ethical-legal framework based on existing guidelines and instruments. An interdisciplinary expert group was established to reflect on this proposal and a stakeholder meeting was organized at the national level to validate the framework. The report generated following this validation was adopted as the ethical and legal framework within the CRCs and presented to other Belgian national – regional biobanking initiatives. This multidisciplinary research collaboration model will create a decision-supporting framework for innovation policies with both economic developments and social benefits.
Traceability and Safety in a Cancer Blood and Tissue Biobank
The cancer biobank of the National Cancer Institute, Aviano (Italy) (CRO-Biobank) aims to collect human blood and tissue samples for research purposes. The collection comprises more than 30,000 samples from cancer patients and healthy individuals. Sample and personal data are managed by software which employs scanners and readers for the identification and localization of collection tubes marked with a unique bidimensional code. This software is integrated with an external registry platform, safeguarding privacy upon encoding of the patient's personal data. All the IT (Information Technology) systems are protected by personal passwords to guarantee both the traceability of samples and the privacy of donors. In cases where an IT security is not possible, all documents and records of traceability are signed and held sub key. The storage room is provided with a fingerprint recognition system to protect access and with an apparatus that ensures safe oxygen levels while storing in liquid hydrogen. This room is equipped with a wireless temperature monitoring system which allows recording the temperature of each freezer for years. It is integrated with the alarm system of the Institute to ensure rapid sample transfers to backup freezers in case of temperature increases. The entire process is based on Quality standards in order to guarantee the homogeneity of storage conditions and long-term stability of samples. In conclusion, our biobanking process is implemented to guarantee the safety of the operators, the privacy of the patients and the traceability and quality of samples.
Tissue Processing and Quality Controls in a Cancer Biobank
Many factors might reduce the quality of the tissue samples stored in a Biobank: environmental factors (like contamination, humidity, and temperature), materials, human factors, methods, and instruments. All these parameters have to be monitored and analyzed in order to reduce the potential negative effects that might impair the quality of samples. Since its foundation in 2007, The cancer biobank of the National Cancer Institute, Aviano (Italy) (CRO-Biobank) has developed Quality Control procedures for the OCT Optimal Cutting Temperature (OCT) tissue-embedding process to achieve optimal freezing and to prevent hot and cold tissue ischemia. Morphological studies by H&E staining of tissue sections, immunohistochemistry and biomolecular tests including DNA, RNA and Protein analyses are routinely performed with positive quality control results. Accuracy of pertinent analyses derived from previous experiences with the tissues stored in the Department of Pathology of CRO during the last 25 years. Aliquoting stored tissues is another useful option we have implemented by frozen sample sectioning, which permits (i) making samples available for many studies; (ii) establishing the histological percentage of necrotic/fibrotic areas, (iii) testing the consistency of biomolecular analyses from multiple cryostat sections of the same tissue block obtained at different times and levels; (iv) performing studies on micro-dissected selected targets from frozen sections; (v) optimizing the use of biological material and (vi) warranting the reliability and reproducibility of experimental researches.
Furthermore, we are evaluating a novel tissue preservative that allows good morphology for histological diagnosis, optimal feasibility of molecular analysis, including phosphoproteomics, and biobanking. Our first results suggest that this tissue preservative might in future substitute for formalin for any purposes, possibly replacing frozen procedures for biobanking.
Introduction of Culture Collection of Antimicrobial Resistant Microbes
Treatment for disease caused by antimicrobial resistant microbes has emerged as a critical issue worldwide. The abuse of antimicrobials in human as well as agricultural products in Korea has led to a high rate of occurrence of antimicrobial resistant microbes. Drug resistance is easily transferred from one resistant species to another related one in many ways. There is a demand for communication and cooperation among researchers in diverse fields in order to solve the resistance to antimicrobials. Culture Collection of Antimicrobial Resistant Microbes (CCARM) was established in 1999 by Prof. Yeonhee Lee who served as the first director, with support from the National Research Foundation of Korea, an affiliate organization of Korea's Ministry of Education, Science and Technology. We collect antimicrobial resistant microbes from humans, animals and environmental fields, either directly or taking deposits from researchers. We identify, classify and store them according to their origins, species and antimicrobial-resistance mechanisms. To date, CCARM has a collection of over 20,000 strains of bacteria and yeast from 100 genera. We provide antimicrobial resistant microbes with known mechanisms of antimicrobial resistance information. CCARM has been a member of the Clinical Laboratory Standards Institute since 2000, the World Federation for Culture Collection & World Data Center for Microorganisms since 2003, the International Society of Biological and Environmental Repositories since 2007, the Korea National Research Resource Center since 2008, and Biological Repositories since 2009. We expect to progress further by introducing operation and management techniques which come from domestic and international networks of biological resource centers.
How to Prove that your Biobank is 100% Correct
Samples in a biobank must be stored and retrieved for decennia. At some moment, and that can be 20 years from now, you must be able to prove that an individual sample is indeed the right sample: from a certain person, handled by the right procedure, and stored according to the right conditions. The value of samples depends on this proof, but not according to current rather lax norms, but by the more rigorous standards of 2032. What are those standards? Based on well-established proving methods in philosophy and mathematics we can determine now the proving requirements of a Biobank system. We need in any case three kind of subsystems: an operational system, a control system, and a supervisor system.
A good operational system improves on current systems by storing samples in a database, and not in Excel, helps; the database contains software to prevent and detect human errors, using automatic readable labels, like barcodes. It is, however, by far, insufficient for your future proof. You need control system checks that only the agreed protocols are followed by authorized Laboratory Personnel. And you need a supervisor system that prevents and detects disturbances. It detects changes to the Biobank system and any bypassing by users or ICT personnel of the agreed protocols and safeguards. We will provide examples of well-meant bypassing of procedures and systems by ICT capable people. We give examples of common errors in the architecture of Biobank management systems, errors that later are impossible to correct.
Centro Superior de Investigación en Salud Pública (CSISP)
The Valencian Biobank Network (RVB) has unified the skills of codification in order to attend to the necessities of integration of its own Biobank Data Management System (BDMS). With this study, we report the definition of a subset of terms referred to the activity of biobanks. The first steps we performed were based on the SNOMED CT codification of the preanalytical variables defined by the SPREC code terminology. The SNOMED CT codification guarantees the decodification and interpretation of the SPREC codes which do not become compromised by the limitations found in the system. Once these objectives were reached, and based on the necessities of interoperability of our BDMS, we also coded terms related to the legal-administrative field and to the information associated with the samples. As expected, the mapping of the variables based on SNOMED CT was not always possible. For these cases we have designed a series of algorithms in order to generate a local extension of codes. Currently, the RVB is still working on the generation of a list of terms of the biobanking activity within the context of SNOMED CT criteria. In addition, the functionality of such a subset of terms is being examined for semantic interoperability with different information management systems devoted to the mental health, reference population and pathological fields.
This study is financed by the grants RD09/0076/0058 and RD09/0076/00163 from the Instituto de Salud Carlos III, Madrid, Spain.
Adding Value to your Biobank
Cancer is a heterogeneous disease and treatment targeting in the future will require knowledge of inter- and intra-tumor variability with respect to tumor type and individual patients to be able to best target expensive diagnostic tests and treatment. The biospecimens stored within biobanks are of considerable value in the identification of links between common oncogene mutations with differing clinical presentation phenotypes and outcomes. The Wales Cancer Bank is aiming to add significant value to collected tissue samples by submitting them for molecular characterization. Funding to characterize 950 samples has been gained and an application to test a further 2000 samples is awaiting decision. Results for the first 119 colorectal cases are currently available, with a further 200 expected by November. Initial results showed that a higher proportion of cases were positive for Braf mutation than previously reported[1] and in three cases where multiple blocks were tested there were additional changes in p53 sequence in the second block. In one case a PIK3Ca mutation was found in one block but not the other suggesting a degree of tumor heterogeneity and highlighting the importance of complete and accurate sample annotation so that results are correlated to the block from which they were generated. Results from this characterisation will allow construction of tissue micro-arrays by molecular as well as pathological information and it is hoped that it will encourage research groups to ask more targeted, intelligent research questions when requesting samples.
Laboratory for Surgical Research, Department of Surgery, University of Lübeck & University Medical Center Lübeck, Lübeck, Germany
Certification of Biobanks: Adaption of the DIN EN ISO 9001:2008 Norm to Implement a Quality Management System for the North German Tumorbank of Colorectal Cancer
Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Spain
Pulmonary Biobank Consortium CIBERES (PBP) is a non-profit network of 10 hospital biorepositories to promote biomedical research, through improving the diagnosis and treatment in respiratory diseases by collecting and distribution of samples to national and international researchers.
Since 2009, it has registered lung tissue and peripheral blood samples from more than 1,000 patients who underwent lung surgery for therapeutic reasons. Systematically, samples were obtained and processed following consensus standard operation protocols (SOPs) and controlling the lung ischemia time. All samples are registered on a common database accessible via WEB, along with relevant respiratory clinical data and CT scans. This strategy allows real-time coordinated management of the activity and effective response to researcher requests.
Focusing on the demanding quality requirements of current biotechnology, the Quality Management System of PBP has been established according to the International Organization for Standardization. Since January 2012, PBP has been certified according to ISO 9001:2008 in order to ensure that its management and samples are reliable and of good quality, meet research's requirements and that this system is consistently improving.
Working under a quality management system allows detecting weakness of the system and areas for improvement, as well as helping to establish procedures to face the new requirements for research. Difficulties inherent to multicenter network have been solved by adapting innovative technology. Moreover, the constant control of the system allows detecting and solving upcoming challenges, becoming a robust and dynamic infrastructure.
Institut Bergonié, Bordeaux, France
Because of the exponential increase in the number of DNA and RNA samples to be stored, classical preservation in freezers, always subject to risks of technical failure or natural disasters, is becoming more and more cumbersome and costly in energy and maintenance. In this context, room temperature storage of DNA and RNA samples presents real economical and ecological advantages, while being compatible with the high throughput and traceability for sample management of biobanks and bio-resources centers.
Water, oxygen and atmospheric ozone are involved in the degradation of nucleic acids. A thorough dehydration slows down RNA and DNA degradation and additives may add to their stability. However, air exposure of dehydrated nucleic acids accelerates degradation rates and, for DNA, leads to aggregation. Therefore, full protection from air is essential, but standard laboratory vessels are unable to protect samples from air exposure. In contrast, in our procedure, samples can be maintained under an anoxic and anhydrous environment in small glass vials fitted in stainless-steel, laser-sealed capsules. These minicapsules are tamper-proof and have a unique engraved data matrix code allowing complete and unalterable traceability of the samples. We conducted accelerated aging studies that enabled mathematical prediction of the nucleic acids' behaviour in these storage conditions. Degradation was also monitored at room temperature over several years. Our results showed that after long term storage in the minicapsules, nucleic acids can be quantitatively recovered in a form compatible with any downstream analysis and manipulation. The minicapsules are therefore an innovative tool for improved sample management.
TMF – Technology, Methods, and Infrastructure for Networked Medical Research, Berlin, Germany
As medical research using human biospecimens becomes increasingly collaborative in Europe, questions as to the legal, organizational and technical framework for biobanking require more and more harmonization of national specifications with issues from foreign countries. To ensure legal certainty for researchers the biobanking working-group (BMB-WG) of the TMF has set out to develop legal opinions, specimen transfer contracts, quality assurance checklists and model guidelines for the development, operation and management of biobanks, data protection concepts and informed consent declarations. The solutions and generic concepts are firmly anchored in the German legislation, and data protection and ethics are widely used by the biobanking community; these provide starting points for international cooperation.
The BMB-WG was installed in 2004, as one of several activities of the non-profit organization TMF - Technology, Methods, and Infrastructure for Networked Medical Research e. V. TMF receives funding from the ministries of Education and Research (BMBF), Health (BMG), Economics and Technology (BMWi), and the German Research Council (DFG). TMF represents a scientific umbrella organization for more than 80 members from academic medical research institutions, and aims at improving the organization and infrastructure for networked medical research, i.e. clinical, epidemiological and translational research. It serves as a platform for interdisciplinary exchange as well as cross-project and cross-location cooperation to identify and solve legal/ethical and technological/organizational problems of state-of-the-art medical research. Solutions range from expert opinions, generic concepts, and IT applications to checklists, practical guides, training, and consultation services, which are available to the public free of charge.
Transfer of Collections of Human Samples to Biobank HUMV – IFIMAV. Optimization of the Quality of DNA Samples for Inclusion as Characteristic of Biobank Collections
The DNA and fluids Node of the HUMV-IFIMAV Biobank was created in 2009, one of its objectives being to host and manage collections of samples from Marqués de Valdecilla Hospital researchers. Since then, the biobank has incorporated DNA collections from different diseases. To do this, the collections have to meet three criteria: scientific, ethical and sample quality.
Samples of each collection that met the first two criteria were analyzed to evaluate the quality parameters. In a first step, concentration, volume and the 260/280 and 260/230 ratios were assessed. Some DNA samples showed optimal concentrations and volumes but the ratios were altered, whereas others showing good quality parameters had low concentrations. To define the processes that should be carried out in the samples prior to inclusion, an algorithm was established. High concentration or/and high volume DNA samples with low quality parameters were re-extracted with a DNA purification kit and most of these samples were then included.
Finally, samples with optimal concentration and purity underwent a second quality control to determine DNA integrity and functionality.
The strict application of these criteria in all the collections transferred to the biobank has yielded homogeneous collections from heterogeneous ones.
Introduction of the Pathogen Resource Management System
The National Culture collection for Pathogens (NCCP) has isolated bacteria, virus, and fungi from domestic patient specimens in Korea and manages the pathogens, their distribution, donation, and quality control. A systematic management of pathogen resource information, named the Pathogen Information Management System (PIMS), has been constructed and operated.
PIMS can be divided into enrollment, retention, distribution, and quality management. Resources are classified depending on the type of resource information into 13 categories including the kind of resource, quantity, kind of specimens, and date etc. and 11 items of isolation information, such as isolation regions, isolation date, and the separator etc. and 5 items of attribute information based on biological characteristics, 55 of antibiotic information, 18 of clinical information on hospitalized patients, 11 of mechanics, and more than 113 of information on the pathogen are maintained in the registry. After registration of the resource conservation process, a 2D-barcode system in PIMS specifies the location information and storage of the resource depending on the kind of conservation, resource numbers, production numbers, and each kind of information is preserved in the record.
The resource management functions are divided from registration of resources and quality control regularly. Quality control items include culture, biochemical analysis, and nucleic acid sequence. In particular, regular timed checks of the target resource can be built into the alarm system, as well as the list of target resources in the system to be checked automatically for quality control. Distribution of pathogens in the management system is also a controlled application; an applicant can find a breakdown of historical information, details of application resources and entries of applicants into the database are maintained.
In the future, PIMS extension to the total portal site will include expanding the database to provide statistics, preservation and resource information.
Hospital-Integrated Biobanking - When Gates are Opened to the Freeway of Biobank Sample Collection
Uppsala Biobank started a hospital-integrated biobank in the spring of 2010.Through the hospital integrated biobanking it is now easy for researchers to collect, and store samples without using their own staff. It's simple, efficient, safe, qualitative, and a new collection can start within a week.
In order to start collecting samples, the researcher contacts Uppsala Biobank. The first step is to make sure that there is an approval from the ethical committee to collect samples and store information about them in an electronic system (Biobank LIMS). The second step is to ensure that the correct IT freeways will be accessed for the specific clinic and their staff. With these two issues solved, the researcher can order samples for biobanking in the common hospital journal system, just like any other analysis.
The blood samples are taken by a nurse at the clinic and later processed at Clinical Chemistry and Pharmacology using robotic equipment. Serum or plasma from one primary tube is aliquoted in 2D bar-coded micro tubes, which are stored in low temperature freezers in Uppsala Biobanks storage facility.
Researchers and staff at the hospital and university have reacted positively to the biobank service offered. The major questions regard the unknown aspects of how analytes are affected in the sample collection process; therefore Uppsala Biobank welcomes researchers performing “pilot studies” before starting a large scale sample collection. The results of pilot studies help Uppsala Biobank to strengthen the process, and everyone becomes a winner.
Challenges Associated with Coordinating Multi-site Collection and Single Dispatches from a Multisite Tissue Bank
The trend towards the development of biobanking networks involving multiple sites is driven by advantages such as higher collection rates, access to larger numbers of rare specimens and greater access to a broader range of population cohorts. Benefits to researchers are maximized where networks also implement a centrally coordinated application process. The Victorian Cancer Biobank, a consortium of tissue banks has implemented a centralized application process that streamlines researcher access to the general archival inventory and clinically related research support.
To ensure that uniform high quality of specimens is available from all consortium member sites the collection of specimens, for our inventory of tissue and blood products as well as for project-specific collection and clinical trial support, is performed by scientists whose expertise is harmonized by SOPs and regular, centrally-managed training within the guidance of international best practice.
To support project-specific research and clinical trials the VCB offers the service of processing blood and collecting tissue according to study-specific protocols. This requires a centralized liaison point with an understanding of the project requirements. However, for multi-site trials it is important that the researcher can also liaise with tissue bank managers at each collection site to understand local issues associated with handling their specimens.
Operational challenges associated with coordinating collection and processing across the consortium, as well as ensuring that all specimens are delivered with all relevant clinical and QC data in a single package, will be presented.
