ESBB Abstracts

1 Animal Tissue Bank of Catalonia (BTAC), Barcelona, Spain AR-01. Animal Tissue Bank of Catalonia (BTAC)

The Animal Tissue Bank of Catalonia (BTAC) is a not-for-profit entity which collects, processes, diagnoses, stores and distributes animal nervous tissue samples to the scientific community. The BTAC is included in the European NeuroPrion Animal Tissue Bank network and in the ESBB.

BTAC offers samples of a great variety of species and a wide range of ages. Animal tissues, come from the Veterinary Pathology Service of the Universitat Autònoma de Barcelona (UAB), the PRIOCAT Lab (The Catalonia Reference Laboratory for Animal Prion Diseases) and the Barcelona Zoological Park. Normal and pathologic specimens are available.

BTAC performs well established protocols for sample processing which can be modified upon the applicant requirements; routinely, half of the sample is frozen at −80°C and the other half is formalin fixed and paraffin embedded. DNA samples are now also available.

All samples included in the bank are submitted to a quality control check in order to assure the optimal conditions of the processed tissue for research purposes. Furthermore, all samples have been exanimated by a team of specialized pathologists. These and other data about the tissue, i.e. samples origin, clinical information, processing details etc, are also included in our database.

The bank samples are available upon request and after the approval of such request by the BTAC Scientific Committee.

Sample database and more information is available on the website http://btac.uab.cat/

BTAC carries out its own research lines and actually is focused in nervous tissue aging and neurodegenerative diseases.

1 Marbank, University of Tromso, Tromso, Norway AR-02. Marbank – A National Repository for Marine Resources

Marbank is a marine biobank located in Tromso, Norway. Marbank has a national responsibility for collecting, preserving and cataloguing marine organisms from Norwegian waters for research, commercial and exploitation purposes. The mission of Marbank is to provide an easy accessible repository of marine resources from Arctic and sub-Arctic areas for R&D institutions and industry that search for novel compounds in marine organisms. In addition to the collection in Tromso, Marbank coordinates a network of marine collections in Norway. The overall aim of the network is to better coordinate marine collections in order to make resources and data more accessible to both Norwegian and international users. Marbank is established in close cooperation with the Norwegian Ministry of Fisheries and Coastal Affairs.

1 Fraunhofer-Institute for Biomedical Engineering, St. Ingbert, Germany 2 Fraunhofer-Research Institution for Marine Biotechnology, Lübeck, Germany AR-03. The Cryo-Brehm Project: A Prototype Of A Living Biological Encyclopedia

With the loss of each species, fundamental biological information that evolved through millions of years of evolution is irretrievably lost. The storage of cell lines including adult stem cells isolated from different tissues of an animal primarily provides the opportunity to save the entire information of an organism, its genome and proteome. Cells can be used for nuclear transfer and the recently rising possibility of reprogramming of somatic cells into induced pluripotent stem cells combined with modern reproductive techniques opens new possibilities for conservation measures. The Cryo-Brehm Project (German Cell Bank For Wild Animals “Alfred Brehm”), established by the Fraunhofer-Research Institution for Marine Biotechnology and the Fraunhofer-Institute for Biomedical Engineering in Germany, aims at collecting and storing biological materials from endangered animals. In cooperation with German zoological gardens only samples from animals that die through natural cause will be saved. Following standardized protocols, somatic cells and adult stem cells will be isolated from glandular tissues, skin and placental tissue. These valuable samples will then be stored in two independent modern cryobank systems to guarantee a maximum safety. The Cryo-Brehm is a vital member of the Frozen Ark Project, an international consortium of museums, zoos, aquaria and research institutes, all committed to preserve the DNA and living cells of endangered species in their own cyrorepository to retain the genetic knowledge for the future. This talk will give insights into this modern biobank, the cryotechnology used, and will give an overview of the diversity of already established cell lines.

1 Fraunhofer-Research Institution for Marine Biotechnology, Lübeck, Gemany 2 Fraunhofer-Institute for Biomedical Engineering, St. Ingbert, Germany AR-04. Organization and Implementation of a Modern Biobank: Current and Future Applications for Cryoconserved Wildlife Cell Cultures

Background: Given the rapid decline of wildlife biodiversity, the collection of genetic resources is essential to save the biological information of species and enable various research applications. The German Cell Bank for Wildlife “Alfred Brehm” (“CRYO-BREHM”) is a biorepository for wildlife propagatable cell lines. It was established by a consortium consisting of experts in cell culture, cell cryoconservation and wildlife conservationists. The cell bank exhibits unique technical and organizational features.

Methods: On all levels from sample collection, sample processing, cell culture, cryoconservation, cryogenic storage to inventory management and documentation of sample related data standardized procedures are followed. Latest technological equipment ensures long-term maintenance of cell viability as well as mistake proof sample and data storage. Standard laboratory operating procedures result in a constant quality of the generated cell lines.

Conclusions: These features accumulate to produce a biobank of high scientific value, which can be used long-term and sustainably for research and development and to document wildlife biodiversity. The collection can contribute to solving questions related to wildlife, human and environmental research. Moreover, the cells can be used in wildlife reproductive technology. Though today associated with technical complexity, recent research indicates that fundamental problems can be solved. Therefore, a wide range of applications exists enabling for breaking new grounds in captive breeding of endangered species. Organizational and technical features of the biobank, research results applying wildlife cells in pharmacological research, further examples for current scientific uses as well as future applications will be summarized in this presentation.

1 RTS Life Science, Northbank, Irlam, Manchester, United Kingdom AT-01. Quality Control in Biobanking: Once the Collection Phase is Complete, What Next? How Do You Know What You Have in Storage, and That You Are Delivering What you romise?

Biobanking studies can be viewed as consisting of a number of phases – recruitment, storage, supply and analysis. Depending on the type of organization and, indeed, the type of study, these phases may run sequentially or in parallel. Further, the process may be wholly carried out by the biobank or may involve a number of different departments or even different organizations. For example, biological samples may be delivered to the biobank from an external organization for storage and analysis, or a sample within the biobank may be retrieved from storage and shipped (in whole or in part) to third parties to satisfy research requests.

Whether samples are processed wholly in-house or received from/shipped to internal or external clients, exchange of samples without some form of quality check can ultimately lead to problems downstream when the samples are analyzed.

Vision based sample inspection systems initially developed for small molecule drug discovery compound QA, offer the possibility of reliable, non-contact goods-in and goods-out QA checks.

The benefits of implementing such a QA system will be presented, supported by case study examples from leading international biobanks.

1 Istituto Superiore di Sanità, Rome, Italy BN-01. The Construction of the Italian Hub of Population Project

HIBP Participants: A) Coordination Unit (Filippo Belardelli, Franca Moretti, Maria Puopolo, Department of Cell Biology and Neurosciences (BCN), ISS, Rome), B) Project manager and interoperability Unit (Elena Bravo, Filippo Santoro, Mariarosaria Napolitano, ISS, Rome); C) Informatics Unit (Paolo Roazzi, Information Technology, ISS, Rome); D) Population Biobanks: 1. CNESPS Biobank (ISS, Rome) including following collections: - CUORE (Simona Giampaoli, Chiara Donfancesco, Luigi Palmieri); - Italian Twin Register (Maria Antonia Stazi);- IPREA (Emanuele Scafato, Lucia Galluzzo); 2. EURAC Biobank (Bolzano), - MICROS (Peter Pramstaller, Alessandro De Grandi, Deborah Mascalzoni); 3. GEHA Project biobank, University Bologna, (Claudio Franceschi, Federica Sevini; Elisa Cevenini); 4. Moli-bank (Univ. Cattolica del S. Cuore of Campobasso):- Moli-Sani, -Gendiabe, -IMA-families, -Immidiet collections (Maria B. Donati, Amalia de Curtis).

Recently, it has been established in the HIBP: In Italy, the potential capability of population biobank collections to contribute to preventive and predictive medicine was hampered by the lack of a common platform of epidemiological biobanks.

The project for the construction of the HIBP, founded by National Centre for Disease Prevention and Control (Ccm), aims to construct the network of the Italian population biobanks, which will function as a tool for common and fast information as well as for standardization and harmonization of the archives of biosamples. HIBP promote the values concerning predictive and preventive medicine of national biobanking and increase competitiveness of HIBP in European and international initiatives. A detailed description of HIBP's collection and activities is reported at the site: www.iss.it/hibp.

1 Center for Medical Innovation, Heverlee, Belgium 2 CRC Antwerp, Edegem, Belgium 3 CRC Brussel, Brussel, Belgium 4 CRC Gent, Gent, Belgium 5 CRC Leuven-Hasselt, Diepenbeek, Belgium BN-02. Virtual Biobank as Model for Translational Biomedical Research Collaboration in Flanders

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, which is often bi-directional.

An intergrated approach which facilitates harmonization between all stakeholders in Flanders will stimulate and improve the position in translational biomedical innovation. The Flemish government established this integration in setting up the Center for Medical Innovation, a strategic research center. The mission of CMI is to support a faster and more efficient translation of research findings into the development and application of innovative strategies for prevention, diagnosis and treatment of diseases with medical priority.

The CMI assembles all stakeholders involved in translational biomedical research into one single virtual platform in Flanders, which in turn functions as an interface with international translational biomedical initiatives. The first activity of CMI is to set up the Flemish biobank project. This virtual biobank infrastructure involves organizational and structural measures that are crucial to support translational research in Clinical Research Centers (Antwerp-Brussels-Ghent-Hasselt-Leuven). Validated and harmonized biobanks with patient samples linked with clinical data will be put in place, reflecting international guidelines and achieving critical mass.

This multidisciplinary research collaboration model will reveal options for orienting scientific research and technological development while at the same time create a decision-supporting framework for innovation policy and its relationship with both economic developments and social benefits.

1 Belgian Cancer Registry, Brussels, Belgium 2 Radiation Oncology Dept & Center for Molecular Imaging and Radiotherapy and Oncology (MIRO), Université Catholique de Louvain, St-Luc University Hospital, Brussels, Belgium BN-03. The Belgian Virtual Tumourbank- a Tool for Translational Cancer Research

Cancer is one of the leading causes of death worldwide. Over the last decades, tremendous biological and technological advances have been observed and to some extent translated into clinical practice. In this framework, access to human samples to look for new therapeutic targets and/or assess how the new discoveries could impact patient care is of paramount importance. In this respect, tumorbanks are valuable tools. However, the availability of tumor samples in single research institutions is often limited, especially for rare disease entities. To avoid this scattering of samples amongst different institutions, clinical and technical data from the available tumor samples from all university hospitals in Belgium are being centralized in one central database, the so-called Belgian Virtual Tumourbank. This Tumourbank can be consulted via an electronic catalogue tool, allowing scientists to query the database and trace the samples they are interested in to conduct their research. The linkage of the data available in the biobanks with clinical information from the Cancer Registry assures not only completeness of the dataset but also an optimal quality of the data being registered. Furthermore linkage with longitudinal databases (e.g. on survival, treatment or exposure) offers a rich source of information for scientists, allowing progress in the knowledge of the mechanism, the diagnosis and the treatment of cancer, which is beneficial to all future cancer patients.

1 Vanderbilt University Medical Center -Cooperative Human Tissue Network (VUMC-CHTN), Nashville, TN, USA BN-04. Video Procurement: An Essential Educational Tool for Obtaining Quality Research Specimens

High quality human tissue is a pressing need for research, but institutions interested in establishing a biorepository may not have stringent protocols in place to ensure the tissues procured are of high-quality and meet the intended research need. Staff may be inexperienced due to lack of exposure to pathology laboratories and specimens.

