The International Society of Biological and Environmental Repositories presents Abstracts from their Annual Meeting Bridging the Canyon – Connecting Biobank Communities through Innovations in Global Health,Research and Environmental Preservation May 5–9,2015 Phoenix,Arizona

Human tissues are usually stored as formalin-fixed paraffin- embedded (FFPE) samples in biobanks. However, its application for clinical research use has been limited. Although combining micro-dissection of tissue samples with LC/MS spectrometry has been applied for the analysis of FFPE tissues, there have been few specific protein biomarker of human diseases. Here, we were successful in identification of biomarker of acute myocardiac infarction (AMI) using FFPE archive and frozen blood in our Kyoto University tissue biobank. We also applied this methodology using Electro Spray Ionization (ESI) with LC/MS.

To identify biomarkers of acute myocardiac infarction, we selected tissues from five patients (mean age ± SD: 59 ± 12 years) and five normal controls (57 ± 14 years) in Kyoto University Repository. Cardiac tissues with contraction fibers and/or wavy fibers were collected with excluding large capillaries and fibrotic area. To extract proteins followed by liquid chromatography/mass spectrometry (LC/MS), each microdissected sample was suspended in a buffer containing CH₃CN for peptide extraction. 10²-10³ proteins could be identified in the use of various FFPE tissues. Our studies found levels of 21 proteins to differ significantly between AMI patients and control subjects. Cytoplasmic, mitochondrial, and extramyocardial proteins were detected, as validated by detection of the conventional marker, H-FABP. As a result, we found the marker Sorbin and SH3 domain-containing protein-2, (SORBS2).

SOBS2 mediate cytoskeletal change by physical stress and signal transduction. SORBS2 normally localizes along the Z-line in myocardial cytoplasm and is observed in the intercalated disk in control heart tissue. Using peripheral blood that was frozen in our respository, western blot analysis revealed that SORBS2 levels were markedly lower in AMI tissue than in control tissue and are detected at significantly high levels in serum of AMI patients. These observations indicate that SORBS2 is released from cardiac myocytes in an acute lethal infarction. Further, immunohistochemistry revealed that SORBS2 signal was significantly weaker than that in normal lesion. These data indicated that SORBS2 was one of the promising marker for AMI patients. Label-free LC-MS accompanied by precise laser micro dissection enabled in situ proteomic analysis that corresponded with pathological findings (J. American Heart Association 2013, L'Oreal- UNESCO International Award, 2014).

O3-23 Fixation Alternatives and Effect on RNA Degradation: New and Old

Hostetter G. 1 Collins E. 1 Jewell S. 1

1 Van Andel Research Institute, Grand Rapids, Michigan, United States

Background: Formalin fixation (FF) remains the standard for tissue preservation in clinical and research settings but still suffers from an inability to preserve RNA integrity. Alternative preservation fixatives have been developed and used over the past 50 years, largely for specific enhancements to tissue staining but have not been thoroughly evaluated for RNA integrity. PAXgene has been developed to preserve RNA in tissue, but has the unfortunate requirement of storage at −20 deg. C when embedded in paraffin to prevent RNA degradation. One other candidate is the HOPE fixative to maintain morphology and high content and integrity of nucleic acids.

Methods: An experimental murine model provided same tissue harvest aliquots of brain, muscle, kidney, liver, colon and spleen for comparable analyses of PaxGene versus Hepes- Glutamic Organic solvent Protection Effect (HOPE) in direct comparison to FFPE using standard fixation protocols and varied fixation duration (24, 48 and 72 hrs.) for FFPE and HOPE arm. The PaxGene tissues were fixed and processed per specific protocol (Qiagen, Inc). Tissue processing protocol varied as recommended for each fixative. All tissues underwent automated tissue processing (Sakura, Inc) and embedded in pure paraffin of 52–54 deg. C We tested RNA integrity in variable paraffin block storage of −20 deg. C and RT for HOPE and PaxGene.

Results: Direct comparison of FFPE and HOPE fixative showed marked stability of RNA in HOPE by RIN and comparable yields by Nanodrop and Qubit. Average RIN values at 24 hr. preservation were 2 fold higher than FFPE. FFPE showed uniform degradation across all organs at 24 and 48 hr. timepoints. PaxGene and HOPE storage of blocks at RT result in significant RNA degradation related to block storage at RT vs. −20 deg. C. A panel of 4 IHC markers, E-cadherin, alpha-synuclein, CD3 and CD31showed comparable scoring of expressed proteins in HOPE vs. FFPE.

Conclusions: Our findings indicate more similarities than differences between the HOPE and PaxGene tissue fixatives and both show significant less RNA degradation than FFPE. Additional experiments are planned to test longterm retention of RNA integrity in routine paraffin block storage.

O4-29 Establishment and Use of a Cardiac Transplantation Biobank

Bowles D. 1 Watson M. J. 1 Schechter M. 1 Feger B. 1 Mishra R. 1 Schroder J. 1 Daneshmand M. 1 Milano C. 1

1 Surgery, Duke University School of Medicine, Durham, North Carolina, United States

Background/Information: Two major problems in the field of heart transplantation exist: i) inadequate number of donor hearts to meet demand and ii) cardiac dysfunction post implant. Dysfunction occurring within 24 hours of the implant is termed primary graft dysfunction (PGD). PGD is observed in 10–30% of transplant cases and is the most important cause of death during the first year after cardiac transplantation. There remains an incomplete understanding of the mechanisms by which PGD develops during the clinical heart procurement and preservation process.

Methods: As part of the Duke Human Heart Repository, a human cardiac transplant biobank has been developed from biomaterials obtained from the 60–70 heart transplant surgeries performed yearly on Duke patients. These biomaterials include: i) myocardial tissue of explanted recipient hearts, ii) myocardial tissues of unused donor hearts and iii) preservation/transportation fluid from donor hearts. We hypothesized that biomarkers of cardiac injury are released from the stored heart into the preservation solution and that the levels of these biomarkers may correlate with PGD observed in the recipient.

Results: Numerous biomarkers are detectable in the preservation/transportation fluid. Thus far, we have found that the levels of at least two cardiac injury biomarkers correlate with patient outcomes. Normalized cardiac troponin I (cTnI) levels were significantly increased (p = 0.031) for those cases which exhibited PGD. Preservation solution CK-MB levels similarly trended higher for cases with PGD but did not reach significance (p = 0.096).

Conclusion: To the best of our knowledge, this is the only biorepository of its kind as well as the first report linking the presence of cardiac injury biomarkers in clinical preservation fluid to functional outcomes after transplant. The levels of injury biomarkers in the preservation fluid and their correlation with subsequent cardiac dysfunction support the concept that the preservation period is associated with myocyte disruption. These findings stress the need for the continued evaluation of biomarkers in preservation fluid to provide a better understanding of preservation injury, as well as insight into the prediction, early treatment, and elimination of PGD. Such study may eventually lead to the development of optimal preservation/transport solutions as well as early preparedness for mechanical circulatory support in the early post-transplant course.

Ethical, Legal, and Social Issues

O2-15 Community Engagement for Development of CDC Policy Governing Management of Specimens Obtained from American Indian/Alaska Native (AI/AN) Populations

Giri J. 1 Howard S. 1 Garba I. 1 Satter D. 1

1 Centers for Disease Control and Prevention, Atlanta, Georgia, United States

Background: In the course of fulfilling its public health mission, the US Centers for Disease Control and Prevention (CDC) obtains specimens from a broad spectrum of the US population including American Indian/Alaska Native (AI/AN) individuals. Specimens are submitted to the CDC for various purposes and studies such as surveillance testing, reportable disease monitoring, emergency response, assistance during disease outbreaks, evaluation of environmental exposures, population health and nutrition surveys, newborn screening, and other related public health activities.

During the process of developing a comprehensive CDC specimen management policy, a need for unique provisions to address management of specimens obtained from AI/AN populations was identified. Moreover, examples of research misconduct (e.g. the recent Havasupai case against the Arizona Board of Regents) have highlighted the need for explicit policies governing AI/AN specimens.

Approach and Progress: Our goal is to develop policies for ethical and culturally responsive management of AI/AN specimens during all phases of custody: from collection, handling, use, and storage to the respectful disposition of specimens. Therefore, the CDC's Office of Public Health Scientific Services (OPHSS) and the Office for State, Tribal, Local and Territorial Support (OSTLTS) are employing a multi-pronged strategy including purposeful efforts at community engagement, to ensure that the values and concerns of AI/AN communities are considered in policy development. Multiple community dialogues and listening sessions (e.g. at the Native Research Network Conference, Denver Indian Center, etc.) have been conducted in partnership with the Association of American Indian Physicians (AAIP) and will continue throughout the policy development effort. In addition, AAIP facilitated development of background papers from external experts to inform policy development. The completed background papers address the following topics: socio-cultural factors, models of tribal policies, legal and ethical issues, and relevant international guidelines regarding biobanking and biospecimen management.

The presentation will summarize information gathered to date from community dialogues and listening sessions and input from multidisciplinary experts. The views expressed reflect the importance of respect for Native specimens and participation in a transparent AI/AN specimen policy development process.

O4-24 Issues Concerning Clinical Research in Japan Using Human Biospecimens for the Era of Regenerative Medicine: Efforts of Kyoto University

Ttsuruyama T. 1 Inoue H. 1

1 Pathology, Kyoto University, Kyoto, Japan

In Japan, the promotion of regenerative medicine is being emphasized as a national strategy, especially after Prof. Shinya Yamanaka won the Nobel Prize for Physiology or Medicine in 2012. The Act on Securement of Safety of Regenerative Medicine, etc. went into effect in 2014, and it is expected to encourage developments in the field of regenerative medicine.

Kyoto University hosts the Center for iPS Cell Research and Application (CiRA), and hopes to make progress in regenerative medicine using iPS cells. Although clinical studies are crucial for the development of new therapies, human specimens available for research are critically insufficient nationwide. The key factor for this is the lack of proper procedures to obtain informed consent (IC) on the use of biospecimens. Conventionally, consents used to be obtained by medical doctors or researchers and within the compass of particular research projects. On the other hand, ‘carte blanche’ consent has been garnering criticism from both patients and researchers.

In 2013, we proposed a new informed consent format:

i. This new ‘biobank-type consent’ seeks active participation in medical research in the form of permitting the use of the donor's blood, tissue, etc. A role similar to a co-researcher is assigned to the donor.

ii. With this IC, biospecimens can be used for a variety of research under certain conditions by researchers belonging to Kyoto University and their collaborators.

iii. It has become the standard form within the university; doctors in every diagnosis and treatment department can use the same form.

Both patients and researchers can now avoid the burden of giving and obtaining multiple consents, respectively. This directly positively affects the promotion of clinical research and the development of regenerative medicine.

O4-25 Implementing New Consenting Programs in a Cancer Biobank: Innovation or Ethical Minefield?

Parry-Jones A. Wales Cancer Bank - Cardiff University, Cardiff, United Kingdom

Background: The Wales Cancer Bank (WCB) consents cancer patients in Wales to donate surplus tissue and blood samples to be banked for future cancer related research. Reductions in core funding and the evolving requirements for sustainability have initiated reviews into the consenting processes and procedures to ascertain where efforts can be streamlined and costs can be reduced.

Methods: Two areas were identified and initially discussed with a focus group of patients, lay representatives and research nurses. Volunteer consenting: A sub group of the focus group visited a center in England currently operating volunteer consenting to see the process in action. Feedback to the focus group was positive and a recruitment and training standard operating procedure was drafted. A tertiary cancer center was proposed as a pilot center and a task and finish group was convened. Electronic consenting: The WCB IT group were involved in writing an electronic consenting module for another research group and WCB were able to adapt the screens and information for biobanking use. Two separate substantial amendments to the WCB's ethics approval were submitted to the UK's National Health Service (NHS) Wales Research Ethics Committee (REC) 3.

Results: Both amendments were approved by the NHS REC 3 in the autumn of 2014 and no ethical issues were highlighted by the committee. The focus group were supportive of both new initiatives. However, several issues were highlighted by the task and finish group and current consenting nurses. One (out of four) NHS Local Health Board (LHB) Risk Review Committees has refused to approve the volunteer consenting program, calling it ‘a most unusual step’.

Conclusion: Prior to piloting the two programs in 2015/16, there are several questions to be addressed including; the implications of paperless consenting on downstream information processes, data security, whether it is appropriate to utilize volunteers to consent patients, patient privacy, potential legal issues, LHB concerns and accountability and audit. Once satisfactory conclusions are reached, information regarding the acceptability of both programs with donors will be captured during the pilot phases to provide empirical data for future presentation.

Looking forward and utilizing technology and innovation to progress are not without pitfalls but, in order to develop and keep pace, biobanks must not be afraid of challenging convention and embracing change.

O4-28 Determining Clinical Actionability of Research Results Generated in the Mayo Clinic Biobank

Winkler E. M. 1 Olson J. E. 1 McCormick J. B. 1 Lindor N. M. 2 Sharp R. R. 1 Liebow M. 1 Takahashi P. Y. 1 Cicek M. 1 Cremer U. 3 Ryu E. 1 Riegert-Johnson D. L. 5 Van Norstrand M. D. 4 Mandarino L. J. 2 Parker A. S. 5 Cerhan J. 1 Thibodeau S. 1

1 Mayo Clinic, Rochester, Minnesota, United States 2 Mayo Clinic, Scottsdale, Arizona, United States 3 Mayo Clinic Biobank Community Advisory Board, Rochester, Minnesota, United States 4 Mayo Clinic Health System, La Crosse, Wisconsin, United States 5 Mayo Clinic, Jacksonville, Florida, United States

Background: The Mayo Clinic Biobank is a large clinic-based, non-disease focused collection of samples, including blood and blood derivatives, and health information with >47,000 participants enrolled. The Mayo Clinic Biobank has the capacity to generate large amounts of genetic data, some of which may have health implications for participants, raising the need to address return of results (RoR). Recently, recommendations for management of research results suggest a minimum obligation to return urgent, clinically actionable results to participants. This raises the challenge of determining which results are considered to be clinically actionable. While gene lists have been suggested, they are not all inclusive and there is no consensus among experts as to what is considered actionable.

Methods: The Mayo Clinic Biobank has adopted a RoR policy to return research results that have preventive measures and/or treatments available and for which individuals with pathogenic mutations might not otherwise know their status. The Mayo Clinic Biobank uses the gene list curated by the American College of Medical Genetics as a starting point for return. Additional genes are considered using dynamic guidelines to evaluate individual sample requests for the potential to generate clinically actionable research results. A multidisciplinary ad hoc group including disease experts, geneticists, genetic counselors, primary care physicians, researchers, bioethicists, and others is convened to make recommendations to the Mayo Clinic Biobank regarding clinical actionability. Active projects are reviewed annually for changes to the research plan and to evaluate for unexpected clinically actionable results that may have been generated during the research process. Completed projects are not retrospectively reviewed for clinically actionable results.

Results: We will describe the Mayo Clinic Biobank RoR policy and the process implemented for determining clinical actionability. Additionally, we will provide examples of results that have been reviewed for clinical actionability and the final outcomes, including Factor V Leiden and APOE genotype.

Conclusions: This process will continue to evolve as a national consensus is reached. Our experiences add a tangible example of how a biobank within a large medical institution reaches the conclusion to return results, which may be useful for other researchers as they develop and implement a RoR plan for their biobank participants.

Hot Topics

O2-14 Continuous and Sustainable Enabling of Biobank-Based Medical Research: 10 Years of Lessons Learned in Germany

Semler S. 1 Siddiqui R. 1 Kiehntopf M. 2 Hummel M. 4 Krawczak M. 3

1 TMF e. V., Berlin, Germany 2 Institute of Clinical Chemistry and Laboratory Diagnostics, Friedrich-Schiller University of Jena, Jena, Germany 3 Institute of Medical Informatics and Statistics, Christian-Albrechts University of Kiel, Kiel, Germany 4 Institute of Pathology, Charité Universitätsmedizin Berlin, Berlin, Germany

Background: TMF - Technology, Methods and Infrastructure for Networked Medical Research is a state-funded non-profit umbrella organization that provides a platform for bottom-up knowledge generation and transfer in patient-based research. Its major aim is to ensure the interoperability of research methods and infrastructures through the avoidance of inefficient, redundant and competing developments. TMF currently counts more than 80 academic medical research networks in Germany among its members.

Methods: Since 2004, TMF has been fostering the establishment, maintenance and practical use of human biomaterial banks through its interdisciplinary working group on biobanking (TMF AG-BMB).

Results: From 2004 to 2006, TMF AG-BMB pursued a multi-tiered project on biobanking, including a survey of its legoethical framework and of relevant quality issues. Parts of the project outcome were elaborated further in the context of international biobank collaborations (2006 to 2008). Following a feasibility analysis in 2007 to 2010, TMF gained funding from the German Federal Ministry of Education and Research (BMBF) to establish a national biobank registry in 2012 which, for the first time, allowed access to comprehensive information about medically relevant biobanks in Germany (www.biobanken.de). TMF also supplied IT tools and published multiple reports and expert opinions on pertinent legal regulations, including the German Gene Diagnostic Act (2008), the Biobank Declaration of the German Ethics Council (2010) and the European draft General Data Protection Regulation (2014). The work of TMF AG-BMB has left many marks at the research policy level in the past, for example, through the BMBF-funded National Biobanking Initiative (2010 to 2014) destined to integrate existing biobanks into centralized infrastructures. To further advance biobanking in Germany, TMF has launched the annual National Biobanking Symposium in 2012. Under the motto of “Improved Use through Better Networking”, the 2015 Symposium is scheduled for early December. Broadening international activities, TMF has become ISBER member and supports the German Biobank Node within the European BBMRI network.

Conclusions: Continuous interdisciplinary collaboration on infrastructural, legal and methodological topics, fostered by a support structure enabling bottom-up approach in self-administration by the scientific community, were key issues on the road to success for biobanking in Germany.

O4-31 Next-Generation Cancer Biobanking for Next-Generation Sequencing: the New Frontier in Personalized Medicine

Robinson S. 1

1 University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States

Background: The development of new molecular targeted therapies for melanoma has created a need for genomic profiling of melanoma specimens in order to further translational research and identify potential new therapeutic targets.

Methods: The International Melanoma Biorepository and Research Laboratory (IMBRL) was established at the University of Colorado Anschutz Medical Campus in 2005. More than 2800 melanoma tissue specimens have been collected and have been utilized in translational research. Genomic DNA was extracted from fresh frozen tumors, FFPE blocks, and concordant peripheral blood samples stored in our biobank. Using the Illumina HiSeq 2500 sequencer, we have done whole genome sequencing on 50 samples. The sequencing data is analyzed by bioinformatics and correlated with clinical data.

Results: As of January, 2015 over 50 primary and metastatic melanoma specimens have been sequenced. Over 800 protein-changing somatic mutations were found. Many of these mutations are novel and within uncharacterized genes which could have biologically relevant effects. All specimens with known mutations (e.g. BRAF V600E, NRAS, KIT) were confirmed by whole exome sequencing. Novel mutations were discovered to be present in a high percentage of the melanoma tumors, with mutations corresponding to sites of metastasis. Mutational profiles of the primary melanoma samples were found to be distinct from metastatic melanomas.

Conclusion: Next-generation biobanks will play an increasing role in genomic and molecular profiling and in personalized medicine. Classifying melanoma at the molecular level by whole genome sequencing could serve as a valuable resource for precise diagnosis, prognosis, and personalized treatment of melanoma, and also lead to an increased understanding of tumor biology and the molecular events involved in disease progression.

Human Specimen Repositories

O1-4 Legal and Regulatory Obstacles Affecting Implementation of an Inter-Institutional Biobank Network

Akervall J. 2 Blanc V. 1 Pruetz B. 2 Tomlinson T. 3 Wilson G. 2 Rohrer D. 4 Valley D. 5 Larson D. M. 2 Carey T. 6 Jewell S. 4

1 UMHS Central Biorepository, University of Michigan, Ann Arbor, Michigan, United States 2 BioBank, Beaumont Health System, Royal Oak, Michigan, United States 3 Center for Ethics and Humanities in the Life Sciences, Michigan State University, East Lansing, Michigan, United States 4 Program for Biospecimen Science, Van Andel Research Institute, Grand Rapids, Michigan, United States 5 Quality Assurance Supervisor, Van Andel Research Institute, Grand Rapids, Michigan, United States 6 Otolaryngology/Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan, United States

Background: In 2013, 6 Michigan institutions (William Beaumont Health System, Van Andel Research Institute (VARI), University of Michigan, Michigan State University, Henry Ford Health System and Wayne State University) formed Great Lakes Biorepository Research Network (GLBRN). The initiative was based on the need for harmonization of biobanking processes, increased collaboration and focus of improving QA/QC for biobank-related science. During 2014 a founding committee developed by-laws, membership criteria, a Memorandum of Understanding (MOU), a Universal Biospecimen Material Transfer Agreement (UBMTA), common elements for informed consent, a website and has held its first official Annual Scientific Symposium. The goal was to open the network for new members during 2014, but legal and regulatory obstacles at the founding institutions legal departments have slowed down the process.