Integration of a Biobank in the Circuits of a Hospital to Improve Procedures for the Identification, Acquisition and Management of Bioresources for Research
The Hospital Universitario San Cecilio (HUSC) has extensive research experience, with commitment to translational research integrating basic and clinical information to improve the transfer of results to patients. To support and promote research, HUSC has created structures that involve diverse professionals from all the hospital areas.
A representative structure is the Tumor Bank, a unit of RBTA. The success of this model led to export it to other Biobanks, in order to include other types of samples. The existing biorepositories are pursuing further harmonization of procedures and management.
The basis for our success is that the circuits for the donation, procurement, and input of samples and associated data to the biobank, is integration with clinical hospital care information. We identified circuits for samples for healthcare activity (origin and destination), personnel involved (clinicians, surgeons, orderlies.…), material resources and infrastructure available, and associated information sources (LIS, HIS,…). All items that are relevant to samples and data for healthcare are common to the elements necessary for the entry of bioresources to the biobank, so integration only required development of protocols with point adaptations. The implementation of these circuits allows the entrance of the vast majority of samples that are candidates for a biobank, since both the samples and associated information can be requested and sent from any hospital source (queries, extraction room, hospital rooms, surgeries, peripheral centers…), ensuring quality and traceability. That facilitates the communication protocols between computer systems of all services and laboratories of the hospital. All this is possible with a minimum additional investment.
At present, the HUSC Biobank is part of BBSSPA, and also part of RNBB through the RETICS program of ISCIII, and during its two years of operation has been successfully integrated as a unit within the hospital to manage all samples for research
HUSC: Hospital Universitario San Cecilio. RBTA: Tumour Bank Network of Andalusia BB SSPA: Biobank Andalusian Public Health System RNBB: National Network of Biobanks ISCIII: Instituto de Salud Carlos III RETIC: Thematic collaborative research network.
Link between RetePath and Bioebank: A Way to Empower Our Samples
Nowadays it is becoming important not just to have well-preserved biological samples but also to have the associated clinical data, to facilitate research.
In our institution, Biobanco del Hospital Universitario Virgen de la Victoria, we have the opportunity to use in concert two different applications: RetePath, which allows us to collect in a continuous, methodical and thorough way, clinical data including follow-up, and pathological data on characteristics of the tumors from patients of our hospital; and Bioebank, which includes the traceability of the samples.
Here we described the potential of the link between them, exemplified in colon tumor samples collected from 2006 to 2008.
Research Ethics in Latin-America: The Main Challenges
Research ethics in Latin American countries face great common challenges in areas such as guidance, committees and institutional bodies; there are elements intending to promote ethical standards in clinical research at national and regional levels. Biobanking internal regulations are attempting to achieve integral frameworks which protect research participants and promote regional cooperation involving biobanking. Scientific development and economic goals need to be more balanced in this respect.
The recently increased work of the international community is resulting in the incorporation of international standards by Latin-American countries, questioning traditional ways to solve conflicts between international and internal rules. Although most of countries share the same legal system, the incorporation of international rules varies with each country. It is difficult to envisage common frameworks, similar to those encouraged by European countries, as regional cooperation instruments in terms of research ethics in biobanking. Economic disparities are still a great obstacle. In order to increase unification possibilities and solutions for common ethical issues, it is necessary to identify the main reasons why current frameworks have not been completely effective.
Development and Implementation in a Network Biobank of Request Management Processes for Distribution of Bioresources for Research
Biobanks are guarantors for obtaining and processing samples for research, which involves an adequate bioresource request management. To coordinate this activity, the Andalusian Public Health System Biobank, organized as a network biobank, has the problems of a single-center biobank and additional issues derived from its organization with 31 different nodes. Andalusia is one of the largest communities and has different foundations (4), public institutions and technology transfer offices, which manage the different nodes of the Biobank. This diversity makes some aspects more complicated in relation to request management in the Biobank, such as material transfer agreements, signing of cooperation agreements or charge backs.
We organized a working group for the development of the Request Management Processes. Previous to this work, biobanks have responded to some requests but there was not a common process or requests registry.
Through reviews of legal, ethical and institutional specific requirements, analysis of received request complexities and the documentation necessary for the process, a consensus emerged for two processes: “Requests reception, analysis and organization” and “Request execution, distribution and monitoring”. Processes implementation has been carried out by six nodes, achieving 67 handled requests with a total of 3950 distributed bioresources up to May of 2012.
These processes make possible bioresources request management in different nodes of the Biobank as a “single window”, creating a unique database of handled requests. In this way, researchers can obtain biobank bioresources derived from several nodes through only one request independent of their location.
Department of Health Sciences, University of Leicester
BIOSPECIMEN RESEARCH (BR)
Department of Haematology, Oncology and Molecular Medicine
The project for institution of the Italian hub of population biobanks (HIBP) includes, in addition to other activities, the setting of a pilot study; it aims to demonstrate that synergism among available and already collected data is useful to address scientific questions on preventive and/or predictive medicine.
Participants in the pilot study of the HIBP Project, namely Coordination ISS- Units, Informatics Unit-ISS, EURAC-biobank (MICROS-study), C.I.G-Biobank (GEHA-project), CNESPS biobank (FINE, MATISS, MONICA, OEC1998 collections, Italian Twin Register, and IPREA projects), MOLI-BANK (Moli-Sani project), first established the necessary steps to initiate the pilot, such as:
- Discussion on scientific question to be addressed; - Definition of required data; - Preliminary verification of the ethical issues; - Drafting of Data Transfer Agreement (DTA); - Setup of dataset; - File data upload; - Data harmonization; - Data Statistical analysis; - Dissemination of results.
Following an intensive preparatory phase, the network determined to assess correlation between lipidemic profile and geographical provenance of subjects enrolled in the studies participating in the pilot. Demographic data, physical and hematochemical parameters were identified and shared in the HIBP pilot.
The DTA, stating data definition, modality for sharing and analysis of data, time range for data to be included, intellectual properties and results dissemination, was signed by representatives of biobanks and collections. The biobanks data were uploaded into a common database using a dedicated informatics infrastructure. Harmonization of collected data was completed. In this study methodology to perform each step and preliminary results will be presented and discussed.
Controlled Analysis of Preanalytical Variables in Clinical Blood Sample Collection, Processing and Storage
Blood sample collection, processing, handling and storage protocols are based mainly on accepted practices rather than careful comparative analysis and testing. We set out, therefore, to examine variables intrinsic to each step in the process of obtaining and storing clinical samples, beginning with collection of samples from healthy subjects and cancer patients in controlled studies. Various tube types were tested including EDTA, heparin, serum and protease inhibitors. Various times on bench and temperatures of incubation were compared, before and after centrifugation of the blood. The effects of freeze-thaw cycles and time in freezer were also examined. Sample analysis has been performed by high resolution mass spectrometry, leading to the identification of specific proteins that are affected by the various parameters tested. While different blood collection tubes can be used with reproducible results, there is a marked difference in the protein content obtained from each type. Freeze thaw cycles affect only a few specific proteins and only after multiple cycles. A multiplexed assay is currently being assembled for the analysis of stored samples in order to determine sample integrity and utility for use in clinical research.
Supported by NCI contract HHSN261200800001E
LPCE Biobank and Biobank PACA, University of Nice Sophia Antipolis, France
Department of Pathology, Josephine Nefkens Institute, Erasmus MC, Rotterdam, The Netherlands
Tissue banking research has resulted in guidelines on how to procure tissue samples in such a way that high quality RNA (RIN value 6.5 or higher), considered the least stable tissue derivative, can be obtained from those samples. Still many uncertainties remain on tissue handling and its effects on RNA integrity, especially the influence of pre-analytical factors. For the European FP7 project SPIDIA, gene expression was investigated in the pre-acquisition phase as well as RNA integrity in the acquisition phase; the pre-analytical phase, the acquisition phase and years of storage were studied for effects on RNA integrity.
Human gene expression arrays were performed to explore the influence of warm and cold ischemia on liver-derived RNA. The effects of sample size, transport method and time and freezing method on RNA integrity were monitored (Agilent Bioanalyzer RIN measurement) by use of pig tissues (liver and spleen). RNA integrity after short (1 year) - and long term (>20 years) liquid nitrogen and −80°C storage was measured in various human tissue types, as part of standard biobank quality control.
Warm ischemia has considerable impact on gene expression, but only on 3% of 45,000 measured genes, whereas during 6 hours of cold ischemia RNA expression is, apart from patient variation, stable. RNA also appeared stable regardless of sample size, transport- or freezing method. Storage temperatures of −80°C are sufficient to store tissue for at least 20 years.
In conclusion, it seems that RNA of acceptable integrity can be derived from tissue that was, according to current standard operating procedures, procured sub-optimally. The SPIDIA consortium is currently developing qRT-PCR assays to perform in depth RNA quality control studies on the above described samples. Hereby we aim to provide more general conclusions on tissue procurement and RNA quality.
Fraunhofer-Institute for Biomedical Engineering IBMT, St. Ingbert, Germany
Over the past decades, human biomonitoring (HBM) became increasingly important in support of chemical regulation, e.g., the European regulation on chemicals REACH. Samples stored in biobanks are increasingly used for chemical risk assessment and the evaluation of risk reduction measures. The German Environmental Specimen Bank (ESB) has collected, stored, and analyzed human samples since the 1980s. Every year, the German ESB generates important information on internal exposures of humans by initial real time monitoring. Moreover, cryopreservation of samples allows for rapid access to samples collected over decades for retrospective analyses and trend evaluation. National and European authorities can use these data for risk assessment of chemicals which are or will be of public health concern. To elucidate human exposure to chemicals and other pollutants, Fraunhofer-IBMT collects whole blood, plasma and 24 h-urine samples of young adults on an annual basis in four German cities on behalf of the Federal Environment Agency. Medical history, socio-demographic data, exposure-relevant behavior and events are documented for each participant via standardized questionnaires. All processes are conducted following ESB-specific standardized operation procedures according to Good Clinical Laboratory Practice. Latest results document the success of regulatory efforts to reduce human exposure to, e.g., hexachlorobenzene, polychlorinated biphenyls, and phthalates like DEHP. In contrast, ESB data indicate an increase of other phthalates, e.g., DINP, used to replace those classified as reproductive toxicants. Thus, the German ESB supports competent authorities in the assessment of chemicals and provides vital information on human exposures to emerging substances of regulatory concern.
Department of General Medicine
Human Biological Materials (HBMs) are an invaluable resource in biomedical research.
BioKryo GmbH, Sulzbach/Saar, Germany
In cases of secondary hyperparathyroidism, cryopreservation of the parathyroid glands may be necessary to provide the patient a possibility of later autotransplant of the parathyroid glands. This cryopreservation and cryostorage of parathyroid glands had been done so far by the clinicians themselves. Due to the small number of cases and the low required standards, the hospital investment in providing necessary equipment was poor in some cases.
The aim of this project was the evaluation of a new combination of a cryopreservation method with a transporting process. The intention was to facilitate the process of cryopreservation in the hospital and to store the tissue in a GMP-conforming facility. Furthermore, the tissue vitality and functionality can be kept on a high level to optimize the effects of autotransplantation for the patient. By providing standards in the cryopreservation process and by providing necessary equipment, hospitals were able to fulfill the Good Storing Practice (GSP) and to reduce process costs. At the central facility, a new standard of storing this tissue had been introduced, which enables a closed cooling chain and automated data collection as well as storage of the tissue. Establishing tests for vitality of parathyroid tissue will give us the opportunity to improve the fitness of parathyroid cells by adapting the process to new cryomedia.
Nephrology, Radboud University Nijmegen Medical Centre, The Netherlands
Chromosome Numbers and Genome Size of Lygeum spartum L
The Lygeum is a monospecific gender of the Poaceae family, represented by the perennial Lygeum spartum L. This kind of distribution in the Mediterranean basin has a double role, ecological in the fight against desertification and sand dune stabilization and economic, in manufacture of paper pulp making and basketry. On the cytogenetic side this species has been poorly studied. Preliminary observations on two Algerian samples have revealed the existence of two very different chromosome numbers: 2n=16 and 2n=40. One of the populations studied is located on the coast of Oran (Algeria), in a semi-arid climate and a clay muddy soil (2n=40) and the second in the highlands of south-west Oran in the region of El-Kheiter in an arid climate and sandy soil (2n=16). The cytotype with 2n=40 has already been reported in Spain and Egypt, while the one with 2n=16 has been so far only in Algeria. We expanded the study of Lygeum spartum to a larger number of populations from Algeria, Spain, Italy and Greece. Given the presence of two very different basic chromosome numbers (n=8 and n=10) in the populations studied, it would be reasonable to expect the existence of two species. The conventional cytogenetic studies were complemented by genome size determinations.
Integrative Tissue Microarray and Biochemical Studies for Functional Validation of Novel Regulators of Breast Cancer Progression to Metastasis
Interference of the Optimal Cutting Temperature (OCT) in the Extraction of RNA and DNA from Sections of Frozen Tissue
The biomedicine research area of the Andalusian Public Health System Biobank (BB SSPA) obtains, processes, stores and distributes quality biological samples for use in research projects. The coordinating node of the Biobank has opted for the QIAGEN QIAcube robot based on an advanced fully automated technology that uses columns of silica- membrane for the extraction of RNA. Using the AllPrep DNA/RNA Micro commercial kit, we extract RNA and DNA simultaneously from frozen tissue preserved in OCT, a specific compound to preserve ultracellular structures. DNA samples were obtained with good integrity; however, following the protocol offered by QIAGEN, it was not possible to obtain RNA. When the samples were pre-washed with PBS to remove the OCT, RNA obtained. In conclusion we observed that OCT interfered with the RNA extraction kit used in this work.
Optimization of DNA Extraction from Frozen Tissue Conserved in Optimal Cutting Temperature (OCT)
One of the objectives of the Andalusian Public Health System Biobank Coordination Node is the continuous improvement of nucleic acid extraction methods to obtain maximum quantity and quality of nucleic acid to be supplied to applicant researchers. It's possible to find different commercial methods for nucleic acid extraction from frozen tissue preserved in Optimal Cutting Temperature (OCT), a compound commonly used for ultracellular structures and nucleic acids preservation. Some authors describe the good quality of DNA obtained from frozen tissue preserved in OCT, while other authors claim the inhibitory effect for PCR observed in DNA purified from OCT blocks.
In this work we have optimized DNA extraction using a magnetic beads automated kit (Chemagic DNA Tissue Kit Special, Chemagen). We showed how introducing slight modifications in the extraction procedure improved the quantity of DNA that is obtained. We have tested proteinase K at multiple timed treatments – 1, 4 (treatment time recommended in the kit), 6 hours and O/N treatment. The results obtained were compared with a column based technology kit (QIAamp DNA minikit, Qiagen). DNA yield was analyzed by spectrophotometry. A qPCR analysis was performed to check the possible interference of the OCT and magnetic beads remains in the eluted DNA. The DNA yield obtained was optimum using the O/N treatment with Chemagen method. The lower DNA yield was obtained with the Qiagen kit. In conclusion, the proteinase K O/N treatment is considered the choice method for tissue samples conserved in OCT.
Optimized Treatment of Heparinized Blood Fractions to Make Them Suitable for Analysis
It has been known for decades that many cytokines (IL-2, IL-6, IL-12 etc) bind to heparin. Even though some Enzyme Linked ImmunoSorbent Assays (ELISA) use antibodies recognizing epitopes not affected by this binding, this is not always the case making ELISA manufacturers advert that heparinized plasma or serum fractions containing more than 3IU (international units)/ml of heparin should not be used in the assay. In addition, nucleic acid amplifications from heparinized samples have been shown defective by several research groups. The aim of this study was to determine if the degradation and/or removal of heparin from heparinized blood samples could convert heparinized fractions into samples appropriate for cytokine ELISA and RT-PCR analysis. For that purpose a colorimetric reporter assay based on the metachromatic effect of the binding of heparin to toluidine blue has been developed. This spectrophotometricly sensitive assay was used to determine the optimal conditions for the removal of heparin by enzymatic treatment (heparinases I, II and III) or by adsorption to ecteola cellulose. Optimal treatments were applied to a collection of frozen plasmas and RNA preps derived from blood that had been collected in heparin tubes and then respectively assayed. Preliminary results indicate that some of these treatments could make these heparinized, otherwise unuseful, blood-derived collections suitable for analysis by C4a ELISA and RT-PCR methods.
Analysis of Quality Indicators in DNA Samples Obtained from Different Types of Biological Samples for the Consolidation of DNA Isolation Service in the Biobank of the Andalusian Public Health System
The development of molecular biology techniques has accelerated research on genetic determinants of disease and interactions between them and environmental, lifestyle and/or social factors. However, this progress would not have been possible without high-quality biological samples and associated information of a large number of individuals. Biobanks act as a support infrastructure for the scientific community by providing biological samples, so it must have methods for their preparation to ensure their integrity and long-term functionality for the broadest type of test. Quality indicators determine the usefulness and quality of the samples, being in the case of DNA, the purity and integrity analysis.
This work analyzes the quality indicators in DNA samples derived from human blood, saliva, cells, frozen tissue in OCT (optimal cutting temperature) and FFPE tissue. DNA samples were obtained by the magnetic beads based extraction method selected in the Biobank of the Andalusian Public Health System. The goal is to have a balance between the availability and usefulness of the original sample in the target study and the quantity and quality of DNA obtained. The result of this balance will determine the choice made by researchers of the genomic DNA source that which is most appropriate according to the subsequent application of the DNA samples.