Established biorepositories can provide videos as refined visual guides that allow less experienced biobankers the opportunity to learn how to procure quality samples. An important objective of these videos is the education for both novice biorepositories and future staff. Video instructions for collection and preparation aid the understanding and importance of the complex methods involved in obtaining and providing adequate specimens and high quality tissue, and in standardizing procedures across collection sites.

The Cooperative Human Tissue Network Western Division at Vanderbilt University Medical Center has implemented tissue procurement videos for staff training to ensure consistency of high quality specimen collections. The videos utilize certified pathologist's assistants, residents and surgical pathologists to show proper specimen sectioning and inking techniques. Videos focus on specific organ/anatomic sites and include education on disease processes, pathologic staging requirements, relevant clinical history, treatment effects, sterile technique, specimen transport, and procurement of obtained tissues.

Condensing the information into a visual guide allows staff and researchers utilizing the specimens to view and understand the process from start to finish. Procurement videos are valuable instructional tools that have the potential to expand the biobanking community by offering concise direction to biorepository personnel on proper procurement methods.

1 Fraunhofer IBMT, Potsdam-Golm, Germany BN-05. Simultaneous Tissue Bank Query in Switzerland and Germany: biobank-suisse and CRIP are Coupled via Web Services

Background: Both biobank-suisse (BBS; www.biobank-suisse.ch) and the Central Research Infrastructure for Molecular Pathology (CRIP; www.crip.fraunhofer.de) are meta-biobanks or biospecimen locators. Both serve to acquire research projects for their partner biobanks by displaying anonymized data on biospecimens available at the partners' hospitals and by processing project requests on-line.

Methods: Based on a cooperation agreement, BBS and CRIP have synchronized their users' registration and log-in procedures, and mutually coupled their web-based interactive query tools by web service protocols operated through secure communication channels (HTTPS).

Results: We demonstrate the single sign-on process, coupled web-based interactive query tools, and search results retrieved simultaneously in BBS and CRIP. The former tedious consecutive search with two web tools in two databases has now been upgraded to a quick and easy user-friendly one-step-query. It covers the entire information pool offered to researchers by CRIP and BBS without affecting their access rules, contractual framework, privacy regimes, workflow, and corporate design. The underlying trans-national data transfer compromises neither country's data protection legislation since only anonymized data, which is lawfully and globally accessible for researchers through the internet anyway, is being displayed. Putting the principle of data sparing into practice, data is transferred only upon a user's focused request.

Conclusions: Coupling CRIP and BBS provides a model for networking meta-biobanks without impairing their individual governance, regulatory framework, workflow, and infrastructure.

Funded by grant 01EZ1021A from the German Fed. Ministry for Education and Research (BMBF).

1 Istituto Superiore Sanità, Rome 2 VAS-Vascular-Independent Research and Education - European Organization c/o University of Milan 3 BioRep, srl, Milan 4 G. Gaslini Institute, Genoa 5 IRCCS-Burlo Garofolo, University of Trieste 6 Istituto Tumori “G. Paolo II” IRCCS, Bari 7 Istituto nazionale per la Ricerca sul Cancro, Genoa 8 IRCCS Ospedale Maggiore Policlinico, Milan 9 Regione Liguria, Genoa 10 Alliance Against Cancer, Rome 11 Department of Medical Sciences, University of Trieste 12 da Vinci European BioBank (Sesto F.no - Florence) BN-06. The Italian Node of the Research Infrastructure BBMRI

Biobanking and Biomolecular Resources Research Infrastructure (BBMRI) will be implemented under the ERIC (European Research Infrastructure Consortium) legal entity. BBMRI-ERIC foresees central headquarters in Graz, responsible for coordination of the activities of National Nodes established in participating countries.

The Minister of Health, aware of these initiatives, and convinced of the importance for the Italian researchers to participate in BBMRI, gave mandate to the Istituto Superiore di Sanità (ISS) to establish the Italian Node of BBMRI to coordinate the formation of the Italian network.

Elena Bravo was appointed as Coordinator and an Advisory Committee, constituted by scientists involved in biobanking activities and representing stakeholders as well, was set to collaborate with the Italian node of BBMRI. During the first year of activity, BBMRI-IT promoted virtuous collaboration among scientists and with the Regional Authorities.

A website (www.bbmri-eric.it), reporting all ongoing activities of the Node, has been rapidly published and constantly updated to allow participation of whole biobanking community.

BBMRI-IT worked to recognize the main criticalities and to improve the Italian system of biobanking. As Italy lacks a specific legislation for research biobanks, BBMRI-IT aims to contribute to the definition of criteria and shared rules for the management of research biobanks. For this purpose, a working group (WG) has been instituted with the aim, as well, of drafting documents related to the Partner-charta of BBMRI. In parallel, a pilot initiative to set the national bioresources catalogue has been launched and constitution of the Italia Group of Stakeholders is being promoted.

Alliance Against Cancer has strongly supported this work.

1 Istituto Nazionale per la Ricerca sul Cancro (IST), Genoa, Italy BN-07. The Biological Resource Center of the National Institute for Cancer Research of Genoa

The Centro di Risorse Biologiche (CRB-IST) has been recently established as an institutional facility of IST, coordinating seven biobanking and cell banking activities already existing in the institute. The main aims are: to facilitate high quality translational research dependent on biological material and data, to address ethical issues on biobanking, to promote the project at the population level, to harmonize technical and management SOPs according to international best practices, to help reduce costs for collection and storage of biological material, to favor institutional recognition at a regional, national and international level. CRB-IST participates in the Liguria network of biobanks, in the National networks Rete Italiana BioBanche Oncologiche (RIBBO) and Network of Italian Pathology Biobanks (NIPB) and in the European Infrastructure of Biobanks and Biomolecular Resources (BBMRI).

Seven specialized biobanks belong to CRB-IST: the Tumor tissue biobank (biological material from diagnostics and surgery of IST patients); the Hereditary Tumor Centre Biobank; the Cancer of RESpiratory Tract (CREST) biobank; the Lymphoproliferative disorders Biobank; the Interlab Cell Line Collection (ICLC); the European Collection For Biomedical Research (human B lymphoblastoid cell lines); the Urological Tumor Biobank.

CRB-IST has developed common SOPs for collection and preservation of samples, a common procedure for informed consent and a common Material Transfer Agreement for distribution of samples and information. All projects are evaluated by a Scientific Committee and by the Ethical Committee of IST. CRB-IST has produced a website and brochures for the patients that keep the population informed on the ongoing scientific projects.

1 Istituto Nazionale per la Ricerca sul Cancro (IST), Genoa 2 Istituto Giannina Gaslini, Genoa 3 Agenzia Regionale Sanitaria Liguria, Genoa, Italy BN-08. Regional Accreditation of Biobanks and Liguria Network

Disease-oriented biobanks are recognized as a key resource for biomarker discovery and are closely related to the health care system. In Italy, the governance of the health care system is devolved to regional authorities.

Liguria region is traditionally rich in initiatives in the field of biobanks and recently the region has officially recognized the role of biobanks for diagnosis and research. In the resolution (n.34 Jan.2010), the region has established the criteria for accreditation of existing resources and further initiatives.

To be accredited, the Biobank should: a) be formally established within the Hospital - research center, b) have dedicated space and equipment, c) be active for at least three years, d) use dedicated staff to ensure quality and continuity of services, e) operate within a certified quality system, f) document the presence of SOPs for involvement of patients, acceptance, preparation and storage of samples, information management and catalogue, distribution of biological material, g) act as a service unit and document “in” and “out” activities.

The regional network includes:

The network coordinates the State-Regions Conference working group on biobanks and participates in the BBMRI national node.

1 SSD Lab. Diagnosi Pre-Postnatale Malattie Metaboliche - IRCCS G. Gaslini, Genova, Italy 2 SC Lab. Genetica - EO Ospedali Galliera, Genova, Italy 3 Centro Parkinson e Disturbi del Movimento - ICP, Milano, Italy 4 UOC Genetica Medica, Dip. Biologia Molecolare - Univ. di Siena, Italy 5 Dip. Neuroscienze - Univ. di Padova, Italy 6 UOS Diagnostica Malattie Neuromuscolari - Centro D. Ferrari, Fond. IRCCS Cà Grande Osp. Maggiore Policlinico, Milano, Italy 7 UO Malattie Neuromuscolari e Neuroimmunologia - Istituto C. Besta Fond. IRCCS, Milano, Italy 8 Serv. Genetica Medica - IRCCS Casa Sollievo della Sofferenza, S.G. Rotondo (FG), Italy 9 Dip. Medicina Sperimentale - Seconda Univ. di Napoli, Italy 10 SOS Diagnostica dei Disturbi del Movimento e Disordini del Metabolismo Energetico - UO Neurogenetica Molecolare, Ist. C. Besta Fond. IRCCS, Milano, Italy BN-09. Telethon Network of Genetic Biobanks (TGBN)

TGBN is the first Italian coordinated resource of biospecimens from patients affected by genetic diseases. Supported by Telethon Foundation, TGBN interconnects well-qualified Biobanks with the aim to support both the biomedical community as well as the donors, viz patients and their families. TGBN operates in a harmonized environment which ensures privacy protection and donor confidentiality, and the quality throughout the entire process of biobanking that includes collection, storage, distribution and related data recording.

TGBN collects various types of biological materials: fetal/adult cell lines and tissues, DNA/RNA, blood/plasma samples from approximately 700 different genetic diseases.

Activities and policies are stated in The Charter, which includes ethical guidelines, organization and governance policies, expected benefits and undertaken duties.

The governance bodies are represented by the decision-making Network Board and by a consultive Advisory Board composed of legal/ethical experts and a family association representative. Additionally, TGBN can rely on a Coordinator Emeritus and a Telethon Advisor.

To achieve its main objectives, TGBN has created a public website (www.biobanknetwork.org) and has adopted a common IT-infrastructure, managing all data collection, sample submissions, requests and inventory.

Aggregated data are published in the online catalogue. The IT-system manages and monitors the complete in/out workflow of samples which is therefore fully handled and shared online by all Partners. Samples will be made available to users for research purposes, provided that an adequate portion of the samples derived from individuals affected by undiagnosed and rare diseases are safeguarded to the patients' advantage to allow retrospective analyses.

1 Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Spain 2 Hospital Universitario Son Espases, Mallorca, Spain 3 Hospital Universitario Doce de Octubre, Madrid, Spain 4 Hospital Clinic, Barcelona, Spain 5 Hospital Universitario de Getafe, Madrid, Spain 6 Hospital Universitario de Bellvitge, Barcelona, Spain 7 Hospital Universitario del Mar-IMIM, Barcelona, Spain 8 Consorcio Hospital General Universitario, Valencia, Spain 9 Fundación Jiménez Díaz Capio, Madrid, Spain 10 Hospital Universitario Germans Trias i Pujol, Badalona, Spain 11 Hospital Universitario Joan XXIII, Tarragona, Spain BN-11. CIBERES Pulmonary Biobank Consortium: Quality Assurance and Translational Research

The CIBERES Pulmonary Biobank Consortium (CPBC) is an association of ten hospital biobanks focused on the selective and systematic preservation of lung tissue samples, blood, serum, plasma and phenotypic information relevant for respiratory research. Samples are obtained from patients who underwent thoracic surgery for therapeutic reasons, mainly lung cancer (90% of cases). The mission is promoting the collaborative and translational respiratory research, making available samples and data to be used in scientific approved research projects.