Methods: The strategy was then to write and receive approval for the MOU and the UBMTA from one institution (VARI) that would provide a foundation for adoption at other network Institutions. The MOU, UBMTA and a set of By-laws would then be submitted to the other institution's legal departments in order to finalize the agreements.

Results: After a relatively fast acceptance of the documents by VARI's legal department the process of review by other institutions has been slow. Three of the institutions have completed their review and a final set of documents will have been presented for approval during the first quarter of 2015.

Conclusions: GLBRN was founded with two clear goals: to increase inter-institutional collaborations and to enhance biobank-related research. By creating mutually agreed legal documents such as a MOU, UBMTA and a consenting elements, members of the network would much faster be able to initiate collaborative studies. The legal obstacles from the founding institution's legal and regulatory departments have been lengthy causing a delay in opening the network to new members until the spring of 2015.

O1-32 Hand, Foot, and Mouth Disease Epidemic Caused by Coxsackievirus A6, A10, And A12 in Beijing, China from 2010 to 2012

Liang Jin-Qiu 1 Li Hong-Jie 1 Pang Lin 2 3 Meng Yi-Xing 2 4 Lu Hong-Ping 1 2 Cao Jin-Feng 1 2 Wang Qi 1 2 Liang Pu 1 2 Chen Zhi-Hai 2 5 Liu Shun-Ai 1 2 Cheng Jun 1 2

1 Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China 2 Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China 3 The Department of Pediatrics, Beijing Ditan Hospital, Capital Medical University, Beijing, China 4 Beijing Ditan Hospital, Peking University Teaching Hospital, Beijing, China 5 The Center of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China

Background: Hand, foot, and mouth disease (HFMD) is a significant public health issue in China. Currently, almost all studies in China still focus on enterovirus 71 (EV71) and coxsackievirus A16 (CVA16). In recent years, there have been reports of HFMD epidemics caused by other EVs besides EV71 and CVA16 in the world. However, the other EVs detected in these surveys were ignored in Chinese research. The objective of this study was to understand coxsackievirus A6, A10 and A12 distribution and their hereditary feature among patients suffering from HFMD in Beijing, China.

Methods: 836 hospitalized HFMD cases in Beijing region were enrolled from May 2010 to December 2012. These cases were genotyped by Real-time PCR and amplification of enterovirus VP1 sequence. Genetic similarities of the human EV strains were assessed by phylogenetic analyses of partial VP1 sequences.

Results: Results showed the EV-positive rate was 57.54%. Of these, the EV71-positive and CVA16-positive rates were 29.90% (250/836) and 8.49% (71/836), respectively. CVA10, CVA6, and CVA12 were detected in 32 (6.65%), 16 (3.33%), and 10 (2.08%) cases, respectively. Phylogenetic analyses of the partial VP1 sequences showed that all CVA12 strains found in this study were clustered in a group, but the CVA10 and CVA6 strains were clustered in several different groups.

Conclusions: EV71 and CVA16 were the major pathogens of HFMD in Beijing, China during 2010–2012. EVs, excluding EV71 and CVA16, were detected in a higher proportion, and in particular, more attention should be paid to CVA10, CVA6, and CVA12.

O2-9 The Women's Health Initiative (WHI) Biorepository: A Comprehensive Resource for Women's Health Research

Herndon M. S. 1 Mann S. L. 1 Johnson L. G. 1

1 Fred Hutchinson Cancer Research Center, Seattle, Washington, United States

Background: In the mid-1990s, the Women's Health Initiative (WHI) enrolled a racially/geographically diverse cohort of 161,808 post-menopausal women. The WHI design included 3 clinical trials (CT; N = 68,132) to study the effects of hormone therapy, calcium/vitamin D supplements, and a low-fat diet, and an observational study (OS; N = 93,676) to study the relationship between lifestyle, health, and risk factors for disease. The main WHI outcomes of interest were breast and colon cancers, cardiovascular disease (CVD), and fracture. The trials officially ended in 2005, but follow-up for health outcomes continues.

Methods: The WHI collected biospecimen and health/lifestyle data at baseline and longitudinally from enrollment through 2005 using a standard protocol at 40 clinics across the US. Biospecimen and data were collected to support the CT and OS and to establish a resource for future research. In 2012–13, additional blood and data were collected from 7,875 of the oldest women at their homes. Blood products, urine, DNA, and RNA are stored at −80°C in the biorepository and are available for approved research. Biospecimen aliquoting and DNA/RNA extraction occur at a central lab to ensure consistent sample handling. Lab results must be returned to WHI for incorporation into the repository. QC protocols are used to monitor the quality of the biospecimens and returned lab results. Data collection is ongoing via annual mailed surveys, with verification of cancers, CVD and fracture outcomes. Tumor tissue (FFPE) collection is ongoing for several cancers.

Results: Over 5 million vials of blood, urine, DNA and RNA are stored in the biorepository. 91% of the 93,567 women alive and still enrolled have returned a health history form within the past 2 years. Rare outcomes, such as ALS, have been reported in addition to the main WHI outcomes. Over 150 ancillary studies have been funded to use WHI biospecimens, and the WHI data repository has generated 941 published manuscripts. Baseline blood is still available for >98% of the 32,474 women with any of the main WHI outcomes.

Conclusions: The quality, quantity and variety of the samples and depth of accompanying health and lifestyle data available render the WHI biorepository invaluable for women's health research. Much can be learned about biobanking and data sharing from WHI's experiences. Managing and justifying the size and cost of the biorepository will be one of the main issues WHI faces in the future.

O2-10 Alliance for Maternal & Newborn Health Improvement (AMANHI): Establishing Standardized In-Country Biobanks to Improve Maternal, Fetal, & Neonatal Health Outcomes in Low-Resource Countries

Dhingra U. 1 Dutta A. 1 Ali S. 2 Deb S. 1 Bahl R. 3 Polasek O. 4 Russell D. 5 Manu A. 3 Makame S. 2 Black R. 7 Collaboration A. 6 Sazawal S. 1

1 Center for Public Health Kinetics, New Delhi, Delhi, India 2 Public Health Laboratory-IdC, Pemba, Zanzibar, Tanzania, United Republic of 3 World Health Organization, Geneva, Switzerland 4 Medical School, University of Split, Split, Croatia 5 Donna Russell Consulting, Renton, Washington, United States 6 AMANHI Collaboration, Pemba, Zanzibar, Tanzania, United Republic of 7 Johns Hopkins University, Baltimore, Maryland, United States

Background: Constraints to establishing biobanks in developing countries include ethical, legal, social issues and limited resources. AMANHI breaches these barriers by establishing harmonized community-based locally owned biobanks in 3 countries: Tanzania (Pemba), Bangladesh and Pakistan.

AMANHI involves large maternal, newborn health research studies in East Africa & South Asia to help understand the epidemiology of maternal mortality, morbidity, stillbirths and neonatal deaths; associations of maternal morbidity and care with maternal, fetal and neonatal outcomes and underlying biological causes.

Methods: We are presenting implementation of AMANHI at Pemba site, a small island in Zanzibar archipelago off the east coast of Africa. Pregnant women identified through a pregnancy surveillance system are invited to participate. Mobile clinics are setup in the community for gestational age confirmation by USG and sample collection. Blood and urine samples are collected at 3 time points (2 antenatal, 1 postpartum) in addition to placental tissue, cord blood and paternal saliva. Women are encouraged to deliver in facility so that majority of samples can be collected and processed within 30 minutes of delivery. We believe this is the only biobank in developing country settings with this rigor.

Standardized SOPs and data collection tools are used. Sample collection kits are labeled with temperature controlled barcode stickers. All specimens collected have unique ID for sample identification and quality control. Samples collected in field are stored and transported in −80 portable freezer to the central laboratory. After processing samples are transferred to central biobank freezers. To ensure continuous power biobank has 3-tier power supply a) Grid b) Solar c) Generators. Freezers have been attached to GSM, GPRS based alarm system to send SMS alerts if temperature fluctuates.

Results: Kit registration, sample collection, processing, aliquoting, and archival; QC and metadata are recorded real time using an in-house custom designed software. So far 900 + women have been enrolled, 55 delivered. Blood, urine, placental and saliva samples have been collected and biobanked.

Conclusion: Challenges include getting ethical approvals; collecting and processing samples within 30 minutes of community deliveries, most of our participants live in remote areas and never had blood draw earlier. These and other issues are continually addressed through regular community meetings.

O3-18 Immune Cell Profiles as Biomarkers of Occupational Ionizing Radiation Exposure: Results from the Russian Radiobiological Human Tissue Repository

Loffredo C. 1 Zakharova M. 2 Sokolova S. 2 Revina V. 2 Goerlitz D. 1 Leondaridis L. 1 Kirillova E. 2

1 Georgetown University School of Medicine, Washington, District of Columbia, United States 2 Radiobiological Human Tissue Repository, Southern Urals Biophysics Institute, Ozyorsk, Russian Federation

Background: The Radiobiological Human Tissue Repository (RHTR) at the Southern Urals Biophysics Institute (Ozyorsk, Russia) was established in 1951 to study effects of occupational exposure to plutonium in nuclear weapons production: it provides biospecimens and annotated data to interested scientists worldwide (see www.rhtr.subi.su). Blood samples from workers and non-exposed residents from the community (controls) are routinely collected and stored. We investigated whether occupational radiation exposure affected the distribution of circulating immune cells, as a potential biosensor of early biological alterations.

Methods: Blood specimens from 120 workers and 111 age-matched controls were analyzed by flow cytometry to identify T and B cell lymphocytes, natural killer cells, CD95 and CD3 positive cells, and other components of the immune system. T tests compared mean levels between cases and controls, followed by multivariate regression to take into account gender, age, and other important covariates.

Results: Compared to controls, workers (mean external gamma radiation accumulation of 0.16 ± 0.02 Gy, and mean ²³⁹Pu body burden of 0.42 ± 0.11 kBq) had significantly deceased levels of T killer cells (-28%) and CD95 cells (-37%), but increased levels of B lymphocytes (1.4 fold), natural killer cells (1.3 fold), and CD4/CD8 double positive T cells (2.2 fold).

Conclusions: The biospecimens from this unique resource are useful for investigating the molecular mechanisms of innate and acquired immunity that may either help prevent or predispose to chronic and acute health effects of ionizing radiation. Biomonitoring workers for early effects on the immune system may aid in early diagnosis and treatment.

O4-26 Building a Disease-Agnostic Sustainable Biobank in India with Apollo Hospitals: Ethical and Regulatory Hurdles in Conducting Human Biospecimen-Enabled Research and Development

Jain J. 1 Chinta D. 1 Khandrika L. 1 Syed N. 1 Mahalingam M. 1 Anand A. 1 G S. 3 Bavisetti S. 3 Kintalu R. 3 Gautam P. 3 Samal B. 3 K G. 2 B S. 2 Jauhari S. 2 Natarajan S. 1

1 Sapien Biosciences, Hyberabad, Andhra Pradesh, India 2 AHERF, Apollo, Hyderabad, India 3 Apollo Hospitals, Hyderabad, India

Sapien is building a diverse biobank in a unique partnership model with Apollo Hospitals. The biobank is integrated within Apollo hence, has access to high quality samples & associated data. Apollo's ∼60 multi-specialty hospitals are spread across India; surgical/diagnostic ‘waste’ samples from its network are tapped with appropriate ethics approvals. Our goal is to use them for developing personalized medicine solutions for Indian and global patients.

Biospecimens span cancer and other diseases including non-communicable diseases, a growing bane. Sapien has adopted caTissue database. Retrieval of retrospective data across different IT database/software at Apollos is being streamlined; solutions to achieve data-interoperability will be shared. SOPs to get sterile surgical material without compromising patient diagnosis have been successfully implemented. Cancer and other tissues are routinely used at Sapien for translational research. Matched sets of cancer & non-cancer (adjacent tissue or blood) samples are used to determine specificity of target and marker expression. Disease-specific collections to spur research in under-served areas e.g. autism, metabolic or rare diseases, are under consideration. These would benefit from participation in international consortia.

Sapien aims to be self-sustainable by leveraging its expertise in utilizing patient samples for translational research into understanding the basis of disease, validating new molecular diagnostics and treatment response markers. Two products have been launched, one each in theranostics and prognostics, towards generating revenue and attaining sustainability. Our database of disease prevalence, treatment response, risk factors etc is itself a monetizable resource. Custom biobanking in a public-private partnership (PPP) mode also holds tremendous promise of finally capturing India's vast population's disease germplasm.

Biobanking is a new area for India. Ethics Committees need clarity and education to understand its implications, especially since Indian ethical guidelines were written from the point of view of conducting clinical trials, rather than non-interventional research use of left-over samples. Current Indian guidelines relevant to Biobanking, including gaps, will be discussed. Also suggestions on ‘opening up’ Indian samples for international collaborations in a transparent and responsible manner to help realize the benefit of resulting research products for Indian patients will be shared.

O4-27 Establishment of an ISO15189 Accredited Biobank for Global Clinical Research Studies

Keys J. 1 Hall K. 1 Bamford K. 1 McQueen M. 1

1 Hamilton Health Sciences CRCTL, Hamilton, Ontario, Canada

The Clinical Research and Clinical Trials Laboratory (CRCTL) has evolved over 25 years from small-scale to a 12,000 ft², ISO15189 accredited analytical laboratory and Biobank for large, multinational clinical trials and epidemiologic studies. The academically based, investigator-driven biobank stores well-characterized samples in nitrogen vapor (∼3.1 million) and in mechanical freezers (∼500,000) from ∼85 countries representing 6 continents.

Substantial logistical, financial and quality management challenges were met in the development and accreditation of the CRCTL. Extensive expertise was developed in standardized collection, shipment, receipt, storage and analysis of large numbers of biospecimens. Laboratory medicine professionals brought a unique understanding of the wealth that biological samples bring to clinical research, and used best practices and continuous quality improvement to set standards for biospecimen handling, analysis and related data. Close clinical and laboratory collaboration produced numerous publications in top-tier journals.

High-quality samples stored from large, international, well-designed and successful clinical and epidemiological studies strengthen conclusions derived from these studies and enable investigation of novel questions. The large Biobank is a unique discovery and validation resource that reduces the need for new and expensive studies and has encouraged international and industrial collaborations. Several hundred researchers use the biobank; samples are safeguarded and held in trust for each research project. Samples in the Biobank are from population genomics, peri-operative medicine, diabetes, hypertension, stroke, thrombosis, cardiovascular surgery, renal disease, childhood obesity, bone, trauma, pediatric and cancer studies, representing many years of international collaborative clinical and epidemiological research by experts in biobanking, laboratory medicine, genetics, clinical epidemiology, clinical trials and genomics.

Successful ISO15189 Accreditation for the CRCTL and Biobank was attained based on development of a comprehensive Quality Management System, ∼500 Standard Operating Procedures to cover our complex operations, several internal audits, and an audit by an external consultant prior to the formal accreditation audit. This required substantial staff time and internal funding, made more cost-effective through step-wise implementation.

Repository Management

O1-2 Make Each Touch Count: Leveraging IT Tools to Maximize Space and Operational Efficiency in the NHLBI Biorepository

Shea K. 1 Krzystan J. 2 Marchesani L. 1 Adebambo O. 1 Wallop J. 2 Loehr M. 2 Wagner E. 3

1 Precision for Medicine, Inc., Frederick, Maryland, United States 2 Information Management Services, Inc., Calverton, Maryland, United States 3 National Heart, Lung, and Blood Institute, Bethesda, Maryland, United States

Background: The US NIH National Heart, Lung, and Blood Institute's Biologic Specimen Repository (NHLBI Biorepository) has served as a valuable scientific resource for almost four decades. The repository acquires biospecimens from NHLBI funded clinical studies and distributes them online through the NHLBI Biologic Specimen and Data Repositories Information Coordinating Center (BioLINCC) to qualified investigators. Currently, 39 contemporary and historical collections comprised of 4 million specimens are available at www.biolincc.nhlbi.nih.gov.

The Biorepository has received specimens as bulk relocations and as intermittent shipments. Boxes received in bulk relocations were not consolidated prior to transfer and had partially filled boxes. Vials from intermittent shipments were placed in the next available location to fill boxes, resulting in collections being spread over multiple boxes and freezers. In addition, non-consecutive unoccupied spaces occurred as repository vials were requested and distributed. This resulted in specimen retrieval inefficiencies, given that it is much more economical to retrieve one box and remove multiple samples, than to retrieve small numbers of specimens from multiple widely distributed boxes.

Methods: To maximize the use of available freezer space and increase the efficiency of specimen retrieval, an IT tool developed to visualize freezer space was adapted to assist with inventory management.

Optimal thresholds and storage patterns for samples per collection and samples per box were established. Task assignments, optimal retrieval orders, and redistribution of specimen locations were then developed to increase operational efficiency. When samples are requested and a partially filled box is accessed, the tool locates optimal new locations for the remaining samples in that box. The researcher's samples are packaged for distribution and the remaining samples are relocated to boxes storing samples from the same collection, thus increasing storage and future retrieval efficiencies.

Results: As new research requests are received, specimens from boxes with low occupancy rates are redistributed into new locations, thereby reducing the number of repository boxes and increasing the efficiency of future retrievals.

Conclusions: Redistribution of specimens from inefficient locations when a box is being accessed for research sample retrieval increases both retrieval and space efficiency. Data illustrating this will be presented.

O1-3 Development of the NIST Marine Sample Tracking and Analytical Reporting (Marine STAR) Data Platform

Pugh R. Reiner J. L. Pol S. S. Vander Ragland J. M. Becker P. National Institute of Standards & Technology, Charleston, South Carolina, United States

The National Institute of Standards and Technology has been involved in environmental specimen banking for over 35 years and maintains >85,000 aliquots of cryogenically archived samples at the Marine Environmental Specimen Bank (Marine ESB), Charleston, SC. Over the last 25 years efforts have focused on the marine environment with samples primarily collected as part of ongoing environmental monitoring research with various federal, state, and local government agencies, as well as non-profit organizations and universities. Metadata that is collected with each sample is provided on handwritten data sheets specific to each project and includes information such as field identification, sample type, species of animal, collection location, collection date/time, etc. This data is transferred by hand into a specimen tracking database maintained at the Marine ESB along with specific storage location information as well as additional processing information for each aliquot. Once aliquots or sub-samples, are shipped out of the Marine ESB for analyses (i.e. environmental contaminants, health parameters, etc.), the analytical data that results is often not reported back or is difficult to access. This makes performing data analysis outside of specific projects goals extremely challenging. The Marine Sample Tracking and Analytical Reporting (Marine STAR) data platform is being developed to provide easy access to both sample metadata as well as analytical data generated on each sample aliquot. The development of this web-based data product, which includes (1) housing and retrieval of analytical data (including associated QA measurements and contextual information regarding how data were collected), (2) streamlining of sample metadata recording and storage (currently manually inputted and housed in a specimen tracking database), (3) linking of analytical and sample metadata, (4) generating data suitable to browser-based data exploration and visualization, and (5) generating data reports in a manner to support statistical testing, will be discussed. Less than 10% of the aliquots in the Marine ESB have been analyzed but this still corresponds to over eight thousand aliquots and as more aliquots are analyzed managing the data generated will only escalate. The development of Marine STAR data platform will ultimately stimulate additional avenues of inquiry on samples associated with the Marine ESB and enable global perspectives about environmental pollution and its effects.

O1-5 Disaster Recovery Feasibility for Biorepositories: An Analysis of Standard Regulatory, Operating and Technical Procedures

Salvaterra E. 1 2

1 Philosophy of Science/Phil of Mind, eCampus University, San Fermo della Battaglia, Italy 2 ISBER Science and Policy Committee, Vancouver, British Columbia, Canada

Background: Although disaster recovery plan (DRP) is widely recognized as critical element for biobank governance and sustainability there are not presently internationally standardized procedures for disaster prevention, mitigation and recovery. Apart from the ISBER Best Practices for Repositories (2012), the NCI Best Practices for Biospecimen Resources (2011) and the OECD Guidelines for Human Biobanks and Genetic Research Databases (2009), disaster recovery planning is committed to the management of singular biobanks. However, standardization of disaster recovery processes could outline basic conditions for handling calamities, human errors or technical failures. This study aims to identify common regulatory, operating and technical procedures for disaster recovery planning and feasibility.