Laboratory of Molecular Biology and Biobank, Fundacion Instituto Valenciano de Oncologia, Valencia, Spain
This study is financed by the grants FIS PI10/01206, FI11/00505 and RD09/0076/00163 from the Instituto de Salud Carlos III, Madrid; ACOMP12/029, Generalitat Valenciana; and Astra Zeneca, Spain.
Biobank, INCLIVA Institute of Health Research, Valencia, Spain
MicroRNAs (miRNAs) have been described to regulate many biological processes, so studies based on miRNAs are continuously increasing. miRNAs have also been involved in cancer, so the study of these small molecules expression patterns may be useful in the development of new diagnostic and predictive markers. On the other hand, the preservation and integrity of miRNAs along different types of biological samples, an essential question in scientific research, has been rarely addressed in the literature.
In this work we analyze cryopreserved tumor tissue samples (n=24), and their paired formalin-fixed paraffin-embedded (FFPE) samples (n=24), from patients with breast cancer subjected to surgery and with no prior treatment, collected during 2011 in a hospital-based biobank.
Some of these cryopreserved samples underwent a severe thawing process, so this study presents a comparative analysis between optimally preserved frozen samples (n=14), thawed samples (n=10) and their paired FFPE samples (n=24), to evaluate the potential usefulness of all three kinds of samples in future RNA-based molecular studies.
Thus, we carried out an integrity analysis of total and small RNA (including miRNA) of all samples. We also analyzed by quantitative PCR the recovery of specific RNA molecules (miRNAs has-miR-21, has-miR-125b and has-miR191; snoRNA RNU6B; and mRNAs GAPDH and HPRT1) in all three sample groups (optimally frozen, thawed and FFPE samples).
Our results indicate that miRNAs are preserved along the three types of samples (optimally frozen, thawed and FFPE), thus making samples of compromised quality good candidates to carry out molecular studies based on miRNAs.
Royal Dutch Academy of Sciences, Brain Bank Consultants, Amsterdam, The Netherlands
Biobanks provide specimens for both basic and clinical research, who in turn apply a broad battery of techniques. Neuroproteomics, using MALDI mass spectrometry (MS), strongly illustrates the convergence between molecular and clinical research and the additive value of combining both on specimens available from biobanks.
The potential to generate clinically useful tests by measuring protein expression from clinical samples in a reproducible way is only limited by available sample sets, which is a challenge to biobank networks. The merger of technologies implemented on biospecimens by basic researchers combined with extensive clinical annotation is the key to future success of proteome biomarker validation and development.
Long-term Cryopreservation of Fungal Strains
Long-term conservation of micro-organism strains is essential for their in-depth study. Biobanking may play a key role in the support of infectious diseases research. Since fungal cells stability, especially dermatophyte strains, is not ensured with previously described methods, a system based on cryogenic vials stored at −80°C was evaluated.
A One-Step Low Cost Method for Long Term Storage of Enriched Leukocyte Fraction Compatible with DNA Automated Isolation
Biobank sample handling and storage is aimed to obtain the maximum yield and quality, but it is difficult when the final application of samples is unknown. Usually, for secondary biomarkers studies, blood samples are collected at the study visit and included in biobanks where immediate DNA isolation and aliquots storage takes place. We propose a one-step low cost procedure for leukocyte enriched fraction storage from whole blood (buffy coat collection) as an alternative to immediate DNA isolation or whole blood preservation into aliquots; and describe a modified protocol for automated DNA isolation. For the buffy coat collection, the blood was centrifuged at 2000g for 15 min, 600μl of the white cell layer was transferred to a microtube in duplicate and stored at −80°C until use. For DNA isolation, each aliquot was thawed and phosphate buffer saline (PBS) was added to 2ml, and a modification of the automated purification protocol for buffy coat using Chemagic MSMI (Chemagen, Germany) was applied. The optimized method included a reduction of volume wash, elution buffer and magnetic beads as well as running time when compared to the standard whole blood kit procedure. We obtained comparable DNA yield (mean 157.66μg) and similar quality/purity (the A260/280 was 1.87 and A260/A230, 2.10). With this method, (in contrast to the Chemagen recommendations) we avoid the necessity of performing a buffy coat by Ficoll gradient, reduce the DNA storage and the handling cost, and develop a good strategy for biobanks aimed to collect specimen long- term for future DNA isolation.
Laboratory of Experimental Hematology, Jessa Hospital, Hasselt, Belgium
An Effective Tool for Biomedical Research in Children: Biobank and Biorepository
Pediatric biobanks are an important resource for the research that will be needed to convert advances in personalized medicine into pediatric medical care. Researchers developing pediatric biobanks have struggled with the ethical, legal, and social issues related to the collection, storage and use of biospecimens and data derived from children. The HIV HGM Biobank receives, processes, stores and provides samples of children with infectious and non-infectious diseases, including rare diseases, for research projects focused on pediatric diseases. The biobank has samples from children from birth up to 18 years; the amount of each sample obtained is dependent on the age of the child. For certain studies we have stored samples collected during a long temporal follow-up of the children. We have stored blood, saliva, tissue, cells, DNA, RNA and virus isolates. These samples constitute critical resources for basic and translational research which is integrated with diagnostic and therapeutic interventions on several human diseases. Strict compliance to ethical norms is always guaranteed. The objective of this presentation is to show the structure, function and quality of the different samples of the Pediatric HIV HGM Biobank. The different collections of infectious and non-infectious diseases provide samples for research projects at the international level. Finally, we discuss the differences between adults and children biobanks.
Rare Diseases in the Spanish HIV HGM Biobank – Congenital Surfactant Protein B (SP-B) Deficiency
One of multiple definitions of rare disease can be any disease that affects a small percentage of the population. In the HIV HGM Biobank we have stored samples of different rare diseases such as: Barth syndrome, Familial hemophagocytic lymphohistiocytosis, Congenital Surfactant Protein B and C deficiency, Long QT syndrome, Autoimmune Lymphoproliferative Syndrome etc.
Hereditary SP-B deficiency is an autosomal recessive disorder that causes fatal respiratory distress syndrome in newborns. Around 70% of hereditary SP-B deficiency cases are caused by homozygosity for the 121ins2 mutation in SFTPB gene. We have performed a study to estimate the allele frequency of SP-B mutations, in exons 2, 4 and 7 of SFTPB gene, in a CM population. 2366 DNA samples were obtained from blood spots obtained from a healthy population and purified using a Gentra DNA extraction protocol, after exons 2, 4 and 7 were amplified by PCR, sequenced and detected with AbiPrism 3100 sequencer.
Tissue Weighting Procedure is Critical for RQI Determination
The University of Navarra Biobank carries out a systematic screening of most of the solid specimen being snap-frozen by measuring RNA integrity through the RNA Quality Indicator (RQI, Bioanalyzer, BioRad). Tissue aliquoting takes place at the pathology service or next to the operating theater and aliquots are immediately snap-frozen in liquid nitrogen. One of these aliquots with two random fragments of tissue is reserved for subsequent RNA analysis procedures. Results from the first 70 samples included in this regular screening procedure showed that only 40% of samples exhibited RQI values over 7. Thus, the entire quality control protocol was reviewed focusing on dissection and a weighting step which is needed to calculate RNA yield. We realized that during this step the tissue fragment of a few millimetres in size was unprotected from RNAases for some seconds, suffering from slight defrost. Thus, we modified the weighting procedure using RNA-stabilizing solution (Tri-Reagent) and to avoid more fragment cuts. After these modifications, the percentage of samples showing RQI values over 7 raised up to 79%.
Given that many pre-analytical factors may affect RNA integrity, we performed a statistical analysis of six pre-analytical parameters recorded from 200 specimens. All samples were obtained from anesthetized patients and a cut-off point of 60 minutes for cold-ischemia was established. Pre-analytical variables included in the study were tissue origin, tumor or non-tumoral condition, specimen weight, cold ischemia time, the extraction place and hour/date of collection. Our results indicated that none of the analyzed factors were individually critical for RQI value.
Biobank
Biobanks need to take advantage of the archived material, which is of high value and sometimes scarce. Fresh-frozen specimens are not always large and at times it is required to optimize the use of these samples so that some portions can be distributed among different investigators. Our group usually tries to divide tissue samples to maximize their use for different research projects, but these could eventually be detrimental for the aliquots (histological sections, genetic material, or proteins) obtained after working on the same archived sample once and then again. In this work, we study the degree of preservation for quality in fresh-frozen breast cancer specimens embedded in OCT after several rounds of obtaining cryostat sections, which implies several temperature changes from −80°C and −20°C back and forth, analyzing in each round the morphological pattern by staining with hematoxylin-eosin and determining the integrity of total RNA in both initial and late extraction. These parameters are considered to be informative as to the quality for fresh-frozen samples in biobanks.
In our previous experience, several rounds of extraction of RNA from melanoma and breast tumor tissues resulted in good quality genetic material to study gene expression, but these assays were not done in time to compare the results effectively. Now in this study we propose to analyze results after some systematic rounds of −80°C (ultrafreezer) to −20°C (cryostat) and vice versa for a chosen set of samples. We expect that the results of this technical study will be informative and helpful for the best management of solid tissues in biobanks.
Biobank
Biobanks usually store and process samples with different characteristics depending on the route by which these samples have been obtained. In our biobank, some solid tissue samples have been acquired by different methods and formats and it seems interesting to evaluate differences between them in conservation and quality.
Specifically, in this work we study preservation and quality of lung tissue samples – tumor and healthy, frozen with different protocols (liquid nitrogen or isopentane) and stored for different times. Samples initially stored in liquid nitrogen have been recently changed to isopentane-OCT cryomolds, from which we can evaluate accurate sampling and tissue preservation by studying hematoxylin-eosin staining as well as extracting RNA from cryostat sections and testing for RNA integrity. Moreover, we have a positive experience in our biobank obtaining good quality DNA, RNA and proteins from cryostat sections of different tumor and healthy solid tissues, which allows for good yields from every sample embedded in OCT blocks.
We also study in this work sampling and tissue preservation in the related paraffin blocks of those paired lung samples, performing immunohistochemistry assays targeted to vimentin, CD34, and Ki-67 proteins. Fixed and paraffin embedded tissues are of great value for immunohistochemistry diagnostics and prognostics and is essential to finding new biomarkers, even though they allow for limited molecular studies depending of the size of DNA or RNA templates, because these molecules become rather fragmented.
The use of agreed quality control protocols in different biobanks is highly recommended to share human samples between network projects.
How to Improve the Quality of our Samples: Testing for RNA Quality
Our biobank is focused on the collection of frozen tissue from solid tumors, so it is crucial for us to determine whether our procedures work. These are harmonized procedures followed by every member of the Andalusian Public Health System Biobank.
We have tested different aspects of the collection procedure, including freezing (times, temperatures and methods), the area of the cut, the grade of humidity (especially for small samples), the grade of necrosis, and the stability of the specimens over time, all in relation to their RIN.
Whole Genome Amplified Genomic DNA: Quality Characterization and Applicability in Hospital Biobanks
Whole genome amplification (WGA) represents a feasible in vitro approach to amplify a limited amount of genomic DNA (gDNA) sample in order to obtain a WGA DNA (wgaDNA) for genetic or genomic studies. The more suitable technique for high performance WGA has been proved to be the multiple displacement amplification (MDA) approach, which was first described in 2002 (Dean et al., 2002) and relies on the high degree of processivity and fidelity using the isothermal strand displacement activity of the Phi29 bacteriophage DNA polymerase. Nowadays, there are several available commercial kits that allow for obtaining more than 40 μg from 10 ng of input DNA and the suitability of the resulting wgaDNA has been demonstrated in real-time quantitative PCR, DNA sequencing and genome-wide SNP genotyping assays (reviewed in Lovman and Syvänen, 2006).
Although it has been noted that starting gDNA quality is critical to obtain a resembling wgaDNA sample and that DNA degradation limits its usefulness in many applications, quality of wgaDNA samples has not been described in detail.
Here we characterize wgaDNA samples purity, integrity and functionality and define a qualitative quality score. wgaDNAs tested have been amplified from different quality gDNA starting samples isolated from blood fresh or Carnoy fixed leukocytes and Oragene® collected saliva. Our results show that nearly all the wgaDNA samples tested achieved similar quality marks as their gDNA forerunners. Finally, we propose many uses of this approach in a hospital biobank to overcome valuable samples low yields.
Tumour Bank, Hospital Clínic – Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS) Biobank, Barcelona, Spain
Present address: Department of Pathology, Hospital Vall d'Hebron, Barcelona, Spain
Translational research is moving towards a scenario of personalized medicine, where it relies on human samples to achieve it. It is therefore of vital importance that biobanks guarantee samples of the highest quality. To address this issue, the effects of post-surgery cold ischemia in frozen samples have been explored during the past few years. While no significant degradation of RNA is observed during the early stage after surgery, gene expression is very sensitive to short cold ischemia times. However, to our knowledge, the analysis of molecular pathways has never been analyzed in different tissues at the same time.
In this study we have analyzed the effects of cold ischemia in three different tissues (colon, breast and uterus) at different times, up to two hours. Samples collected at eight minutes and at two hours of ischemia were hybridized on Affymetrix expression microarrays. We found no statistically significant changes in the integrity of RNA and we neither observed significant differences in gene expression. However, surprisingly, we observed that the ERK/MAPK pathway was significantly affected by cold ischemia in all tissue types. Although more tissues and more samples need to be analyzed, our results suggest that this pathway could be used as a surrogate marker to assess the effects of cold ischemia on the expression profiles of tissues harvested in biobanks, and that it could become an additional quality control to RIN analysis in order to guarantee the highest quality of stored samples.
BioBanco Hospital Universitario Central de Asturias-Instituto de Oncología del Principado de Asturias (IUOPA)
Our objective is to find a method to take fresh samples from the tumor, before fixation, in a way that preserves its anatomic characteristics in order to allow adequate compliance of the established macro protocol.
The method proposed includes partial slicing, permitting anatomic preservation by closing partial incisions along the fixation procedure.
Ambient Temperature Biobanking: Validation of an Automation Compatible Workflow
Most groups involved with patient care, including medical centers, universities, clinical research organizations (CRO), pharmaceutical companies and diagnostic test developers recognize both the medical and fiscal value in biobanking. Biobanking is essential for studying complex diseases such as attention deficit hyperactivity disorder (ADHD), cancer, heart disease and diabetes. The volume of samples associated with biobanking is enormous and growing, driving the adoption of automated solutions to improve specimen handling and storage. Conventional protection of nucleic acids requires very expensive “cold chain logistics” during collection and sample transport, and RNA species in particular require cold shipment and ultra-low temperature (−80°C freezer storage), an impractical and expensive proposition for large scale collection and banking.
Biomatrica has developed an all ambient temperature automation-compatible workflow for biobanking of whole blood specimens, stored either in the initial unaltered state or as isolated nucleic acids. In this abstract, we present the results of a twenty clinical specimen study evaluating the workflow in the collection, processing, storage, and recovery of nucleic acid analytes. We demonstrate the performance of the workflow with regards to the yield, purity, and integrity of isolated nucleic acids from stabilized blood collection devices and in the long term stabilization and recovery of stored nucleic acids. We have developed a complete ambient biobanking workflow from collection to storage that is scalable and allows a sustainable biobanking solution that is energy independent and reduces biobanking costs. The implementation of our ambient biobanking workflow will result in maintaining the highest quality biosamples for retrospective molecular analysis.
RNAgard Blood Tubes: Effective Memorializing of Gene Expression in Blood Cells
Gene expression profiling conducted on peripheral blood cells is an emerging diagnostic technology. In Vitro Diagnostic Multivariate Assays (MIA-IVD) are one version that has utility in a wide variety of illnesses, with as many as 200 different MIA-IVD tests currently under development. IVDMIAs seek to answer clinical problems not sufficiently addressed by other diagnostic approaches by taking advantage of simultaneous gene expression measurements made on a collection of sentinel genes. The pattern is then evaluated using a diagnostic, prognostic and/or predictive algorithm. Because decisions about patient care are based on MIAIVD outputs, it is absolutely imperative that original gene expression patterns remain intact and unaltered during the preanalytic processing of blood.
Biomatrica has developed a blood collection device for whole blood which stabilizes the RNA present in blood cells and allows for ambient temperature handling and storage of the blood specimen. We demonstrate the performance of the blood collection device for maintaining RNA levels at their initial input levels. Comparative testing conducted using microarrays reveals that blood collected in the Biomatrica RNAgard Blood Tube exhibits significantly less variability during microarray analysis than a leading product by a competitor. Our blood collection device can serve as the front end to exacting MIA-IVD measurements that are more likely to deliver accurate gene expression patterns and prove of value to patients.
ELSI (EL)
Public Perspectives on Biobanking in Nigeria
More than just a “Bioresource”: Ethical and Practical Implications of Operating an Infectious Diseases Biobank on the Model of a Legal Trust
Human tissue biobanks are key players in developing ‘personalized medicines', as well as advancing the understanding of disease pathogenesis. Inevitably, biobanks raise a range of legal and ethical issues: not least of which is propriety. Traditionally, such archives acted as a ‘custodian’ of the materials they held. We propose that this view should be re-assessed, since it promotes the perception that biobanks have a passive role, lacking operational flexibility.