The CPBC objectives are the assurance of the quality of the samples and their associated data as well as to guarantee the purpose of their use. For that reason, a centralized management and standard normalized protocols were established in the CPBC, and multidisciplinary collaborative working groups were created in each hospital. These working groups are essential for the accurate implementation of the tissue preservation protocols, the control of the lung tissue ischemic time and data management.

An average of twenty-five patients has been recruited each month by the CPBC. Fifty six percent of them present respiratory comorbidities, being the most frequent COPD, followed by OSAS bronchiectasis, asthma, diffuse interstitial lung diseases and cystic fibrosis.

In two years, CPBC has distributed samples to national and international researchers focused on COPD, idiopathic pulmonary fibrosis, asthma, lung cancer and smoking effects. The researchers are committed to send the raw data to the consortium, once the results have been published, in order to enrich the information associated to the samples for future studies and guarantee their use.

1 HIV HGM Spanish BioBank, Laboratorio de Inmunobiología Molecular, Hospital General Universitario Gregorio Marañón, Madrid, Spain BN-12. HIV HGM Spanish BioBank on Networks

Excellence in translational research depends on the high quality of the bioresources (samples and their associated data) and the high amount of cases needed in order for it to have statistical power. This is closely related to biobanking networks. These systems are cooperative infrastructures of individual biorepositories. The HIV HGM Spanish BioBank is an infrastructure of the AIDS Research Network and the Spanish National Biobank Network and collaborates with International Biobanking Network systems and societies such as ISBER.

Biobanking networks do exist, but they are not homogeneous. Different operational and business models coexist depending on the medical and research objectives of their home countries. The different biobanking networks including HIV HGM Spanish BioBank facilitate the access to high quality bioresources, the exchange of information, the creation of regulations and the development of useful contacts. These networks also provide an opportunity to increase the positive impact of the biobanks' activity as providers of controlled high quality specimens to ensure excellence in research.

International biobanking network systems and societies such as ISBER had already standardized some biobanking issues such as technical procedures in biobanks, ethical guidelines or access policies. However, some key issues remain to be standardized. Standard biobanking procedures should be implemented worldwide in every key issue related to the running of biobanks, in order to ensure an optimal working order of the international networks. All recommendations currently known should be unified into a single one in order to establish the basis for the formalization of specific legislation on biobanking activities.

1 The Dutch Collaborative Biobank, Lelystad, Netherlands BN-13. The Dutch Collaborative Biobank- A Novel Approach for a Shared Biobank Infrastructure

Setting up and maintaining biobanks that contain well preserved and documented sample collections requires distinct skills in several scientific, operational and technical areas.

Unfortunately, the lack of an appropriate local operational scale is often the main cause for compromised quality and effectiveness of biobanks. Also the sustainability of sample collections can be insufficient due to an inappropriate local handling of samples and information.

To overcome the above problems, the non-profit organization ‘Dutch Collaborative Biobank’ deploys a high quality, user friendly and cost efficient physical and digital biobank infrastructure.

This approach is based on the shared utilization of existing capacities and competences. A shared centralized biobank infrastructure is provided for the hosting of existing freezers and sample collections. For the support of the local working processes and information handling, a readily accessible web based bioresearch suite can be used, that contains modules for sample handling, track & tracing, project management and document management.

Open standards are applied to ensure sustainability and interoperability of these modules and exchangeability of the stored information. However, full deployment of these features requires further development of existing open standards.

A knowledge base is set up to ensure an appropriate skills level of researchers with respect to sample handling and regulatory affairs.

Challenges are encountered with the collaborative hybrid business model based on publically funded institutes and commercial (SME) partners.

The aim of this presentation is to share experiences of the Dutch Collaborative Biobank with respect to technical and operational aspects of setting up a shared biobank concept.

1 TMF – Technology, Methods, and Infrastructure for Networked Medical Research, Berlin, Germany 2 Institute of Medical Informatics and Statistics, University of Kiel, Germany 3 Institute of Pathology, Charité Universitätsmedizin Berlin, Germany 4 Institute of Clinical Chemistry and Laboratory Diagnostics, University of Jena, Germany BN-14. The TMF Fosters International Visibility of Biobanking in Germany by Establishing a National Biobank Registry with an Integrated User Portal

Human biobanks are collections of samples of human bodily substances (e.g. DNA, blood or tissue) together with clinical and sociodemographic data on the respective donors. Biobanks are an essential prerequisite for patient-based medical and epidemiological research. Given the emerging possibilities of in-depth genetic analysis and other “omics” technologies, including metabolomics for biomarker research, major challenges are likely to arise for biomaterial quality, maintenance, and for the legal framework of their long-term use.

As a scientific umbrella organization, the TMF (Technology, Methods, and Infrastructure for Networked Medical Research) provides general support in terms of their organizational and infrastructural development to medical research networks in Germany. Some 5 years ago, the TMF adopted research using human biobanks as one of its major topics of interest. As one of the first steps towards any efficient usage of such resources, it is essential that biobanks become widely visible to the scientific community. Since there is currently no structured access to information on individual biobanks available in Germany, the TMF has set out to establish a national biobank registry with integrated user portal. This registry will allow participating biobanks to easily maintain an up-to-date and publicly accessible overview of their material and data, and of their research activities. The registry will greatly facilitate scientific collaborations at both the national and international level. The project is funded by the German Federal Ministry of Education and Research (BMBF) and is currently being implemented at www.biobanken.de.

1 Office of Biorepositories and Biospecimen Research (OBBR) at the National Cancer Institute,Rockville, MD, USA BN-15. Solving Global Health Challenges in Cancer Through International Harmonization in Biobanking

The United Nations is now recognizing cancer as one of the major non-communicable diseases, placing it under the international spotlight. This comes as no surprise given that WHO estimates that by 2020 there will be 16 million new cancer cases worldwide and 70% of these cases will be in the developing world due to an aging population, cancer-causing lifestyles, and environmental factors. Most efforts will be geared towards promoting healthier lifestyles, on replenishing human capacity with trained staff, and in building physical infrastructures for patient diagnosis and treatment. Yet still, we anticipate that the developing world will lag behind developed nations that have moved forward towards personalized cancer medicine. Here we propose reducing health disparity and moving towards personalized cancer medicine by building a global knowledge exchange society with biospecimen science serving as its platform. We envision that international collaborations formed between the Office of Biorepositories and Biospecimen Research at NCI and other nations can be leveraged so that resource-poor countries can benefit from evidence-based SOPs and emerging technologies derived from biospecimen science research. Albeit we recognize that some biobanking lessons learned in technologically advanced countries might not necessarily be applicable to those in developing countries due to genetic and epidemiologic differences among patient cohorts. Hence to effectively build a global knowledge exchange society, we recommend including data derived from biospecimens from patients in the developing world as well as raising representation from researchers working in the developing nations at our international biobanking conferences.

1 Promega Corporation, Madison, WI, USA BR-01. Add-Mix-Read Assays for the Assessment of Cell Health Using an iPS Cardiomyocyte Cell Model

Evaluating cell health is a necessary step in the biobanking process while preparing samples for storage and when propagating cells after cryopreservation. Membrane exclusion dyes are commonly used to evaluate cell viability, but one drawback to this method is the lack of distinction between viable and apoptotic cells with an intact membrane. In addition, the visual scoring of a viable cell is subjective and can vary among users. Homogeneous (add-mix-read) assay reagents are user- friendly alternatives to traditional methods of monitoring cell viability. Reagents have been developed to monitor various aspects of cell health, including viability, cytototoxicity, and apoptosis. The assay reagents can be used individually, or in some cases multiplexed together, to generate a multi-parameter readout of cell health in the same assay well. The process of performing these cell-based assays is simple: reagent is added directly to cells in an assay plate, or to cells in a tube, and incubated for a period of time. Luminescent or fluorescent signal is quantified, depending on the assay. Shown here are data generated with these cell health assays using an iPS cardiomyoctye cell model. Cells were subjected to various treatments in order to elicit an effect for the parameter being measured. Multiplexing assays together conserves cell usage and enables a more complete cell health profile of biorepository samples compared to using a single parameter methodology. Incorporating a quantifiable assay signal removes subjective visual scoring of viable and non-viable cells.

1 Unit de Recherche Genetique Cardiovasculaire, EA-4373, Universit Henri Poincar-Nancy I and Biological Ressources Center Interactions Gene-Environnement en Physiopathologie CardioVasculaire (BRC IGE-PCV), Nancy, France 2 ICAREB Biological Ressources Center (BRC), Pasteur Institute, Paris, France 3 Biobanque de Picardie, Salouel, France 4 Integrated Biobank of Luxembourg, Luxembourg BR-02. Influence of Pre-analytical Variables on VEFGA Gene Expression and Circulating Protein Concentrations

Background: The extended role of vascular endothelial growth factor (VEGF) in human physiopathology led us to evaluate pre-analytical parameters possibly influencing the levels measured in peripheral blood. The effects of the presence and of the type of anticoagulant, of the blood storage delay before centrifugation and of freeze-thaw cycles on circulating levels of VEGF and on VEGF165 mRNA expression in peripheral blood mononuclear cells (PBMCs) have been checked.

Methods: Blood from healthy donors was sampled in EDTA, ACD-A, hirudin and serum separation tubes. From each anticoagulant, one tube stood for 2 hrs, one for 4 hrs and one for 48 hrs at 4°C before centrifugation. To evaluate the effect of the number of freeze-thaw cycles, for each type of tube, one, two and ten cycles were performed. VEGF was quantified using a quantitative sandwich enzyme immunoassay technique. After standard isolation of PBMCs, quantification of the transcripts coding for the VEGF165 isoform, and the β-2 microglobulin control gene, was performed by real time polymerase chain reaction (RT-PCR).

Results: The period of stagnation and the number of freeze-thaw cycles influenced the levels of circulating VEGF and its expression in PBMCs. The most important effect of freeze-thawing was observed in ACD plasma, where a significant increase of both was observed between 2 and 48 hours of blood storage. Values were higher in serum. However, values were rather stable when centrifugation of serum was operated within 4 hours and freeze-thawing was done only once.

Conclusions: The most reliable conditions for measuring both circulating VEGF and its gene expression are to reduce time between blood collection and centrifugation, and to avoid multiple freeze-thaw cycles. Samples with no additive were less sensitive to the pre-analytical variations analyzed in this study.

1 CRA - Centro di ricerca per l'Agrobiologia e la Pedologia, Italy CP-02. Development of a New Approach in Insect Egg Cryopreservation by Vitrification

An important conifer forest pest is the arthropod Leptoglossus occidentalis, an insect belonging to Coreid order indigenous from North America. The new alien-species invasion lead the Italian Ministry of Agricultural, Food and Forestry Policies to activate a specific research program aimed to control L. occidentalis using different strategies, including biological control by the use of egg parasitoids native to North America in collaboration with the Kalamalka Forestry Center (Ministry of Forests & Range, British Columbia).

A new and alternative approach to mantain an extensive colony of parasitoids, can be cryopreservation by vitrification of parasitoid embryos. The first point in the vitrification technique for arthropod samples is the removal of chorion in order to let cryoprotectant enter inside the egg. But in many arthropod species this procedure is not applicable without compromising the egg integrity.