Methods: A review of a) international recommendations for biorepositories, b) disaster recovery case studies and c) quality management policies was performed. The international literature on disaster recovery plan for biobanks was also considered. From this perspective, academic publications on the ethical and legal aspects related to disaster recovery were analyzed. Furthermore, reports describing procedures and means used from private companies for handling disaster recovery were reviewed. All the aforementioned materials were publicly available online and accessible by using common search engines like Google, Pubmed or Scopus.

Results: Although disaster recovery feasibility is remarkably influenced from the geographical location of the biobank and the type of disasters (natural Vs human), there are several conditions common to disaster recovery planning. These standard conditions can be identified as regulatory, operating and technical requirements. Regulatory requirements include the recommendation for biobanks to a) have a written disaster recovery plan as part of a business continuity plan (BCP) and to b) test and update them periodically. Operating requirements comprise specific guidelines for handling disaster recovery as part of the policy or quality manual governing the local biobank. Finally, technical requirements include procedures to be followed in case of disaster like, for example, back-up storage processes or power supply emergency services implementation.

Conclusions: Although this analysis present several limits, it shows the feasibility of standardization of some elements of disaster recovery planning and procedures for biobanks.

O1-6 Optimizing Repository Information Management Systems

Berlin D. Coriell Institute for Medical Research, Camden, New Jersey, United States

Background: Modern biobanks can contain a vast number of samples and often perform a variety of services, ranging from biospecimen processing, storage and shipment to order processing and document management. Providing these services requires a Repository Information Management System (RIMS) that can effectively meet all of the biobank's information technology needs and adapt to future needs. Coriell Institute for Medical Research (Coriell) recently engaged in an extensive redesign of its RIMS.

Methods: An interdisciplinary team of Coriell scientists, laboratory staff, application developers, and other stakeholders identified critical attributes essential in a new RIMS. Based on these requirements, both commercial off-the-shelf (COTS) software and RIMS modules designed and produced in-house were implemented and put into production. The functionality, usability, and performance of the COTS and Coriell-designed RIMS modules were evaluated.

Results: COTS software supplied some, but not all, of the functionality required for Coriell's biobanking operations. Despite extensive efforts to modify the COTS software to meet Coriell's needs, significant challenges were encountered. Issues included scalability, user interface, and configurability. Although the creation of in-house RIMS modules involved a large investment of time and staff resources, the resulting end product better supported Coriell biobanking.

Conclusions: Coriell opted to design and create its upgraded RIMs in-house. Maximum RIMS module functionality, usability, and performance resulted from close collaboration between the application developers and staff who would be using each module. Additional benefits of an in-house RIMS solution are the ability to quickly modify the RIMS and the flexibility to introduce new functionalities. For a large, complex biobank, a customized solution built in-house is likely most effective to meet existing and emerging RIMS needs.

O4-30 Emerging Opportunists to Sustain and Develop Biospecimen Curation: Sustaining Biorepositories and Training the Next Generation of Research Professionals

McNally J. 1 2

1 NACDA Program on Aging, University of Michigan, Ann Arbor, Michigan, United States 2 ISR, University of Michigan, Ann Arbor, Michigan, United States

Background: Growing funding crisis at the federal and state level, make the financial stability of repositories increasingly problematic. Laboratories are reducing staff, hours of operation or closing entirely as the funds requires to maintain preservation are reduced or eliminated as the need for specimen preservation only increases, with many repositories operating at or beyond their storage capacity. Addressing this crisis requires a unified effort to illustrate the value added that well run repositories bring to research dollars and the need for training the next generation of repository scientists.

Methods: The NACDA Program on Aging is the world's largest electronic repository on aging, health and medical data. Funded by the National Institute of Aging since 1978, it has grown substantially as a repository and increasingly, NACDA mission of preserving research outcomes is embracing collaborations with repositories that specialized in specimen preparation, preservation and distribution. Working with NIA and NIH more broadly NACDA seeks to collaborate directly with biorepositories in the development of sustainable funding initiatives that will support the ongoing work of biorepositories as well as provide the funding essential to growth and the training of next generation of biological curation experts.

Results: Recent initiatives such as the Early-Stage Development of Innovative Technologies for Biospecimen Science, ongoing efforts such as the Secondary Dataset Analyses in Heart, Lung, and Blood Diseases and Sleep Disorders, and the recent the Biomedical Data Science Training Coordination Center reflects the growing opportunities that directly support the development of biospecimen best practices. NACDA has a long history of working closely with researchers to identify opportunities and to discuss ways in which the best practices in the preservation sciences can be translated into competitive grant applications. With its partners, such as ICOSR and the UM science community, NACDA has developed a well-established infrastructure focused on building sustainable research that involves the preservation of information, both electronic and specimen based.

Conclusions: As a P30 Center, NACDA's mission is to collaborate with research partners to ensure the long term preservation and sustainability of repository sciences. This presentation will review existing and forthcoming funding opportunities and how they can increase the sustainability of biorepositories.

Repository Standards

O1-1 Creation of a Registry of Standard Operating Procedures for Tissue Collection

Labaer J. 2 Magee M. 2 Freedman L. P. 1

1 Global Biological Standards Institute, Washington, DC, District of Columbia, United States 2 Biodesign Institute, Arizona State University, Tempe, Arizona, United States

Biospecimens are a key resource for multiple fields of biomedical research such as disease progression, prevention, diagnosis, and treatment. The acquisition of useful data from each tissue sample requires that the sample is processed appropriately for its intended use and that the relevant clinical information, sample provenance, and sample processing details are appropriately attached. Unfortunately, biospecimens currently stored in many repositories may be inadequate in one or more of these areas. Further, numerous non-biological variables can affect experimental outcomes and reproducibility, including the manner and frequency a sample is thawed, times spent at different temperatures, and the use of specific equipment at defined settings. However, it is impossible to know if any of these variables has affected collected samples because there is often no information available about how individual sample sets were collected. Best practices, SOPs, and standardized language—as part of broader Quality Assurance/Management programs—for biospecimen collection and biorepository activities can provide an efficient means to help drive high quality research by identifying important variables and ensuring proper procurement and handling of samples and associated data. A first step in improving SOPs is sharing them publicly, so that the methods used for any sample collection are traceable. The Global Biological Standards Institute and the Biodesign Institute of Arizona State University recently launched the development of a highly functional and flexible relational database and web-based interface (Registry) to store, search, compare and analyze SOPs for biospecimen collection and storage. Within a few years, a widely-adopted registry is envisioned that will be a resource for sharing and evaluating SOPs based on their use.

O3-21 Optimal Sampling of Resected Ovarian Tumors: Do Omental Metastases Contain Less Necrosis Than the Primary Ovarian Tumor?

Judd A. Higgins K. Martinez C. Schultz F. Bocklage T. U New Mexico School of Medicine, Albuquerque, New Mexico, United States

Background: Ovarian tumors are desirable for human tissue banking because of the relatively high disease incidence in developed countries, presentation often at an advanced stage, the stalemate in effective therapy, and intense investigation into biomarkers for diagnosis, prognosis and prediction of response to targeted therapies. Most banks collect samples from tumors that are resected for treatment purposes. In the Pathology Grossing Suite, an expert pathologist's assistant or surgical pathologist will visually inspect and then select the most viable tumor for banking, as necrotic tumor is suboptimal for research. We sought to determine whether omental metastases of ovarian tumor comprise a greater percentage of viable tumor than the sampled primary ovarian mass.

Methods: One hundred fifty three ovarian tumors were sampled by the expert pathologist's assistant or senior pathologist with the intent of providing a completely viable sample for banking. The Banking technologist rapidly collected and processed the samples, dividing them equally into frozen and paraffin-embedded formalin fixed (FFPE) blocks. A senior surgical pathologist (the tissue bank medical director) reviewed one H&E section prepared from each block and determined: 1) percent necrosis and 2) the diagnosis. The cases comprised predominantly high grade surface eptihelial carcinomas but also included borderline tumors, sex cord stromal tumors and germ cell tumors. All omental metastases were at least intermediate grade surface epithelial tumors. Statistical analysis was performed.

Results: When comparing omental mets to all ovarian tumors, there was no statistical difference in amount of necrosis of (p = 0.82). When comparing carcinomas against omental metastases, the omental metastases demonstrated less necrosis on subsequent microscopic exam (p = 0.56).

Conclusions: Omental metastatic foci of ovarian carcinomas can provide equally good tumor quality in terms of percent of viable tumor compared to the primary ovarian tumor carcinoma. When feasible, collecting omental tumor deposits are recommended in concert with collection of tumor from the primary site (the ovary) but is unnecessary for the purposes of maximizing viable tumor. The omental tumor deposit may differ at the molecular level from the ovarian primary tumor; molecular analysis of potential differences is currently ongoing.

Innovative Technologies

IT-32 Semi-Automated Biobank Sample Processing with a 384 High Density Sample Tube Robot used in Cancer and Cardiovascular Studies

Marko-Varga G. Centre of Excellence in Biological and Medical Mass Spectrometry Imaging, Lund University, Lund, Sweden

In the post-genomic era, it has become evident that genetic and protein expression changes alone are not sufficient to understand most disease processes cardiovascular-, and cancer- diseases. Today modern in large scale biobanks with millons of patient samples are developed in order to integrate the collection of clinical samples from both health and disease which provides human information to aid the unmet need of patients. Modern healthcare developments are intimately linked to the archiving of patient samples in large scale studies that build our biobank archives.

Biobanking has been identified as an important area for development and discovery of new medicines and diagnostics. Today biobanks are forming important national, as well as international networks that shares and combines global resources. Our biobank practice that is gaining acceptance within hospitals and research units is high-density sample storage with small aliquot sample volumes. The previous standard of 5–10 mL sample volume tubes is being replaced by smaller volumes 50–70 μL of blood fractions that typically result in hundreds of thousands of aliquot fractions in 384-tube systems (REF 1-3).

We have developed and validated a novel biobanking work flow process that utilizes 384-tube systems with a high speed sample array robot with unique processing principles (REF 1). The 384 format and robotic processing is incorporated into a cancer and cardiovascular diagnostic/prognostic research program with therapeutic interventions.

IT-33 An Independent Evaluation of the Cryoxtract CXT350 Frozen Biospecimen Coring Technology Using Tissue and Fecal Biospecimens

Mathieson W. Sanchez I. Mommaerts K. Frasquilho S. Betsou F. Integrated Biobank of Luxembourg, Luxembourg, Luxembourg

The ability to take targeted multiple cores from a single cryopreserved biospecimen means that one biospecimen can feed several research projects, a small piece of a biospecimen can be quality-control tested without committing the whole biospecimen and pathologically discrete areas of a biospecimen (e.g. tumor, stromal and normal tissue) can be selectively sampled for comparative analyses. CryoXtract Instruments` CXT350 Frozen Sample Aliquotter is a liquid nitrogen cooled machine that takes multiple cores from a cryopreserved biospecimen without thawing either the parent biospecimen or its daughter cores. It therefore potentially addresses these issues. However, an independent evaluation of the technology is lacking. We have addressed this by evaluating the CXT350`s performance using 614 cores taken from fecal and tissue (rat liver, kidney, lung, heart and colon) biospecimens. Coring densities of 5 intact plus ≤4 fragmentary cores per cm³ are achievable using 3 mm coring probes. No between-core contamination occurred. Mean core weights were 14-18 mg for tissue; fecal cores weighed ≤250 mg depending on the fill-depth of the tube. So, both tissue and fecal cores are amenable to analyte extraction using kits. Coefficient of variation for core weights of homogenized fecal samples was 11.7% (n = 10). The impact of coring on RNA integrity was assessed by comparing cores with scalpel-cut tissue slices using an Agilent Bioanalyzer (n = 14 core/slice pairs) and by qRT-PCR using β-actin, HMBS and HPRT probes (n = 8 core/slice pairs). Mean RINs were 8.7 for cores and 9.3 for slices (p = 0.003), with 12 of the 14 pairs showing higher RINs in the slices. qRT-PCR results were concordant with the RINs, with Cts from cores being 0.34, 0.4 and 0.27 cycles higher than scalpel slices for the three genes (p < 0.04). Therefore, coring induced a small, statistically significant but inconsequential impact on RNA quality. We conclude that the CryoXtract CXT350 is easy to operate and reliably takes multiple cores from a biospecimen with good reproducibility and without inducing cross-contamination. We believe that this ability to aliquot frozen biospecimens will improve the amount of data that can be obtained from a single biospecimen and thereby significantly enhance the value of each biospecimen for research.

IT-34 Heat Stabilization of Tissue Samples Enables Measurement without Interference from Post-Mortem Events and Allows for Refinement Due to Reduced Intra Group Variability

Söderquist M. Borén M. Sköld K. Denator, Uppsala, Sweden

Background: The action of proteolytic and other protein-modifying enzymes rapidly change the composition of the proteome and post translational modifications (PTM) after sampling. Subsequent analytical results reflect a mix of the in vivo molecular status and degradation products and increased sample variation. Effective enzyme inactivation and standardization of sample handling eliminate this problem.

Methods: The heat stabilization system (Stabilizor T1 Denator AB) has been used to generate rapid, homogenous thermal denaturation of enzymes to stop degradation in tissue samples. Stabilized samples were compared to common snap-freezing and inhibitors using mass spectrometry, western blot, RPPA where the protein and peptide content, including PTMs were examined.

Results: Rapid changes in proteins, peptides and PTMs show only minutes after sample excision whereas after heat stabilization, levels remain unchanged during 2 hours in room temperature. In addition, amounts and identities of the detected proteins/peptides in heat stabilized samples show maintained integrity. Intra group variability of measured peptides levels between replicates in stabilized samples was reduced compared to snap frozen replicates in brain tissue and in cell samples. This refinement enables smaller number of sample replicates to achieve similar statistical significance.

Conclusions: Adequate and sustained suppression of enzymatic activity e.g. proteases, phosphatases and kinases is important to ensure reliable measurement without interference from post-mortem events. Heat stabilized samples keep their integrity throughout the sample preparation and beyond and will thereby enable higher statistical power or reduced number of replicates. We believe that the use of rapid heat stabilization, as an alternative to conventional snap-freezing in combination with inhibitors, instantly and permanently stops enzymatic activity. In this way stabilization prevents post-mortem changes and enables the sample to reflect the in vivo status as closely as possible. This approach may help us refine our experiments and differentiate true biomarkers from those proteins found in any situation where cells are under stress.

IT-35 BioT CryoCarrier - Standardized Cryogenic Temperature Handling of Biospecimens

Comiso S. 1 Kunkel E. J. 1 Fink J. 2 Thompson M. L. 1 Ehrhardt R. O. 1

1 BioCision, San Rafael, California, United States 2 Life Science, Brooks Automation, Chelmsford, Massachusetts, United States

Temperature control during collection, handling, storage and transport of biospecimens intended for biobanking is crucial, as fluctuations can affect sample integrity. However, even when those dynamics are well controlled, samples are exposed to additional temperature-related hazards once they arrive at a biobank.

In many biobanking workflows, biospecimens arrive cryopreserved and open containers filled with dry ice or liquid-phase LN₂ are frequently used to transport cryopreserved samples around the biobank setting. The temperatures of the samples in these containers are assumed to be that that of the freezing material; −50° to −78°C for dry ice and −150°C to −196°C for LN_2. However this is not always the case as recent studies have shown that the temperatures in open containers can widely fluctuate [Kunkel E.J. 2014]. In fact, these approaches introduce temperature cycling (LN₂ to dry ice temperatures), can be unsafe for user handling, and are an unstandardized means of internal transport. Furthermore, multiple studies have shown that transient warming events affect cell viability and function and that tracking the temperature of the cells during any transit period is good cold chain management practice.

To improve standardization in how biospecimens are transported, BioCision and Brooks Automation have jointly developed BioT™ CryoCarrier, a safe, portable solution that, once charged with LN₂, maintains a stable <−150°C environment for over 3 hours. LN₂ is contained in the BioT™ CryoCarrier in a manner that prevents sloshing or spilling, and there is no direct contact between the contents and the LN_2. BioT™ CryoCarrier accommodates one standard freezer box or multiple small bag cassettes, and the integrated electronics module displays and logs temperature and time to provide assurance that the contents have not been subjected to temperature variation.

BioT™ CryoCarrier simplifies and standardizes intra-campus cryogenic transport and provides researchers and biobanks a solution for ensuring the safety of valuable biospecimens and those handling them.

IT-36 Preservation by Vaporization for Biobanking

Bronshtein V. Universal Stabilization Technologies, Inc., San Diego, California, United States

Background: Ambient temperature sample storage and distribution has long been a goal in the biobanking industry, but has proven challenging for the conventional industrial scale preservation technologies such as freeze drying. Long-term thermostability of live biologicals can be achieved by preservation in a glass state to immobilize fragile components. Drying of sugar glasses in thin films has shown success in achieving thermostable products, but the scale is limited to the flat space available for single-layer films. Foam drying technology is the scalable solution, preserving fragile biologicals in sugar glass films for long-term thermostabilization in the dry state at ambient temperature or higher. Preservation by Vaporization (PBV) is the state-of-the-art in foam drying technology.

Methods: Biological samples are equilibrated in formulations with non-reducing monosaccharide derivatives which form glasses during drying. PBV involves primary drying under vacuum by vaporization from a partially frozen slush state, followed by high-temperature stability drying. Sample size and quantity is scalable and can be produced large-scale by continuous load barrier drying.

Results: PBV has been used to thermostabilize many biologicals. PBV-preserved live viruses and bacteria are stable for years at ambient temperatures and for hours at high temperatures (up to 80°C). Successes include live attenuated viral and bacterial vaccines, probiotic bacteria, therapeutic proteins, enzymes, and other fragile samples. The resulting dry foam product can be easily reconstituted with water to restore viability or initial activity, or micronized and incorporated into dissolvable polymeric devices for mucosal and transdermal delivery without need for reconstitution before delivery.

Conclusions: PBV technology using foam drying has shown promise as a useful method for industrial-scale stockpiling and biobanking of biologicals for storage and delivery in the dry state at ambient temperatures.

IT-37 One-of-a-Kind Automated Pipetting Combined with Direct Freezing of Fluids at Biobank Graz

Huppertz B. Riegler S. Sargsyan K. Wolf M. Bayer M. Biobank Graz, Medical University of Graz, Graz, Austria

Background: As all other academic biobanks, Biobank Graz at Medical University of Graz, Austria, intends to improve medical research in particular by storing and providing high quality samples. Regarding the collection of fluid samples, especially blood samples, the period between filling a primary blood tube and freezing of the respective aliquots is critical for sample quality. However, in most biorepositories this time is not clearly defined.

Methods/Results: At Biobank Graz, aliquoting of fluid samples is performed using a unique pipetting robot to surmount the undefined time period of handling fluid samples. The pipetting robot used at Biobank Graz is one-of-a-kind and includes the following procedures:

For each sample and sample type, pre-programed protocols have been defined and are performed automatically in a ”real time request“ routine. Barcodes of primary tubes are scanned and transmitted to the clinical LIS by the robot, which receives back the pipetting information including types of target tubes and samples, volume and number of aliquots.

A camera takes a picture of the primary tubes and image processing software recognizes the sample type and the phase boundary including buffy coat. In combination with capacitively measuring the surface with a respective pipette tip the volume of the fluid sample is calculated.

Scripts are generated to automatically separate fractions (aliquots) into target tubes.

Four pipetting channels and special tools perform opening, closing and transporting of 2D Data Matrix coded target tubes on a single tube level without the need of an operator.

Immediately after pipetting, aliquots are transferred into an integrated freezing system and frozen at minus 20°C, again on a single tube level.

Finally, aliquots are transferred and stored in a fully automated minus 80°C storage system.

Conclusions: Close cooperation between biobanks and respective companies enables the development of infrastructure ideally suited to fit to the needs of biobanks. Here, automated liquid handling is linked to freezing of samples, enabling increased process reliability and stability.

IT-38 Maximum Sample Protection with Full Automation Features: The Automated LN2 Vapour Phase Freezer

Fink J. 1 Zandi B. 1 Jacobs J. 2 Green J. 2

1 Life Science, Brooks Automation, Chelmsford, Massachusetts, United States 2 BioMedical, Chart Industries, Ball Ground, Georgia, United States

Background: The industry standard solution for cryogenic storage of biological samples are liquid nitrogen (LN2) vapor phase stainless steel freezers. These storage systems provide unparalleled sample protection and integrity, plus they maintain temperature for weeks in a disaster situation with loss of power and/or LN2 supply. However, some challenges of LN2 Freezers are operator ergonomics and safety, transient warming events of innocent samples and off-line manual inventory and documentation. Traditional cryogenic automation solutions degrade the benefits of the LN2 freezer. They are very expensive, drastically reduce the emergency hold time, inhibit manual access and have high LN2 consumption and operating costs.