The Infectious Diseases BioBank (IDB) at King's College London (KCL) has developed an alternative model for managing such archives. We suggest that other repositories might also benefit considerably by changing their modus operandi by operating on the same principle as legal trusts. This concept has previously been proposed - though not rigorously explored nor tested – by the suggestion that gene banks should be managed as Charitable Trusts.
For tissue banks with longitudinal sample collections, the idea of operating on the same principle as a legal trust represents an ideological gear-shift, with the implication that there is an intrinsic obligation to enhance the value of the samples held for the beneficiaries (the improved health of the general public). Interestingly, adopting this model has significant ramifications (proactive versus passive) for the way in which biobanks such as the IDB should operate optimally and would significantly redefine their role.
Center for Biomedicine, EURAC Research, Bolzano, Italy
Informed consent is a basic requirement for biomedical research. Genomics cohort studies and work in consortia opens up the problem of how to deal with original informed consent (IC) forms of existing collections. Large scale genetic studies are developing into huge networks sharing data and sometimes samples. While consenting in the traditional setting means to agree to a defined protocol inside a legal framework, working in consortia means to go beyond single studies requirements and to find areas in which different consent forms allow common work. Even working with broad consent and codified data does not allow any kind of research. In fact in order to be ethically accountable there is the need to ensure that security protocols, chosen data-sharing options and withdrawal options are taken into account. We developed a basic tool that allows for comparison of IC forms and to identify areas of possible common work and to exclude the areas that do not comply with original consent. A grid of concepts allowed an in depth comparison of the consent form. Several forms were confronted in the context of the construction of HIPB (HUB of Italian Population BioBanks) in Italy in order to identify areas of possible collaboration and proceed with a common project. This tool may now as well be used for further studies of comparison in the future.
Center of Biomedicine, EURAC European Academy of Bolzano, Bolzano, Italy
New scientific practices are challenging our research ethics tools. The consent form, for example, that is the predominant tool for enacting respect for persons through voluntary and informed choice faces hard challenges. Limitations of broad consent models preferred by research entities have been widely debated for collections where purpose and potential risks may not be defined for biobanking purposes. Ethical boards often stop or limit further possible studies on those collections because of the ethical inadequacy of the collected consent. Recently even the Swedish LifeGene biobank was stopped for the same reason. At the same time models that propose ongoing decision-making strategies, better from the ethical side, have sometimes been perceived as unfeasible by research institutions. We know from public opinion polling that also the public is divided in their preferences for how much information they need and how much contact they want from researchers.
Are there ways of translating ethical participatory principles into practices that also account for usability by researchers? New participant-centric initiatives are showing to facilitate more dynamic control by participants over their involvement in future research and enact the possibility to choose how much control they retain over time.
In this paper, we illustrate the possibilities offered by these tools for helping research in addressing the long term challenge of data and sample management and at the same time account for ethical sounding procedures. We will illustrate it through examples from ongoing initiatives in the United States, Italy, and the U.K.
Biobank of Aragón, Instituto Aragonés de Ciencias de la Salud (IACS), Zaragoza, Spain
Analysis of the survey reflects that people recognize that biobanks produce more social and local benefits than individual ones. These benefits are in consequence of its role in accelerating the knowledge of disease and their capacity to promote collaborative research. This perception is not affected by the relation of the respondent with biobanks.
Self-regulation of ELSI in the Netherlands
The Netherlands does not have comprehensive biobanking legislation but since 2011 it has established a self-regulation through a Code of Conduct on the proper use of tissue for research. This Code of Conduct has been drawn up by the FEDERA, with the active participation of all relevant stakeholders: researchers, custodians of tissue, doctors, patient organizations and ethical review boards. The Code distinguishes the various steps and ELSI responsibilities in the whole chain of tissue for research: from taking tissue from humans to the results of research with it. This type of ‘bottom-up’ self-regulation has various advantages. Regulation will be tailor-made and addresses the concerns and interests of all mentioned stakeholders. It fits neatly with the approach of ‘reflexive governance’. It contains some hard norms, such as privacy protection, but also many ‘comply or explain’ norms. The precondition is a climate where all stakeholders are willing to cooperate and patient organizations are sufficiently organized to act as relevant counterparts. Self-regulation can have disadvantages as well. Funds are necessary to draft it. Though remaining within the boundaries of existing legislation, it may lack democratic legitimacy and oversight is not automatically assured. Implementing measures are necessary. Among other things, the Dutch biobanking community will institute a website together with patient organizations which informs the public at large about biobanking and the Code of Conduct and uses social media to interact with visitors. Self-regulation is never ready but a continuous challenge to balance all relevant interests in a transparent way.
Impact of the Coming EU Data Protection Regulation
Research with tissue is about data and hence privacy legislation affects how such research can be performed. The European Commission has launched a proposal for a new data protection Regulation (2012/0011 (COD)). Unlike the present Directive 95/46/EC such a Regulation does not need to be implemented in national law of member states but is binding by itself. It will therefore create one data protection regime in the EU. The Regulation proposes new norms such as ‘the right to be forgotten’ and the requirement of a privacy impact assessment. It empowers the Commission to issue delegated acts and institute a new regulatory body. Rules on transfer of personal data to third countries will change. The Directive had been implemented very differently across Europe in respect to data for research. Legal harmonization can further international collaboration, even though the possibilities for exchanging data in the present system of diverging privacy legislation are often misunderstood. Countries with a lenient regime to use personal data for health research mistrust the present emphasis on the use of coded-anonymous data for such research and fear that the Regulation will lead to stricter rules and additional bureaucracy. That remains to be seen. The research exemption to the explicit consent principle, if certain conditions are met, will become binding in the EU. Yet, that might change during the discussion in the European Parliament and Council. Much also depends on the delegated acts of the Commission. A close watch is necessary especially for research into rare diseases.
Radboud Biobank, Radboud University Nijmegen Medical Centre, The Netherlands
Most studies using biomaterial and patient data from prospective clinical biobanks do not fit with Good Clinical Practice (GCP) guidelines for human experimental research because the burden for donors is minimal. Yet some form of ethical review is needed:
I. At the establishment of a biobank, when it is decided at institutional level to collect and store biomaterial from clinical patients for future scientific studies. Criteria: relevance for future research; adequate procedure for informed consent; minimal risk for the donors; professional organization. II. Each time a specific request is made for use of the biomaterial and accompanying patient data in a specific research proposal. Criteria: study objective fits the scope of the biobank and informed consent; proposal relevant and valid; specific request for material fits the study objective; track record of applicant; privacy protection.
For clinical biobanks we propose a model with an REC-light to deal with the formal assessment on these two occasions in a way that guarantees both quality and efficiency. REC-light is a formal research ethics committee with multidisciplinary senior expertise to review non-experimental studies using biomaterial with associated patient data. With a standard ‘fit-for-purpose’ procedure, standard internet forms, frequent REC-light meetings (every other week), the board needs to find a balance between assessment-quality and efficient, fast decision-making. The procedures should be easy to navigate by senior experienced applicants supported by a biobank manager where needed. A positive assessment should be followed by an immediate authoritative decision and fast delivery of the requested material.
The Roslin Institute & R(D)SVS, University of Edinburgh, Easter Bush Campus, Midlothian, UK
The past half-decade has seen the completion of a draft equine genome sequence, the release of a 50K SNP chip and its succession by a 70K chip. This is a feasibility study to determine whether an equine biobank would enable the UK horse industry to better exploit these new genomic technologies.
Semi-structured interviews were conducted with a cross-section of industry representatives and experts in biobanking. Interviews were primarily conducted face-to-face, taped, transcribed and evaluated using logical analysis. Key informants were consulted for clarification on issues that were unresolved following the interviews. An online survey, aimed at the general horse-owning public, was also implemented.
There are unique issues associated with biobanking horse biospecimens that have not previously been dealt with in the literature or legal frameworks. Some of these issues might be expected to be mirrored in other livestock and companion animal species. The frequent transfer of ownership could represent a significant barrier to the implementation of an equine biobank. It not only makes achieving continuity in longitudinal projects challenging, but also raises major questions regarding sample rights and ownership. These questions become all the more pertinent when one considers the considerable monetary value of some horses, in particular breeding stock. From a more practical perspective, the research highlighted an apparent conflict between the most accessible and the most data-rich biological samples. Such issues need to be resolved and while this study represents a first step in this process, extensive consultation between researchers and the industry is now needed.
IdiPAZ Biobank, IdiPAZ Institute for Health Research of La Paz University Hospital, Maternity Hospital
Biomedical research requires large amounts of high quality human biological samples. Because of this, in the last few years, the collection, storage and use of these samples, has become of great importance. This need for management of samples and their associated data for biomedical research is reflected in the exponential emergence of biobanks worldwide.
However, there are ethical and legal issues that must be considered when using human biological samples in biomedical research. One of the most important is to maintain the confidentiality and privacy of the donors. This is where the biobank has a major role as manager of the samples and associated data, commonly known as “Honest Broker”. A misuse of personal data by third parties can bring unexpected and negative consequences for the donor.
The fields of collection and use are governed by a complex and heterogeneous nature of regulations, laws and guidelines (different approaches reflect different national styles in addressing regulatory challenges), as in the protection of personal data with human biological samples for biomedical research. All these documents are highly fragmented and focus more or less in Europe, but to date there is no specific law about it. Europe should develop a consistent and coherent legal framework for biobanking that should protect participants' fundamental rights, in particular in the areas of privacy, data protection and the use of human tissue in research.
Feedback to Research Participants on Findings of Potential Health or Reproductive Importance - How do Ethics Committees Guide Researchers on this Topic?
Who is the Qwner of the Sample Managed by a Biobank?
Understanding and Perception of an Informed Consent Document For Biobanking
The aim of this exploratory study was to assess the level of understanding, perception, acceptance and readability of the Informed Consent (IC) document for biobanking of the Hospital Universitari de Bellvitge (HUB) and associated centers.
The general public was questioned about their understanding of an IC document (aim of the study, purpose of biobanking, use and disposal of requested samples), typographical aspects (length, type and font size, format) and acceptance of the document (availability to be signed). The readability of IC document was evaluated using the program and scale INFLESZ.
The survey's results (N=41) showed that the overall assessment of the understanding, perception and acceptance was good. The worst aspects were the use and disposal of samples and the perception of the length and format of the document. However, personal opinions showed that there were some unclear aspects that generate mistrust. The readability level according to INFLESZ scale was “quite difficult”. Text is not suitable for a regular readability level people (general press).
In conclusion, the survey results and readability analysis indicate that the IC document for biobanking of HUB should be improved. An immediate plan to improve comprehension and readability of that document was proposed. An additional study with a sample population size and characteristics more adapted to HUB's patients is recommend for a better assessment of understanding, perception and acceptance of IC document for biobanking.
Sample Collection and Use from Control Healthy Patients in a Pediatric Biobank
Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
• Commitment to adherence to international standards;
• Prospective collection of donor health information including follow-up at regular intervals. The information, while secure, will be available to biobank staff;
• The potential for drug/patent development for which the donor will receive no remuneration;
• Biospecimens may be used for foreign research;
• Institutional biobank fulfilment of a yearly donor quota in order to maintain government funding. Otherwise samples will be transferred to another funded institution;
• Cost-recovery measures require investigators to pay for biobanking services.
Research Centre for Pharmaceutical Care and Pharmaco-Economics, Leuven, Belgium
Some biobanks claim ownership on human biological material (HBM) and associated data stored by them; others consider the concept of such ownership inappropriate and suggest a model of ‘custodianship’ or ‘stewardship’ (1–3).
Few biobank projects studied the legal nature of custodianship of HBM (1).
No legislation exists defining custodianship of HBM. It is therefore uncertain which responsibilities and/or rights a custodian holds in relation to HBM and associated data. “Many academic scientists express confusion, if not consternation, over the meaning and practical implications of possession, custodianship, ownership, database rights and intellectual property (IP) generally.”(4)
A comparative analysis of 90 access arrangements revealed several definitions of ‘custodianship’; the following common elements were found: (a) responsibility to safeguard (i) confidentiality, integrity and security of the collection and (ii) the interests of donors; (b) right to control use, access, transfer and/or disposal of HBM and associated data. These responsibilities and rights are determined by the purpose for which a biobank is set up and the terms stipulated in the consent form, unlike in the case of ‘ownership’, which is in principle unconditional. Access arrangements furthermore often do not clearly stipulate which person or institute holds custodianship.
The current project investigates to which extent the nature of custodianship of HBM can be determined on the basis of existing legislation and whether it differs from custodianship of data as defined in data protection legislation. It furthermore looks into the relationship between custodianship and (intellectual) property rights/ownership rights and/or possession of HBM.
References: (1) Yassin R., Lockhart N., Gonález del Riego, et al., Cancer Epidemiol. Biomarkers Prev. 2010, 19(4), 1012–1015; (2) Hallmans G. and Vaught J, Methods in Molecular Biology, 2011, 675, 241–60; (3) Vaught J. and Lockhart N, Clin Chim. Acta, 2012, 1569–1575; (4) Cambon-Thomsen A., Rial-Sebbag E. and Knoppers B., European Respiratory Journal, 2007, 30(2), 273–382.
Spanish National Centre for Cardiovascular Research (CNIC), Madrid
Aragon Workers' Health Study (AWHS) is a longitudinal cohort study that pretends to characterize the factors associated with metabolic abnormalities and subclinical atherosclerosis in a middle-aged population in Zaragoza free of clinical cardiovascular disease (CVD). The study takes advantage of the annual medical examination of the General Motors Spain (GM) workers to collect biological samples and data (anthropometric, biochemical and habits) using standardized protocols.
Two striking features of AWHS cohort are its sky-scraping response rate (94.8%) and the high score obtained in a satisfaction survey carried out in late 2011. Several factors could have contributed to these results:
- The long-standing collaboration between study investigators and the Medical Services of GM.
- The workers confidence in their doctors and ATS advice
- The strong communication initiatives (leaflets, posters, articles in magazines of the sector, talks of trade unions…)
- The objective of the study: the detection of early cardiovascular disease is an area of great interest, severity and population awareness.
- Individual results are returned in a report issued by the Unit Cardiovascular Prevention of the study. Those include a complete analysis of cardiovascular risk factors (biochemical and diet-based), diet and physical exercise recommendations and last generation imaging tests to quantify the calcium in the coronary arteries and the assessment of Subclinical Atherosclerosis.
The AWHS project arises partly within the corporate social responsibility actions of GM, to contribute actively and voluntarily to improve society, economy and environment, and reconcile the interests of business with the expectations of the community.
Biomedical Reseach Center, Navarra Health Service, Pamplona, Spain
A new regulation for biobanks and the use of human samples in the biomedical research setting has been recently published in Spain. For the first time in Spain, this specific legislation includes,the regulation for the use of human samples collected in the context of clinical trials (CT). One singular issue comprised in this new regulatory scenario concerns the investigational management of those human samples collected during CT, once the study is finished, and the remaining samples want to be stored for future research projects. Those studies could be related or not with the CT in which the samples were collected. However, there is wide legislation where multiple interpretations about how it should be applied can be done. In fact, it involves deep changes regarding key managing aspects of those biosamples that affect not only investigators but also the pharmaceutical industry, biobanks, ethics and scientific committees as well as regulators. Meanwhile, R&D for drug development is also moving rapidly towards personalized medicine. This new focus includes the discovery of targeted therapies using the bench to bed side translational research strategy as the paradigm, where research on human samples becomes mandatory. Thus, this new regulatory frame is a challenge for the development of new drugs. The main goal of all this complex process is to progress in the scientific knowledge for new drug development being able to prevent, diagnose, and treat illnesses, always according to a precise ethical and legal setting that assures the donor rights.
What's in a Name? Examining Different Definitions of the Word “Biobank”
There are numerous definitions of the term “biobank” in use today. National laws, national and international guidelines, and the literature make use of various key words and criteria to describe biobanks. As a rapidly evolving field that is being widely addressed in the academic literature and for which new regulations and guidelines are being suggested, the fact that there is no single, agreed-upon meaning for the term is noteworthy.
We have carried out over 30 interviews with biobank stakeholders in Switzerland, and our empirical data show that these individuals also use a variety of definitions. We present the results of our findings on this subject, and compare them to the definitions used in regulatory documents and academic articles. We also identify possible reasons for the variance, such as the scope of the biobank, its intended purposes, and the nature of what it stores.
The definitions found in these three groups of sources differ internally and between one another. Hence, certain organizations may be identified as “biobanks” by regulatory or governing bodies, but not by the organization themselves, or vice versa. This may have consequences for the oversight and operations of the organization. Furthermore, attempts at networking, harmonization, and even identification of biobanks may be affected by the existence of diverse definitions. We explore the differences in understanding and definition of the word “biobank”, and study the possible reasons behind these divergences. Ultimately, we question whether this variation presents problems for the future of biobanking.