In this framework CRA-ABP Cryobiology Laboratory in Florence is developing two new types of permeabilization protocols: one for long term storage of Leptoglossus embryos, the other for medium and long term storage of different egg parasitoids inside the host egg. In the attempt to define a specific strategy to build genetic cryobanks of both, host and parasitoid, we studied ultrastructure and permeability of the egg chorion of L. occidentalis at cryoprotectant molecules, the resulting chorionic structure explains high resistance at permeabilizating agents we found. Starting from this data, present studies are targeted to develop an efficient cryoprotectant loading protocol for L. occidentalis eggs without chorion removal.

1 Centre for Ecology and Hydrology, Wallingford, UK 2 Lancaster Environment Centre, Lancaster University, UK ER-01. The UK Fish Tissue Archive and its Application to EU Priority Substances

Scientists from CEH and Lancaster Environment Centre are working with the Environment Agency to develop a National Fish Tissue Archive for the UK. The main purpose of the archive is to enable chemical contamination in rivers to be assessed and spatial and temporal trends to be observed.

Starting in 2007 samples of roach (and to a small extent bleak and eel) were collected annually from a number of rivers in England. Fish were frozen on site in liquid nitrogen and thereafter stored at −80°C. The majority of samples are stored long term for future retrospective monitoring of chemical pollution, but a subset has already been analyzed for a variety of persistent pollutants. This presentation will focus mainly on mercury and hexachlorobenzene (HCB) which are two of the three priority substances for which an EU environmental quality standard (EQS) has been set for biota.

HCB, a fungicide which is no longer used in the EU was well below the EQS of 10 μg/Kg fresh weight (max 6.4 μg/Kg), in all fish analyzed so far, but mercury exceeded the EQS of 20 μg/Kg in around half the fish analyzed but was generally an order of magnitude or more below the limit of 500 μg/Kg set for fish for human consumption.

1 Leiden University Medical Center, Leiden, Netherlands HR-01. Biobank Data Integrity

A biobank contains millions of samples; stored/ retrievable for decennia. This needs high quality demands on data integrity.

At any given time in the future, scientists must be able to prove that a sample is indeed the right sample. That it's from a specific source, handled correctly, and stored according to protocol. The value of samples is dependent on the ability to provide this evidence.

To provide this evidence, a biobank needs three systems: an operational, a control and a supervisor system. From the moment the first sample is stored in the database all 3 systems must be up and running.

The operational system registers samples. Software must prevent/detect human errors, by using automation compatible labels such as barcodes. Laboratories must follow strict SOPs which are automatically generated when entering the sample. The data of the biobank must be stored in an industrial strength database. The control system safeguards biobank access; it controls user access. Only those permitted can access data and functions for which they are authorized. It logs all user activities. The supervisor system safeguards data integrity. It prevents and detects disturbances. It supervises changes of the application software, database structure, content, and implementation parameters and detects changes made to the biobank bypassing the operational and control system.

Not having the combination above leads to a high risk of corrupt data.

In the presentation there are examples of common errors, well-meant bypassing of procedures and influencing systems.

Conclusion of the presentation will be how software provides databank integrity.

1 Hacettepe University, Faculty of Medicine, Department of Medical Biology & DNA Cell Bank, Sıhhiye, Ankara, Turkey HR-02. Hacettepe University Biobank - A Research Infrastructure for Rare Diseases

Turkey has a population of about 70 million of which 28% is below the age of 15. Like the rest of the world in Turkey, due to stringent public health programs and vaccination strategies mortality rate due to infectious diseases in the pediatric age group has diminished. With better capacity of testing and diagnosis, hospital admissions due to genetic disorders are on the rise. Diagnosis of rare disorders (RD - prevalence less than 5/10000) is complicated and therapy is not available for most of them leading to mortality at an early age. Thus being able to identify new genes and disease pathways is an important contibution for the development of genetic tests and new modalities of genetic lesion specific treatments. In this context, biobanking is an important infrastructure capability of research in RD. Hacettepe University Biobank for Rare Diseases was established in 1995 as a repository for tissues and medical information. It is a nonprofit organization that has reached a sample capacity of 22500 DNA and 1200 tissue samples. Demographic indices specific to the population such as consanguinity (21%), long age of childbearing leading to multiple affected in one family, cohabitation of multiple generations to create a complete family tree are being used as an advantage for homozygosity mapping to identify new genes. Besides medical research, bioethical issues such as informed consent, privacy and confidentiallity issues are being addressed and guidelines are being drawn that will facilitate the sharing of samples within the RD scientific community.

1 BioBanco Hospital Universitario Central de Asturias-Oficina de Investigación Biosanitaria del Principado de Asturias (OIB) 2 BioBanco Hospital Universitario Central de Asturias-Instituto de Oncología del Principado de Asturias (IUOPA) 3 Oficina de Investigación Biosanitaria del Principado de Asturias (OIB)-CAIBER, Biobanco Hospital Universitario Central de Asturias, Asturias, Spain HR-03. Comparison of Different Methods of Genomic DNA Purification from Tissue

Introduction: Optimization of genomic DNA (gDNA) purification method is necessary to obtain high performance and elevated concentration and hereby improve the samples quality.

Materials & Methods: Five gDNA purification methods were compared: gDNA Tissue by MACHEREY-NAGEL (method 1), ReliaPrep^TM gDNA System by PROMEGA (2), QIAAMP^® DNA Blood by QIAGEN (3); Gentra^® Puregene^® by QIAGEN (4) and ArchivePure DNA Purification by 5 PRIME (5). We tested 10 samples of 30 mg for each method, all from the same donor. To evaluate the amount and quality we used Nanodrop^® spectrophotometer by ThermoFisher. Absorbance ratios at 260 and 280nm (A260/280) and at 260 and 230nm (A260/230) are used to assess the purity (larger than 1.8 for pure gDNA). Continuous variables are described by medians and non-parametric tests are used in order to compare them.

Results: Concentration medians for methods 1, 2, 3, 4 and 5 respectively: 160.60, 199.27, 48.12, 48.02 and 54.80 ng/μL. A260/280 medians: 1.99, 1.98, 2.06, 1.99 and 1.98. A260/230 medians: 2.17, 2.11, 0.85, 0.78 and 0.85. For concentration and A260/230, methods 1 and 2 are homogeneous (P-values 0.123 and 0.165) and methods 3, 4 and 5 too (P-values 0.285 and 0.295). For A260/280, methods 1 and 3 are homogeneous (P-value 0.739) and methods 4 and 5 too (P-value 0.909).

Conclusions: All methods yield high quality gDNA (A260/280 > 1.8). However, methods 1 and 2 obtained concentrations at A260/230, which were larger than methods 3, 4 and 5. Therefore, it can be concluded that the best methods among the five studied ones was 1 and 2.

1 Vanderbilt University Medical Center -Cooperative Human Tissue Network, Nashville, TN, USA HR-04. Patient Comprehension of Informed Consent and Participation Trends Influenced by Emotional and Environmental Factors

The purpose of this study is to determine the most appropriate time to approach patients for consent to participate in a research study. Currently, we have a 96% participation rate with patients being consented during the preoperative waiting period on the day of surgery.

To investigate the relationship between patient environment and cognitive clarity, four surveys have been developed. Study data will be collected and managed using REDCap. The surveys will be distributed to four groups of participants: patients, family and friends, doctors and nurses, and medical students. The surveys are designed to allow participants, friends, family and caregivers to indicate at what moment from diagnosis, through treatment, and to surgery they would be most comfortable and willing to participate in a research study. Based on these results we will be able to understand when patients are at their most comfortable state with complete willingness to participate in research studies. Additionally, we will survey medical students and medical personnel to assess when they feel it is most appropriate to approach patients for research studies and tissue and or bodily fluid donation.

This study will give concrete validity to the process of informed consent obtained during the pre-operative waiting period prior to surgery. With this validation, the research team will have evidence to support the current participation rates. This study will have a positive impact on the informed consent process at institutions across the country and enhance education and training.

1 Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy HR-05. Human Tissue Bank Facility of the Fondazione IRCCS Instituto Nazionale Tumori (INT) of Milan: The Tissue Issue and Beyond

Access to biological material (tissue, blood, body fluids) in sufficient quantity and quality to investigate pathogenetic mechanisms, classify tumors, assess disease prognosis and treatment efficacy, is considered one of the major bottlenecks hindering a successful translation of information from bench to bedside. In order to produce clinically valid and comparable results, standard sampling and operating procedures (SOPs) represent the most critical points that worry researchers. Focusing on tissues, it is of primary relevance to trace and monitor the path from the operating theater to the biobank, since non-correct preprocessing procedures might affect molecular analyses, which are based on the assumption that samples under investigation closely resemble in vivo conditions. Moreover biobanking is often conceived as non-core by other units which are focused on primary processes like surgical operation, daily pathological diagnostics, even in research institutes. The lack of integration and of a common view of the biobanking process might lead to the loss of specimens and to a decay in sample quality. In order to overcome these bottlenecks, at INT, a new organization has been activated to support biobanking activities along the entire path from Surgery to Pathology to Research. To assure the quality of specimens we have identified some key challenges as organization, quality assurance, process control (SOPs and traceability with RFId technology), creation of complete case profiles merging data from clinical subsystems, adequate investments in laboratory instrumentation and storage sites, networking and research to exploit the value of local biological assets through shared knowledge and joined research projects.

1 Inbiobank, Fundacion Inbiomed, San Sebastian, Spain HR-06. 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 catalog mesenchymal stem cells from bone marrow, adipose tissue and umbilical cord (Warthon's jelly) as well as primary skin fibroblasts and keratinocytes. 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.

1 Department of Clinical and Molecular Pathology and Laboratory of Molecular pathology, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University and University Hospital Olomouc, Olomouc, Czech Republic HR-07. Importance of miR-21, miR-126 and miR-205 Detection in Archived FFPE Samples in NSCLC Patients

Background: Lung cancer is the leading cause of cancer deaths worldwide. Hence, lots of lung cancer samples are stored in archives in pathology departments. Currently, miRNA arises as a new diagnostic, prognostic and predicting tool. miRNAs are small non-coding RNAs regulating protein levels in cells through inducing mRNA degradation and translational repression. One of the miRNAs advantages is their stability. miR-21, miR-126 and miR-205 deregulation has been seen in NSCLC (non-small cell lung cancer) samples. Therefore, we decided to test their levels in our NSCLC patients.

Methods: We tested 65 lung cancer samples from patients treated in Faculty Hospital Olomouc (Czech Republic) from years 1996-2000. We prepared tissue microarrays from tumor areas of paraffin blocks and isolated total RNA from individual cores. We followed Ambion instructions for miR-21, miR-126 and miR-205 detection using TaqMan® MicroRNA Assays. We assessed and obtained results using statistical methods.

Results & Conclusions: Our results suggest that miR-21 and miR-126 levels are not significantly different in lung cancer histological subtypes and they do not affect the length of DFS (disease free survival) and OS (overall survival). However, we observed the higher miR-205 levels in squamous cell carcinomas than in adenocarcinomas (p < 0.002) and also the longer DFS (p < 0.015) and OS (p < 0.01) in patients with higher miR-205 expression. Therefore, we concluded that the detection of selected miRNA in archived formalin-fixed paraffin-embedded samples may be an important tool for diagnosis and predicting the prognosis of NSCLC patients.

This work was supported by grants IGA521100331, GACR501100021, GACR303/09/H048, MSM6198959216 and CZ.1.05/2.1.00/01.0030.