Method: Brooks Automation and Chart MVE have jointly developed an Automated Stainless Steel LN2 Vapour Phase Freezer that retains the benefits of a manual LN2 freezer while adding all the advantages of automation. This innovative device delivers affordable cryogenic automation storage that offers the highest assurance that samples will be controlled and stay cryogenically frozen below Tg in all situations.

Result: The Automated LN2 Freezer fully automates the storage and delivery of cryoboxes. It does so in an insulated environment to protect innocent samples in the rack. The PC software controls, monitors, and records all inventory, statuses, and user interactions. Disaster safety and operation is accomplished by maintaining weeks of below Tg (<−135°C) hold time without LN2 supply and full manual access to all samples without electrical power. User interaction is seamless and ergonomic. Complete cold chain management workflow can be ensured by using the BioT^™ CryoPod carrier for cryobox transportation or manual picking operations.

Conclusion: The highest sample safety and protection and the benefits of automation have been innovatively designed into an affordable Automated LN2 Freezer by Brooks Automation and Chart MVE.

The storage system offers unparalleled sample safety and cold chain management. Scientists will have assurance of their samples' handling and temperature records and can feel confident knowing their samples are safe and accessible if a disaster strikes.

IT-39 Use of Electronic P-Chips in a Single and Dual Tagging System for Sample Tubes used in Biorepositories

Mandecki W. Craelius A. Ertwine V. Katie G. Kopacka W. Morris R. G. Qian Z. Reinhardt D. Rodriguez E. PharmaSeq, Monmouth Junction, New Jersey, United States

We addressed the question of whether small electronic chips can replace barcodes used to label samples tubes used in biorepositories. In particular, we were searching for a method that improved reading reliability in situations where a layer of frost covers the tube, which is typical when working with samples that are stored in freezers or in liquid nitrogen. The approach we used involved “p-Chips” that emit an RF ID number when illuminated with laser light. p-Chips have been previously used to tag small animals (insects, laboratory mice), as well as applied in bioassays.

p-Chips were incorporated into the bottoms of a number of different types of polypropylene sample tubes. The p-Chip tags were placed in the center bottom of each tube, which allowed the use of adhesive 1D barcode labels around the circumference of each tube in addition to the p-Chip. A p-Chip ID reader was built to allow reading the ID of a p-Chip mounted in a tube. To read the ID, the tube is placed into this desktop ID reader device, which is about the size of a computer mouse. The time needed to read a single vial is very short; in practice it is well under 1 second.

We conducted short- and long-term stability studies of the p-Chip-tagged tubes at low temperatures (−150°C and −80°C). We observed that the readability of p-Chips was not affected by storage at low temperature for periods up to one year, or by cycling of the temperature (low temperature to RT).

We also demonstrated that, under conditions where a layer of frost builds up over the sample vials, the p-Chip IDs were readily readable 100% of the time while 1D barcodes, or 2D barcodes on bottoms of commercially-available vials could not be easily read. Often, these barcodes could not be read at all because of the frost.

These results demonstrate that the low-temperature storage workflow for samples in biorepositories may benefit from the use of p-Chipped sample tubes. The p-Chips can be used as either an alternative to, or in addition to 1D or 2D barcodes. Due to the ubiquity of barcodes in biorepositories, it is proposed that a dual system incorporating both a p-Chip and a barcode on the same tube would be useful in high volume settings by providing a system that offers both the human readability of labels along with the ability to process samples covered with frost. Overall, the implementation of p-Chips as a tag on sample tubes will reduce errors, loss of samples and save time and money in biorepository settings.

IT-40 Sample Tracking and Qualification with iPLEX^® Pro Sample ID

Nakorchevsky A. Keng S. Flores E. Nygren A. Agena Bioscience, San Diego, California, United States

Modern biological and clinical researchers often conduct high-throughput analyses where samples are shuttled between various instruments or shared between different institutions. These processes are susceptible to chain-of-custody events such as sample contamination, mislabeling and mishandling. The iPLEX® Pro SampleID panel is a high-throughput and scalable solution that is ideal for sample tracking, qualification, and identity confirmation. The panel utilizes targeted genotyping of pre-defined DNA regions containing single nucleotide polymorphisms (SNPs). Target regions are amplified and interrogated with multiplexed single nucleotide base extension reactions. The SampleID panel includes three types of assays in a single reaction: 44 SNP genotyping assays, 5 DNA copy number assays and 3 gender markers. The genotyping assays are used to determine and confirm matches or mismatches among samples the copy number assays are used to measure the DNA quantity and quality. The gender assays establish the gender of the sample donor. We estimate that the discriminatory power of the technology, which is the probability of a random match between any two unique samples to be 1.8x10⁻¹⁹ Following biochemical processing, samples are analyzed with the MassARRAY^™ MALDI-TOF mass-spectrometer to obtain genomic profiles which are captured in a database. The powerful SampleID reporting software enables a systematic profile comparison between incoming samples and any historical sample profiles in the database. This enables matching between normal tissues, as well as normal versus tumor tissues at various timelines. This robust and scalable technology will accommodate the needs of sample tracking and confirming identities and integrity within any large sample repository. Here we present a large-scale study using the SampleID panel and a data reporting structure that compared paired genomic cell lines and NGS-library DNA samples.

IT-41 Cell Line Authentication Using the SNP Trace™ Panel: a High-Throughput, Cost-Effective SNP-Based Platform for Fingerprinting, Identifying Contamination, and Determining Origin of Derivative Cell Lines

Liang-Chu May Min Yian 1 Yu Mamie 1 Haverty Peter M. 2 Koeman Julie 4 Ziegle Janet 3 Lee Marie 3 Bourgon Richard 2 Neve Richard M. 1

1 Department of Discovery Oncology, Genentech, Inc., South San Francisco, CA 2 Department of Bioinformatics and Computational Biology, Genentech, Inc., South San Francisco, CA 3 Fluidigm Corporation, 7000 Shoreline Court, South San Francisco, CA 4 Van Andel Research Institute, Cytogenetics, Grand Rapids, MI

Curating thousands of cell lines is challenging and essential for effective annotation and quality maintenance. Misidentified and cross-contaminated cell lines are ongoing problems. It is estimated that 15%–35% or more of human cell lines are misidentified, resulting in a waste of resources and publication of false or misleading data. The current ANSI standard for cell line authentication is short tandem repeat (STR) profiling, a methodology with several acknowledged disadvantages causing misclassification. Here we introduce and evaluate a high-throughput panel of 96 single-nucleotide polymorphism (SNP) assays on Fluidigm^® microfluidics technology for authentication of human cell lines and tissues. The Fluidigm SNPtrace Panel was tested on 925 human cell lines previously characterized by 8- or 16-locus STR profiling. Pairwise comparison of the 925 cell lines indicated SNPtrace discriminated between unrelated samples with a high degree of confidence. We also report gender typing of cell lines and show SNPtrace was able to identify cell lines from a single origin and detect intrahuman cross-contamination as low as 5%, which is equal to or better than detection by STR.

In conclusion, SNPtrace rapidly and accurately identified the fingerprints of human samples in a cost-effective and time-efficient manner. This study has generated a database of 925 SNP fingerprints for future comparison and provides a reliable, fast, and economical alternative to STR profiling.

Poster Abstracts

BP-1 The Mayo Clinic Biobank – Approaching Completion

Olson J. E. Ryu E. Winkler E. M. Sharp R. R. Liebow M. Takahashi P. Y. Van Norstrand M. D. Sharma R. G. Anderson K. S. Hathcock M. A. Bublitz J. T. Lindor N. M. Parker A. S. Thibodeau S. Cerhan J. Mayo Clinic, Rochester, Minnesota, United States

Background: To report the progress to date after 5.5 years of enrollment in the Mayo Clinic Biobank.

Methods: The Mayo Clinic Biobank is quickly approaching our goal of 50,000 participants. Eligibility includes: being an adult patient (18 or older) at Mayo Clinic or the Mayo Clinic Health System (MCHS), able to provide informed consent, and a US resident. Subjects provide risk factor information and disease history via a questionnaire, a blood sample, access to their medical record data (past and future), and agree to future contact from the Biobank (no more than 2 times a year). Subjects are recruited from two Mayo Clinic sites (Rochester, MN and Jacksonville, FL) and two MCHS sites in Wisconsin (La Crosse and Onalaska). Four years after enrollment, subjects are asked to update selected risk factors.

Results: After 5.5 years of recruitment, approximately 42,500 subjects have completed enrollment by providing consent, providing blood samples and completing questionnaires. Enrollment should to be completed in 2015. Of those with completed enrollment, 84% were recruited from Mayo Clinic Rochester, 11% from Mayo Clinic Florida, and 5% from MCHS sites. Fifty-nine percent were female. 94% were non-Hispanic white (self-reported). 12% were between 18–40 years of age, 11% between 41–50, 22% between 51–60, 26% between 61–70, 21% between 71–80, and 7% over 80. To date, 8385 (92% of requested) have provided updated risk factor information. The five most common self-reported health conditions included: hyperlipidemia (38%), hypertension (35%), osteoarthritis (30%), acid reflux disease (26%) and cataracts (23%). The top 5 laboratory values measured in the cohort include: complete blood count (80%), creatinine (78%), glucose (76%), lipid screen (75%) and aspartate aminotransferase (AST) (70%). Electronic medical record data are available for up to 20 years on some subjects. More than 130 projects have been approved to access samples and/or data since the project inception.

Conclusions: The Mayo Clinic Biobank is a well-established valuable resource for scientific projects both within the Mayo Clinic system as well as outside the system.

BP-2 The Wesley-St. Andrew's Research Institute Tissue Bank

Rogers R. Tissue Bank, Wesley Research, Auchenflower, Queensland, Australia

The Biobank was established in 2007 as a service linking medical researchers with surgeons and patients at the Wesley Hospital. In 2014, operations have expanded to encompass all major hospitals and health sites within the whole State of Queensland in Australia. From 2015, State and National collections beginning in the field of Skin Cancer, Autism in Children and Brain Cancer to name a few. Operational aspects and processes of becoming a multi-site and state-wide operation will be discussed.

BP-3 Developing a Sustainable Cancer Biorepository in a Community Health System

Perkins R. 1 2 Ost J. 1 2 Fitzpatrick P. 1 Cioffi J. 1 2 Wackym P. 1 2

1 Tumor Bank, Legacy Research Institute, Portland, Oregon, United States 2 Legacy Research Institute, Portland, Oregon, United States

Background: In 2002, National Dialogue on Cancer researchers indicated “appropriately collected, consented, and annotated tissue” as a critical need for new cancer treatment development. The Legacy Tumor Bank, a division of the Legacy Research Institute, was founded in response to this need. As a community-based healthcare system performing the highest volume of cancer surgeries in Oregon and southern Washington, consistent engagement of nearly 40 surgeons representing 25 practices has resulted in the storage of over 1,000 tumor samples (over 7,000 aliquots of tissue) for disbursement to researchers at a national level. Our contributions have helped the Legacy Cancer Institute to achieve an outstanding commendation by the American College of Surgeons' Commission on Cancer. We proposed that pursuing accreditation by the College of American Pathologists (CAP) would improve process quality and specimen integrity.

Methods: We based our protocols on NCI and ISBER best practices according to an IRB-approved research protocol, including 1) tracking of multiple variables that affect specimen integrity; 2) quarterly RNA analyses for quality control; 3) liquid nitrogen storage in a dual alarmed system with backup storage availability; 4) initiating a nonconformance event and root cause analysis process; and 5) forming an advisory committee to ensure ethical specimen distribution. We also instituted a continuing education and assistance process for our clinical staff.

Results: One of the challenges of being a community-based biorepository is that participation is not necessary for direct patient care. Pursuing CAP accreditation increased surgeon interest and contributions, as standardization of our processes to national benchmarks requires frequent reporting for quality management. Expertise from our CAP-accredited clinical laboratory faculty during our “mock” site visit highlighted additional opportunities for process improvement. As our tumor bank exists within a nonprofit healthcare system, pursuit of CAP accreditation made our tumor bank more attractive to philanthropic support.

Conclusion: As our team prepared for CAP accreditation, additional quality assurance, documentation, and standard operating procedures were implemented. Ensuring compliance with the highest standards in the industry is necessary to provide quality samples to researchers. We anticipate that CAP accreditation will broaden and increase requests for tissue for research purposes.

BP-4 Fully Automatic Cryopreservation to Optimize the Quality of Data-Rich Specimens

Brochhausen C. Winther H. Kirkpatrick C. REPAIR-lab, Institute of Pathology, University Medical Centre, Mainz, Germany

High quality of biological specimens, the appropriate clinical data annotation of and a high confidence in the collected data of biobank specimens are essential for the performance of a biobank. However, loss of data, loss of specimens and incoherent results after repeated analyses in biobank specimens remain a relevant problem of biobanks all over the world. To give an example for the potential optimization of biobanking solutions we use a fully automated cryotechnology to support evidence-based practices for “Best Practices for Biospecimen Resources”. We use a fully automated cryopreservation system (Smartfreezer^®) with a nitrogen phase to compare the biological quality of parallel stored specimens using −80°C. Based on a “cherry picking” technology this system allows freezing and defreezing of single specimen tubes without moving any other tube in the tank. Thus, none of the other tubes will be exposed to a change of the environment, especially temperature deviation with the risk of ice crystal formation. The use of the nitrogen phase guarantees the complete biological preservation and prevents temperature undulations. By using a two-dimensional code as a unique identifier the specimens will be annotated with relevant data in the biobank data management System (Freezer Pro^®), which is FDA approved (FDA 21 CFR Part 11). The automated registration makes a one-click stocktaking of the tank possible. As a result of our comparative experimental analysis the viability, quality and proliferation behavior of different cell lines during storage of more than 4 years is clearly better in the nitrogen phase. These findings are in line with former experiments, indicating the need for very low temperature to preserve several enzymes [4]. The fully automated cryopreservation prevents uncontrolled thawing of specimens and ice crystal formation. Finally, this procedure saves time during loading and un-loading of specimens, minimizes sampling errors and facilitates easy stocktaking without atmospheric changes for the specimens. Actually we have combined this system with our clinical information system and the laboratory system. To prevent loss of data we will implement a second level of data management, which will be linked to an ontology coded in Web Ontology Language (OWL) 2.

The combination of full-automated cryopreservation with ontology based data management will further improve the quality of data-rich biobank specimens.

BP-5 Next Generation Biospecimen Sciences: Innovations at University Health Network, Canada's Largest Academic Hospital System

Chadwick D. Roehrl M. H. University Health Network, Toronto, Ontario, Canada

Background: Personalized precision medicine requires optimal procurement, processing and storage of biospecimens for deep molecular characterization. We describe how the University Health Network (UHN) Program in Biospecimen Sciences has evolved into a next-generation multidisciplinary research program that actively collaborates on high impact clinical, translational and basic research.

Methods: Biospecimen Sciences at UHN is a large academic BioBanking Program. Recent innovations in research specimen collection, processing, utilization and database annotation are described.

Results: Ultra-rapid intra operative banking – excess tissue from cardiac and other surgeries have been banked in the operating suite immediately following resection.

Processing and distribution of viable tissue and body fluids – excess fresh solid tumor and body fluids have been harvested from oncology patients to establish xenografts and organoids, and to isolate tumor infiltrating lymphocytes. Viable non-malignant tissue has been used to study normal cell biology and pathobiology such as carcinogenesis and inflammation.

Circulating tumor DNA –blood samples have been collected and processed into plasma derivatives to evaluate tumor specific mutations and methylation patterns in circulating tumor DNA

Rapid autopsy program – Multiple metastatic tumor deposits have been sampled from more than 50 patients immediately post-mortem to compare the molecular signature of the primary tumor to therapy-resistant metastases

Banking of serial research specimens for clinical trials – fixed and frozen research biopsies, blood and urine have been processed and banked for investigator driven clinical trials

Clinical trials coordination – Biospecimen Sciences Program staff coordinate workflow from request to pathology review, processing and submission for analysis

Tumor cell enrichment - Laser capture micro dissection has been used to highly enrich tumor cells for whole genome sequencing as part of the International Cancer Genome Consortium pancreatic cancer project.

Research database integration – a state-of-the-art information technology system linking biospecimen and clinical data has been developed and implemented.

Conclusion: Multidisciplinary input from surgeons, oncologists, cardiologists and pathologists ensures that specimens in the UHN Program in Biospecimen Sciences are optimally collected, processed, annotated and stored for research using next generation ‘omics’ technologies.

BP-6 Biobanking and BioMolecular Resources Research Infrastructure - European Research Infrastructure Consortium (BBMRI-ERIC)

Kinkorova J. Laboratory of Immunoanalyses, Faculty Hospital Pilsen, Plzen, Czech Republic

Biobanking and BioMolecular Resources Research Infrastructure is a big pan - European project with the beginning in 2008. BBMRI is funded by the European Commission's Framework s 7. Within three years BBMRI grew into a 54- member consortium with more than 225 associated organizations from 30 European countries, making it one of the largest research infrastructure projects in Europe.

The idea of the BBMRI project consortium is to increase efficacy and excellence of European biomedical research by facilitating access to relevant human resources through associated data, with respect to ethical and legal issues, reducing fragmentation at European level fostering high-level collaboration and capacity building.

The Czech Republic is a member of the consortium with five national biobanks, located at different institutions and regions. The contribution to the European research area, the national characteristics of the biobanking in the Czech Republic and the cooperation in the European Union is the topic of the presentation: samples, storage of samples, harmonization and standardization of all processes, access to the samples, legal issues, patient consent, national and EU legislation.

Biospecimen Research and Science

BRS-9 Effect of Different Diluents on the Motility and Viability of Chilled Red Sokoto Buck Semen

Bassi R. Theriogenology and production, ABU Zaria, Nigeria, Abuja, FCT, Nigeria

Type of diluent and semen to diluent ratio can have significant effect on the viability of semen. This study was designed to determine the best diluent for the preservation of chilled semen of Red Sokoto buck. Semen samples were collected from 5 Red Sokoto bucks aged between 18–24 months using an eletroejaculator, once weekly for five weeks. Semen samples were evaluated for colour, volume, pH sperm concentration and percent live spermatozoa. Semen samples were extended with five different diluents namely Cow milk (CM), Goat milk (GM), Cow milk plus egg yolk (CME), Goat milk plus egg yolk (GME) and Egg yolk citrate (EYC) using two semen: extender dilution rates (1:2 and 1:4). Semen samples were observed for motility before and after dilution. Daily post thaw sperm motility at 37^oC and the percent live spermatozoa following staining were assessed until zero motility was observed. Results indicated that type of extender had a significant effect (p < 0.05) on post thaw sperm motility and percent live spermatozoa. A drastic decrease in motility and percent live spermatozoa was observed by the second day when EYC and CME were used to extend buck semen EYC and CME showed zero motility by day 2. Post extension sperm motility was highest at 37°C in GM than in GME, CM, CME and EYC. Semen to extender dilution rate did not significantly (p > 0.05) affect post thaw sperm motility and percent live spermatozoa although higher sperm motility was observed with the 1:2 than the 1:4 dilution rates. From this study, it was concluded that GM was the best extender for the semen of Red Sokoto buck. Further work is required to evaluate the effect of different storage conditions and temperature on the viability of semen of Red Sokoto buck using GM.

BRS-10 Alternative to Dry Ice for Specimen Processing and Shipping

Gaunt E. E. Verna N. Emerson J. Baker S. Public Health Sciences, Social & Scientific Systems, Inc., Durham, North Carolina, United States

Background: The quality and integrity of specimens placed into long-term storage for future research depends in part on how they are shipped, processed and stored by other labs before they arrive at the biorepository (BR). Various types of foam containers and refrigerants are used when shipping specimens from the field to the lab or within the lab for processing, but some perform better than others. Dry ice (DI) is used when transferring frozen specimens from one location to another (e.g., between labs) but poses shipping and handling hazards. Sublimation allows contents to shift during transit. We sought DI alternatives for specimen processing and shipment because of these issues and because it is not always available in the field.