Brazil's New Regulations on the Use of Human Biological Materials for Research
In 2011, two new regulations on the use of human biological materials for research were implemented in Brazil, specifically, Resolution CNS 441/11, enacted by the National Health Council, and the National Guidelines for Biorepositories and Biobanks (Ordinance No. 2201), published by the Ministry of Health. Differences between sample collections for single studies and large-scale collections for multiple studies were clearly established. In Brazil, to distinguish these storage structures, it was decided to set different terminology for sample collections, respectively Biorepository and Biobank. The consent of the subjects regarding the collection, storage and use of samples stored in Biobanks is necessarily established through the Informed Consent Form. For purposes of individual manifestation, this term must include the following two options, mutually exclusive, about the use of the stored material in each research: need for new consent or waiver of new consent. Despite allowing the so-called “broad-consent” to subject's decision, it maintains individual rights. In many countries, there is an ethical concern regarding the return of research results to participants, particularly the return of incidental findings. In Brazil, research participants have the right to decide whether or not be informed about research results and to receive genetic counselling when findings with known clinical implications are obtained. The subject who consents to the collection and custody of his biological sample, whether in Biorepository or in Biobank, and allows its use for research purposes, remains the holder of rights on it. This is a fundamental precept of the current Brazilian guidelines.
Biobanking: An Infrastructure of Knowledge
An informed and conscious donation of biological material for research is basic to good biobanking and makes tangible every citizen and health professional's proactive roles, not limited to the material collection but also to the research development and co-production of knowledge.
Therefore, correct information is the condition of possibility for biobanking and at the same time it determines the final quality of scientific data, ensuring common standards, from sample collection to their final research use.
Here resides a fundamental mission for a biobank: it may play a proactive informative role towards citizens, researchers and professionals.
Through information, the biobank exercises its civil service together with its function as a carrier of scientific knowledge, from collection to reporting of any results and patents generated from the samples.
Through information on biobanking, the biobank expresses its responsibility, from the proper use of samples to the information management contained therein: the biobank makes explicit its compromise to protect individual and community's rights and interests.
But to exercise this public function it is necessary that the biobank plays a role of independence, impartiality towards citizens, researchers and institutions. It is crucial how transparent research projects are evaluated and actors involved in the results' assessment, monitoring and return.
It could be a consolidated biobanking model which assumes in practice biobank civil service in terms of standards of quality and activity, its participatory nature, and in its being a true infrastructure of knowledge. BBMRI could be a good example in this view.
Building Public Trust in Biobanks Through Participatory Governance
Biobanks must sustain the trust of those who contribute materials and provide funding. Concerns about privacy, intellectual property and possible uses of samples and data, as well as episodes of misadventure or inappropriate use of stored samples challenge biobank managers' ability to maintain trust and regain it once trust is lost. Experience with public deliberation involving members of the public in Canada, the US and Australia has demonstrated the capacity of participants to understand biobanks and related issues and to provide informed advice. The participants incorporate technical and regulatory information as well as diverse social perspectives to produce practical advice that they support despite persistent disagreements on other issues. When events incorporated managers and biobank policy makers in the design of the questions, as informants and observers, the advice from the participants was immediately useful. Further, managers and policy makers involved in the deliberations have built participation of the public into their management structures. Setting thresholds based on the deliberative events and incorporating public and stakeholders in the management of the biobank can provide guidance for emerging issues and determine responsibility for renew informed consent or public consultation based on the thresholds. This model of participatory governance supplements and reduces inappropriate dependence on informed consent and other ethical procedures, providing a robust approach to justifying and maintaining broad trust and support for biobanks.
EDUCATION AND STANDARDS (ES)
Harvesting Prostate Cancer for Tumor Banking: Role of the Pathologist
LPCE biobank and PACA Biobank, University of Nice Sophia Antipolis, Nice, France
Considering the increase in the number of biobanks, there is an urgent need to improve management in the biobanking field in order to set up high quality networks of biobanks for research projects. Moreover, some oncology biobanks are at the crossroads between patient health care (with a strong connection with the pathology and the molecular biology hospital laboratories) and the translational research programs. Thus, it seemed to us important to create an educational program in order to offer a new and specific information in the biobanking area. The new profession of biobanker opens new and different avenues for medical or science students. In this context we have set up in 2011 the first national master course, called “Management of Biobanks” at the University of Nice Sophia Antipolis (Nice, France), in collaboration with the ESTBB (University of Lyon, France). This course is aimed at training executive managers in the biomedical field to work in the health industry, public or private research centers, and public and private hospital structures. The masters course “Management of BRC- Biobanks and Biospecimen Sciences” is organized over two years (four semesters). It allows the students to validate 120 European credits (ECTS, European Credit Transfer System). Over the two years there is a total of 700 hours of classes that will include lectures, laboratory classes, group work, case studies and e-learning. We aim to develop in coordination with other EU countries a European Master degree in order to accelerate the exchange of students among different biobanks.
Loss of AgroBiodiversity Genes Bank in Georgia
In terms of global warming and climate change, the implementation of national gene (BIO) bank collections requires organizational participation of Academia, NGO's, Government and the Public to prevent the loss of Biodiversity. Because of an exponentially increasing human population and the rate of resource consumption, human activities have a great impact on the environment. Habitat degradation and destruction, the introduction of non-native species into natural habitats and the overexploitation of wild plant and animal species are the primary causes of accelerated loss of biological diversity. The importance of biological diversity has been acknowledged by the world's scientific community and its conservation has been targeted by numerous international agreements, and national programs. However, the exploitation of natural resources is ongoing and biological diversity is declining. Nevertheless since the root cause of this problem is based on a disharmony between humans and nature, social investigation in this field is rather limited and carried out mostly in the economic domain. Therefore preservation of local Agro Biodiversity (flora and fauna) through a genetic fund in Georgia assumes not only scientific, but also great practical importance.
Knowledge for Compliance with RD 1716/2011: Information Guide
The coming implementation of the Real Decreto (Royal Decree) 1716/2011 means that researchers using biological samples will need to match without further delay to one of the three regimes clearly established for such samples handling: determined project; collection beyond the scope of a biobank; and biobank.
Researchers will be required to change any non-compliant procedure with this new legislation, which may require substantial additional effort. It is essential for Researchers to have a wide knowledge of such new legal requirements in order to comply with them.
An anonymous poll has been conducted among researchers at Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS) in order to ascertain the level of knowledge and potential uncertainties about the RD 1716/2011.The profile of researchers who participated in the poll shows that most of them use samples obtained under informed consent for research purposes, corresponding mainly to the project regime followed by the collection regime, and to a lesser degree the Biobank regime. The results also showed a low degree of knowledge about the RD 1716/2011 and a number of doubts and misunderstandings were identified.
According to the results obtained in this poll and the need for wider communication of the RD 1716/2011, an informative guide for researchers has been developed, focusing on the relevant aspects of RD 1716/2011 and Ley de Investigación Biomédica 14/2007, together with answers to the doubts and misunderstandings detected.
This guide has been spread among IRYCIS researchers through a number of channels:
• Ordinary Mail
• Intranet at Hospital Universitario Ramón y Cajal
• IRYCIS website
• Specific informational speeches
• Bulletin Boards
Biobank Certification: Update on the Canadian Tumour Repository Network (Ctrnet) Program
Effect of Freeze Thaw Cycles on RNA Quality in Human Tissue Samples Using Manual and Automated Extraction Methods
Vacuum Packed Transport Maintains the RNA Quality
Aims: In this study we aimed to test the impact on RNA integrity of storing tissue samples under vacuum conditions prior to processing.
Peter MacCallum Cancer Centre, Research Department, Kathleen Cuningham National Consortium for Research into Familial Breast Cancer (kConFab), Melbourne
Accepted for publication July 2012. Genetics in Medicine
Healthy Blood Donors: Accomplices in Biobanking
Blood samples from healthy donors have a fundamental value for disease-oriented biobanks. They serve for comparison with pathological samples to investigate diagnostic factors, pathology biomarkers or pharmacological targets. The cancer biobank of the National Cancer Institute, Aviano (CRO-Biobank) started a collaboration with healthy blood donors byeducating them about biobanking research. We also investigated their habits concerning the main factors that are predisposing to cancer, in order to understand if they could be representative of the general population or if they have a healthier lifestyle, as it is commonly thought.
From October 2010 to August 2011 we recruited 253 participants (110 female and 143 male) aged 18 to 65. We asked them to donate samples of blood (18 ml) for biobanking in addition to blood donation. We investigated their personal and anthropometric data, smoking and alcohol habits, some food consumption and obstetric and gynaecologic data. We compared this information with official data issued by the main Italian supplier of official statistical information. This study confirmed that collected data about smokers and drinkers are comparable with the general Italian population. The same is true for some food consumption and physical activity, although less robust statistical data are available. Particularly we found that females are most careful than males about appropriate diet recommendations. Blood donors can be seen in a new perspective: in addition to assisting in health care with their blood for transfusions, they might contribute to research by donating biological material for biobanking. A further advantage for CRO-Biobank is represented by the possibility to monitor these subjects over time and use their samples for prospective-longitudinal studies.
St. James's Hospital, Dublin
Biobank, INCLIVA Institute of Health Research, Valencia, Spain
UMG Biobank, University Medical Center Göttingen, Göttingen, Germany
Analysis of the Reliability of Different Extraction Methods Versus Quality Indicators for DNA Samples from Peripheral Blood
During the last few years, an important development for molecular biology techniques is the necessity for availability of DNA for many studies. Several DNA extraction procedures with different results in both quantity and quality have been proposed.
HIV HGM Spanish BioBank: Peripheral Blood Mononuclear Cells for Prospective Research in HIV-Immunological Therapies and Vaccines
Peripheral blood mononuclear cells (PBMC) collection is one of the best physiological models in research, and particularly in HIV-immunological therapies and vaccines. The methods used in cellular isolation and cellular cryopreservation are crucial in obtaining the maximum yield in the number of viable cells recovered maintaining their initial properties. Serum is commonly used as a supplement to basal growth medium in cell culture. The most common type of serum used for cell growth is fetal bovine serum (FBS), also known as fetal calf serum (FCS). Occasionally, there may be use of other bovine sera, such as newborn calf serum or donor bovine serum. In cell culture, serum provides a wide variety of macromolecular proteins, low molecular weight nutrients, carrier proteins for water - insoluble components, and other compounds necessary for in vitro growth of cells, such as hormones and attachment factors. Serum also adds buffering capacity to the medium and binds or neutralizes toxic components. The selection of a serum supplement for cell culture applications is primarily dependent on the chemical definition of the basal medium, the type of cell to be grown, and the culture system being employed. Moreover, DMSO has toxic effects on cells at room temperature and DMSO concentration has to be reduced significantly. We have analyzed freezing approaches to minimize the cytotoxicity of cryopreservation and maintain T-cell functionality. We compared different FCS lots at different concentrations in PBMC. We found an appropriate FCS lot and appropriate concentration of DMSO. Therefore, our cryomedia resulted in very good viability, recovery and functionality of PBMC after cryopreservation.
Biosecurity: Essential Requirement for Infectious Disease-oriented Biobanks
The HIV HGM Biobank hosts samples from infectious and non-infectious diseases (HIV, hypothyroidism, cancer…) under a strict biosecurity system. To comply with biosecurity requirements, an initial analysis to identify and evaluate potential risks has been done. A high level of organization in defined procedures has been implemented to ensure the maximum guarantee of security for our staff.
The measures below describe the Biosecurity System developed for the HIV HGM Biobank:
• Biosecurity Plan: This refers to the requirements needed to minimize the risk of exposure to biological agents in the different sample handling processes: packaging, shipping, processing, management of waste, storage and transportation. Risk versus security requirements also refer to infrastructureand equipment.
• Standard Operating Procedures for the proper use, maintenance, and cleaning of the equipment and infrastructures have been developed.
• Safe Work Rules and Equipment: these mandatory guidelines have been established for our staff. They also are required to use safety equipment (safety glasses, gloves, lab coat, masks), work flow cabinets and hygiene measures to prevent the spreading of biological agents.
• Safety Protocols and training in case of accident or laboratory spill situations.
• Continuing Biosafety Training Program: Regular seminars are given by a specialized consultant to develop comprehensive information for our staff who are responsible for responding to needs in these matters.
• Implementation of corrective and preventive actions, so that perceived deficiencies are corrected efficiently.
• Control Mechanisms for established procedures, instructions and standards.
NEW TECHNOLOGIES (NT)
Sample Integrity and Risk Management as Central Themes for Establishment of a Fully Automated Storage Facility
Research of Epstein-Barr Virus Genome and Quantification of Viral Load in Breast Cancer Tissue From Algerian Women (Area High-Risk NPC)
Nearly all persons are infected with Epstein-Barr virus (EBV) by adulthood and remain chronically infected for life. While almost all EBV infections are benign, a small percentage of infected persons develop certain cancers (lymphomas, stomach cancer, nasal cancer) with this virus present. More and more studies have shown interest in the possibility that breast cancer may be caused by EBV, but the association of EBV with breast cancer remains controversial. The etiology of breast cancer is still unclear.
In this work, we reviewed the studies on EBV and its association with breast cancer, including EBV detection and quantification of viral load in breast cancer frozen tissues using real-time quantitative PCR, as well as serological tests and clinical analyses.
Our results show that the EBV genome was detect in 78,or 12% of tumor samples. Our findings also show a very high heterogeneity in viral load distribution, within the same tumors at different locations.
LPCE Biobank and Biobank PACA, University of Nice Sophia Antipolis, Nice, France
The hospital at Nice Sophia University France launched a pilot program using a custom-built RFID-based system in order to develop a more efficient, accurate and secure way to identify biospecimens within the biobank, and to track them as they moved from the pathology laboratory to the biobank. We evaluated the benefits of the RFID technology in the biobanking field, in particular for the control of pre-analytical variables. A total of 1110 patients having surgery for lung cancer were included in this study. For recording data, the system included handheld HF 13.56 Mhz RFID readers which were equipped with wireless LAN radios and used by hospital personnel for checking inventories of cryotubes containing surgical samples. The RFID stations were linked to an administration database to seamlessly manage specimens. In the operating room, the specimens were placed in plastic bags identified with passive high-frequency RFID tags. The cryotubes moved to the pathology laboratory via a pneumatic tube. After gross macroscopy selection the samples located in cryotubes were frozen in nitrogen. The tubes were scanned into the database via a system with a fixed compact RFID station. For each surgical specimen, time between the departure from the operating room until the frozen procedure was accurately measured and recorded (mean=19 min; range: 10–32 min). One benefit of this RFID system is that it enables the hospital to know when specimen tubes are moved from one location to another, thereby helping the facility to keep track of them and to reduce the time of cold ischemia.
LPCE Biobank and PACA Biobank, University of Nice Sophia Antipolis, Nice, France
Multiple factors can severely affect quality and traceability in biobanking and among the most important are sample management and tracking, and frozen specimen quality. It is of great value to use a powerful software tool to centralize all biological and clinical data associated with each sample stored in a biobank. Moreover, the list and the number of items linked with a targeted pathology have to be well defined in order to be able to develop different specific projects with research partners. We have set up a non-tumoral and tumoral thyroid pathology biobank and collected more than 280 items for each patient, who were recorded in a dedicated and sophisticated database (CRESALYS® data base). Samples from more than 1900 patients with thyroid disease are currently recorded in the data base. This latter system is well adapted for the management of a local biobank as well as networks of biobanks. Each specimen is assigned automatically by CRESALYS® a unique identifier that can be printed as a barcode to label the corresponding tube. CRESALYS® provided us an environment to register as much annotation as required for research projects. From patient demographics, epidemiology and history through clinical annotation and patient follow-up to pathology annotation, CRESALYS® host as much annotation as required to ensure that selection of thyroid specimens for research projects was as precise as possible to guarantee more efficient methods for discovery. Results can be provided as a list with a dynamic link to allow fordirect access to the thyroid specimen or patient of choice by double-clicking in the list.
DNA Extraction and Amplification by Whole Genome Amplification from Small Volume Blood Samples: Applicability in the HCB-IDIBAPS Biobank Routine Work
In the biobank routine environment sometimes it is difficult to obtain the large volumes of blood that are needed for DNA extraction, especially in the case of certain diseases and specimens. In this situation, alternate technical protocols are required to obtain enough sample material for research purposes. In the current project, we have obtained DNA by an automated method from 3697 patients who each provided 200 ul of blood. The average quantity of DNA extracted was of 1.023 ug. To increase the quantity of DNA available for downstream purposes, we amplified 1 ul of DNA from each sample by standard whole genome amplification techniques. A total of 3558 samples amplified correctly (> 20 ng/ul, > 400 ng total), obtaining an average quantity of DNA of 198.24 ng/ul (3.98 ug total). These results open the possibility of using small quantities of precious samples for biobanking processes and research projects that otherwise would be discarded.
The Next Frontier of Biostabilization at Ambient Temperature: Viable Virus and Cells
Biomatrica is a biostability company focused on the development and commercialization of biospecimen stabilization technology. In this abstract, we describe results obtained in the fields of viral and prokaryotic cell stabilization. In the virus field we show proof-of-concept studies on generating prolonged stabilization of viruses in a liquid state. Using viable AAV (a replication-defective non-enveloped parvovirus) and adenovirus (a replication-defective non-enveloped virus) as model systems, candidate biostabilization compounds were identified which yielded cultures where >90% of the initial titre was recovered after 6 days at ambient temperature. Recently Biomatrica successfully applied this approach to improved live prokaryotic cell stabilization where chemical stabilization has been used successfully to increase the viability of prokaryotic cells even at extreme temperatures of up to 50°C. These technologies can be used to transport environmental samples safely to the storage and analysis facility without loss of viability. We will present stabilization studies for the collection of gram-positive and negative bacteria that include surrogates for health hazards and biothreat agents.