1 Centro Superior de Investigación en Salud Pública (CSISP) 2 Hospital Universitario Peset 3 Hospital Politécnico Universitario La Fe 4 Hospital Clinico Universitario 5 Oficina del Plan del Cancer de la Dirección General de Salud Pública 6 Fundación Instituto Valenciano de Oncología; Valencia, Spain HR-08. Improvement in the Performance of the Information Linked to Human Origin Biological Samples of Interest to Biomedical Research in the Context of the Valencia Network of Biobanks

Biobanks are understood as technical resources specialized in the management and distribution of biological samples mainly for research proposes. They constitute the basis for the expansion of biomedical biotechnology, not only through the provisioning of high quality material, but also concerning the associated information linked to these samples. This aspect takes on special significance in the context of disease-oriented biobanks where the availability of clinical information would considerably increase the value and the potential use of the biological specimens. Hence, standardization of the type of information to be associated to the samples and interoperability between the information management systems (IMS) within the context of a network of clinical biobanks should be considered a priority. In order to reach this optimal context in the Valencia Network of Biobanks (VNB) we proposed two main objectives. First, to establish a process of normalization of a minimum data set associated to the specimens that are being collected at the biobanks integrating the VNB by analyzing the different sources of acquisition of clinical information, by defining the data collection systems of the biobanks and through the implementation of a universal codification system such as SnomedCT; and second, to improve the quality of the information associated to the samples in the field of biomedical research by orienting the research groups linked to the VNB as well as research groups outside the context of biobanks.

As a result the IMS of the VNB represents a dynamic and robust tool that has enhanced a close collaboration between biobanks and research groups within the Valencia area and that ensures a systemic interoperability with other IMS thanks to the integrated SnomedCT codification system.

This work has been possible thanks to the grants RD09/0076/00058 and RD09/0076/00163 from the ISCIII, Madrid, Spain; and Farmaindustria, Valencia, Spain.

1 Laboratory of Molecular Pathology, Department of Clinical and Molecular Pathology, Institute of Molecular and Translation Medicine, Faculty of Medicine and Dentistry Palacký University and Faculty Hospital in Olomouc, Olomouc, Czech Republic HR-09. Utilization of Different Biobanking Technologies for Multilayer Analyses of Gonadal Cancer Samples

The archives of the Department of Clinical and Molecular Pathology has provided various cancer tissue type samples for a number of years. Since 2009 it has also had an available cryobank. To date, seven different cancer- and control tissue types – brain, lung, intestine, ovary, testes, lymphatic nodes and breast are collected directly during surgery by a specialized pathologist into liquid nitrogen and fixative stabilizing RNA molecules. Brain, prostate, ovary and testes cancer tissues are also used for the preparation of primary cultures.

Our study is focused on ovarian and testicular tumors from the viewpoint of the influence of two homologous genes – TSPY and TSPX. Paraffin-embedded tissues are used for sample characterization by immunohistochemistry. Nucleic acids are isolated from frozen tissues and further used for real-time PCR, RT-PCR, microchip and other molecular analyses. Populations of primary cultures are studied by FACS. We aim to link traditional methods of human biological material storage with new technologies for comprehensive analysis of the studied problematics.

Acknowledgement: This work was supported by grant GAČR 303/09/H048, Operational Programme Research and Development for Innovations (project CZ.1.05/2.1.00/01.0030) and by the Ministry of Education of the Czech Republic - grant MSM 6198959216.

1 IMID-Biobank, Grup de Recerca de Reumatologia, Institut de Recerca Hospital Universitari Vall d'Hebron, Barcelona, Spain HR-11. IMID-Biobank: Biobank of Immune-Mediated Inflammatory Diseases (IMIDs)

Genomic analysis technologies are enabling an unprecedented characterization of human molecular variability. This high analytical power will be essential to meet the challenge of personalized medicine. More than ever, the quality of the biological samples will be essential to make the most of these new technologies. In order to obtain a large collection of samples from patients with Immune Mediated Inflammatory Diseases (IMIDs), the IMID-Biobank was created in 2007.

In collaboration with the Spanish National DNA Bank different working protocols were implemented, regarding the collection, processing and storage of the IMID samples. The IMID-Biobank is itself an operating infrastructure that consists of a steering unit, a technical coordinator, a team of laboratory technicians and Quality control unit. The purpose of the biobank to provide samples of high quality depends on the proper coordination of each of these elements. For this purpose, the IMID-Biobank has implemented an ISO 9001:2008 certified quality management system that allows continuous evaluation of all processes and procedures that take place in the biobank.

The IMID-Biobank has collected, processed and stored blood and urine samples from more than 11,000 patients with IMID diseases (rheumatoid arthritis, Crohn's disease, ulcerative colitis, psoriasis, psoriatic arthritis and systemic lupus erythematosus). Taking into account that different products like genomic DNA, RNA, plasma, buffy coat or immortalized cell lines have been obtained from blood samples, the IMID-Biobank is actually storing more than 70,000 products derived from IMID patients. For each patient, epidemiological data, clinical data (i.e. therapeutic response) and disease activity at the moment of sample collection were recorded.In the next expansion phase of the IMID-Biobank a logitudinal follow-up of patients will be established.

1 HIV HGM Spanish BioBank, Laboratorio de Inmunobiología Molecular, Hospital General Universitario Gregorio Marañón, Madrid, Spain HR-12. HIV HGM Spanish BioBank Contribution to Research and Treatment of Diverse Illnesses

One of the most important limitations in any disease investigations is the low availability of patients' samples. To solve this lack, biobanks have been developed.

The HIV HGM Spanish Biobank was created in 2004. It receives samples from infectious, rare and pediatric diseases.

The objective of the HIV HGM Biobank is to promote the progress of scientific knowledge. The internal process according to research purposes is made through reception, processing, storage and donation, based on biological samples belonging to numerous patients. For example the HIV Biobank has six different cohorts (Adults (CoRIS), Long Term Non-Progressors (LTNP), Rapid Progressors, Acute or Recent Infection, HIV-infected patients with liver organ transplant (OLT-HIV) and Paediatric Cohort (CoRISpe)), the pediatric Biobank has samples from 6 different diseases, and we have samples from 5 rare diseases.

All the processes carried out in the HIV HGM Biobank are done under a severe quality system control, following the policy ISO 9001:2008, which ensures the quality of the samples and the fulfilment of the ethical and legal policies.

Nowadays, this biobank receives samples from 38 hospitals all around Spain. Over 134000 vials of different kind of samples, donated by nearly 7000 patients, are stored. At the moment, more than 3400 of these samples are taking part in 26 national and international research projects.

This framework contributes to medical research, represents a strategic commitment that seeks the cooperation among working teams and development of specialized networks along with the investigation and treatment of diverse illnesses.

1 Basque Biobank for Research, Sondika, Spain HR-13. The Basque Biobank is a Research Tool for Predictive, Preventive and Personalized Medicine

The Basque Biobank for Research-OEHUN (www.basquebiobank.com) is a public institution with the mission of providing resources for predictive, preventive and personalized medicine to promote strong partnership between the health system, academia and industry. It forms a network of 7 main hospitals of the Basque Public Health System in Spain that covers a 2.1 million population.

The Basque Biobank processes and stores under Standard Operating Procedure (SOP) conditions across the 7 hospitals, blood, serum, normal and tumoral tissue, brain, and other biological samples from more than 15000 patients with a wide-range of diseases including cardiovascular disease, diabetes and metabolic disorders, respiratory diseases, cancers, mental and neuromuscular disorders.

The Basque Biobank has an Independent Review Board (IRB) and offers sample collections with genetic, clinical and lifestyle information. Clinical information linked to biospecimens is managed and updated in a central database interconnected to the network of 7 hospitals that allows the dynamic longitudinal follow up of the patients. The database works under a double coding protocol that can guarantee the traceability while protecting donors' privacy. Patient data is therefore provided to researchers in pseudo-anonymized form. Up to now, the Basque Biobank has collaborated in more than 120 projects.

1 Uppsala Biobank/UCR, Uppsala, Sweden HR-14. Hospital Integrated Biobanking

Uppsala Biobank is a biobank organization that started in September 2008. The primary reason for the principals, Uppsala University and Uppsala Academic Hospital, to start the biobank was to make sure they fulfill the demands set by the Swedish biobank act. The biobank Act states that samples should be accessible for research while the sample donors integrity are protected, which also includes managing samples in a qualitative and secure manner. Uppsala Biobanks activities include three parts; biobank administration (agreements, registries, advice and templates), biobank informatics (implementing a LIMS) and biobank service (sample collection and management). In Uppsala the strategic cancer project U-Can has driven the need for a biobank service integrated into hospital care. The U-Can project aims at prospectively collecting blood and tissue samples routinely from cancer patients. To be able to succeed the samples need to be taken by the ordinary hospital staff at the different hospital department where they receive their care. To do this, Uppsala Biobank has set up an automated sample management at the central clinical chemistry laboratory at the hospital and by transferring information from the EPJ to the laboratory information system at the clinical chemistry laboratory to the biobanks laboratory information management system (LIMS). Samples are then stored and managed by the biobank. Researchers can apply to U-Can/Uppsala Biobank for access to samples.

1 Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland HR-16. A Swiss Hospital Reorganization and Strategy in Response to the New Legal and Ethical Frame on Human Biological Material Research

As an academic hospital, research on human biological material is at the center of preoccupations at the Centre Hospitalier Universitaire Vaudois (CHUV). In this regard, a project on the problems of biobanking and rules to be established at an institutional level is in progress.

After a survey on collections of human biological material at the hospital, 59 active collections have been identified, 23 of them are interventional collections (diagnostic, therapeutic and judiciary), 24 are created for a specific project and 12 are biobanks. The close collaboration established with the managers of these collections as well as the requirements of the future federal law on human biological material research allow us to propose different actions that could be grouped in three main fields.

First, the hospital should offer a support to the management of collections, both for existing and new collections. This support should be based on procedure and directives and propose tools such as templates for consents (general and specific) and material transfer agreements.

Secondly, a virtual biobank should be developed through a website including a public registry, but also through a joint database gathering data and sample information from all these collections.

Thirdly, the question of a physical centralized biobank and of identified platforms for a high-standard quality of samples should be examined.

As a pioneer hospital in Switzerland on that topic and initiative, its willingness is to demonstrate that research could be favored despite a strict and scary future within an ethical and legal framework.

1 Fondation du Centre Pluridisciplinaire d'Oncologie, CHUV, Lausanne, Switzerland HR-17. The Challenge of Developing and Promoting a State-of-the Art Biobank in Switzerland

Since 2007, a state-of-the art biobank called “Biobanque de Lausanne” has been developed at the Coordinating Center of Oncology (CCO) in Lausanne. This biobank includes consented patients with a suspicion or diagnosis of cancer for whom tissue and blood derivatives are conserved with high quality standards. This biobank anticipates the new and strengthened swiss ethical and legal rules for any kind of cancer research approved by the local ethics committee.

Up to now 1560 patients have consented to it and only 55 have refused (3%). 94% of patients have blood processed in the biobank and 53% have tissue frozen.

This biobank is now open to researchers for one year and already manages more than ten research projects, retrospective as well as prospective ones.

The particularity of this biobank is to be an independent structure offering regulatory and operational services to the interested researchers. The structure is composed of clinical research associates and lab technicians, whose functions include selecting consented patients, sample collection, processing, and storage.

Promotion, development, communication and funding, as well as submission and organization of research projects is assumed by two managers closely collaborating with clinicians, surgeons, pathologists and researchers.