Methods: We tested varying combinations of shippers (1″ - 3″ thick EPS foam; densities from 15 to 25 kg/m³) and refrigerants (blue ice gels, phase change foam bricks or PCFBs, and DI) to assess thermal stability during simulated shipment conditions and with shipping durations of up to 1 week. For bench-top cold processing we evaluated both DI and frozen PCFBs in foam ice pans to see how well both maintained temperatures when transferring storage boxes between freezers or when adding new specimens to partially-filled boxes.

Results: During tests, rates of warming decreased as we increased EPS foam thickness and density, and mass of refrigerant used. Fifteen pounds of PCFBs warmed to 0°C within a few hours after removal from freezer, but maintained shipping temperatures at 0°–4°C for 3–7 days before gradually warming to ambient, whereas the same quantity of DI maintained shipping temperatures below −20°C for 1 to 1.5 days, but then rapidly warmed to ambient within 3 days as the DI sublimed. Blue ice gels were less effective than PCFBs and DI in maintaining cold conditions as temperatures gradually ramped between + 4° and ambient. PCFBs at −80°C in foam ice pans maintained the frozen contents of 5″x5″ storage boxes at temperatures ≤DI when inserting new specimens.

Conclusions: EPS foam density and thickness positively affects shipper ability to keep specimens cold during transport. PCFBs are a good alternative to DI for keeping frozen storage boxes cold when inserting new specimens and may be a good alternative to DI for frozen specimen transport to the BR if transit time is less than 6 hours. PCFBs are better than blue ice gels at maintaining cool temperatures for up to a week for fresh specimen transport.

BRS-11 Formulation and Characterization of Gefitinib Loaded Chitosan Nanoparticles for Lung Targeting

Venkatesh N. Department Of Pharmaceutics, Jss College of Pharmacy, Udhagamandalam, Tamil Nadu, India

Lung cancer is one of the most prevalent cancer and leading cause of mortality in the developed world. Lung cancer is divided into two types namely small cell lung cancer and non-small cell lung cancer (NSCLC). In particular, non-small lung cancer accounts for approximately 80% of all lung cancer. Intravenous injection of microspheres and inhalants are the possible administration routes for targeting drugs to lungs. However, some studies have shown that microspheres with a particle diameter greater than 5 micrometers blocks the capillaries and leading to chronic obstructive pulmonary emphysema (COPE). On the other hand, frequent inhalation may induce lung fibrosis. Gefitinib, a drug used in treatment of lung cancer, having half-life of 6–49 hours with oral bioavailability of 59%. Hence, our present study is focused on the preparation of nanoparticles of gefitinib, which would be expected to prevent the incidence of COPE by blocking the capillaries and also to reduce the hepatotoxicity and to enhance organ biodistribution. In the present study, gefitinib loaded chitosan nanoparticles were formulated by ionic gelation method. Prior to the formulation, a compatibility study between drug and polymer were assessed by FTIR and DSC studies. These studies indicated that there was no interaction between the drug and polymer. The formulated nanoparticles were characterized for certain parameters such as effect on polymer ratio on drug loading, particle size, zeta potential, polydispersity index, in vitro dissolution study and in vivo bio distribution study. The average size of the nanoparticles was found to be 251 nm, polydispersity index of 0.359 and a zeta potential value of 13.8 mv. The release of the drug from the chitosan nanoparticles was found to be sustained up to 24 hours. The nanoparticles follow first order kinetics obeying fickian diffusion. The organ biodistribution studies were carried out Swiss albino mice. The biodistribution study revealed that the nanoparticles exhibited 1.757 folds increase in drug concentration in lungs as compared to drug in the solution form. Thus, it can be concluded that the nanoparticulated formulation of gefitinib may decrease in dose frequency prolonged therapeutic level, reduction in dose and dose related side effects. Based on body distribution pattern and disposition kinetics, the developed nanoparticles may be suitable for effective targeting of gefitinib to lungs for treating lung cancer effectively.

BRS-12 Protein Oxidation as a Metric of Biospecimen Integrity

Borges C. R. 1 2 Jensen S. H. 1 2

1 Chemistry & Biochemistry, Arizona State University, Tempe, Arizona, United States 2 The Biodesign Institute - Center for Personalized Diagnostics, Arizona State University, Tempe, Arizona, United States

Backgroun: Protein oxidation as a result of exposure to air and ever-present trace metals is a well-recognized biochemical phenomenon. Oxidation of intact proteins can disrupt function and/or protein-protein interactions—potentially ruining clinical or otherwise important protein measurements. Most proteins do not experience the type of sulfur-based oxidation in vivo that they may be susceptible to ex vivo—namely non-native mixed disulfide formation and/or methionine sulfoxidation. Here we present evidence that the S-cysteinylation of albumin and methionine sulfoxidation of apolipoprotein A-I (apoA-I)—two protein oxidation events that have been posed as candidate markers of diseases associated with oxidative stress—may actually be due to exposure of plasma/serum to temperatures above their freezing point.

Methods: One-half microliter of plasma or serum was diluted 1000x in 0.1% (v/v) trifluoroacetic acid and analyzed without further processing by a simple trap-and-elute form of liquid chromatography-electrospray ionization mass spectrometry. Protein charge envelopes were deconvoluted and the peak heights of the native and oxidized forms of albumin and apoA-I were measured to determine the relative abundance of the oxidized form of each protein.

Results: Neither albumin or apoA-I oxidation was elevated in freshly obtained plasma/serum samples from acute myocardial infarction patients or prostate cancer patients. However, a systematic stability study on freshly obtained samples from healthy and poorly controlled type 2 diabetes (T2D) volunteers revealed that storage of plasma/serum at −20°C (i.e., above their freezing point of −30°C) resulted in elevated albumin S-cysteinylation within a matter of days and apoA-I methionine sulfoxidation within four months, with no differences in the rates or degrees of protein oxidation between the samples from the healthy and T2D donors. Notably, oxidation was stable at −80°C, but dramatically increased in rate at 25°C. Freeze-thaw cycles and the degree to which plasma/serum samples were sealed during storage did not affect oxidative stability.

Conclusions: Given these properties and their ease of analysis, these oxidized proteoforms, once fully validated, may represent the first markers of blood plasma/serum specimen integrity based on direct measurements of oxidative molecular damage that occurs under suboptimal storage conditions.

BRS-13 Next-Generation DNA Sequencing Using Long-Term Stored Serum Samples

Lauritzen M. 1 Rounge T. 1 Langseth H. 1 Enerly E. 1 Lyle R. 2 Gislefoss R. 1

1 Department of Research, Cancer Registry of Norway, Institute of Population-based Cancer Research, Oslo, Norway 2 Department of Medical Genetics, Oslo University Hospital, Oslo, Norway

Background: The impact of sample treatment and long-term storage conditions on the quality and quantity of DNA from archived serum has not been fully assessed. These variables may compromise downstream analyses, for example by introducing a bias in DNA sequence representation and/or a loss of quantitative data. We have evaluated the quantity, quality and variability of DNA in samples stored up to 42 years in the Janus Serum Bank. The aim of this study was to establish a method for isolation of DNA from long-term stored serum, identify potential variations in DNA yields caused by different storage times or sample treatment. Importantly, we wished to determine whether the DNA was of sufficient quality and quantity to be used in next-generation sequencing.

Methods: 153 Janus samples collected in six different time periods (1972–78, 1979–86, 1987–2004, 1973–79, 1980–1990 and 1997–2004) and with different sample treatments (e. g addition of iodoacetate, lyophilization or prolonged clotting time) were included in the study. 24 fresh serum samples were collected and used as reference material. DNA was isolated using the serum protocol for the QIAamp DNA Blood Mini kit (Qiagen). DNA quantity was measured using the Qubit^™ dsDNA HS Assay kit (Life Technologies). DNA quality was assessed using the Agilent 2100 Bioanalyzer with the High Sensitivity DNA kit (Agilent Technologies). Genome-wide shotgun sequencing was performed on 12 selected samples on an Illumina NextSeq500.

Results: The median DNA yield was 10.65 ng/500 μl serum (SD = 10.99 ng/500 μl serum), N = 174. 11 out of 12 samples, including samples collected in 1973, produced high quality genome-wide sequences. One sample with added iodoacetate displayed lower yields and produced fewer sequences in the sequencing reaction.

Conclusions: We show that DNA is stable in serum during long-term storage and of sufficient quality and quantity for genome-wide sequencing, making large serum repositories an invaluable source for DNA biomarker discovery. However, pre-analytical conditions may influence serum DNA yields and should be taken into consideration in the project design.

BRS-14 Urinary Nucleic Acids can be Concentrated, Dried on Membranes and Stored at Room Temperature in Vacuum Bags

Zhang F. 1 Yuan Y. 1 Wu J. 1 Gao Y. 2 1

1 Institute of Basic Medical Sciences, Beijing, China 2 Beijing Normal University, Beijing, China

Urine accumulates traces of changes that occur in the body and can potentially serve as a better biomarker source. Urinary nucleic acids are a promising class of non-invasive disease biomarkers. However, long-term frozen human urine samples are not a good source for the extraction of nucleic acids. In this paper, we demonstrate that urinary nucleic acids can be concentrated, dried on membranes and stored in vacuum bags at room temperature for several months. The amount of total RNA on the membranes after storage at room temperature for three months was unchanged. The levels of miR-16 and miR-21 exhibited no significant differences (P = 0.564, 0.386). This simple and economical method makes the large-scale storage of clinical samples of urinary nucleic acids possible.

BRS-15 Reuse of DNA Extracted from already Immunostained Formalin Fixed Paraffin Embedded (FFPE) Slides: Technique Refinement and Application in Downstream Molecular Analysis of Cancer

Al-Attas A. Assidi M. Dallol A. Schulten H. Al-Qahtani M. Abuzenadah A. Buhmeida A. Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia

Background: Huge milestones have been achieved to improve the quality of healthcare delivered to patients. Despite the development of cutting-edge technologies, many diseases (e.g. cancer) are still threatening human welfare mainly because of their polygenic, complex and yet poorly understood molecular processes. In genomic medicine era, the quantity and quality of biological samples are crucial to develop more effective tools and drugs that enhance the clinical service offered to patients. So far, the conventional FFPE (Formalin Fixed Paraffin Embedded) technique is the gold standard for preserving histomorphology, while cryopreservation is the gold standard for biomolecules' preservation. Once these tissues stained, the slides are routinely archived along with FFPE blocks for long at biobanks/hospitals. However, the reuse of already fixed and stained biospecimens to extract DNA is not a common practice worldwide. This study focused on the feasibility of extracting DNA from already immunohistochemistry (IHC) stained slides to assess its quality and usefulness for further downstream molecular analysis and validation at genetic and epigenetic levels. DNA was extracted and reused to evaluate the mutational and methylation profiles of selected cell-adhesion molecules (CAD). With the shortage in high-quality and fully annotated biospecimens, we believe that this technique will improve further our best practices associated to the use of biospecimens in biorepositories and medical research.

Methods: FFPE IHC slides from colorectal cancer (CRC) consent patients were made and stored in the CEGMR Biobank, King Abdulaziz University. A workflow designed by our group consists successively of removing the slide cover-slip (Xylene), crude dissection of the IHC stained tissue and DNA extraction using the QIAamp DNA FFPE Tissue Kit according to manufacturer guidelines. After DNA quality assessment, mutation analysis of CTNNB1 (β-catenin) and the methylation profile of CDH1 (E-Cadherin) were achieved.

Results: A high quality DNA was obtained allowing around 60% concordance rate between CDH1 methylation and membranous E-Cadherin expression pattern. For CTNNB1 sequencing, clean DNA chromatograms with evenly-spaced peaks, each with only one color were observed.

Conclusions: The study suggested a promising technique to recycle and reuse DNA from IHC stained slides with suitable concentration and integrity as starting biomolecule for further downstream molecular applications.

BRS-16 Primary Human Cancer Cell-Based Platforms for Screening New Drugs and Drug Targets that Inhibit Cancer Growth and Metastasis

Jain J. 1 2 Ragamouni S. 2 Mahalingam M. 1 Chinta D. 1 Kulothangan P. 2 Musmoorie S. 1 Natarajan S. 2 1 Gandhari M. 2 Khandrika L. 1

1 Sapien Biosciences, Hyberabad, Andhra Pradesh, India 2 Saarum Sciences, Hyderabad, Andhra Pradesh, India

Many cancers are detected late, many others relapse despite treatment. Hence, better diagnostic markers to identify cancer early, monitor its aggressiveness and metastatic potential, and its response to treatment are needed. Translational cell models that reflect the heterogeneity and complexity of human cancers are needed to improve the clinical success of drug candidates.

Epithelial-to-mesenchymal transition (EMT) is a normal developmental process that is reactivated in cancer. Epithelial cells transform into mesenchymal cells thereby acquiring the ability to detach, invade and migrate through the extra-cellular matrix to reach distal locations. They form metastatic loci leading to secondary tumors that cause death. The EMT process may also confer resistance to therapy leading to relapse of cancer.

We are building an Indian cancer cell bank with appropriate ethical approvals and associated pathological data. Fresh tumor samples are obtained sterile from operation theatres and either cultured for cells/spheres, or flash frozen for genomics/proteomics research. These cells are used to set up functional assays e.g., cell proliferation and apoptosis, generation of cancer stem cells, wound healing, invasion etc. Panels of gliomas, breast and prostate cancers have been cultured successfully. These cancers represent a diversity of cancer stages, somatic and germline mutations, expression of different molecular markers and resistance to standard of care therapy. An EMT model has been set up using normal epithelial cells obtained from breast reduction surgeries. The epithelial cells were immortalized and transformed by known inducers of EMT. Reporter genes that serve as assayable markers of EMT have been engineered in to enable high throughput screening including high content cellular imaging.

In conclusion, our biobank's access to human tumors has been used to develop disease-relevant cellular platforms, capturing many of the critical steps and pathways involved in human cancer growth, metastasis, chemo-resistance etc. These cell systems are valuable in identifying markers of cancer progression, new drug candidates that can inhibit cell migration, invasion, generation of cancer stem cells etc. These can be used to screen new drugs in a phenotypic drug discovery mode. Molecular drivers of Indian cancers can be determined, as also Indian cell lines derived along the lines of ATCC, offering the promise of personalized medicine for Indian cancer patients.

BRS-17 Biospecimen Science -Establishment of a Biobank Quality Panel

Gislefoss R. Department of Research, Cancer Registry of Norway, Oslo, Norway

Background: The prospective value of a biobank is determined by the quality of the samples, i.e. to what degree they may reflect the biological, or biochemical state of the donor at the time of sample collection. The sample quality is crucial to achieve reliable scientific results.

The aim of the project was to investigate the impact of freeze- thaw cycles and storage time for ten biological components in serum. For this purpose we established a quality panel that covered biochemically different components, based on samples from 40 fasting voluntary donors of both genders.

Methods: About 50 mL blood was collected from each donor. The blood was left to coagulate for minimum 1h and less than 2h. Subsequently the vials were centrifuged for 10 min at 1300 × g (RCF). Serum from each donor was separated from the cells and distributed in 20 aliquots in 1.5 ml polypropylene tubes. One aliquot was analyzed fresh at baseline while the others were frozen at −25°C.

Study 1. One aliquot from each donor will be thawed and refrozen 1, 2, 3, 4, 5, and 10 times. The samples will be analyzed for ten different components: sodium, potassium, bilirubin, aspartate-aminotransferases (ASAT, enzyme), albumin (transport protein), immunoglobulin G (IgG), cholesterol (lipid), C-reactive protein (CRP), thyroid stimulating hormone (TSH) and vitamin B-12, and compared with baseline values.

Study 2. One aliquot from each donor will be analyzed after storage for 3 months, 6 months, 1, 2, 3, 5, 10, 15, 20 and 25 years and compared with the baseline measurements.

Statistics: Distribution will be tested for normality. For group comparisons ANOVAs for repeated design and post hoc t-tests with Bonferroni correction will be used. Results will also be presented graphically by boxplots.

Results: Results from the freeze- thaw study will be presented.

Conclusion: Correct biospecimen handling is crucial in biobanking. The strength of the present study design is that aliquots from the same sample are reanalyzed several times. Thus other external factors i.e. age and change in lifestyle (e.g. diet, smoking pattern) will have no influence in contrast to the situation with sequential sampling.

BRS-18 Amyloid Ab42 Measurement: a Tool to Evaluate (1) Adsorption Properties of Specimen Containers and (2) Novel Cerebrospinal Fluid Processing Methods

Kofanova O. A. 1 Mommaerts K. 1 Perret-Liaudet A. 2 Saka E. 3 Silvia S. 4 Oliveira C. 5 Simonsen A. 6 Mollenhauer B. 7 Verbeek M. 8 Betsou F. 1

1 Integrated BioBank of Luxembourg, Luxembourg, Luxembourg, Luxembourg 2 University de Lyon, Lyon, France 3 Hacettepe University Hospitals, Ankara, Turkey 4 National Neurological Institute, Milano, Italy 5 University of Coimbra, Coimbra, Portugal 6 Copenhagen University Hospital, Copenhagen, Denmark 7 Georg August University, Göttingen, Germany 8 Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands

Amyloid ß peptide fragment 1-42 (Aß1-42) is present in human cerebrospinal fluid (CSF) and is one of the biomarkers used in the diagnosis of neurodegenerative diseases (ND). Different peptides and proteins, like Aß1-42, bind in a nonspecific manner to plastic and glass tubes, and recommendations include the use of polypropylene collection and storage containers.

In this study, we evaluated two pre-analytical factors during CSF processing: (1) type of specimen containers and (2) specimen stabilization through freeze-drying versus standard freezing. Specimen containers were prototypes specifically manufactured by Fluidx for the purposes of the study. Aβ1-42 concentration was determined with the INNOTEST β-amyloid (1–42) sandwich ELISA (Innogenetics), according to the manufacturer's instructions.

We compared the impact of various polypropylene (homo- and co-polymer) storage tubes on Aß1-42 concentration, measured in pure solution. We showed that prototypes polypropylene tubes made of homopolymer had significantly lower binding properties than those made of copolymer. The lower binding properties of homopolymer were compromised by irradiation, to a point where irradiated homopolymer tubes showed similar binding characteristics to copolymer.

We also evaluated Aß1-42 concentration in CSF samples in glass vials, applying freeze-drying as a novel CSF processing method. This part of the work was performed in the context of the JPND BIOMARKAPD consortium. We showed no significant impact of freeze-drying in glass vials, neither on the Aβ1-42 concentration, nor on the concentration of other protein ND biomarkers, measured after several months at 4°C and below. Therefore, freeze-drying can be applied for the processing of CSF and its storage, in the scope of several protein ND biomarker analysis.

Overall, investigation on optimal CSF container material (plastic, glass) and chemistry (homo-, co-polymer) is still not finalized; container type certainly represents a critical pre-analytical factor which should always be documented in order to avoid analytical bias.

BRS-19 Biological and Physicochemical Factors Causing Human miRNA Variability

Ammerlaan W. Betsou F. IBBL, Luxembourg, Luxembourg

miRNAs are candidate biomarkers. For being an appropriate disease biomarker, the miRNAs should have stable in vivo homeostatic levels and be robust to specimen processing. In this study we assess the biological stability of blood miRNA expression levels in various blood components from healthy donors over a one year period. Additionally, we analyze stability of tissue miRNA to two physicochemical factors: heat stabilization using Denator, and embedding substance OCT.

For the miRNA profiling we used the WaferGen SmartChip Human miRNA Panel v3.0. This platform permits qPCR analysis of 1036 miRNAs (based on miRBASE 16) in a single assay.

For the biological stability, blood was collected over 6 time points, with a 2 months interval from 2 healthy donors. Blood was separated in the following components: Serum, Plasma, WBC, T cell, Monocytes and Granulocytes. miRNA profiling was performed on each individual component. The miRNA expression levels were compared using qBase plus program. Stabile miRNA detection levels were arbitrary defined as having a CV < 10% (e.g.HSA-MIR-137) and particularly unstable ones having a CV > 150% (e.g. HSA-MIR-626 and HSA-MIR −219-2P-3) over a one year period, per donor, per blood component. From the panel of 1036 miRNAs analyzed we have compiled reference lists of human miRNA (in)-stability expression levels in the above blood components.

For the physicochemical stability, we extracted miRNA from 4 snap frozen tissues and their Denator (95°C, for 25 seconds, at 5 mbar) treated counterparts. The miRNA expression levels from both sample types were compared by linear regression, showing a R² ranging from 0.5268 to 0.8103. We concluded that heat stabilization of tissues is compatible with miRNA analysis, but does not give comparable results with miRNA profiling from frozen specimens.

The impact of OCT tissue embedding was also evaluated. For this, we compared human liver and lung tissues which were either 1) snap frozen, 2) snap frozen with OCT or 3) pre-snap frozen followed by OCT embedding. Results will be presented.