The studies validate that the basic technology underlying Biomatrica's biospecimen stabilization, as well as the selection process used for identifying biostability compounds, have utility extending into the exciting prospect of maintaining viable cells and functional viruses during long term storage at ambient temperatures. Ambient stabilizers of living organisms will expand the tool set for environmental surveys for global collection of environmental samples. Sample logistics will be improved, cost for surveys reduced and higher specimen quality will result in improved analysis.
Safe Cryogenic Freezing and Storage in Liquid Nitrogen of Cell Lines
Cryogenic storage of viable cells is optimal at liquid nitrogen temperature (−196°C). However, cryogenic vials with screw-caps cannot be immersed in LN2 without risk of LN2 penetration that may be a source of contamination for the sample and may lead to explosion of the vial upon retrieval. This study compared standard cryogenic vials (ST) and new cryogenic vials (High Security Tube, CR) that are thermally airtight sealed with a dedicated sealer (SYMS II) before cryopreservation. Growth and viability after 6 days of freezing and thawing of 1 mL of 106 of 3 different cell lines (MRC 5, BXPC3 and CCRF-CEM) were compared: 2.0x106_ 93% viability and 1.9x106_ 95% viability for MRC-5, 2.3x106_ 98% viability and 1.9x106_ 97% viability for BXPC3 and 42x106_ 95% viability and 53x106_ 95% viability for CCRF-CEM cells were found for ST and CR vials respectively. PK15cl28/BS cells contaminated with mycoplasma orale and MDBK cells contaminated with bovine enterovirus distributed, frozen and thawed in ST and CR vials showed comparable viability (94/99% and 78/77% respectively) and no cross-contamination was found between tubes immediately after thawing or after 5 days cultivation. All the tested CR vials resisted to the cryogenic conditions of the freezing process and long term storage under LN2. Conclusion: based on the results of this study, the new cryogenic vial sealed with the dedicated thermal sealer can be considered a safe alternative for storage of cell lines in liquid nitrogen.
Fundación Tecnalia Research & Innovation, Parque Tecnológico de Bizkaia, Zamudio, Bizkaia, Spain
Pathologists take histological images of thin slices of tissues for microscopic examination in order to study the manifestations of disease. Although many biobanks and pathology departments adequately capture and digitalize these histological images, they are currently spread all over different systems stored in different formats, databases and facilities belonging to different institutions. These image collections comprise a very valuable knowledge in several fields, but the exploitation of this potential requires mechanisms to gather, access, visualize, process, understand and maximize the potential of large image collections. Here we describe a new EU funded project, BIOPOOL, which has the objective to build a system to link pools of digital data managed by biobanks (comprised of histological digital images of the biologic material and the data associated to these images) and to develop added value services through the internet for the exploitation of this information (data sharing, image visualization, text and image based search queries and advanced functions such as region-of-interest extraction or automated pathology information extraction in certain cancer types). The project will develop the needed technology to extract and gather digital information from different pools, analyze it, compare it and score images similar to one provided as a search pattern based on an innovative Content Based Image Retrieval (CBIR) system capable of searching histological images using different mixed text and image queries. Safety, security, and standards for data sharing will be evaluated. BIOPOOL aims to establish an intelligent pan-European Biobank network, demonstrating the potential of clinical and histological data pool for medical research, diagnosis and educational activities.
Erasmus MC Tissue Bank, department of Pathology, Rotterdam, The Netherlands
Pathology departments and biobanks are increasingly using Digital Pathology (DP) images for sharing of research results, ring trials, education, fast second-opinion diagnostics, pathology panels, digital back-up of slides, image analysis algorithms, et cetera.
To fully exploit the potential of DP, the BIOPOOL project develops software for extracting and gathering DP slides with well-defined associated data from multiple biobanks and pathology archives, to create pools of images on which clinicians and researchers can search for references, score for similarities with their own images using an innovative Content Based Image Retrieval system, and perform in-depth image analyses.
Here we describe the main requirements to facilitate a large amount of DP images with associated data to be used for testing and validation of the BIOPOOL developments:
• Pathology slide scanners with adequate resolution and experienced operating personnel;
• Sufficient storage capabilities with secured access to the internet to enable image sharing outside one institute;
• Facilities to retrieve the associated data with DP images in an ethically and legally compliant manner, similar to data associated with biospecimens, e.g. a caTissue compliant biobank management system or LIMS;
• IT support to enable and maintain connection of different databases and to facilitate the transport of high volumes of DP imaging data;
The more institutes with well-defined DP image collections that contribute to BIOPOOL, the more robust and diverse this pool of images becomes. BIOPOOL may then serve as a leading example for using the full potential of DP imaging and to justify these required investments.
Div. Clinical Protein Science & Imaging, Biomedical Center, Dept. of Measurement Technology and Industrial Electrical Engineering, Lund University, BMC C13, SE-221 84 Lund, Sweden
Pulmonary diseases such as lung cancer and Chronic Obstructive Pulmonary Disease (COPD) are currently among the major leading causes of death and their prevalence is increasing. The leading cause of COPD is smoking and an estimated 600 million patients suffer from the disease. Biomarker discovery studies undertaken in Japan and Europe, where the objective was to identify marker-assisted diagnosis for targeted therapies, has been undertaken in several clinical studies. Within these studies, many years of personalized medicine clinical study experience for biomarker discovery and development, including studies with a cohort close to 7,000 patients, are predictive of efficacy and safety in late stage lung cancer. These studies have been performed with lung cancer patients with IRRESSA treatment, a targeted personalized medicine drug, with EGFR-tyrosine kinase affinity binding with a kinase inhibitory efficacy. The aim of this study is a novel automated sample-processing concept for future proteomics and clinical research, performing patient studies from blood fractions in various disease areas. A key part of these developments is a large scale biobank infrastructure. Biobank storage of small sample volumes is important, in order for each sample aliquot to be used for a dedicated clinical analysis and end-point measurement, and in order to preserve sample integrity and value over time. Both 96 and 384 format sample storage tube systems were utilized for preservation and archiving of clinical patient samples. Automated sample processing and aliquoting were achieved using robotic liquid handling instrumentation, followed by biomarker assay quantitations. Sample workflow was documented and tracked by a Nautilus LIMS. Validation by repetitive processing and analysis confirmed the reliability of automated high-density 384 format aliquoting. This high density scaling allows for reproducible aliquoting of 70-μL volumes of blood. Plasma with EDTA, lithium-heparin, and citrate as anti-coagulants were fractionated along with the buffy coat (leukocytes) and the erythrocyte fraction. Large scale processing of 11,000 sample aliquots resulted in a 99.8% process fulfilment. Our results demonstrate that robust results can be generated from an automated sample processing strategy, isolating plasma, buffy coat, erythrocytes, serum and whole blood, proven by quantitation of 23 common markers used in everyday healthcare around the world. In addition these developments will be of great value and importance to programs such as the Chromosome Human Protein Project (C-HPP), that will associate protein expression in healthy and disease states with genetic foci along of each of the human chromosomes.
Developing of a qPCR Strategy for Evaluating HER2 Status on Archived FFPE Samples from Tumor Biobanks
OTHER TOPICS (OT)
Assessment of the Awareness and Perception of the Use of Biosamples in Research in Patients at King Hussein Cancer Center
A questionnaire was distributed to assess the awareness and investigate the perception of the use of surplus blood and archived tissue samples in research in a sample of cancer patients at King Hussein Cancer Center. Most patients did not have a clear idea of the destination of surplus blood/tissue after clinical care. The vast majority of patients (98%) accepted using their surplus blood samples and archived tissue in research. Eighty-three percent did not mind donating blood samples for research purposes only. A majority of patients (67.8%) did not demand being consented each time their samples are used, although many were interested in the results (p-value 0.02). Eighty-one percent of patients did not object to sending their samples to outside laboratories as part of a research protocol without being consented (p-value 0.05). The views of a predominantly Muslim Arabic community on use of tissue for research are not different from those expressed in the international literature.
Aspergillosis Impact in Pathology in the Resuscitation Services of the Central University Hospital of Oran
The presence of mould in hospitals has become a concern for both health professionals and patients. It is well established that organic contamination in the hospital from multiple sources such as air, water, blouses, renovations is a major risk for weakened patients undergoing invasive procedures. During the month of June, cases of fungal contamination have been reported in the intensive care unit following construction in the basement that included the stripping of plaster wall coatings without protecting the surrounding areas.
Collaboration of Biobank and Dutch Center for Personalized Cancer Treatment Leads to Optimal Working Processes, Standardized Procedures and Maximal Traceability
The UMC Utrecht Biobank collects a variety of samples (blood, urine, DNA and tissue) in collaboration with different research groups; one of the research groups is Medical Oncology. This group founded the Center for Personalized Cancer Treatment (CPCT), a collaboration between the three large cancer hospitals in the Netherlands. In this CPCT workflow, Next-Generation Sequencing (NGS) is applied to sequence actionable genetic variations (diagnostics), in combination with mutational profiling of 2000 cancer related genes (research) using core needle biopsies of metastatic lesions. Involvement of the Biobank is sought to guarantee proper collection, preparation, documentation and storage of samples by means of a LMS (Laboratory Management System). For the various CPCT studies a specific protocol was developed that supports the workflow from the moment of arrival of the samples from collaborating hospitals till the presentation of findings in the research group. The workflow was designed to reduce possible mistakes, guide the work process, guard the decision making process, and document all relevant sample information in a standardized way. Samples (biopsies and blood) are coded in each hospital, transported to Utrecht and incorporated in the Biobank. Subsequently, an H&E slide of the biopsy is prepared and presented to the pathologist to determine the tumour percentage. If the tumour percentage exceeds 20%, LMS releases the material to start isolation of DNA from all samples. Specific quality checks are registered in LMS and subsequently LMS calculates the DNA amount sufficient for NGS. Remainders of blood, biopsies and DNA are stored in the Biobank.
Inbiobank, the First Adult Stem Cell Biobank Authorized in Spain
Inbiobank is the first authorized biobank in Spain for the banking of adult stem cells and primary cells for biomedical research. Inbiobank belongs to Fundación Inbiomed, a private, non-profit research foundation dedicated to stem cell research and regenerative medicine located in San Sebastian, Spain.
Inbiobank currently holds in its collection mesenchymal stem cells from bone marrow, adipose tissue and umbilical cord (Warthon's jelly) as well as primary skin fibroblasts and keratinocytes. Dental pulp mesenchymal stem cells and cord blood hematopoietic progenitors (CD34+) will be incorporated shortly. These cells have been extracted and cultured using proprietary methodology developed in the research laboratories of Fundación Inbiomed.
Inbiobank facilities include a white room laboratory for the extraction and growth of stem cells from altruistic tissue donations obtained from local hospitals (Hospital Donostia and Policlínica Gipuzkoa) after informed consent from the donors. Inbiobank holds ISO 9001:2000 certification for quality assurance and has developed a LIMS system (manufactured by Labware) for the management of sample and stock information and for the distribution of samples to interested researchers. Inbiobank has developed a web page (www.inbiomed.org) where info of the collection as well as ordering information can be obtained.
CIBERER Biobank, Centro Superior de Investigación en Salud Pública (CSISP), Spain
CIBERER Biobank (CBK) processes and stores high quality biological material and its associated data, and assigns the samples to national and international, public or private research groups whose research projects pass evaluation by the Scientific and Ethics Committee. In addition, CBK is currently working to support research on Rare Diseases (RDs) by implementing new protocols to offer new services to the international scientific community.
In addition to current services (DNA extraction, fibroblasts culture from skin biopsies, B cell immortalisation, etc.), CBK is also offering a new service: muscle satellite cells/myoblast isolation and culture from muscle biopsies obtained from human donors affected by muscular dystrophies and neuromuscular disorders.
CBK is also working on a protocol to generate iPS cells from fibroblasts in the foreseeable future. iPS cells provide an invaluable source of pluripotent stem cells for cell transplantation therapy, etc., due to the fact that iPS cells can proliferate vigorously
In summary, in order to facilitate studies in different areas of RDs research, CBK is working on the establishment of a variety of new services for the scientific community to provide diagnostic and therapeutic solutions for patients and in some way, give the CBK an added value as a biobank.
Institut de Recherche en Sciences de la Santé, Bobo-Dioulasso, Burkina Faso
Single nucleotide polymorphisms (SNPs) in the P. falciparum pfcrt, pfmdr1, pfdhfr and pfdhps genes are associated with decreased response to aminoquinoline and antifolate and have been shown to be selected by use of these drugs. The degree of selection by intermittent preventive therapy regimens (IPTc) is unknown. We assessed the baseline prevalence and selection of common SNPs by IPTc in children in Burkina Faso. We randomized 1500 children to receive monthly dihydroartemisinin-piperaquine (DP) or amodiaquine-sulfadoxine/pyrimethamine (AQ/SP) during the malaria transmission season. From random samples of 120 children for each study arm and 120 of 250 untreated controls, we evaluated the prevalence of key resistance-mediating SNPs. We then assessed the prevalence of the same SNPs in samples collected one month after the third dose of IPTc. The prevalences of SNPs was 68.5% (178/260) for Pfcrt 76T; 29.1% (75/258), 58.5% (151/258) and 7.70% (20/260) for Pfmdr1 86Y, 184F and 1246Y, respectively; 58.1% (151/260), 54.8% (143/261), and 55.0% (143/260) for Pfdhfr 51I, 59R and 108N, respectively; and 35.1% (91/259) and 56.8% (147/259) for Pfdhps 436S and 437G, respectively. After three monthly IPTc, AQ-SP selected significantly for mutant sequence pfcrt 76T, pfdhfr 59R, 108N and triple mutant 51I, 59R and 108N. DP did not select for polymorphisms in pfcrt, pfmdr1, pfdhfr and pfdhps as described elsewhere in DP clinical studies. Our results indicate that IPTc with AQ-SP selected for polymorphisms linked to resistance to AQ and SP probably because of increasing use of these drugs. DP may therefore be an excellent alternative for malaria prevention in children.
Hospital Integrated Biobanking – How to Develop a Proof of Concept Within an Existing Hospital Health Care Organization
Access to biological samples and data of high quality is essential for successful medical research to improve medical treatment and increase quality of life. Uppsala Biobank has created an excellent opportunity for research by setting up a biobank service. The service makes the collection of blood samples possible in an efficient and safe way, with high quality. Samples are collected from patients in routine health care, and stored and managed by the biobank. To achieve this it was vital to identify, involve, and enthuse stakeholders within the county council and the University hospital in Uppsala. This led to the recognition of established partnerships between existing laboratories and biobanks. A hospital integrated biobank service was established by utilizing existing infrastructure for ordering blood samples and printing labels, managing information between different hospital IT-systems, handling samples within an existing clinical chemistry laboratory, and adding a biobank LIMS system. Members from the different stakeholder groups gathered as a project team led by a project leader. Today the blood samples that are collected for the biobank are handled by the routine health care system at the University hospital. We have shown that it is possible to do hospital integrated biobanking in a successful way by collaboration and professional management. Our next project will cover the same issues, but this time for the collection of tissue sample and cells, following the same successful method.
p-BioSPRE - An ICT and Contractual Framework for Transnational Biomaterial Sharing and Access
Biobanks represent key resources for clinico-genomic research and are needed to advance the area of personalized medicine. For these fields it is crucial that scientists can securely access and share high quality biomaterial and related data. Therefore, there is growing interest in integrating biobanks into larger biomedical ICT infrastructures.
The European project p-medicine (www.p-medicine.eu) is currently building an innovative ICT infrastructure to foster the advancement of personalized medicine. This platform provides tools and services to semantically integrate and analyze heterogeneous biomedical data and comprises an ontology-based trial management system called ObTiMA (http://www.obtima.org) to design and conduct clinical trials. Another main component is the biobank access framework p-BioSPRE. Technically based on the CRIP toolbox (http://crip.fraunhofer.de) and mainly driven by user scenarios from the fields of Acute Lymphoblastic Leukemia and Wilms Tumors, p-BioSPRE is currently developed as a generic platform to enable secure sharing of biomaterial within open and closed research communities.
The p-BioSPRE framework enables scientists to search for and request biomaterial fitting their research purposes. It allows biobank owners to share their biomaterial and related data stored in their biobank management systems and to provide their data for data integration within the p-medicine platform. Furthermore, the framework comprises a trial biomaterial manager that enables biobank owners to manage their biomaterial in ObTiMA, thus providing an integrated solution for managing and analyzing biomaterial and clinical data. Legal aspects are considered by providing a common contractual setting to facilitate and regulate the cooperation between the involved parties.
Acquisition of High Quality Tissues to Support Genome Wide Association Studies
The NIH Common Fund's Genotype Tissue Expression (GTEx) program will provide valuable insights into gene regulation by assessing expression and regulation in multiple human tissues. In order to achieve this objective, high quality and appropriately annotated biological specimens must be collected in order to perform this research. The National Cancer Institute's Cancer Human Biobank (caHUB) infrastructure, which is detailed here, has provided the necessary accrual of more than two dozen tissues from 170 post-mortem and surgical donors for the pilot of this initiative. caHUB's real-time pathology review has resulted in improved tissue site identification, fixation, and immediate remedies of procurement issues. The quality assurance operations have allowed for tracking and reporting of issues at the individual level which has led to an overall decrease in incidents related to procurement, shipping, and reporting. Through continuous monitoring and evaluation of metrics, along with identifying and addressing opportunities for improved efficiency and quality, caHUB will continue to meet the needs of GTEx with fit-for-purpose specimens. Over the next three years, this robust infrastructure will provide tissues from up to 900 donors. The caHUB program has demonstrated how a high quality biospecimen resource can help implement Genome Wide Association Studies which can lead to the identification of gene expression targets.