The challenge of this general cancer biobank is to be well recognized locally but also internationally and to adapt itself not only to the researchers' needs, but also to the top-quality levels required for human biological material preservation and usage.

1 Vanderbilt University Medical Center -Cooperative Human Tissue Network(CHTN), Nashville, TN, USA IT-01. Reducing Complexity and Increasing Flexibility of Biorepository Systems by Utilizing Web Services

Biorepository solutions are often large monolithic applications, incorporating functionality for all business functions required to collect, manage and distribute human specimens at a particular institution. Web Services allow functionality to be replaced, optimized or consumed in various ways without impacting the core functionality of the repository system.

A Web Service can be defined as ‘a software system providing functionality that can be accessed over a network’. The Donor System developed for the CHTN Western Division at the Vanderbilt University Medical Center makes use of two leading Web Service standards to integrate with other systems: SOAP (XML representation of requests and responses) and RESTful (Uses standard HTTP Methods to respond to requests, often returning JSON, or Javascript Object Notation, as a response).

The Donor System integrates with the following systems: VUMC Scheduling Software, CHTN Investigator Information, CHTN Disease List Vocabulary. For example, utilizing a system designed for Patient Scheduling is more beneficial than bolting on scheduling as an after thought. Because this functionality is isolated behind a Web Service interface, it can be replaced or changed without affecting the Donor System itself.

The Donor System utilized Web Services to leverage existing functionality in external and internal systems, providing functionality that may not have been possible due to time and money constraints. The Donor System has the flexibility to easily replace or change functionality provided by these Web Services.

1 Department of Animal Health and Anatomy, Universitat Autònoma de Barcelona, Barcelona, Spain 2 Institute of Zoology, London, United Kingdom IT-03. Biobanked Amphibian Samples Confirmed to Species Level using 16S rRNA DNA Barcodes

The DNA barcoding technique is often used as a tool for validating species identity in biobanks. In the case of amphibians, the mitochondrial DNA 16S ribosomal RNA gene is reported to fulfill the requirements of a universal DNA barcoding marker. The 16S primers are designed to bind specifically to the 16S rRNA gene, which is a very well conserved mtDNA gene sequence in amphibians. DNA was extracted from thirteen known but different species of amphibians within the Zoological Society of London/Amphibian Ark's cryobank. Following this, the DNA was amplified and analyzed by (1) the traditional DNA barcoding procedure that involves conventional PCR and DNA sequencing and (2) a novel procedure, involving real time PCR and melting temperatures, both proceedures used the same 16S primers. Successful DNA amplification and validation to the species or genus level was achieved in 10 out the 13 cases using the traditional approach. Nevertheless, after real time PCR and melting temperature analysis, some variability was found between Common frog samples but more concerning, the same melting temperature was recorded in unrelated species (Common Toad, Common Frog and Amazon Milk Frog), despite their 16S sequences exhibiting a high degree of variability. We conclude that traditional DNA barcoding using 16S rRNA sequences is suitable for validating the specific identity of amphibian samples within biobanks and that modification of the current 16S real time PCR and melting temperature analysis is required before it can be employed as a cheaper and faster alternative.

1 Institute for Molecular Medicine Finland, University of Helsinki, Finland IT-04. The SAIL Platform: Enhancing Biobank-based Collaborative Studies

Biobanks are the archives of human samples and act as the guardians of data that have been accumulated over the past decades. In order to maximize the discoveries that can be made based on the collected biomaterial and information, they actively build partnerships with research groups in academia and industry.

While access to the biobank content is restricted for ethical and legal reasons, informatics may enable controlled data transparency and through that it can assist in building efficient research collaborations.

SAIL (sail.simbioms.org), the Sample avAILability System, is an on-line resource, which allows researchers to locate and estimate the amount of relevant biomaterial available from a sample collection. One of the most common obstacles on the way to an effective research partnership is the absence of flexible means for data access control: access options are often reduced to a choice between ‘open to all’ and ‘completely private’. SAIL provides information for each sample on whether a value for a given phenotypic variable exists or not, without storing or disclosing the value per se. Phenotypic variables are organized in controlled vocabularies, taxonomic structures and studies.

The resource has been successfully used for retrospective harmonization of phenotypic information from hospitals and biobanks, and it currently contains around 200000 samples from 14 collections. The SAIL mission as an online resource is to increase the visibility of the biobank content and to ease the set up of population-wide genetic and molecular studies.

1 Fondation du Centre Pluridisciplinaire d'Oncologie, CHUV, Lausanne, Switzerland IT-05. Research Projects : From Sample Demand to Sample Shipment – A Journey Through Sapphire and MS Access

After three years collecting samples, the Biobanque de Lausanne (BbdL) has opened to researchers in 2010. Research projects submitted to the BbdL have to be evaluated and accepted by both a scientific and an ethics committee. Once approved, the management of sample demands requires two tools: a complete database containing data and samples, as well as a data extraction tool.

The BbdL uses a database called Sapphire Biobanking, a web-oriented software developed by Labvantage, which was adapted to the needs of the BbdL and enables data, sample and research project management. Each patient is identified by a unique code automatically generated by the software, and the access to the database is secured by a personal login, ensuring patients confidentiality. Each sample is virtually stored and linked with patient's clinical and epidemiological data - actually more than 500 fields concerning each patient can be completed.

In order to determine which samples correspond to researchers demands, Microsoft Access is used, which enables the listing of all samples corresponding to specific criteria registered in the database. It is then possible to print clinical and epidemiological data linked to each sample, as an anonymized report. As an extraction tool, MS Access allows quality controls of the database as well as statistical analysis of the biobank activity.

In the BbdL, these two computer tools are thus complementary and could not be dissociated. They are not only essential to answer investigator demands, but also to register and follow quality indicators.

1 University of Leicester, Leicester, United Kingdom LE-01. Barriers to Biobank Harmonization: Evidence from Professionals and Practice

Background: International calls have been made for organizations that collect, store and transport human tissue samples for research purposes to standardize their practices to enable more effective scientific collaboration. Cooperation between cancer tissue banks could encourage higher quality samples and data, allow larger, more powerful research projects to take place, and provide opportunities for rare cancers to be studied. However, lack of standardization and non-cooperation remain the prominent features of the field. We seek to use ethnographic data and social science theory to identify and characterize key barriers to biobank harmonization.

1 Radboud Biobank, Radboud University Nijmegen Medical Centre, The Netherlands 2 Dept Epidemiology, Biostatistics and HTA, Radboud University Nijmegen Medical Centre, The Netherlands 3 Board of Directors, Radboud University Nijmegen Medical Centre, The Netherlands 4 Radboud Biobank Steering Committee NIJMEGEN, Radboud University Nijmegen Medical Centre, The Netherlands LE-02. Involvement of Patients in a Clinical Biobank

Patients are primary stakeholders in clinical biobanks. They donate samples for medical research and innovation for benefit of future patients. Sometimes, they initiate biobanks themselves. Still, patient representation in institutional biobanks has been limited to membership of advisory boards.

The Radboud Biobank is a new initiative for a comprehensive, clinical biobank, based on the standards of the String of Pearls Initiative, a national project setting the standard for clinical biobanking in the Netherlands. The Radboud Biobank aims to collect samples and clinical data of all new patients admitted to Radboud University Nijmegen Medical Center.

Consultation with stakeholders showed that, based on normative, substantive and political arguments, patient representation is of importance in strategic policy, research agenda setting and communication of the Radboud Biobank. Therefore, patient representation in the Radboud Biobank will be organized as follows:

• A patient representative with a track record in advocating patient interests in research chairs the steering committee.

In the future, we seek to set up formative evaluations to assess and further improve the effectiveness of patient involvement in the Radboud Biobank.

1 Research Centre for Pharmaceutical Care and Pharmaco-Economics, Leuven, Belgium 2 AC Biobanking UZ Leuven, Leuven, Belgium 3 Centre for Biomedical Ethics and Law, K.U. Leuven, Leuven Belgium 4 Centre for Intellectual Property rights, K.U.Leuven, Leuven, Belgium LE-03. Access Rules within Biobank Networks

Great promises are expected from sharing biological specimen and associated data within and between networks or partnerships of biobanks.

Several projects studied and developed guidelines and best practices in relation to the governance of biobanks and/or biobank networks; however, with limited focus on access rules (1-2).

In the first phase, the project investigates the following aspects of arrangements on access and use of biological specimen and associated data in research projects: (a) custodianships of samples shared within the network; (b) existence and mandate of access committee; (c) criteria for review of research proposals and priority setting between different proposals; (d) scope of access and use; (e) return of samples; (f) sharing of research results within the network; (g) cost recovery plan and differentiation between researchers inside and outside the network and industrial partners; (h) acknowledgement and intellectual property arrangements; (i) commercialization of research results and benefit sharing; (j) incentive mechanism to share human biological specimen and data; (k) protection of interests of the donors; (l) sanction and dispute resolution mechanism (3-7). The investigation is based on a review and analysis of access policies and guidelines developed by amongst others ISBER, TubaFrost, EORTC, P3G, BBMRI.EU, OECD, Privileged, Integrated Biobank of Luxembourg, String of Pearls Initiative.

In the second phase, the project will study to which extent these access rules stimulate and/or hamper the exchange of biological specimen and associated data in research activities. The results of the project can assist biobanks and biobank networks to develop their access rules.

References: (1) Hallmans G. et al., Methods in Biobanking, Methods in Molecular Biology, 241-260 (2011); (2) Riegman P.H.J. et al., Molecular Oncology, 213-222 (2008); (3) Fortin S et. al, Public Health Genomics, 104-114 (2011); (4) Joly Y. et. al., Human Genetics (2011); (5) Yuille M. et.al., Briefings in Bioinformatics, 14-24 (2008);(6) Lemrow S.M. et al., Cancer Epidemiol. Biomarkers Prev., 1533-1535 (2007); (7) Lopez-Guerrero J.A. et al., European Journal of Cancer, 2924-2929 (2006).

1 HIV HGM Spanish BioBank, Laboratorio de Inmunobiología Molecular, Hospital General Universitario Gregorio Marañón, Madrid, Spain LE-04. HIV HGM Spanish Biobank: Ethical and Legal Conflitcs in the Yield of Biobanks

In recent years, biobanks have acquired great importance due to the quality of biological samples associated to clinical data.

In these biobanking activities some guaranties and rights from researchers and donors should be fulfilled. These rights and guaranties collide causing discussions related with ethical and legal aspects. Nowadays the ethical and legal conflicts are focused in:

- Difficulties in designing an Informed Consent that allows simultaneously being restrictive to actual policies and extensive enough to include the future possibilities of the usage of the stored samples, and therefore unpredictable in its details.

An indicator of this discussion relevancy is that one of the aims of both national and international biobanks must be the establishment of common values that promotes the acquisition of a balance between science progress and the respect to individual rights and freedom.

We will present the HIV HGM Spanish Biobank experience in this area acquired in the last years.

1 Institut Pasteur, Collection de l'Institut Pasteur, Département de Microbiologie, Paris, France 2 Banque d'ADN et de cellules, Généthon, Evry, France 3 UMR AGAP, INRA, Montpellier, France 4 Institut de Chimie de Nice, Parc Valrose, Nice, France 5 Centre de Biotechnologie Cellulaire, Groupe Hospitalier Est, Bron, France NT-01. DNA Encapsulation: A New Method for DNA Long Term Preservation at Room Temperature

Background: Current methodologies rely on maintaining DNA samples in cold environments during storage procedures and transport processing. In view of the exponential increase of the number of DNA samples to be stored on one hand, and the cost and the risks of freezer breakdowns on the other hand, room temperature storage of dehydrated DNA appears as an alternative solution having significant advantages, particularly in long term DNA storage and in the area of sample shipment.