As a conclusion, in Vivo variability during specimen collection, and in Vitro physicochemical factors during specimen processing, introduce significant bias in intra-individual miRNA quantification, and should be taken into account by biobanks.

BRS-20 Ticks Collection and Tick-borne Viruses Isolation in China

Shen S. 1 Duan X. 2 Wang B. 1 Su Z. 1 Zhang Y. 3 Sun S. 2 Hu Z. 1 Deng F. 1

1 Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China 2 Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi, Xinjiang, China 3 Center for Disease Control and Prevention of the Xinjiang Uyghur Autonomous Region, Urumqi, Xinjiang, China

In recent years, tick-borne viral diseases, such as tick-borne encephalitis (TBE), Xinjiang hemorrhagic fever (XJHF) and severe fever with thrombocytopenia syndrome (SFTS), have attracted much attention in China because of the increasing incidence and significant threat to human health. Therefore, it is going to be more and more important to survey the tick vector ecology and the diversity of tick-borne virus in China. So we focus on the establishment of the tick vector repositories of different species, hosts and geographic origins, and the methods for tick-borne virus detection and isolation. Ticks were collected from livestock and hilly and jungle areas of different representative geographic environment in four provinces of China. Tick species were identified by morphology and molecular markers, and then grouped according to different hosts and geographic distributions. RT-PCR and metagenomic methods were used for the detection of tick-borne viruses. To isolate viruses, positive samples were incubated with cells for blind passages or applied to mice brain. So far, bunyaviurses were isolated from Dermacentor and Hyalomma and then sequenced for further characterization. All these will facilitate the understanding of the distribution of different ticks in different areas of China and the prevalence of tick-borne viruses in different tick species. It will help to propose a warning of potential emerging tick-borne viral diseases in certain area, and further provide great resources for phylogenetic and virological studies.

BRS-21 Defining Fit-For Purpose Use of Plasma Biospecimens; The Impact of Time to Processing and Preservative Type on Biomarker Analysis

Everett C. 1 Neville-Golden J. 1 Tworoger S. 1 2 Sawyer S. 1

1 Brigham and Women's Hospital, Boston, Massachusetts, United States 2 Harvard Medical School and Harvard School of Public Health, Boston, Massachusetts, United States

Background: The Cohorts Biorepository currently houses biospecimens and data from large U.S. based study cohorts dating back as far as 40 years. With over 3 million specimens in inventory matched to participant level data, these collections represent an irreplaceable resource for cutting edge biomarker and genomic studies in relation to risk of multiple chronic diseases. Similar to other geographically diverse specimen collection efforts, delays to processing of blood derived biospecimens and variation in preservative used are common among the collections. The extent of analytic variation derived from these variables is largely unknown, but widely speculated to be both minimal and detrimental. We have implemented an experimental approach aimed at ensuring fit-for-purpose use of cohort biospecimens.

Methods: Blood biospecimens were collected from consented research volunteers. Identical specimens collected with either K2EDTA or Sodium Heparin as a collection preservative, were triaged into three different batches, 1) processed within 10 minutes of collection, 2) stored at 4 degrees overnight prior to processing and 3) stored and 4 degrees for 48 hours prior to processing. Plasma samples from the above batches were sent to a reference laboratory for analysis of the matrix metalloproteinase (MMP) family of proteins and a panel of related cysteine, B vitamin and folate markers. Assays were performed using commercially available antibody based kits. All assay batches included reference standards and replicates of pooled plasma quality control samples. Resulting data were analyzed for assay reproducibility, variance between different preservative types and variation due to time to processing (as determined by coefficient of variation, Spearman correlation and inter-class correlation).

Results: Results indicated differential susceptibility of biomarker assays to preservative type and processing delay. Among the closely related markers within a single commercial panel, several markers showed very strong correlation of results among all variable categories, while others were very poorly correlated.

Conclusions: Determination of “fit” of a biospecimen for its designated purpose must be assessed on the basis of specific and individual biomarker assays. In our experience, even closely related biomarkers assessed with similar methodologies are differentially susceptible to processing pre-analytic variables.

BRS-22 Isolation of Distinct Stomach Cell Populations by Laser Capture Microdissection of PAXgene-Fixed Paraffin Embedded (PFPE) Specimens

Rao A. Barcus M. Valentino K. Roche N. Warner A. Golubeva Y. Moore H. NIH, Rockville, Maryland, United States

Background: Laser Capture Microdissection (LCM) has been used successfully to isolate distinct cell populations from complex tissues in frozen or formalin-fixed paraffin embedded samples. Isolated material can be used for DNA, RNA and protein analysis. As part of the Genotype-Tissue Expression program, quality control (QC) metrics were established to evaluate similarity among samples of a particular tissue type. Molecular analysis using RNA from PAXgene Tissue-fixed stomach specimens revealed an outlier, which may be due in part to a mixed population of mucosa and muscularis cell types. LCM was undertaken in order to facilitate RNA sequencing of these different stomach cell types.

Methods: Frozen adrenal and muscle tissues that had been PAXgene Tissue-fixed and paraffin embedded (PFPE) were used to isolate RNA as a baseline assessment for LCM laboratory qualification. Stomach samples were chosen based on specific inclusion and exclusion criteria, including a reported high RNA integrity number (RIN) from RNA isolations of corresponding PAXgene Tissue-fixed tissues. Block quality QC was then performed to determine the quality of RNA in the PFPE block. Board-certified pathologists identified and annotated the study specimens and then annotated reference slides to define collection areas. The LCM laboratory prepared slides, collected the designated specimens, captured pre- and post-microdissection images, extracted and performed QC on RNA and finally distributed RNA for sequencing.

Results: There was a 2-3 point reduction in RIN value between PAXgene Tissue-fixed and PFPE samples, indicating a significant effect of the paraffin embedding process on PAXgene Tissue-fixed biospecimens. In comparison, there was a negligent drop in RIN values when block QC was performed on frozen specimens. A number of other LCM process variables were assessed, including slide material and staining method, in order to optimize the quality and quantity of sample retrieved post LCM.

Conclusions: This study combines the use of a well-established technology, LCM, with novel starting material, PFPE specimens, in order to isolate distinct stomach cell populations. Currently there are no publications to date that describe LCM on PFPE samples. In the near future, RNA sequencing will determine whether distinct stomach cells can successfully be isolated and analyzed from PFPE material, and thereby allow assessment of gene expression changes to individual cell populations of interest.

BRS-23 Emerging Results from the NCI Biospecimen Preanalytical Variables (BPV) Program

Carithers L. 1 Odeh H. M. 1 Agarwal R. 2 Guan P. 1 Roche N. 2 Moore H. 1

1 US National Cancer Institute, Rockville, Maryland, United States 2 Leidos Biomedical Research, Inc., Rockville, Maryland, United States

Background: The National Cancer Institute's (NCI) Biorepositories and Biospecimen Research Branch (BBRB) initiated a program, Biospecimen Pre-analytical Variables (BPV), to collect data on how variations in standard operating procedures for tissue collection, handling, storing and shipping affect downstream molecular analysis results.

Methods: Four medical centers around the country are collecting tumor samples that are dissected into four experimental pieces. Each piece receives a different treatment based on the preanalytical factor of interest. The current tissue preanalytical factors being studied by the BPV program are 1) cold ischemic time prior to formalin fixation, 2) duration in formalin, 3) freezing method (dry ice or liquid nitrogen vapor), and 4) frozen storage temperature (−80 or liquid nitrogen vapor).

Results: Initial results show that longer time intervals in formalin can result in lower yields of RNA and DNA. A prolonged cold ischemic time interval can also affect the expression of protein markers analyzed by immunohistochemistry and liquid chromatography-mass spectrometry. Additional analysis is being conducted to evaluate analytical platforms that evaluate DNA and RNA.

Conclusions: Information gathered from the BPV program will be used to develop biospecimen evidence-based practices specific to the analysis platform of interest and to develop biospecimen quality assays which can be used to qualify a banked specimen for a particular assay. Notably, individual biological and clinical biomarkers can have different reactions to various preanalytical factors, and different analytical platforms also exhibit different tolerance to preanalytical variability. Assay developers are encouraged to evaluate how preanalytical factors impact their marker of interest for their particular platform.

BRS-24 Evaluation of Preanalytical Factors on Detection of Copy Number Variations in FFPE Tumor Tissues

Guan P. 1 Goerlitz D. 2 Mathew J. 2 Li X. 2 Ressom H. 2 Agarwal R. 3 Carithers L. 1 Odeh H. M. 1 Roche N. 3 Moore H. 1

1 National Cancer Institute, NIH, Bethesda, Maryland, United States 2 Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC, District of Columbia, United States 3 Leidos Biomedical Inc, Rockville, Maryland, United States

Background: Formalin fixed, paraffin embedded (FFPE) tumor tissues are a readily available biospecimen type for today's drug development and therapeutic research. The ability to use modern genomic, transcriptomic and epigenomic methods with nucleic acids derived from FFPE tissues would allow enormous archives of routinely stored tissues, often with well-annotated clinical data, to be used for translational research. DNA derived from FFPE tissues have been utilized for array comparative genomic hybridization (aCGH) and single nucleotide polymorphism (SNP) array analysis. However, the compromised quality of FFPE-derived DNA can confound the use of these archived specimens for array-based genomic studies and the interpretation of the derived data.

Previous studies have reported false positive/false negative findings using FFPE tissues compared with cased-matched fresh-frozen (FF) tissue in array-based genomic studies. However, no systematic evaluation has been done to elucidate the impacts of various formalin fixation parameters on such studies.

We are conducting experiments to evaluate the effects of duration of formalin fixation and time delay to fixation on copy number detection using aCGH on case-matched FFPE and FF tumor tissues.

Methods: Whole‐genome copy number variation analysis was performed using Agilent SurePrint G3 Human CNV Microarray 400K (Agilent Technologies, Santa Clara, CA). This array was designed for the screening of CNV regions using 442,892 distinct probes. The samples were collected from 40 donors with clear cell renal carcinoma (20 cases for duration of fixation evaluation (6, 12, 23 and 72hrs) and 20 cases for delay to fixation evaluation (1, 2, 3 and 12 hrs)). Case-matched fresh frozen tumor tissues as well as peripheral blood were used as controls in the evaluation.

Results: Results are currently being generated and will be presented at the meeting.

Conclusions: The results will provide novel information on the effects of various formalin fixation parameters on CNV and mutation detection, indicate optimal fixation times to minimize such effects, and generate evidence to validate the application of FFPE-derived DNA in translational research.

BRS-25 Frozen Tissue Core Study: Analysis of RNA Extracted From Frozen Uterine Tissue Cores with the CryoXtract™ CXT 350 Frozen Sample Aliquotter

Wieczorek D. 3 McGarvey D. 2 Fraone J. M. 1

1 Cryoxtract Instruments, LLC, Woburn, Massachusetts, United States 2 Eastern Division, Cooperative Human Tissue Network, Philadelphia, Pennsylvania, United States 3 Scientific Application Department, Promega Corporation, Madison, Wisconsin, United States

Limiting pre-analytical variability in biological samples is crucial for scientific and translational medicine research. Inconsistent and improper handling of frozen biological samples is often a significant source of such variability and can result in the obscuring of data sets and scientific outcomes. CryoXtract's frozen dispensing technology presents a novel method for targeted and repeated access to frozen tissue samples without the need for freeze-thaw sampling. Labile biomolecules, such as RNA, are better preserved over repeated samplings when the parent sample is maintained in an ultra-cold state.

In this joint study between Promega, CHTN Eastern Division, and CryoXtract Instruments, human uterine tissue treated in RNAlater^® from a single donor was handled under two scenarios. Scenario A maintained the parent tissue in a frozen state through two rounds of frozen aliquotting while scenario B subjected the parent tissue to a single freeze-thaw cycle and 4°C storage in between aliquotting rounds. Total RNA was extracted from each frozen tissue core produced in scenarios A and B and characterized for yield, RIN scores, A260/A280 and A260/A230A ratios.

In general, cores that were produced under conditions where the tissue sample was not exposed to any freeze-thaw cycling or 4°C storage (scenario A and time point 1 of scenario B) exhibited good average RNA yields (1.29–3.29 micrograms), high average A260/A280 and A260/A230 ratios (1.92–2.03 and 1.74–1.84, respectively), and high average RIN scores (8.3–9.2). However, all RNA quality criteria decreased significantly for cores that were produced after the parent sample had experienced one freeze-thaw cycle and storage at −80°C (Avg. Yield = 0.79 micrograms, avg. A260/A280 = 1.85, avg. A260/A230A = 1.37, and avg. RIN score = 6.3).

The results of this study suggest that frozen aliquotting can be used to access frozen tissue samples multiple times with no appreciable impact to the RNA contained in the cores or frozen parent sample. Moreover, the study also demonstrates the susceptibility of labile biomolecules (such as RNA) to degradation when the parent tissue is not maintained in a frozen state, even when the parent tissue is actively treated with a stabilizer such as RNAlater^®.

BRS-26 An Experimental Approach to Developing Best Practices for Thawing Plasma Biospecimens

Neville-Golden J. 1 Bradwin G. 2 Everett C. 1 Sawyer S. 1

1 BWH/Harvard Cohorts Biorepository, Brigham & Women's Hospital, Boston, Massachusetts, United States 2 Clinical & Epidemiologic Research Laboratory, Boston Children's Hospital, Boston, Massachusetts, United States

Background: In recent years, significant experimental evidence has emerged around the process and approach for freezing and storing liquid biospecimens. The increase in knowledge and attention to these processes begs questions about processes at the other end of the spectrum, namely thawing. How should you thaw a sample? And, does the thawing method matter? Through collegial connections with a number of biorepositories, we discovered a variety of different thawing practices in common use for blood derived specimens, namely: 1) warm water bath; 2) room temperature water bath; 3) a gentle, room temperature, sonicating water bath; 4) 4°C overnight; and 5) wet ice on the bench. We designed a simple experiment to address the impact of thawing methodology on analytic measurement of 5 different plasma biomarkers.

Methods: An informal survey of collaborating biorepositories was conducted to gather protocols for thawing plasma samples that had been store in the vapor phase of liquid nitrogen freezers (−150° to −190°C). Five different common approaches were identified. Biomarkers of interest were identified to represent a range of plasma analytes, based on size and complexity. They were 1) IgG, 2) HDL-Cholesterol, 3) Free (T4) Thyroxin; 4) Vitamin-D Complex; and 5) lactate dehydrogenase (LDH). Plasma samples for the experiment were purchased from a commercial blood product supplier and collected under a prescribed standard protocol. Identical samples were split and treated experimental conditions performed in triplicate. Biomarker analysis was performed with commercially available assay kits. All experimental steps included additional samples with previously established biomarker levels to monitor quality and reproducibility.

Results and Conclusions: There is a wide array of established approaches to thawing biospecimens; for the purposes of this experiment we tested 5 different approaches. While some biomarkers we analyzed appear relatively stable among all 5 thawing procedures, others show marked difference in assay results dependent on thawing methodology. In conclusion, thawing methodology should be carried out in a standardized and know fashion that is suited to the downstream use of the specimen.

BRS-27 Evaluation of Fluidigm SNPtrace™ Panel, with a Comparison to DNA QUAL and Bioanalyzer Fragment Analysis, for DNA Quality Assurance within the Tumour Bank Program

Zhou L. Catchpoole D. R. The Tumour Bank, Children's Cancer Research Unit, The Children's Hospital at Westmead, Westmead, New South Wales, Australia

Translational research is the key component to apply basic science findings into practical medicine. High quality human biological specimens are the foundation of accurate and reproducible research result and will maximize the productivity of translational research. To assure that the best samples are provided to translational research, quality assurance (QA) programs are an essential part of biobanks' routine.

To identify the most feasible technology for regular biobank QAP daily practice, two technologies promoted from use in biobanking QAP have been compared, the Fluidigm SNP trace panel (Fluidigm, USA) and DNAqual (Eurobio, France). 93 samples, including 80 DNA samples from 4 donors and 13 DNA samples isolated from bone marrow aspirates (BMA) smeared on slides, were examined using both technologies. BMA slides had been stored at the room temperature and exposed to air for 2–14 years. In addition, to create a range of possible conditions occurring in biobank daily practice, DNA samples from donors were treated with multiple freeze-thaw cycles (0-20), varied snap delay period (0-21 days), radiation, sonication, heat, UV and mixed contamination (MC) respectively. DNA qualities have been verified using Bioanalyzer DNA 7500 Kit (Agilent, USA).

The results showed that the Fluidigm panel could detect 50% MC between samples accurately. The sensitivity of the contamination detection need to be further tested. It also reported the degraded DNA qualitatively instead of quantitatively. By contrast, DNAqual can provide the quantitative DNA quality index although it is not designed for detecting MC at all. The accuracy of the index need to be further validated.

In addition, the consistency rate of the Fluidigm panel is 100% within the plate due to its qualitative feature, but it is not optimal to compare the results across the plates, whereas due to its qPCR feature, DNAqual can compare the readings across runs. All these results will be further validated and elucidated.

These results form the basis of a better biospecimen QA solution for the Australian biobanking community. Furthermore, we will discuss the ongoing implementation of these new QA platforms into daily biobank practice and how these will benefit translational research involving genomics.

BRS-113 An Evaluation of Frozen Aliquotting Technology for the Stabilization of Small Molecule and Peptides in Bio-analytical Application

Smith G. A. 2 Fraone J. M. 1

1 Cryoxtract Instruments, LLC, Woburn, Massachusetts, United States 2 Bioanalysis, GlaxoSmithKline, Research Triangle Park, North Carolina, United States

The ex vivo lability of some drug compounds and molecules in bio-analytical assays can add complexity and uncertainty to results and can pose significant challenges in drug development efforts. This can be especially true for compounds that are subjected to long-term cryogenic storage and that may need to be tested multiple times (e.g. samples collected for clinical trials). Frozen aliquotting technology may offer a simple solution for stabilizing target compounds in frozen biological specimens, helping to streamline bio-analytical assay development and execution. In this regard, GlaxoSmithKline (GSK) performed an evaluation of the CXT 750 Frozen Sample Aliquotter in order to determine its suitability for compound stabilization and use in bio-analytical assay development initiatives.

A test mixture of labile small molecule compounds and peptides was spiked into human and rat plasma at a single concentration and frozen in 2ml cryogenic vials. The samples were then subjected to 4 rounds of freeze-thaw aliquotting (liquid aliquotting of a thawed sample) and frozen aliquotting on CryoXtract's CXT 750 Frozen Sample Aliquotter. Both freeze-thaw aliquots and frozen aliquots were precipitated and then analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS). Compound recovery for each aliquotting cycle was based on the peak area counts generated by the LC-MS/MS.

In general, compounds that exhibited an extreme decrease in recovery when subjected to freeze-thaw aliquotting exhibited significantly better recovery when processed on the CXT 750. For example, the small molecule drug analogue, cisatracurium, was not detectable after 1 - 2 and 2 - 3 freeze-thaw cycles from the spiked rat and human plasma, respectively. In contrast, 68% and 75% of the spiked drug (in rat and human plasma) was still detectable by LC-MS/MS after 4 aliquotting rounds on the CXT 750.

Overall, the evaluation demonstrated that frozen aliquotting can improve compound stability for bio-analytical assays utilizing technologies such as LC-MS/MS. Though further work is needed to validate the results in this study, it is GSK's assessment that frozen aliquotting technology has strong potential for pharma-based applications, in particular, those dealing with the bioanalysis of biological samples.

Ethical, Legal, and Social Issues

ELSI-28 Opinions of Adolescents and their Parents Regarding Common Topics in Pediatric Biobanking

Tarling T. 1 2 Vercauteren S. 1 4 Strahlendorf C. 1 5 Kong C. 1 3 Dittrick M. 1 Milner R. 1 3

1 U British Columbia (UBC), Vancouver, British Columbia, Canada 2 Hematopathology, BC Children's Hospital, Vancouver, British Columbia, Canada 3 Child and Family Research Institute, Vancouver, British Columbia, Canada 4 Pathology and Laboratory Medicine, BC Children's Hospital, Vancouver, British Columbia, Canada 5 Hem/Onc/BMT, BC Children's Hospital, Vancouver, British Columbia, Canada

Background: Biobanking is a growing field and Research Ethics Boards (REBs) are progressively more involved in ensuring that this practice is carried out with best interests to its participants. These issues are especially complicated in the pediatric setting, where parents and guardians are responsible for the initial consent agreement of their children. Pediatric biobanking raises some ethical concerns, such as parental/guardian consent, age for patient assent and consent, re-contacting patients for consent when they reach the age of majority, and the subsequent status of specimens if re-contact is unsuccessful as well as a willingness to contribute specimens to a biobank.