Setting up Public-Private Partnerships: Experience of the LPCE Biobank (University of Nice Sophia Antipolis, Nice, France)
The increasing use of human biological samples is of great importance for the understanding of human disease pathophysiology, as well as for the development of new biomarkers for the diagnosis, prognosis, and predictive response to treatment. The use of human samples is strictly controlled by an ethic assessment according to the laws of each country. These laws allow control of partnerships between biobanks of the academic sector and industry. These private-public partnerships can be limited for several reasons, which can strongly hamper rapid discovery of new biological tests or of new active molecules targeted to human diseases. The bottlenecks and roadblocks to establishing these partnerships are due to a number of causes, such as weak organization of the public structures that prevents rapid implementation of such a collaboration, the difficulties in making contracts, and the fact that the public and private partners do not share the same objectives when using human samples. Moreover, it is difficult to harmonize the cost of the biological samples from one biobank to another, both in the same country or between different countries. However, such partnerships with private companies are critical to sustain the future of academic biobanks. The purpose of this presentation is to describe the major bottlenecks in our own institution and how we tried to optimize partnerships with private companies.
RESOURCE DEVELOPMENT (RD)
Do Only Healthy Persons Participate in Population Studies? The LifeLines Study
Innovation in Assistance Circuits Based on the Use of Human Tissues and Cells from Living Donors or Cadavers - Advantages in the New Spanish Legal Framework
1. Spain regulates the activity of biobanks, guaranteeing the rights of donors and providing established norms of sample collection thus combining the interests of concerned citizens and biomedical research.
2. Andalusian biobanks are pioneers in this activity resulting from the synergy among different care areas involved in the handling of human samples. This allows for sampling in a controlled manner to meet the demands of the biomedical research field.
3. Collection of samples for research will depend on the quantity that can be obtained by the SSPA, through the Andalusian biobanks.
Sheba Medical Center's Breast Repository
Sheba Medical Center, which is a university-affiliated tertiary hospital, is the largest medical center in the Middle-East. Sheba's-Breast-Repository is composed of two, IRB-approved branches. The first, established on 06–2009, is surgical. Biospecimens are collected from patients undergoing breast-resection due to cancer or breast-reduction for cosmetic reasons. The second, established on 08–2011, is the first Israeli bank for breast biopsies from women diagnosed with cancer who are facing neo-adjuvant therapy. Both branches collect, document and preserve biospecimens with linked-data (clinical, pathological, demographic, other).
The surgical branch holds biospecimens of 272 donors, including 68 tumor, 87 blood-only, 84 blood+tumor-free tissue, 20 ascites fluid for culturing cells. Molecular, biochemical and pathological QC tests confirm that all samples are of the highest -quality. Only 25% of samples are of tumor origin, as many breast biospecimens don't meet the following rigid criteria for collection:
No proven biopsy of invasive breast cancer A tumor size less than 1.5–2 cm A specimen that cannot be assessed macroscopically (e.g. from DCIS patients) Patients who had neo-adjuvant therapy
We recently established the second branch for biopsies from cancer-diagnosed women facing neo-adjuvant therapy. Samples are collected when the patient arrives to mark the tumor prior to neo-adjuvant treatment (35 biospecimens so far). This new approach will enable an increase in the number and diversity of breast biospecimens to be included in research. Sheba's-Breast-Repository encourages studies that examine biological components/genes which may be involved in tumor development, the risk of developing cancer, the tumor's progression or expansion, as well as the cells response to various treatments.
Hospital Universitari Vall d'Hebron Biobank: A Hospital Integrated Biobank
Biomedical research is a key tool for improving knowledge of diseases and for developing methods of diagnosis, prevention, and treatment of diseases to improve the quality and life expectancy of human beings. Therefore, in the last years there has been a growing interest in the development of human sample biorepositories of a variety of human diseases.
Spanish Biomedical Research Law (Law 14/2007, of July the 3rd, Biomedical Research) and Royal Decree 1716/2011 (Royal Decree that developed after the Biomedical Research Law) were passed to regulate the proper collection, storage and use of biological samples of human origin, and to promote their use for biomedical research by following good ethical and scientific practices.
The Hospital Universitari Vall d'Hebron Biobank (HUVH Biobank) is a research support unit that collects human biological samples for biomedical research purposes in compliance with the current legislation, and whose objective is to make available to the scientific community the biological material necessary for research in optimal conditions to ensure competitiveness and research excellence.
The HUVH Biobank is part of the Red Nacional de Biobancos promoted by the Instituto de Salud Carlos III.
The collections of biological samples for biomedical research purposes integrated within the organizational framework of HUVH Biobank are:
- Tumor Bank
- Fetal Tissue Bank
- Pediatric Endocrinology Bank
- Immune Mediated Inflamatory Diseases Bank
An overview of this hospital integrated biobank will be presented.
LPCE Biobank and Biobank PACA, University of Nice, Nice France
Conditions for setting up a human biobank, in particular in France, have been upgraded by taking into account, (1) the laws that integrate the ethical and societal dimension of biobanking and delineate the risks for patients associated with the procurement of human biological products; (2) the increasing request by scientists for human samples with proven biological quality and clinical annotations, including information produced through the use of molecular biology in pathology; and (3) the establishment of procedures concerning the safety of the personnel working with biological products. The present work was conducted to describe how we set up a biobank targeting lung cancer, with the aim of rapidly developing translational research projects. The prospective experience of a single institution (Pasteur Hospital, Nice, France) over an 8-year period (2004–2012) is presented from the practical point of view of a surgical pathology laboratory tightly associated with a biobank. We describe different procedures required to obtain high-quality lung biological resources (fixed, frozen and fresh tissues, biological fluid samples, nucleic acids, tissue microarrays, primary cultures) and clinical annotations. The procedures were established for the management of biological products obtained from 1250 patients who underwent lung surgery. The pre analytical steps leading to the storage of frozen specimens were carried out in parallel with diagnostic procedures. The described lung cancer biobank has been set up using criteria established by the French National Cancer Institute to guarantee the quality of different collections stored in biobanks with specific annotations for lung cancer disease.
AP-HP, Paris, France
The pathophysiology of inflammatory bowel diseases (Crohn's disease and ulcerative colitis) is complex. Microbiological, immunological and genetic factors are involved but the aetiology of these diseases is still unknown. A couple of susceptibility genes (such as Nod2, Atg16, IRGM, etc.) can participate in the onset of some subtypes of IBD. Large collections of human biological resources of high quality associated with clinical data are needed to improve our knowledge concerning these diseases through the development of multicenter research projects. The REMIND working group aimed to set up a large collection of biological resources from IBD patients before (digestives biopsies, blood samples, stools, digestive secretion) and after surgical resection (surgical specimen, blood samples, stools, digestive secretion). The general purpose of the research program will be to determine different potential microbiological, immunological and/or genetic factors which could explain an early relapse of the disease after surgery. The entire biological resource had to be sent from different French centers to a single central biobank (LPCE Biobank, Nice, France). The samples of 500 patients originating from 14 different French gastroenterology departments will be included in the LPCE biobank between 2010 and 2013. Eight national research projects have been set up to take advantage of these biological resources. These projects will be done in different French research centers. The scientific advisory board of the REMIND Biobank can also evaluate different external projects requesting use of the biological resources stored in the LPCE Biobank.
Sampling of Haematological Neoplasm Patients in Aragon Biobank
Aragon biobank, in collaboration with the Metabolic and Haematological Rare Disease Research Group from Instituto Aragonés de Ciencias de la Salud, has created the collection of Haematological Neoplasms (HNs) to obtain haematological and bone marrow samples of new diagnostic cases with the objective to understand the genetic origin of these diseases (molecular and genetics changes, miRNAs, polymorphisms, etc.).
Meilahti Integrated Biobank Infrastructure (MIBI): The Leading National Center for Next-generation Biobanking
Biobanks of human biological samples with associated medical data represent a vital resource in unravelling the etiology of diseases, identification and validation of new diagnostic methods, as well as advancing personalized medicine. Finnish researchers have been in the global front-line in the application of biobanks for decades. The Meilahti campus is in a unique position to benefit from the largest patient pool in Finland, as well as their decades-long tradition and experience in collecting both clinical and population sample cohorts.
Between 2009–2011,two institutes, Institute for Molecular Medicine Finland (FIMM), and National Institute for Health and Welfare (THL), joined forces with other stakeholders on the Meilahti campus and created a state-of-the-art biobanking facility, the Meilahti Integrated Biobank Infrastructure (MIBI). MIBI offers full-service biobanking capabilities: consultation on biobank project planning; centralized sample storage services; biobank informatics; and high-quality DNA, RNA, protein, and exosome extraction and aliquoting together with extensive cell and tissue biobanking and molecular pathology facilities.
MIBI can currently provide access to over a million samples from nearly 200,000 subjects and has the capacity to store a million more. The number of samples and subjects is increasing due to several on-going sample collections. MIBI sample storage will be automated in 2012 and connected to automated sample processing. High security is guaranteed by a dedicated LIMS database designed for biobanking logistics. MIBI ensures consistent high quality sample processing and storage.
Establishment of a Process of Detection of Mycoplasma with Prior Validation of the Technique in the Framework of a Quality Management System in the Andalusian Public Health System Biobank
Contamination by mycoplasma of stable and primary cell cultures not only constitutes a major economic problem but is also of biological importance in basic research, and diagnostic and biotechnological production. For this reason, quality control for the presence of such microorganisms should be a mandatory requirement of both the cell stocks and any new culture that arrives at a laboratory or a cell bank. Therefore, the Andalusian Public Health System Biobank includes the detection of mycoplasma by conventional PCR of any cell culture system that is requested within its services portfolio and as an internal necessity. Before including such service, a validation process was carried out that consisted of creating a test using two reagents from two different companies to test the technique, along with two ways to view the data in order to define the best method and provide clear and easy-to-interpret results for the users. Then the detailed diagram of the process along with the documented procedure was established. This diagram, which is presented in this communication, helps not only to identify the correct circuit that must be tracked from any specimen to be processed, but also to make decisions that are to be carried out when problems arise within that circuit to offer fast, efficient service of high quality. Any future improvement that occurs in the process will be reflected in the diagram.
Proposal for a System of Traceability of Samples in a Biobank Based on the Consideration of the Unique Identity of Each Sample
An operating system ensuring traceability should have the following specifications
- Identification using a two-dimensional barcode reader.
- Check each point in the process from the log storage and transfer.
- Monitoring of the processes applied to samples and identification of the professional responsible for each stage of the procedure.
- Real time information on the status of the sample.
- Applicability to all kinds of samples (liquids, cells, cultures, solid tissues)
- Exploitation and data export.
- Communication and compatibility with other applications.
- Dynamism and adaptability to different biobank sites.
- Meet the requirements to enable the certification/accreditation of the BioBank.
The Biobank of the Hospital Clinic – IDIBAPS and CIBERDEM Establishes the First Ancient DNA Bank
Studies of ancient DNA (aDNA), a discipline that emerged in the 1980s, has been growing due to the improvement of molecular biology techniques. Paleogenetic studies are a powerful tool to understand ancient populations, aiding in the determination of their structure, origin, and evolution. A year ago, the HCB- IDIBAPS Biobank, in collaboration with CIBERDEM, established a new working area focused on aDNA studies, supported by the FP7 European grant for the Medigene Project. The aDNA laboratory is located in an isolated area of the Biobank, and is provided with special safety measures such as UV lights and positive pressure due to the special susceptibility of contamination of aDNA with modern DNA. The aim of the project is to constitute the first existing aDNA Biobank from samples obtained from exhumed skeletal remains belonging to different necropolis from the Roman period (I – IV centuries AC) located in Tarragona (Spain), provided by the Catalan Classical Archaeological Institute (ICAC). DNA will be retrieved from teeth and extracted using aDNA techniques. Current advances include the set-up and optimization of the techniques and determination of the quality controls that will be performed following criteria for authentication proposed by the aDNA research community. Together with the samples, a database with archaeological and anthropological information is being built to provide information for future studies. This biobank will add extra value to the HCB-IDIBAPS-CIBERDEM Biobank.
P3G: Providing the Tools, Services and Training to Sustain the Biobanking Research Community
The Public Population Project in Genomics and Society (P3G) is an umbrella organization providing a forum for stakeholders to exchange and develop know-how, tools and policies with the aim of streamlining and harmonizing international collaborative research. With well over 350 members across more than 50 countries, P3G is the catalyst for current exchange amongst the worldwide biobanking community. It is strategically placed within this research community to create an interactive web-based forum.
In its Phase 2, P3G has six main axis: (1) Biobank TOOLKIT providing epidemiological, ethical, statistical and IT instruments for the access and use of existing biobanks; (2) Biobank LIFESPAN, a platform offering users a step-by-step approach for the development and maintenance of biobanks; (3) Biobank CATALOGUES, with information on large population-based biobanks; (4) Biobank TRAINING, with tutorials and information sessions; (5) Biobank HUB, an online forum for those interested in discussion, exchange and collaboration on biobanking projects; and (6) BRIF, generating a unique identifier for each bioresource to be cited in scientific publications.
Providing real-time international expertise in the development of international research initiatives, Phase 2 of P3G will optimize the international potential of biobanks. P3G appeals both to experienced researchers wishing to keep informed of the current issues in the community, as well as to newer members seeking assistance in the development of such research infrastructures.
Helsinki Urological Biobank - New-generation Integrated Biobank for Facilitating Personalized Medicine and Translational Research in Urological Cancers
(equal contribution)
The specimens and associated clinical data of disease cohorts are needed for the development of biomarkers, improved diagnostics, disease prediction, and for the development of personalized therapies. Helsinki Urological Biobank (HUB) is a joint project of FIMM and Hospital District of Helsinki and Uusimaa (HUS) that aims to improve diagnostics and treatment of urological diseases and cancers. Based on informed consent, HUB collects fresh, frozen, and formalin-fixed paraffin embedded tissue samples together with blood and urine samples and comprehensive clinical information from patients with urological malignancies, i.e. prostate (including benign hyperplasia), renal or testicular cancer, or cancer of urinary bladder. Samples are collected at the time of diagnosis and at follow-up visits and processed according to the needs of modern translational research.
In 2012, there will be approximately 900 urological surgical procedures performed in the HUS area. This project aims to enroll at least 80% of those patients to donate samples. Sample collection started in March 2012, and is currently ongoing. Good connections to clinicians are essential and new processes are being brought close to the normal hospital work without compromising patient care and diagnostics.
HUB aims at implementing new procedures for improved transparent, ethical and rapid access to biobanked materials for both academic research and company-initiated research and development. The technologies, procedures and approaches adapted and optimized are communicated nationally via the BBMRI.fi biobanking network in order to facilitate the adaptation and harmonization of new biobanking approaches in Finland.
The Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia-Romagna (IZSLER) is a Veterinary Institution of the Ministry of Health. During the last decades, IZSLER collected numerous samples of both human and animal origin. These resources have permitted the set-up of a collection of different kinds of materials: viral and bacterial agents, parasites, tissue and organ specimens, field sera, monoclonal antibodies, etc. These samples were stored in IZSLER departments, located in two Italian districts (Lombardia and Emilia-Romagna). In order to provide availability of these materials to all IZSLER labs, aa unique facility was found.In order to create a biobanking structure, it was necessary to observe strict criteria: samples census, data recording, quality control system, Standard Operating Procedures (SOPs) and informatic tools. In particular, the main aspect was represented by the features of the samples that determined different biohazard levels and specific storage conditions. Another important aspect was the sharing of materials; limited access to storage areas guaranteed the required safety conditions. Finally, the aim of this project was to organize a structure able to share and distribute samples in order to encourage a possible Italian network in the veterinary field. The plan is to extend this network to others European groups in the future.
Brain Tissue Bank from Temporal Lobe Epilepsy Curative Surgery
Since 2001, we have started to bank biopsy specimens from hippocampus of intractable medial temporal lobe epilepsy patients who underwent curative surgery and whose consent was obtained prior to the surgical procedure. As of today there are 136 hippocampus tissues in the registry. The underlying mechanisms that cause neuronal loss in these cases are still not known. The major aim of this brain bank is to study the degenerative process involved. Besides the basic research component, this study enabled us to analyze the conditions for high quality preservation of brain tissue. Factors such as 1) type of storage vehicle; 2) time of transport from the surgical room to the Biobank; and 3) temperature of transport (liquid nitrogen or dry ice) were optimized during this period. Since the architectural properties of the tissues are evaluated in parallel with the clinical pathologist, the storage conditions and the storage vials should allow a mirror image rendition of the tissue that is shared between the Biobank and the pathology department. Further cytochemistry and RNA expression studies allowed us to evaluate and modify the conditions of brain tissue storage.
Bimetra: a Platform to Facilitate Translational Biomedical Research
Bimetra is the Clinical Research Center from Ghent University and Ghent University Hospital. The mission of Bimetra is to facilitate, stimulate and improve translational biomedical research, from bench to bedside and from bedside to community. By acting as a central point of contact to integrate biobank activities, translational data management, clinical trial management and regulation,and translational research and development, and provide translational core facilities, Bimetra wants to reinforce the leading scientific position of the University Hospital (UZ Ghent) and Ghent University.