Through the French, IBiSA (Infrastructures en Biologie, Santé et Agronomie), a new procedure for room temperature storage of DNA was evaluated whereby DNA samples from human tissues, bacteria and plants were stored under an anoxic and anhydrous atmosphere in small glass vials fitted in stainless-steel, laser-sealed capsules.

Methods: Samples were stored dry at room temperature for various time periods to assess any degradation as compared with frozen control samples. The study included accelerated aging by using a high temperature (76°C, 50% relative humidity).

Results: No detectable degradation of the DNA occurred for 18 months at room temperature. At 76°C, it was necessary to include a small adjustment to the process in order to avoid losses through aggregation or adsorption. In these conditions, the recovered DNA exhibited no detectable degradation. Its quality was confirmed using spectrophotometry, fluorometry, agarose gel electrophoresis and pulsed field gel. Furthermore, no interference or inhibition in PCR applications was evidenced.

Conclusion: This study including accelerated aging results has demonstrated the interest of this DNA storage procedure for room temperature storage.

1 CryoXtract Instruments, LLC, Arlington, VA, USA 2 The Charles Stark Draper Laboratory, Cambridge, MA, USA NT-04. Development of an Automated Frozen Sample Aliquotter: Protecting the Value of Critical Banked Biospecimens

Advances in translational research molecular medicine and biomarker discovery rely on quality biological specimens whose integrity is imperative to protect long term lest a study be compromised. Freezing is a ubiquitous method of preserving sample fidelity during long term storage; however, samples may be exposed repeatedly for aliquot processing over time to freeze-thaw cycles that damage their molecular fidelity. Furthermore, thawing and mixing are manual and time-consuming.

The Automated Frozen Sample Aliquotter was designed to support modern biobanking and enable biobanks to distribute samples without exposing them to repeated freeze-thaw cycling. This novel robot enables hands-free extraction of multiple frozen uniformly-sized aliquots from one frozen sample helping to preserve sample fidelity and maximize its useful life while helping standardize aliquot processing through automation. Reducing freeze-thaw cycles enables sample storage in larger volumes up front, which helps reduce lab costs and administrative burden.

A fully automated platform has been designed that delivers automated operation (e.g. tube management, de-capping/capping, coring, probe cleaning) after samples have been loaded into the system. Independent evaluations have demonstrated the system's ability to extract multiple volumetrically uniform and consistently homogenous frozen aliquots from one parent sample and to eliminate carryover between samples.

This presentation will describe the current generation of the technology and its validation.

1 Institut Bergonié, INSERM U916, université de Bordeaux, Bordeaux cedex, France 2 Imagene company, Research and development, ESTBB, Université de Bordeaux, Bordeaux, France 3 Imagene company, Production Platform, Evry, France 4 Pôle judiciaire de la gendarmerie nationale - Institut de recherche criminelle de la gendarmerie Nationale, Service central d'analyses génétiques (SCAGGEND) - Rosny-sous-Biois, France NT-05. Novel Procedure for High Yield Recovery of Trace Amounts of DNA Stored at Room Temperature

Adsorption of macromolecules on solid surfaces is a well known phenomenon making problematic long term preservation of very low amounts of DNA, such as those involved in forensics. Various degrees of loss are observed whatever the DNA storage conditions, even freezing at −80 °C. Trehalose or commercial matrixes have been shown to enhance recovery but studies have been limited to one year. So there is currently very little knowledge concerning ways to avoid losses upon long term storage of trace amounts of DNA.

We present here preliminary results of empirical studies addressing this goal. Various procedures were tested in order to improve the recovery of low amounts of DNA in conditions where control samples were totally lost. All these treatments, even those using trehalose, were totally ineffective. In contrast, the use of a novel additive allowed up to 100% recovery.

Further, preliminary results indicate that higher DNA template concentration in samples treated with this specific additive is recovered using both real time PCR quantification and STR analysis performed with a 15-STR multiplex amplification kit for human identification and forensic cases. These results demonstrate that our DNA storage procedure may be suitable not only for DNA databasing but also for long term storage of minute amounts of DNA extracted from crime scene stains.

1 Imagene company, Research and development, University of Bordeaux, ENSTBB, Bordeaux, France 2 Imagene company, Production Plateform, Evry, FRANCE 3 Laboratoire Central d'Hématologie, Paris, France 4 Institut Bergonié, Bordeaux, France NT-06. Innovative Technology for Ribonucleic acid (RNA) Biobanking at Room Temperature

RNA is usually stored at temperatures below −20 °C. In these conditions, RNA storage and transportation has an energy and financial cost. In addition, the increase in the number of samples to be preserved leads to space and security issues.

We previously showed that RNA is greatly affected by atmospheric water and oxygen but that a simple desiccation is not enough to stabilize it. However, RNA is very stable when stored in the RNAshell device that maintains a UV-, oxygen- and water-free atmosphere in presence of a stabilizer.

Quantitative universal reference standards are needed for diagnostics and measurement of the evolution of leukemia in patients to guide clinical practice. This requires high stability of RNA and/or its degradation to be random. These conditions were shown to be fulfilled by the RNAshell through analysis of seven transcripts by RT-qPCR experiments. Our results suggest that RNAshells are suited for standard RNA storage.

External validation studies were performed on total RNA extracted from leukocytes of patients expressing BCR-ABL1 at different levels. RNA was encapsulated in RNAshells and heated to accelerate aging and simulate up to a 100 year-storage. RNA recovery was performed by simple rehydration. No loss was evidenced by UV spectrophotometry measurements. In addition, no significant changes in the expression profiles and copy numbers of three differentially-expressed genes were found over time by RT-qPCR.

Therefore, RNAshell is a reliable solution for standard RNA storage and transportation compatible with downstream RNA techniques and high throughput handling of samples such as biobanking.

1 INSERM U862, Neurocentre Magendie, université de Bordeaux, Bordeaux Cedex, France 2 Imagene company, Production Platform, Evry, France 3 Imagene company, Research and Development, ENSTBB, Université de Bordeaux Segalen, Bordeaux, France 4 Institut Bergonié, INSERM U916, Université de Bordeaux Segalen, Bordeaux Cedex, France NT-07. Evaluation of a Novel Method for Room Temperature Storage of RNA

RNA samples are usually stored frozen in solution at −80 °C. This conservation method leads to space and security issues as well as high maintenance and energy costs. Moreover shipping of frozen RNA requiring dry ice is expensive and subjected to transportation hazards. So a procedure allowing room temperature RNA storage and shipping is highly needed.

Imagene company developed a procedure (RNAshell minicapsules) whereby RNA samples are stored in airtight containers under an anhydrous and anoxic atmosphere in the presence of a “stabilizer”.

In these conditions, the degradation rate at 22 °C (1.8x10-11 min-1.nucleotide-1) obtained by extrapolation is such that it should need more than 5 years to degrade 1% of a 200 nucleotide long RNA population (or 17 years to see an 0.1 unit increase of the Cq corresponding to such a target).

A validation was done on rat and mouse total RNA isolated from the brain structure hippocampus, treated according to Imagene's procedure and stored for one month at room temperature. Bioanalyzer analysis exhibited no significant differences in RNA quality between the controls and encapsulated stored samples. Moreover the analysis by RT-qPCR of the profiles from 5 differentially expressed genes showed no modification. While studies involving longer storage periods are necessary (and under way), these results support the fact that RNAshell minicapsules constitute a safe storage and transportation method compatible with downstream RNA analysis and high throughput handling of RNA samples

1 NACDA Program on Aging, University of Michigan, Ann Arbor, Michigan, USA NT-08. Emerging Opportunities for Partnerships in the Long Term Preservation of Biospecimens: The Growth of Biosocial Surveys Designs in Federally Funded Research

In the past decade there has been a tremendous growth in the collection of biospecimen data within the realm of social and behavioral science survey research. Major federally funded studies within the United States including the Health and Retirement Study (HRS), and the National Social Life, Health and Aging Project (NSHAP) as well as international studies such as Social Environment and Biomarkers of Aging Study (SEBAS) and the RAND Family Life Studies have made major investments into the collection of blood, DNA and other biological specimens in the hopes of shedding light on relationships between physical characteristics and social outcomes. Scientific models allowing for the simultaneous use of biological and social covariates are still evolving and it may be many years before the data being collected now can be effectively used in a coherent research design. As a consequence of this lag between specimen collection and research applications, growing concerns have emerged over the preservation and storage of biospecimens. Increasingly, researchers who reach the end of their funding period lack relationships with established biorepositories to ensure the long term preservation of their biospecimen data. NACDA is a leading repository of electronic information related to the study of aging, health and the biological lifecourse. This presentation offers an overview of the growing need for long term partnerships with the biorepository research community to develop best practices that will insure the same level of preservation and viability to biosocial data specimens as is currently available for the associated electronic data records.

1 Illumina, Inc.,San Diego, CA 92121 NT-09. Unlocking the Genetic Potential of Biobanks

Illumina has recently established a biobank genotyping initiative to enable low and high density genotyping, including both array and sequencing technologies, of large biobank cohorts and sample collections. Under this initiative, biobanks can cost effectively access high throughput genotyping products for sample characterization, quality control and fingerprinting. A large portfolio of genotyping arrays, the latest based on recently released 1000 Genomes (www.1000genomes.org) content and assessing up to 5 million markers, can be used for molecular fingerprinting, highly sensitive detection of cytogenetic features such as copy number variation and loss of heterozygosity, and sample stratification. Lower density array formats are ideally suited for inexpensive, standardized sample quality control/quality assurance and ongoing sample tracking and verification mechanisms. In addition, select genotyping, methylation array and sequencing results from material restored from FFPE samples will be shown, which open up previously challenging banks of archival samples to analysis and inclusion. We will overview current array and sequencing technologies and applications, and discuss early results from representative banks.

1 Complete Genomics, Inc. Mountain View, California USA NT-10. Complete Genome Sequencing and a Reference Set of Human Genomes for Biological Interpretation of Biobanked Samples

Accurate, complete human genome sequences provide a powerful method for identifying variants involved in clinically relevant diseases and phenotypes. We have developed a technology platform and laboratory capable of cost-effectively sequencing over 600 human genomes per month at high-depth. To help discriminate causal variant(s) from the millions of other variants in any genome sequenced we recently generated high-depth complete human genome data on 69 ethnically diverse non-tumor cell lines from the NIGMS and NHGRI (CEPH/Utah, HapMap and 1000 Genomes Project) collections. This gender-balanced diversity panel includes individuals of European, Asian, and African descent, as well as admixed individuals. Bioinformatic analysis was performed using our local de novo assembly based pipeline which detects SNVs, indels, and substitutions in addition to copy number and structural variants. These data have all been released on ftp2.completegenomics.com and updates will be available over time. Comparisons against HapMap and 1000 Genomes Project data, in addition to validation by traditional methods, shows high genotype concordance. The frequency and/or novelty of variations observed in a genome of biomedical interest, for example from biobanked samples, can be estimated by comparison against this public repository.

1 Vanderbilt University Medical Center/CHTN-Western Division, Nashville, TN, USA OT-02. Lean Six Sigma Implementation for the Advancement and Innovation of Bio-Repository Operations

CHTN-VUMC has implemented Lean Six Sigma (LSS) as a new model of operations that promotes efficiency and innovation. LSS is a management system driven by the need to continuously improve and eliminate complexities and sustain improvements in every part of an organization.