Methods: In order to address these important issues, we conducted an exploratory survey of four cohorts

(1) Adolescents aged 14–18 years from various high schools in Vancouver, BC, Canada.

(2) The parents of the adolescents described in (1) above. from

(3) Adolescents aged 14–18 years who have been treated at BC Children's Hospital, Vancouver, BC, Canada in either the department of Cardiology, Oncology or Orthopedics.

(4) The parents of the adolescents described in (3) above.

Results: Our results showed that overall clinic participants (both adolescents and parents) rated a higher willingness to donate specimens versus school participants. Additionally clinic participants were more likely to think assent was important and parental consent alone was insufficient. We found the median suggested age for assent was 14.5 years among adolescent responses, and 16 years from parental responses. However, all groups commented that appropriate age of assent is individual to the patient's maturity. Finally we found that school parents were the most conservative in their responses towards their children's specimen donation and associated consent issues.

Conclusions: Adolescents, who were seen in clinics at BC Children's Hospital and their parents, had a more altruistic approach toward pediatric biobanking than those surveyed in the school setting. In addition, the age of assent and consent considered appropriate by parents was higher compared to adolescents regardless of whether they have been exposed to a clinical situation. The results of our survey will contribute to future decision-making around the ethical issues associated with pediatric biobanking.

ELSI-29 Ethical Considerations and Assurances for a Sub-Saharan African Regional Biospecimen Repository (SSA RBR) for HIV-Related Malignancies

Sanderson M. 1 Barsdorf N. 1 Nokta M. 2 Silver S. 3 Schneider J. 1

1 Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, Western Cape, South Africa 2 AIDS Cancer Clinical Program, Office of HIV and AIDS Malignancy, National Cancer Institute/NIH, Bethesda, Maryland, United States 3 Microbiology, Immunology, and Tropical Medicine, George Washington University, Washington, District of Columbia, United States

Background: The aim of the SSA RBR is to collect, store and distribute high quality biospecimens and data sets, obtained with informed consent from HIV-positive and HIV-negative cancer patients for HIV malignancy research. Biospecimens and data are managed according to standard operating procedures of the AIDS and Cancer Specimen Resource utilizing both National Cancer Institute and ISBER best practices. The SSA RBR complies with relevant South African (SA) legislation and ethics regulations. The SA Department of Health provides basic ethical principles for research using stored specimens, but detail specific to the ethico-regulatory framework for biobanking in SA is sparse. Our goal was to obtain ethical approval for the establishment of the SSA RBR from the Health Research Ethics Committee (HREC) of Stellenbosch University (SU), which is registered with the National HREC (SA) and the US Office for Human Research Protections.

Methods: Application for ethical approval for the SSA RBR involved multiple consultations with the SU HREC and major stakeholders. To promote favorable benefit and minimal risk to donors and communities, key local and international legislative and ethical guidelines on secondary use of biospecimens, biobanking operations as well as systems that guarantee donor confidentiality and privacy were investigated and incorporated into the application. Principal concerns included: custodianship versus ownership, informed consent, benefit sharing, confidentiality, involvement of donors and communities and independent review of SSA RBR operations and governance by an accredited HREC.

Results: The SSA RBR obtained ethical approval in July 2014 (N14/03/024). Donors will be consented using a broad informed consent procedure. Compliance with best practices ensures the integrity and quality of biospecimens and protection of individuals' confidentiality and rights. A community advisory board facilitates public involvement. African-based researchers and their international collaborators can access biospecimens through a formal peer-reviewed application process. The Inspector of Anatomy will oversee compliance with SA legislation and regulatory requirements. The SSA RBR will contribute to evolving policies on biobanking in SA.

Conclusion: The SSA RBR application for ethical approval was a comprehensive and inclusive process that can be considered exemplary in fulfilling the ethical and legal requirements for biobanking in SA and Sub-Saharan Africa.

ELSI-30 Assessing the Scope and Constraints of Industry Access to Publicly-Funded Biobanks in Canada

Axler R. Gibson S. Lemmens T. University of Toronto, Toronto, Ontario, Canada

Background/Information: Much attention in ethical and legal studies of biobanking research has been afforded to issues of industry and private-sector use of human biological data and specimens. These studies have most often focused on participant consent and attitudes to industry use and commercialization of research using their samples. Little research, however, has examined how biobanks govern access to samples by industry or private-sector researchers, or the commercialization of research results using biobank samples. This study examines access policies and arrangements of major publicly-funded biobanks in Canada to determine their access arrangements for industrial applicants.

Methods: Major publicly-funded biobanks in Canada were identified through membership in biobank networks and through Internet searches, and their access policies were reviewed to examine access conditions for industry applicants. Where necessary, biobanks were directly contacted to obtain or confirm specific details on their data access policies. As well, analyses draw from ten in-depth qualitative interviews with key informants involved in biobank policy and governance, to determine their attitudes towards industry access.

Results: The majority of publicly-funded biobanks in Canada allow access to industry scientists, though this access is sometimes partial (i.e. industry applicants are only given access to aggregate-level data), and often requires higher access fees or differential levels of research ethics review. Interviews indicate that biobank regulators and policy-makers value universality in access to biobanks; as such, industry access is condoned, so long as researchers hold relevant credentials and research holds the potential to achieve health benefits.

Conclusions: Given the overall lack of attention to the regulation and governance of industry access to publicly-funded biobanks, this study provides a unique perspective in the Canadian context of the nature of access arrangements for industry applicants. As private industry tends to be granted access, and there is consensus from experts that industry should be able to access biobanks, there is a need to attend to how industrial intellectual property arrangements and commercialization initiatives affect the use of this public resource.

ELSI-31 Do People Care What's Done with Their Biobanked Specimens?

Tomlinson T. 1 De Vries R. 2 Kim M. 2 Kim S. 3 Ryan K. 2 Lehpamer N. 1 Krenz C. 2

1 Michigan State University, East Lansing, Michigan, United States 2 University of Michigan, Ann Arbor, Michigan, United States 3 National Institutes of Health, Bethesda, Maryland, United States

Background: Current research ethics standards allow for the use of “blanket consent” for donations of specimens to research biobanks, when those will be de-identified for research uses. Since subsequent research will not involve a human subject, the assumption is that there is nothing ethically significant to the donor in how specimens are used. But does information about future possible uses matter to a donor's decision whether to give blanket consent?

Methods: We fielded a nationally representative survey of the U.S. adult population. Respondents read an introductory description of a fictional biobank, and used a six-point scale to indicate their willingness to give blanket consent for all future studies. We then presented seven potential research scenarios that might present moral concerns to some people. After each one, we asked again about the willingness to give blanket consent, “even if” the biobank might sponsor such research. We also gave respondents short descriptions of the pros and cons of five methods of obtaining consent, asking them to indicate acceptable, best, and worst options. Various demographic and attitudinal information was then collected.

Results: 1599 respondents completed the survey (response rate of 60.2%) At baseline, 68% were willing to donate using blanket consent. For all but one scenario, presentation of potential future projects was associated with an overall reduction in willingness. For some subjects, however, presentation of particular scenarios was associated with an increase in willingness. These effects were associated with a variety of demographic factors, concern about privacy, and trust in medical research. In their evaluations of methods for giving consent, respondents were least favorable toward methods at each end of the spectrum. Blanket consent was the worst option for 37.8%; and specific consent, in which consent is given for each study using their specimen, was considered the worst by 45%.

Discussion: These results raise a series of questions. Should biobanks offer consent options besides blanket consent? What trade-offs with administrative or scientific efficiency should we tolerate? How should biobanks revise their public information policies to address potential concerns among donors? How could information about concerns and attitudes among a biobank's donors be used in crafting policies or informing decisions about when a research project might require the use of specific consent?

ELSI-32 Opt-in Consent Status at the Cincinnati Children's Pediatric Biobank

Cobb B. L. 1 Roach A. 1 Gaines L. 1 Barnes M. 2 Harley J. B. 1 3

1 Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States 2 AssureX Health, Mason, Ohio, United States 3 US Department of Veterans Affairs, Cincinnati, Ohio, United States

Background: Many institutions are using remnant clinical samples for research. Use of these samples has the advantage of simplicity of acquisition, economic efficiency, and increased safety for patients. At the same time, there is a changing consensus regarding how consent for these samples should be obtained or even whether consent is necessary for use of these samples. Herein, we provide an overview of the approach taken by Cincinnati Children's to institute such a project, Better Outcomes for Children (BOfC), a registrar based opt-in procedure.

Methods: Community and institutional input was solicited during the development of BOfC to enhance regulatory clarity and precedent. With input from the Institutional Review Board, Office of Research Compliance and Regulatory Affairs, the legal department and the Cincinnati community, the Better Outcomes for Children project has become a valuable institutional resource. Collaboration between all groups has been vital to the success of this project.

Consent for this project is obtained during registration by trained registrars. Patients and families determine whether they will participate and whether they would like to be notified of incidental findings. The consent document consists of three pages of information about the project in an easy-to-understand format. The signed consent is captured in the medical record system (Epic).

Remnant clinical samples are obtained from the clinical lab after a seven-day clinical embargo period. Consent status is then verified via an automated CCHMC developed software application (Red Light, Green Light) and samples are processed and stored if consented. Samples are available to institutional investigators and their collaborators following review and approval by a Tissue Use Committee.

Results: To date, over 174,000 participants have agreed to donate their leftover clinical specimens for research purposes. Of these participants, 93% have elected to be informed of incidental findings while 7% have elected to participate but do not wish to be informed of incidental findings. Currently, withdrawal rates are below 0.1%, indicating acceptance of the project.

Conclusion: The Cincinnati Children's pediatric biobank has become an important resource to facilitate research through the foresight of many stakeholders. Its implementation has been readily accepted by staff performing the work as well as patients and families asked to participate.

ELSI-33 Mayo Clinic Biobank - Understanding Consent Rates

Hathcock M. A. Ryu E. Sharp R. R. Liebow M. Takahashi P. Y. Van Norstrand M. D. Lindor N. M. Parker A. S. Thibodeau S. Cerhan J. Olson J. E. Mayo Clinic, Rochester, Minnesota, United States

Objectives: To explore the sex, age and temporal trends in consent rates in the Mayo Clinic Biobank.

Methods: The Mayo Clinic Biobank (MCB) began recruiting participants in April of 2009 and will continue into 2015 with a goal of 50,000 participants. Participation occurs through unsolicited invitation of patients scheduled with a medical appointment within 3 weeks of contact or volunteering. At initial contact, basic demographics and consent/refusal information are tracked. Using patients invited in the first 5 years from Mayo Clinic Rochester, MN, monthly consent rates into the MCB were calculated.

Results: As of April of 2014, 134,284 patients have been invited to the Mayo Clinic Biobank, with a consent rate of 25% (N = 33,989). Overall consent rate was similar for men (26%) and women (25%), but varied dramatically with age, with the highest consent rates in the age group 71 to 90 years (34%) and the lowest in the age group over 90 years (12%). There were modest sex differences by age group (male vs. female): age 18–30 (8% vs.15%), 31–50 (14% vs. 20%), 51–70 (28% vs. 30%), 71–90 (37% vs. 32%), and > 90 (16% vs. 9%). Over the 5 years of recruitment, overall consent rates have steadily decreased from 35% in the first year to 15% in the most recent year across all age and gender groups. Additional analysis will be presented to see the association of temporal trends with age and gender. These results will also be expanded to include all recruitment sites.

Conclusions: Recruitment of the Mayo Clinic Biobank provides a unique insight of long term consent rates of a large patient base. While males have generally lower consent rates than females, this was reversed in the oldest age groups. The steady decrease in consent rates observed over time provides insight into what can be expected from long term biobanking projects in similar settings.

ELSI-34 Addressing Pathology Incidental Findings in a Genomics Based Research Study

Carithers L. 1 Keen J. 1 Koester S. 2 Little R. 4 Lockhart N. 3 Rao A. 1 Struewing J. 3 Volpi S. 3 Weil C. 1 Moore H. 1

1 US National Cancer Institute, Rockville, Maryland, United States 2 US National Institute of Mental Health, Rockville, Maryland, United States 3 US National Human Genome Research Institute, Rockville, Maryland, United States 4 US National Institute on Drug Abuse, Rockville, Maryland, United States

Background: The Genotype-Tissue Expression (GTEx) study is a National Institutes of Health (NIH) program that aims to understand the relationship between genetic variation and gene expression in normal human tissues. 30 different tissues are collected for genomic analysis from hundreds of deceased donors who may have also donated organs and tissues for transplant purposes. Pathology review is conducted on all GTEx tissues to ensure that the correct target is sampled and to evaluate autolysis. Rarely, observations have been made in pathology review which may have potential medical significance to either organ transplant recipients or to recipients of banked tissues (skin, bone, tendon, etc). The GTEx program has carefully deliberated over these incidental findings and the ethical obligations that may exist to return this information to the biospecimen source sites to allow notification using the proper medical and regulatory channels.

Methods: The GTEx Executive Committee, made up of lead Program Directors from NHGRI, NIMH, and NCI, requested consultations with representatives of the NIH Department of Bioethics on this issue. They also consulted with relevant clinical experts and with policy experts from the Organ Procurement and Transplantation Network (OPTN), and examined the literature related to the risk of disease transmission to organ and transplant recipients.

Results: The GTEx Executive Committee together with the NIH Department of Bioethics determined that there may be an ethical obligation to inform biospecimen source sites when incidental pathology findings could have potential medical significance to transplant recipients. A formal structure was designed and executed to address this obligation. An expert group, the GTEx Incidental Findings Evaluation Group, was established to evaluate incidental findings identified by GTEx pathologists and make a recommendation to return or not return a finding to the corresponding biospecimen source site.

Conclusions: A framework was designed to address incidental pathology findings discovered when performing tissue quality assessment for a large genomics project. Through this framework, a number of cases with incidental findings have been evaluated. In a few of those cases the incidental findings were determined to have potential medical significance to transplant recipients, and those findings have been returned to the biospecimen source sites for transmission to treating physicians and tissue banks.

ELSI-35 Tracking Governance Procedures across Biobanks- Variance in Stringency for Compliance Procedures

Warner A. W. Global Specimen Solutions, Cary, North Carolina, United States

Tracking initial informed consent for specimen and data usage is critical for biobank compliance procedures. Across business sectors and biobanks, there have been multiple approaches to governance that have been operationalized to maintain compliance. These approaches vary in stringency and risk for potential variance from intended use of specimens and data. We have evaluated 9 implemented governance approaches across sectors (e.g. academia, service sector, pharmaceutical industry) and graded them for risk of potential variance from intended use. Using this algorithm, we can conclude that all approaches have some risk for variance, but 82% have strong risk for variance from intended use. This study demonstrates the need to implement robust, automated governance strategies for biobanks and data stores in order to ensure patient informed consent is not violated during the research process.

ELSI-36 The Return of Results to Participants: an Open Issue in Brazil

Franca P. 2 1 Rocha J. C. 2 4 Venâncio J. A. 2 Motta M.d. 2 3 Marodin G. 2 5

1 Medicine, UNIVILLE - Universidade da Região de Joinville, Joinville, Santa Catarina, Brazil 2 Brazilian Research Ethics Commission, Ministry of Health of Brazil, Brasília, DF, Brazil 3 Department of Science and Technology (DECIT), Ministry of Health of Brazil, Brasília, DF, Brazil 4 Hospital Erasto Gaertner, Curitiba, PR, Brazil 5 Consultant of Bioethics and Ethics in Research, Ministry of Health of Brazil, Brasília, DF, Brazil

Background: The informed consent process provides the basis for the confirmation of the individual's acceptance in research participation. Although assumption, this process does not always indicates to the participant the guarantee of knowing the results pertaining to his participation. In Brazil, the main guideline of the ethical regulation system in research determines that must be ensured to participants the benefits, in terms of social return or access to procedures and research products.

Methods: Systematic review of the literature, focusing on ethical guidelines of Brazil and other countries.

Results: According to Resolution 340/2004 of the National Health Council, every individual can have access to his genetic data and has the right to withdraw them from banks where they are stored, at any time, and must be offered the option to choose between being informed or not on the results. The Informed Consent Form shall ensure genetic counseling and clinical follow-up as appropriate, indicating the responsibles, at no cost to the participant of research. However, the opposite is not standardized in Brazil, that is, if the researcher detects a potentially relevant result for the participant, there is no requirement for active search for reporting it, explanation of the implications involved and indication of referrals. Furthermore, among other issues that remain open in Brazil and in other parts of the world we highlight:

- Who is entitled to access results in situations of disability or death of research participant?

- How to proceed in case of incidental findings?

- In familial risk situations, other members at potential risk shall have guaranteed the access to early diagnosis and primary prevention?

- The research participant can always ask his results invoking personal issues, although associated with non-preventable disease?

- What is the extent of the responsibilities of researchers, sponsors and agencies for research?

Conclusion: Until there is a consensus or clear definition of what is a valid research result and who is responsible for the interpretation and transfer of information, the Brazilian position on this matter has been to ensure that the participant has the right to decide whether or not to be informed of the results from its individual participation and receive genetic counseling when the results show consistent clinical implications. As a result of the dynamics of knowledge, Brazilian regulations on the subject deserve complementation.

Hot Topics

HT-37 Qatar Biobank: Public Health Issues Revealed

Afifi N. M. 1 Althani A. 2 1 Abderrahim H. 1 Rizvi A. 1 Elliott P. 3 Riboli E. 3

1 Qatar Biobank, Doha, Qatar 2 Health Sciences, Qatar University, Doha, Qatar 3 Imperial College, London, United Kingdom

Qatar Biobank is a large-scale, long term medical research initiative for the population of Qatar, which over the next few years aims to recruit 60,000 men and women Qatari nationals and long-term residents (>15 years residence) aged ≥18 years, and to follow up these same individuals over the long term to record any subsequent health conditions. At the baseline recruitment visit, extensive clinical phenotypic information is collected from each participant. Participants are referred when an abnormal out of range clinical measurement is recorded to the ambulatory care clinic at Hamad Medical Hospital or their own doctor. During the pilot phase Sept 2013-October 2014, 530 of the 1,172 participants (45.2%) were clinically referred, 70.38 % of them were new cases and 29.62% were known cases. Most of these referrals were caused by out of range values on related tests for abnormal bone density 25.5%, low FEV1 20.1%, dyslipidemia 19.8%, diabetes 18.8% and hypertension 18.3%.

Chronic diseases such as cardiovascular diseases, hypertension and diabetes mellitus are emerging as a major health problems and are now the major cause of death and disability in Qatar accounting for 55% of years of life lost in the country in 2008 (WHO, 2011b). The population in Qatar is also experiencing a nutrition transition, characterized by replacement of traditional diets with diets higher in fat and refined and processed foods, and a decrease in the levels of physical activity.

Analysis of the pilot phase data indicates that In addition to the primary goal of Qatar Biobank to collect information and samples as a platform to empower research in Qatar, it also plays an important role of early identification and prompt treatment of chronic non-communicable diseases (diabetes, obesity and CV) which will reduce the future burden in health sector.

HT-38 Crucial Steps for Building Biobanks: Step by Step Procedure for Low Income Countries

Sargsyan K. Huppertz B. Macheiner T. Biobank Graz, Medical University Graz, Graz, Austria

Background: The development of a biobank includes a variety of challenges depending on local infrastructure, human and financial resources, laws, ethics and various guidelines such as those regarding privacy. Most of current biobanks are academic; however, the interlinking between a biobank, donors/patients and researchers can be designed in various ways.

Methods: Firstly, analyses of infrastructure, resources and competences are necessary. Then, concept/cohort planning, membership in biobank-networks, business planning and ethical assurance need to be clarified. Therefore, intensive consultation with a panel of biobanking experts from different research and management areas is necessary to meet all requirements. The next step is implementation of processes including SOP design.

Results: A key subject is the definition of adequate storage systems and an efficient data management system in compliance with the existing infrastructure, running costs and competencies.

As an example, the landscape and infrastructure of the Biobank Banja Luka (in Bosnia and Herzegovia) did not allow for cryopreservation using liquid nitrogen; however, due to a low electricity price, cryopreservation via freezers was an obvious solution for biobanking there. Furthermore, it was identified at Banja Luka that the further development of ethics and approval committees was required. In general, proofing of regulatory instances often showed a lack of ethics and approval committees.

Discussion: It is obvious that low and middle income countries have a different degree of access to academic and research infrastructure compared to high income countries. Therefore, it is essential that such countries conduct a resource and competence analysis before building a biobank, rather than copying plans and strategies one-to-one from those of high income countries.