Up to now, department specific-biobanks were spread out over the campus, with varying ethical, quality and data management standards. A 200m2 central UZGhent Biobank facility, under the coordination of Bimetra, will be built by 2014. A smaller biobank facility (75m2) is currently available. The UZ Ghent Biobank facility will store a fraction of valuable historical/retrospective collections, but will focus mainly on establishing future/prospective biobank collections. Bimetra is ensuring that the biobank will operate according to a large quality management system, within a clearly defined ethical-legal framework, combined with powerful data management systems. This quality system is currently being established in a few pilot biobanks, such as the UZ Ghent Tumor Biobank.
Use of Hospital Samples for Derivation of Human Mesenchymal Stem Cells (MSCs)
Developing South Tyrolean Biobank Resources to Promote Research and Health Care
The Center of Biomedicine (CBM) is a multidisciplinary center founded in 2011 by the South Tyrolean Health Service and the European Academy of Bolzano (EURAC). Research areas that were well organized within the EURAC-Institute of Genetic Medicine were further expanded and developed. In addition to these research areas, new translational research programs where there is synergistic cooperation between individual research groups, hospitals, healthcare practices and the population were established; this is helping to facilitate a translation strategy. Two biobanks were built within this program. The first was placed in Merano Hospital and is dedicated to the “Cooperative Health Research in South Tyrol Study” (CHRIS), a longitudinal, population-based study to assess the etiological role of genetic and environmental risk factors and their interactions on cardiovascular, neurological and metabolic conditions. The aim of this collection in the first five years is to preserve biological samples of at least 10.000 participants from the Venosta Valley. The second biobank was placed in Bolzano Hospital and will store biosamples of participants selected for specific neurological and cardiovascular diseases. This biorepository will also provide local storage, one of several services that the CBM will offer to promote research. With this resource, new research projects will be developed that will be the first step towards proactive prevention and improved health care for all of the people of South Tyrol. In fact, the synergistic model of collaboration of the CBM is based on trust, long-term sustainability, and win-win scenarios between all parties concerned.
Royal Dutch Academy of Sciences, Brain Bank Consultants, Amsterdam, The Netherlands
The search for neurological biomarkers is still ongoing. Partly due to variation between individuals, biobanks and their SOP's there is currently no single international acceptable biomarker which can be successfully applied in the clinical situation. Biobanks operating in the framework of ISBER, ESBB and BBMRI including numerous hospital–integrated biorepositories need to intensify efforts to develop collaborative biobank networks, with harmonized protocols, sharing and exchange of specimens and open-access databases.
GeCAT - A DNA Population-Based Human Prospective Cohort of Catalonia for Genomic Prediction and Prevention
GeCAT (Genomes of Catalonia) is a medical project aimed at improving the prevention, diagnosis and treatment of cancer and many other serious conditions such as COPD, diabetes mellitus or heart disease. The project will assemble, store and protect a large bank of medical data and material that will allow researchers to study in depth, in decades to come, how the complex interplay of genes, lifestyle and environment affect the risk of disease. Because it will involve thousands of people, some ofwhom will eventually develop cancer or other diseases, GeCAT will provide a uniquely rich resource that will allow researchers to predict more reliably than ever before what specific diseases some people are likely to develop, and why some people develop a specific disease and others do not. This project aims to generate clinical, pre-emptive practices to be able to prevent disease development, delay it, or minimize it for each individual, based on their genetic profile.
GeCAT will eventually recruit fifty-thousand volunteers between 40 and 69 years of age. Volunteers will answer some questions, have some standard measurements taken, and donate a small amount of blood. Their health will be followed directly, through routine medical records and hospital admissions. Volunteers will also be asked to allow GeCAT to continue to follow their health status. Stringent security measures will be established to protect the data and the biological samples, and GeCAT will comply with all ethical and legal regulations as well as establish mechanisms to review them when changes in legislation occur in the future. Volunteers will be able to withdraw at any time. Participants will be able to access the research findings through a website where a description of the project, media releases, and publications in peer reviewed scientific journals will be located. The results from this project will benefit our children and grandchildren.
Implementation of GeCAT will aid biomedical research in Spain and will establish a precious database and sample collection. It involves future collaboration between the Institut de Medicina Predictiva I Personalitzada del Càncer (IMPPC), the Banc de Sang I Teixits de Catalunya (BsCat) and the Institut Català de Oncologia.
Specialized Service of Epidemiology and Molecular Biology (SEEBMO), Hospital de Santo Espírito Da Ilha Terceira (HSEIT), Azores, Portugal
Urolithiasis is a common multifactorial disease of unknown etiology which is characterized by the presence of stones in the urinary tract. In populations of European ancestry, 5 to 10% of adults experience a painful precipitation of calcium oxalate in their urinary tracts.
The Azores Biobank (AZORBIO) is located in Azores, Portugal, at the local hospital (HSEIT-SEEBMO). It joined the European network of biobanks - Biobanking and Biomolecular Resources Research Infrastructure (BBMRI) – in 2009. The main products stored in AZORBIO are DNA, RNA, plasma, serum, and cell lines.
In order to study urolithiasis in Azores, two departments of HSEIT, SEEBMO and the Urology Service, were approached. To accomplish this objective, AZORBIO will store the biological samples DNA, RNA, plasma, serum, urine and the associated data collected from the urolithiasis patients. Prior to the receipt of the biospecimens and data, legal and ethical aspects and laboratory facilities will be verified and standard operating procedures (SOPs) optimized. These SOPs were specially developed for the collection, receipt, processing, handling and storage of samples. Recently acquired laboratory information management system (LIMS) software is used for sample management as well as storage of all associated data. Finally, to evaluate the quality of stored DNA and RNA samples, different technologies are used to control purity, integrity, functionality and traceability. In conclusion, the addition of this new disease in AZORBIO contributes to the improvement in health as well as to a reduction in morbidity of urolithiasis patients.
Utilizing Global Health Resources o Support African Biobanking Infrastructure
In the last decade a number of global health programs have been directed toward ameliorating health epidemics and pandemics on the continent of Africa. Initiatives such as the U.S. President's Emergency Plan for AIDS Relief; the Global Fund to Fight AIDS, TB, and Malaria; the Grand Challenges in Global Health; and the Clinton Health Access Initiative are just a few examples of plans that have resulted in unprecedented amounts of money being directed at communicable diseases in sub Saharan Africa. As a result, there has been a considerable decrease in morbidity and mortality where these programs have been implemented.
As these and other initiatives have matured, they have been transformed with the goal of establishing sustainable health and research systems that can address diseases and conditions of high incidence in the region (i.e. the U.S. Global Health Initiative) such as cancer and hypertension. In order to have a functioning research structure, high quality biospecimens must be attainable within Africa, necessitating the development of biobanks. While there may be new initiatives such as NIH's H3Africa dedicating money towards enhancing standing infrastructures that can support biobanks, there is still a need to utilize other international and local public health programs to achieve the goal.
Creating sustainable biobanking infrastructures and networks on the continent utilizing these resources will be explored as well as evaluating the educational programs needed to secure official recognition and support of the need for these endeavours.
Fondazione Banca degli Occhi del Veneto ONLUS, Venezia, Zelarino, Italy
The Veneto Eye Bank Foundation ONLUS is engaged in the retrieval, storage and delivery of human tissue from eye donors for use in transplant operations within the Veneto, Friuli-Venezia-Giulia regions. Tissue retrieval is performed by dedicated specialists who take the tissue to the Eye bank for qualification and matching with potential recipients.
Sometimes, for various reasons, donated tissue is unsuitable for transplant purposes and would normally be destroyed. This would be a terrible waste of such a generous donation and desire to help humanity. In order to appreciate this precious material and the initial investment of medical and technical resources, the Veneto Eye Bank has begun non-therapeutic biobanking. Specific consent is requested to preserve cells and human ocular tissue for use in research, diagnostics, therapy and training.
The Transplant Eye Bank adheres to strict regulations for handling transplant tissue and the same measures are applied for non-therapeutic tissue. The biobank follows the same rigorous procedures for quality management, continual availability, training and safety, ensuring the highest quality material for non-therapeutic use. Personal data of donors are handled in a manner that complies with legal obligations regarding data protection (Authority for the Protection of Personal Data of 27 November 2008).
Most of the biobank costs are covered by the Eye bank as they pertain to the same receipt and evaluation processes. Additional funding comes from collaborations, research grants and cost recovery.
The non-therapeutic biobank provides a self-sustaining, essential resource for ocular disease improvement and a vital use of material so caringly donated that would otherwise be wasted.
Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
Since 2008, closed, institutional biobanking has occurred in a number of Israeli medical centers. In 2009, Israel's National Infrastructures for Science forum recommended that government funding be set aside for the establishment of a national biobanking network. Bids from potential branches were received, and a structure was established in mid-2012.
The IJCBR structure includes:
1) Biorepositories in each of four large teaching hospitals in 3 large cities, each with a pathologist, research coordinator, branch manager, technician, and data manager.
2) Four additional peripherally-located partner hospitals - one for each main center.
3) Central management with rotating leadership, information systems management, and financial oversight.
4) A tissue allocation committee with membership on a rotational basis.
5) A board of directors.
A common informed consent form, approved by Israel's Ministry of Health, will be used. Banked specimens will be available to academic, industrial, and foreign (including commercial) end-users. All branches will be required to meet yearly collection quotas to maintain funding.
The total budget for the network is 36M NIS (approx. 10M USD) over 5 years. This sum is low compared with government investments in biobanking in other countries of similar size. Commitment from participating hospitals as well as a creative business model will be critical to ensure the survival of the IJCBR.
An Innovative Approach to Providing Biospecimen-Related Data for Translational Research
Cancer biobanks are playing an increasingly important role in supporting translational research that underpins the development of targeted therapies. Usually this involves providing biospecimens for laboratory research to identify putative targets. However, over the last 12 months, the Victorian Cancer Biobank has received an increasing number of requests for services such as blood and tissue processing according to project-specific protocols and the provision of associated data.
Commonly, at the time of sample collection, biobanks record a minimum set of data. Donor-related demographic data such as age and gender, surgical details, and pathology information is captured. However, interpretation of research results for translational research projects usually requires correlating molecular information with data related to the treatment administered and outcome data, such as the time to relapse or death. In the absence of electronic health records, capturing medical information from paper-based files can be time consuming and resource intensive.
Since the Victorian Cancer Biobank (VCB) consortium was formed in 2006, more than 18,000 donors undergoing surgery have provided blood and tissue that has been processed into almost 400,000 biospecimens. As Australia is only commencing implementation of eHealth records, obtaining follow-up information for such a large number of cases requires an alternative solution. The mechanism for providing secure access to privacy protected medical data through the Victorian Cancer Registry and BioGrid Australia's data linkage platform will be presented.
P2N – A Centralized Biobank Network at the University Medical Center Schleswig-Holstein, Kiel
The PopGen 2.0 Network (P2N): Within the framework of the German National Biobank Initiative, the University Medical Centre Schleswig-Holstein in Kiel (UKSH) was chosen as one of five sites for the establishment of a centralized biobank network, connecting existing biobanks in the various institutes of the UKSH. Within a four-year timeframe, the partner biobanks will be connected through a centralized sample management system, IT infrastructure, quality control, and common approach to ethical, legal and social issues. The major aim of P2N is to provide transparency and accessibility of samples of the partner biobanks, thereby enhancing the usefulness of existing samples for biomedical research.
Partner biobanks: Seven partner biobanks, the population-based biobank PopGen, Comprehensive Cancer Centre North, Centre for Family Medicine, Department of Neurosurgery, Institutes of Pathology and Pharmacology, and University Lung Centre North, will be connected within the P2N framework, combining an overall total of >80,000 DNA samples, >700,000 tissue samples, and >10,000 other biosamples.
First results: By combining existing biobanks, P2N faces unique challenges. A first survey of existing biosamples has revealed an unexpected heterogeneity of sample quality and access rules, including up to 500 different consent forms for existing biosamples. Providing a transparent and searchable database for sample access and informed consent is therefore one of the major goals of P2N.
Conclusion: P2N aims to unify and harmonize seven large existing biobanks at the UKSH, providing a central access point for >1M biosamples available for biomedical research for a broad range of human diseases.
Entity-attribute-value Data Model Implementation to Manage Donation–associated Clinical Ddata
The University of Navarra Biobank collects biological samples for different research areas and groups, each with different requirements regarding the data sets associated with their samples. The definition within each area or group is unlocked, so multiple modifications are expected to be done. To address this issue, we aimed to design a data management model that allows researchers from different knowledge areas to select and modify the data of interest.
We chose the entity-attribute-value model because of its great flexibility in defining and amending the attributes. In addition, traceability of data modifications allows retention of the historical values associated with each pair donation-field. Space saving by the definition of attribute data as sparse matrix is a further advantage of this model. A number of features were implemented including a template-based definition of capture and presentation forms for each dataset so that every donation links to its area or group template, which shows only the appropriate fields. In our development each clinical field has 10 basic attributes that allow the following: validation of required fields, data class testing, correct display of data, data units' definition, and a short information box if necessary, among other functions.
After implementation, we conclude that entity-attribute-value database modelling is an advantageous approach to address the challenge of governing the highly heterogeneous and changing needs of data collection and exploitation in a biobank. Additionally, our template-based system allows a friendly customized display of datasets.
NHS Tayside, Dundee
The Breast Cancer Campaign Tissue Bank (BCCTB) (http://www.breastcancercampaigntissuebank.org) was established following a Gap Analysis that identified lack of access to human breast tissue as an inhibiting translational research (Thompson et al., (2008) BCR 10:R26). The BCCTB is core-funded by the UK-based charity Breast Cancer Campaign as a collaborative operation between four leading UK centres (Bart's Cancer Institute, the Universities of Dundee, Leeds and Nottingham) to prospectively bank high quality biological materials (whole blood, serum, fresh frozen and/or FFPE blocks of normal breast, tumors and surrounding tissues) with associated clinical data according to standardized SOPs. The Tissue Access Committee comprising breast cancer medical staff,researchers and patient advocates, grant access to the samples. We have developed novel IT systems to allow efficient identification and tracking of samples and record data from research studies. It has been designed to allow integration with key European biobanking initiatives. Unique aspects include purified epithelial and fibroblast cells for culture or genomic/protein extraction; a purpose-built Bioinformatics platform that integrates publicly available ‘-omics' and clinical data; and access to specialised collections on a collaborative basis (e.g. male breast cancers, defined Ethnic Groups and patients with defined therapeutic responses). An inbuilt R&D program includes improved collection and storage methods, cell immortalization and IT and Bioinformatics development. The BCCTB, which opened to all UK- and Ireland-based researchers in January 2012, is expanding to receive material from other sites; it will open internationally and to industry in the next 18 months to two years.
A Local Software Solution for Privacy Guard and Data Security in a Disease-based Biobank
The University of Navarra Clinic is a private hospital where exemplary medical and personal patient welfare underpin all activities. Since biomedical research increasingly involved sample and data sharing, it is plausible to anticipate that the exigent measures of safety that are in use for protecting patient privacy might slow down the translational projects traditionally promoted by the Clinic. Therefore, the Clinic biobank aimed to design a model where obtaining high quality data associated with the samples would not compromise the confidentiality and privacy of the patients. Clinical data are stored in the CUN-system which has strict security policies. The biobank management system (BBUN-system) is independent from the CUN-system and no identifiable data from donors is stored. BBUN has its own security profile. Each donor has two codes assigned: one for clinical assistance stored in the CUN-system, and the second for the research proposed stored in BBUN-system. The relationship between these two codes is stored in a database independent from both clinical and biobank systems. For data exchange, we have designed a server communication protocol using Web-services. Requests from the BBUN-system and answers from the CUN-system are encoded in XML messages, wrapped into a Simple Object Access Protocol (SOAP) and transmitted under SSL. Files containing identifiable data are not transferred. A local Ethics Committee reviews all datasets before designation as transferable. In short, this honest broker-like model which is based on server SOAP-communication, permits association of unidentified clinical data with samples and respects patient privacy.
The Development and Improvement of a Pediatric Biobank at Phoenix Children's Hospital
The Biological Materials and Availability Program (BMAP) at Phoenix Children's Hospital was created in October 2010 with the intent to make solid tissue directly available for research to PCH investigators and collaborators, and to scientists across the world through the Arizona Biospecimen Locator (ABL). Initial efforts focused on obtaining authorization for the use of tissues already stored in pathology as required by law; this is still the case for clinical samples. In October of 2011, BMAP expanded by prospectively consenting donors for surplus and discarded materials to be obtained during surgery or bed-side procedures; the collection of biofluids such as cerebrospinal fluid, urine, and blood was also added to the list. These changes increased donor numbers by 1200% and thus the number of materials available for research by 750%. These significant changes are the driving force behind motivating investigators both internally and externally to seek out partnerships with BMAP. While biobanks are usually study specific, or connected to institutions' clinical pathology department, BMAP is not. Specimens from various diseases are collected for research. This makes BMAP a valuable resource because of its unique nature - it is one of the only programs in the country that collects and stores discarded biological specimens for research. This is especially important because all of the samples are collected from the pediatric population.
Footnotes
[1]
de Roock et al., Lancet Oncology 2010, 11: 753–762.
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Abstracts Codes: BM, Biobank Management; BR, Biospecimen Research; EL, ELSI; ES, Education and Standards; NT, New Technologies; OT, Other Topics; RD, Resource Development.