CHTN-VUMC is a federally funded service oriented grant that provides high quality human specimens to researchers to accelerate the advancement of discoveries in cancer diagnosis and treatment. Borrowing the LSS business philosophies and methodologies, CHTN-VUMC has succeeded in the LSS approach by identifying and prioritizing quality improvement initiatives. The LSS philosophy states that high quality goods and services begin with dedicated staff at each level of the operation that is committed to the LSS implementation. Phase one implementation consisted of staff members defining a key job function, which would be considered “critical to quality” and completing all five LSS steps (define measure, evaluate/analyze, improve and control). We have completed an update and reorganization of our ordering, inventory and SOPs, creating a more streamlined and efficient biobanking environment.

The LSS is a process improvement methodology that can be leveraged to enhance any organization by creating an infrastructure that supports a culture of assessment and change through eliminating waste, minimizing downtime, reducing defects and errors, and improving productivity. CHTN-VUMC has adopted the LSS system to foster an atmosphere of continuous improvements to achieve the highest quality customer and employee satisfaction and quality control in biobanking.

1 ESTBB, Catholic University of Lyon, Lyon, France 2 3C-R, Castelginest, France 3 International Agency for Research on Cancer (IARC), Lyon, France 4 Nice Hospital Biobank, University of Nice Sophia Antipolis, Nice, France OT-03. Development of a Curriculum at Master Level for Managers of Biobanks and Biological Resource Centers: A Pilot Program

In recent years, there has been a huge increase in the demand for high quality biospecimens in almost every field of biological sciences, leading to the development of many types of biobanks. Biobanks are often extremely heterogeneous in their scope, design, methods, biospecimen annotations and documentation of individual consent. This situation has led to international efforts for harmonizing biobanking procedures and quality controls. The growth of biobanks and biorepositories is rapidly transforming the business of collecting, processing, documenting, storing, distributing biospecimens and their by-products into a multi-disciplinary scientific activity that requires a strong molecular biology background, literacy with database and laboratory information management systems (LIMS), detailed knowledge of cryopreservation biophysics, proficiency of quality control and quality insurance procedures, and detailed knowledge of ethical norms and regulations on obtaining consent and protecting the privacy of personal data. This vast body of diverse knowledge makes it necessary for managers of biobanks and biological resources to become highly trained, full-time professionals. We describe and discuss here an intiative to develop such a curriculum at Master level through a collaboration between ESTBB (Catholic University of Lyon), the University of Nice - Sophia Antipolis and the International Agency for Research on Cancer (Lyon, France). This is, to our knowledge, the first description of a comprehensive training and teaching program for managers of biobanks and biological resources. This curriculum incorporates recent advances in biobank harmonization and provides both a model and a pilot for enhancing biobanking interoperability through a common core of biobanking knowledge.

1 Tissue Solutions Ltd, Titan Enterprise, Clydebank, Scotland OT-04. Working with Virtual Bio Banks: Pros and Cons

Access to human biomaterial by researchers has changed over the years. It started with direct access to material via clinicians and has transitioned because of legal and ethical concerns to a tightly controlled process. Formal biobanks with controlled access procedures are now the main gateway to research samples. An alternative to this is a virtual biobank which allows researchers to obtain samples from a network of sources at a one stop shop. Most virtual biobanks are commercial organizations which raise a number of concerns especially for people who collect samples. I would like to address some of these in this presentation:

- How does a virtual biobank work in practice?

Each of these points will be explored and hopefully a general discussion with the audience will be generated.

1 St. James's Hospital Biobank, Dublin, Ireland 2 Beaumont Hospital, Dublin, Ireland 3 Cork University Hospital, Cork, Ireland 4 University College Hospital Galway, Galway, Ireland QC-01. Maintaining Breast Cancer Specimen Integrity and Individual or Simultaneous Extraction of Quality DNA, RNA and Proteins from AllProtect-stabilized and Non-stabilized Tissue Samples

Introduction: The Saint James's Hospital Biobank (SJHB) was established in 2008, to develop a high quality breast tissue BioResource. The aims of this work were: (i) to ascertain the quality of RNA, DNA and protein in biobanked carcinomas and normal breast tissues, (ii) to assess the efficacy of AllPrep® in isolating RNA, DNA and protein simultaneously, (iii) to compare AllPrep with RNEasy® and QIAamp®, and (iv), to examine the effectiveness of Allprotect®, a new tissue stabilization medium.

Methods: One hundred and eleven frozen samples of carcinoma and normal breast tissue were analyzed. Tumor and normal tissue morphology were confirmed by frozen sections. Tissue type, tissue treatment (Allprotect vs. no Allprotect), extraction kit and nucleic acid quantification were analyzed utilizing a four factorial design. QIAamp®, AllPrep® and RNeasy® kits were assessed and compared.

Results: Mean DNA yield and A260/280 values using QIAamp were 33.2 ng/μl and 1.86, respectively, and using AllPrep were 23.2 ng/μl and 1.94. Mean RNA yield and RIN values with RNeasy were 73.4 ng/μl and 8.16, respectively, and with AllPrep were 74.8 ng/μl and 7.92. Allprotect-treated tissues produced higher RIN values of borderline significance (p = 0.055). No discernible loss of RNA stability was detected after 6 hours at room temperature or 4°C or in 9 freeze-thaw cycles.

Conclusion: Allprotect requires further evaluation; AllPrep is an excellent option for the simultaneous extraction of RNA, DNA and proteins. The essential pre-sampling procedures which maintain the diagnostic integrity of pathology specimens do not appear to compromise the quality of molecular isolates.

1 IBBL, Luxembourg 2 ISBER, Bethesda, MD, USA QC-02. ISBER Proficiency Testing Program for Biorepositories : Pilot Results for DNA and RNA Schemes

ISBER has developed a Proficiency Testing (PT) program for biorepositories in partnership with IBBL. The PT program allows biorepositories performing quality control assays/ characterization of the biospecimens to assess the accuracy of their testing and to compare their results with those obtained in other laboratories around the world. For biorepositories that want to pursue accreditation, the ISBER PT program will provide a necessary External Quality Assessment tool.

All the Standard Operating Procedures have been written according to the requirements of the ISO17043 norm, reviewed by the ISBER PT Advisory Group and approved by the ISBER PT Coordinating Body. Specific software was configured for the needs of the biorepository PT schemes. The first two schemes that were launched in 2011 are “DNA Quantification and Purity” assessment and “RNA Integrity” assessment. The PT pilots on those schemes were successfully run in April 2011 among ISBER members of the Biospecimen Science Working Group. For the DNA Quantification/Purity scheme, the assigned value was 53.03ug/ml and all participants obtained /z/<1 scores. For the DNA ratio, the assigned value was 1.86 and all participants obtained /z/<1 scores. For the RNA Integrity scheme, the assigned value was RIN 8.76 and 66.6% of participants obtained /z/ scores <1, 22.2% of participants obtained 1</z/<2 scores and 11.1% obtained 2</z/<3 scores.

The DNA Quantification/Purity and RNA Integrity schemes are open to all interested laboratories globally. Two additional schemes (Cell Viability and Tissue Antigenicity) will be added in 2012.

1 Biobanco La Fe, University and Polytechnic Hospital La Fe, Valencia, Spain QC-03. Quality Tools in the Biobank La Fe: What do the Customers Expect?

The Hospital La Fe's Biobank of Valencia, named Biobanco La Fe, carries out the daily activity according to International Quality Standards not only in the organization's core processes but also in the strategic and support ones.

The Balanced Scorecard (BSC) is a management tool which is being used for clarifying the Biobank's vision, mission and values. This framework helps us to keep track the execution of our activities and control/monitor their consequences.

Our BSC considers four perspectives: customer's view, innovation/learning/growth perspective, internal processes and financial perspective.

Nowadays, the Biobank is trying to assess its strategy in this way. This work will make it possible to detect what researchers want or need in response to the society's necessities.

On the other hand, the Biobank is continuously acquiring various types of samples. In order to develop these activities, we are introducing the ISO 9001:2008 that prescribes a systematic control of activities which ensures that the expectations and requirements of researchers and clinicians are met.

These items can result in quality's measurable features. The Biobanco La Fe is using several tools to measure those characteristics and obtain information about the quality of its services and study the processes' running. Generally, the tools which are being used are: Ishikawa Diagram, Control Graphs and Pareto Diagram. Also, the Biobank uses other tools of management such as The House of Quality which adapts the customer's necessities to the service's quality. The House of Quality gives a matrix approach about the external and internal Biobank's requirements.

1 AstraZeneca, Cheshire, United Kingdom QC-04. Global Quality Targets in Biobanking – Pharma Example

The pharmaceutical drug research and development sector depends increasingly heavily on human biosamples (HBS) and is one of the most regulated industries with subject/patient safety being the utmost priority. AstraZeneca (AZ) takes regulatory compliance as an absolute minimum working standard and this philosophy extends specifically into HBS management. Within our internal biobank organization we have set up quality assurance (QA) and quality control (QC) processes to help us meet these regulatory challenges. The target for HBS in all AZ research sites is compliance with no critical or major issues.

The QA processes include internal biobank audits (covering receipt, storage and disposal records), functional departmental audits (looking into sample usage) and global audits (verifying governance). We are also subject to general (ICH Good Clinical Practice) and in the UK, tissue specific, external inspections (Human Tissue Authority).

The audits are organized systematically and results of inspections are assessed against AZ internal and where appropriate, external standards. The audit reports highlight examples of good practice as well as deficiencies, the latter requiring timely completion of corrective action.

QC is covered in clinical study protocols and contracts with commercial HBS suppliers and tissue banks detail minimum quality standards for HBS. QC testing is conducted within the biobanks to ensure that the samples meet the required criteria. QC processes can be split into 3 areas; Tissue, DNA and, Data.

Example QA and QC templates will be presented.

1 HIV HGM Spanish BioBank, Laboratorio de Inmunobiología Molecular, Hospital General Universitario Gregorio Marañó, Madrid, Spain QC-05. Official Accreditation for Human Biobanks

Samples from biobanks should have the widest end product scope possible and the highest sample quality. The standardization of procedures in biobanks makes this task easier. Nowadays, the international accreditations for management and quality control in biobanks are implemented through regulations ISO 9001(processes) and ISO 27001 (systems). However, biobanking makes specific demands on quality management and quality control procedures. A specific certification for biobanks from the ISO 9001 family norm has been implemented in France, named NF S 96-900. This regulation should be promoted internationally but efforts should also be made to increase quality at stakeholder level. We suggest the specialization of human biobanks via an official accreditation. In fact, the HIV HGM Spanish Biobank holds ISO 9001 2008 certification and agrees with most of the procedures of NF S 96-900 certification. Three main types of human biobanks have been defined as follows: Population banks, Epidemiological Disease-oriented banks, and General Disease-oriented biobanks. According to these biobank profiles, different types of biomarkers are sought. The first type sought biomarkers of susceptibility and population identity. The second type is focused on biomarkers of exposure, and the third type seeks biomarkers of disease. The accreditation can be based on these three profiles. Therefore, harmonized procedures and official indicators for quality control can be implemented. Since research is needed in order to discover new biomarkers for biobanking, the feedback from specimen users of different profiles could increase the number of biomarkers. This will therefore ensure a continuous improvement quality program in human biobanks.