HT-39 Strategy Development for Emerging Biobanks on the Example of Kosovo and Albania

Story P. Strahlhofer-Augsten M. Sargsyan K. Biobank Graz, Medical University Graz, Graz, Austria

The developing of a strategy for the setup of Biobanks the following steps were found to be efficient in a workshop with Biobank Graz and two emerging Biobanks at National Institute of Public Health of Kosovo and University of Tirana Medicine.

First a presentation of the status quo of the respective institutions was performed and a questionnaire check was done, to get an overview of the actual situation. Additionally, visits (guided tours) to institutions from Kosovo and Albania were carried out.

To determine the strengths, weaknesses, opportunities and threats of each partner, a SWOT analysis was developed. The participation and involvement of important stakeholders of the relevant institutions in the discussion and group work for the SWOT-analysis has shown to be very beneficial and is a prerequisite for their support in the further setup and establishment of the Biobank.

International collaboration, European/international and private funding were identified as crucial opportunity for these emerging biobanks whereas economic risks and sustainability are the most relevant threats. On the basis of these findings SWOT-Strategies were developed, as a preparatory work for generating the strategy poster. For example: trainings at and cooperation with experienced biobanks or contact to the research community as well as the application for funding are some identified strategies to overcome threats and respectively to use opportunities.

Final step in developing the strategy was the strategy poster. The following main aspects of the strategy were discussed: Vision of the Biobank, Critical success factors, Global definition of critical success factors, strategic direction of impact (3 years), and operational objective planning of activities 2015–2017.

This 3-year strategy is an essential prerequisite for setting up the biobanks and is substantial work paper for the inclusion of stakeholders and decision-makers. This strategy is now on work for the new established two biobanks, and we looking forward to enrich biobanking research society with new-borns!

HT-40 The Establishment of a Biobank and Cohort Network (BCNet) for Low- and Middle-Income Countries (LMICs)

Caboux E. 1 Henderson M.K. 2 4 Toromiro J. 4 Njajou O. 4 Elhadad A. 5 Ezzat S. 6 Faramat I.G. 5 Abdel-Hamid M. 7 Chowdhury A. 8 Dikshit R. 9 Sughayer M. 10 Emonyi W. 11 Gudleviciene Z. 12 Bwotle F. 13 Igbe M. 14 Macondo E.A. 15 Mbaye E.H.S. 16 Thiam S. 15 Babb C. 17 Duma B. 17 Abdelhalim I. Osman 18 Ndyetabura T. 19 Sangrajrang S. 20 Hennig B. 21 Dondeh B.L. 21 Yacoub H. 22 Abdelhak S. 22 Musisi K. 23 Kyobe S. 24 Dhoro M. 25 Matimba A. 26 Litton J.E. 27 Dillner J. 28 Lawlor R. 29 30 Rebbeck T. 31 Carter A. 32 Morente M. 33 Zawati M. 34 Stefanoff C. 35 Sylla B.S. 1 Mendy M. 1

1 International Agency for Research on Cancer, WHO, France 2 US National Cancer Institute – Center for Global Health (NCI-CGH) 3 International Society for Biological and Environmental Repositories (ISBER) 4 Université des Montagnes, Cameroon 5 National Cancer Institute, Egypt 6 Children's Cancer Hospital, Egypt 7 Egyptian National Biobank, Egypt 8 Institute of Post Graduate Medical Education and Research, India 9 Tata Memorial Hospital, India 10 King Hussein Cancer Center, Jordan 11 AMPATH Reference Laboratories, Kenya 12 National Cancer Institute, Lithuania 13 Jos University Teaching Hospital, Nigeria 14 Federal Ministry of Health, Nigeria 15 Laboratoire de Biologie Médicale BIO24, Sénégal 16 Centre de diagnostic et de Recherche en Médecine Moléculaire, Sénégal 17 National Health Laboratory Services, South Africa 18 Radiation Isotopes Centre Karthoum, Sudan 19 Kilimanjaro Clinical Research Institute, Tanzania 20 National Cancer Institute, Thailand 21 MRC International Nutrition Group, The Gambia 22 Institut Pasteur de Tunis, Tunisia 23 National Tuberculosis Reference Laboratory, Uganda 24 Makerere University, Uganda 25 African Institute of Biomedical Science and Technology, Zimbabwe 26 University of Zimbabwe, Zimbabwe 27 Biobanking and Biomolecular Resources Research Infrastructure - European Research Infrastructure Consortium (BBMRI-ERIC) 28 Biobanking and Biomolecular Resources Infrastructure of Sweden (BBMRI.se) 29 European, Middle Eastern and African Society for Biopreservation and Biobanking (ESBB) 30 ARC-NET Centre for Applied Research on Cancer (ARC NET) 31 African Organisation for Research & Training in Cancer (AORTIC) 32 National Cancer Research Institute, UK (NCRI) 33 Spanish National Cancer Research Centre, Spain (CNIO) 34 Centre of Genomics and Policy (CGP), McGill University, Quebec, Canada 35 Insituto Nacional de Câncer (INCA/MS), Brazil (REBLAC)

Biobanks, which facilitate the collection and storage of high-quality biological specimens and associated information, play a key role in scientific research on disease prevention, screening, and treatment. In contrast to the situation in high-income countries (HICs), biobank infrastructures and related standard guidelines and protocols are much less developed in LMICs. This infrastructure and knowledge challenge constitutes a serious barrier to high-quality scientific research projects in disease control in LMICs.

In line with IARC's mission of contributing to worldwide cancer research and, in collaboration with US National Cancer Institute - Center for Global Health (NCI-CGH) and other international partners, a biobank network (BCNet) was set up as an opportunity for LMICs to work together in a coordinated and effective manner and jointly address the many challenges in biobanking infrastructure, including ethical, legal and social issues (ELSIs). In addition, the network will facilitate the sharing of resources (e.g. training, expertise, protocols) and the development of joint projects, with a goal of strengthening the competitiveness of the LMIC biobanks in applying for international funding.

The founding members of BCNet include 30 representatives from 16 LMICs from all the WHO regions and partners. Membership is not exclusive and is open to all LMIC biobank institutions that are willing and able to work together for common interests and agree with the principles and practices endorsed by the BCNet governance. New members from LMICs are encouraged to join. More information can be found at http://bcnet.iarc.fr/

Information will be provided on the setting up of the network, its members, partners, current activities and results of the situational analysis on facilities and infrastructure that was conducted prior to the setting up of the network.

Human Specimen Repositories

HSR-41 Australian Prostate Cancer BioResource, 2015

Yeadon T. Australian Prostate Cancer BioResource, Brisbane, Queensland, Australia

Objectives: The Australian Prostate Cancer BioResource (APCB) provides a unique quality assured facility for the collection, storage and access to tissue to support research into the treatment and improved clinical management of men with prostate cancer. The APCB manages four federated nodes located in Brisbane, Sydney, Melbourne and Adelaide. The APCB is jointly funded by the National Health and Medical Research Council (NHMRC) and Prostate Cancer Foundation of Australia (PCFA).

Results: The APCB provides a significant number of unique services which include:

fresh tissue

paraffin embedded tissue sections,

buffy coat cells, serum, plasma

tissue microarrays

To date the APCB has collected 139,304 samples from 5,453 men (Oct 2005-Oct 2014) and has distributed 7,426 samples to 47 different researcher groups on 86 occasions (since 2007).

The APCB is firmly embedded in translational prostate cancer research within Australia and provides resources to build and contribute Australasian cohorts in large scale genetic, genomic and proteomic biomarkers studies. This includes the following research programs; PRACTICAL Genome Wide Association Study, Irish Biomarker Consortium, the Movember GAP initiative. The APCB also provides expertise and infrastructure to bank samples from the RAVES trial.

Conclusions: The APCB has a collection of high quality prospectively collected prostate cancer tissue with clinical and pathological data acquired at diagnosis and surgery. This collection has become an important resource for prostate cancer research both nationally and internationally. With maturity and recruitment of 5,500 men by end of 2014 with 9 year clinical follow up it will become a significant research resource.

HSR-42 Obtaining Useful and Viable Biospecimens from Postmortem Donors for Research Purposes: The GTEx Experience

Keen J. 1 Foster B. 2 Moser M. 2 Bridge J. 3 Thomas J. 4 Lonsdale J. 4 McDonald A. 4 Undale A. 5 Smith A. 5 Roche N. 5 Moore H. 1

1 Biorepositories and Biospecimen Research Branch, National Cancer Institute, Bethesda, Maryland, United States 2 Roswell Park Cancer Institute, Buffalo, New York, United States 3 UNYTS, Buffalo, New York, United States 4 National Disease Research Interchange, Philadelphia, Pennsylvania, United States 5 Leidos Biomed, Rockville, Maryland, United States

Control or non-diseased biospecimens are in limited supply and often hard to obtain. Most researchers rely solely on surgical samples for research purposes, which further limits the type and amount of tissue that can be secured. Postmortem tissue has been shown to be a viable option when seeking biospecimens for research purposes. The Genotype-Tissue Expression (GTEx) study, a NIH Common Fund study that is collecting non-diseased biospecimens from a total of 900 deceased donors, has successfully partnered with Tissue and Organ Procurement organizations to obtain viable tissues for research purposes. To do so, GTEx has established protocols and standard operating procedures for 1) obtaining consent from next-of-kin, 2) assembling a tissue collection team on site, and 3) initiating the operations to facilitate the collection of tissue for tissue or organ transplant as well as for research purposes. SOPs are available through the BBRB website at http://biospecimens.cancer.gov/resources/sops/library.asp. Postmortem tissues for research can be obtained secondary to those potentially donated for transplant with a low postmortem interval, typically with a first tissue in fixative within 8 hours for donations not including brain and within 24 hours for those including brain. Collection times for acquiring all targeted tissues per donor averages <3 hours. Although some postmortem tissues, such as pancreas, ileum, and spleen, autolyse and degrade quickly, results from molecular analysis show that tissues maintain high molecular integrity with low autolysis scores. Analysis of the RNA integrity number (RIN) of the tissues from up to 30 organs sites per donor that have been collected to date, indicates that 24 of the 30 tissues (80%) have a RIN value of 6 or greater and therefore are a viable source of tissue for research endeavors. This study has shown that obtaining viable tissue biospecimens in collaboration with Tissue and Organ Procurement Organizations is a feasible endeavor that provides flexibility in tissue acquisition.

HSR-43 A Prostate Cancer Biorepository Meeting International Collaborative Demands

Tiwari S. 1 Haynes A. 1 Nguyen Q. 1 Hammond G. 2 Kench J. G. 3 1 Horvath L. G. 4 1 Stricker P. D. 5 1

1 Prostate Cancer Research Program, The Kinghorn Cancer Centre/Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia 2 Information Technology, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia 3 Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, Sydney, New South Wales, Australia 4 Medical Oncology, The Chris O'Brien Lifehouse, Camperdown, Sydney, New South Wales, Australia 5 St Vincent's Prostate Cancer Centre, Darlinghurst, Sydney, New South Wales, Australia

Introduction: The Garvan Institute of Medical Research and the St Vincent's Prostate Cancer Centre, Sydney Australia, developed a biobank in 1994 to house prostate cancer tissue and blood samples from consented men following their radical prostatectomies. The intention was to collect and store high quality prostate biospecimens with associated clinico-pathological, treatment and clinical outcome data. This allows researchers access to a clinically meaningful resource for the investigation of various aspects of the disease including tumor biomarkers, therapeutic response, disease outcome, and genomic sequencing. The biobank has grown and has been consistent with the “International tissue preparation protocols and classification standards” to allow samples to be used in international collaborations.

Methods: Patients at the time of their radical prostatectomies are consented to have part of their prostate cancer tissue collected and to be followed up after their operation. An in-house bio-specimen and clinical database, CanSto, was developed which incorporates SPREC (Standard PREanalytical Code), the international pre-analytical tissue classification system that manages and tracks how tissue samples are collected, stored and processed.

CanSto also marries the tissue collection with clinical information, such as diagnosis data, PSA results, treatment plans, and follow up data to the time of death.

Results: Our biobank and database currently stores prostate cancer biospecimens across a range of stages and treatments. It has developed cohorts with follow up data extending beyond twenty years. Up until November 2014, the biobank has over 13,240 men registered including 2,677 with fresh frozen tissues, 6,344 with paraffin-embedded blocks and 1,706 with blood samples. The collection has produced over eighty peer-reviewed publications since its establishment. It has led to publications in areas of clinical urology, quality of life, molecular markers and the genomic/genetic causes of prostate cancer.

Conclusion: The Prostate Cancer Biorepository, with its extensive collection of tissue samples and clinical follow up data provides a valuable resource for international collaboration in various fields of research including clinical urology, biomarker research and genetic profiling. International collaborative research using the biorepository is encouraged for a better understanding of prostate cancer.

HSR-44 Biobanking Childhood Acute Lymphoblastic Leukemia: a Round Trip from the Bedside to the Bench and Back

Sontag T. 1 Lefebvre A. 1 Saint-Jacques M. 2 Bertout L. 2 Delva Y. 2 Taghzouti N. 2 Delorme I. 3 Marzouki M. 2 4 Laverdière C. 2 4 Sinnett D. 1 4

1 Sainte-Justine UHC Research Center, Montreal, Quebec, Canada 2 Hematology-Oncology-Immunology Clinical Research Unit, Sainte-Justine UHC, Montreal, Quebec, Canada 3 Hematology Unit, Sainte-Justine UHC Research Center, Montreal, Quebec, Canada 4 Department of Pediatrics, University of Montreal, Montreal, Quebec, Canada

We have been recruiting childhood Acute Lymphoblastic Leukemia (cALL) patients diagnosed at the Sainte-Justine Hospital since 1994. cALL represents ∼25% of all malignant childhood diseases, is the most common pediatric cancer and leading cause of cancer related mortality among children. In our laboratory, translational research is geared toward advancing knowledge across the continuum of pediatric cancer care spanning prevention through diagnosis/prognosis, to long-term survival. Our biobank is a resource that houses clinical data and biological samples from 3 patient-based study cohorts: the Quebec childhood Acute Lymphoblastic Leukemia (QcALL) cohort, patients from the PETALE cALL survivor cohort, and patients from the Personalized Targeted Therapy in Refractory/Relapsed Cancer in Childhood (TRICEPS) study. The QcALL cohort currently consists of 8,500 biospecimens from 700 patients, 800 parents and 600 healthy control individuals. For each patient, we collect biospecimens at diagnosis, throughout the 2-year treatment course and at relapse or pre-/post-transplant if applicable. The QcALL study is leveraging large-scale omic studies geared toward identifying novel (epi) genetic driver events to improve diagnostic and prognostic tools in cALL. Since 2012, we have been recruiting patients with a five-year event-free survival period to participate in the PETALE study aimed at identifying the genomic determinants of common treatment related toxicities in cALL survivors. This cohort currently consists of 150 cALL survivors out of the 250 anticipated upon study completion. The TRICEPS study, started in January 2014, currently includes 11 patients and involves timely (12-week time frame) in-depth characterization of tumor genomes to identify actionable mutations and provide personalized targeted therapy for refractory/relapsed childhood cancer patients. To store patient-related clinical, demographic, and genetic information we developed PANDORA 2.0, a Biobank Software System. This in-house solution aims to cover many of the research and operation activities applicable to biological repositories such as inventory tracking, management of patient consent forms, and report generation. All of the information contained in PANDORA actively contributes to translational research, bringing patients, researchers and oncologists closer, with the ultimate goal of improving present diagnostic and therapeutic strategies while minimizing treatment side effects in cALL.

HSR-45 Improving Biospecimen Quality within a Biobank Network: an Australian Perspective

Rush A. Byrne J. Children's Cancer Research Unit, The Children's Hospital at Westmead, Westmead, New South Wales, Australia

Background: There is emerging evidence that inadequate biospecimen quality contributes to the irreproducibility of research results. However, the biospecimen lifecycle includes activities that can and cannot be readily quality-controlled. Thus, a biobank's responsibility lies in maximizing biospecimen quality where possible, and communicating limitations to end-users.

Building on previous survey dataa, our project aims to maximize the uptake of biospecimen handling Standard Operating Procedures (SOPs) and quality testing; improve the communication of measures of and/or potential limitations to biospecimen quality to researchers; and create opportunities for staff to share and learn via community-based initiatives.

Methods: To establish a baseline of activity, we developed online survey questions surrounding the development/maintenance of SOPs; quality control (QC) activities (histological confirmation of diagnosis, percentage of tumor cells, database audits, nucleic acid assays, protein assays, haemolysis); and communication of biospecimen quality results (SPREC, BRISQ tools). We also developed two initiatives to promote/maximize biospecimen quality: an internet resource for biobank staff and applicants; and the staging of a biospecimen quality symposium.

Results: Previously analyzed data (n = 23) showed variable awareness and use of biobanking best practices and formal staff training, and utilization of SOPs not based on best practice guidelines. Statistical analyses from the online biospecimen quality survey will be presented. Website access and enrolments for the biospecimen quality symposium will be reported, to predict the effectiveness of a community-based educational program to improve awareness of biospecimen quality.

Conclusions: Biospecimen quality plays an important role in the translation of biomedical research. Our comprehensive review of biobank quality management activities within a statewide cohort of biobanks highlights variability in the use of standardized documents, QC measures, and staff training. Development of a community-based program including a website and a biospecimen quality symposium provides resources for staff to learn and implement quality activities. Website access and symposium attendance will be measured to indicate their possible effectiveness.

HSR-46 Biobanking for the Born in Guangzhou Cohort Study: a New Resource for Maternal and Child Health Research in China

He J. Guo Y. Kuang Y. Lu J. Liu Y. Liu X. Xia H. Qiu X. Guangzhou Women and Children's Medical Center, Guangzhou, China

Introduction: The Born in Guangzhou Cohort Study (BIGCS) is an ongoing prospective cohort study at the Guangzhou Women and Children's Medical Center, China. The BIGCS was commenced in February 2012 and aims to investigate short and long term health consequences of the genetic, environmental and social factors during pregnancy and the first few years of life. On the basis of the project, a standardized biobank was setup to investigate the possible biological mechanisms behind the early programming of disease.

Methods:

Ethics- The protocols of BIGCS were approved by the Institutional Ethics Committee. Written informed consent was obtained from all participants. All specimens were anonymized and identified by a unique study number.

Sample Collection - Pregnant women in BIGCS will have twice blood samples, once urine and stool sample taken during pregnancy. Umbilical cord, cord blood and the placenta will also be collected. Heel blood dry spots of the neonates will be obtained in 3 days after birth. Blood from child will be collected at the age of 1 and 3 years, respectively. Samples are kept in −80°C freezers for short term storage and in liquid nitrogen for long term.

Quality Control - Standard operating procedures were established with reference to the best practices issued by the ISBER. All the freezers and liquid nitrogen tanks were monitored by a temperature monitoring system. Specific biomarkers are routinely assessed for sample quality.

Results: By the end of 2014, 10543 pregnant women were recruited in BIGCS. There are 171 twins and 1 triplet in the 7942. Around 450000 aliquots of various samples were collected and stored in the BIGCS biobank.

An information system was developed for management of biosample and related clinical and epidemiological information. The functions of this system include: 1) accurate sample coding and sample location; 2) management of storage space; 3) real-time linkage to database of hospital information system.

Conclusions: There are several strengths of the BIGCS biobank: 1) focus on the effects of rapid urbanization on children's health; 2) real-time linkage to the database of the hospital information system and the laboratory information system; 3) prospective collection of various biospecimens from mothers and their children at multiple time points. The comprehensive individual-level data and the high-quality biospecimens of the BIGCS biobank are precious resources to facilitate biomedical research of maternal and child health.

HSR-47 The End of the Golden Age of Biobanking?

Scholze B. P. Shelley C. Medical Research-Oncology, Gundersen Health System, La Crosse, Wisconsin, United States

Background: Over the last 30 years biobanks have evolved from small academic collections acquired for in-house projects to large commercial, hospital and governmental entities that disseminate specimens worldwide. This growth stems from the increasing demand for high quality research specimens that are able to yield reliable results when assessed for labile biomarkers. However, just as biobanking appears to be entering a Golden Age, its demise can already be envisioned. This seems particularly apparent in the field of breast cancer where advances in screening have resulted in 10mm being the median size at which tumors are detected. At this scale biobanking is impossible as standard-of-care dictates the entire specimen be utilized for diagnostic and/or prognostic tests.

Hypothesis: There has been an annual decease in the average size of tumors removed during breast cancer surgery. Extrapolating this trend-line to when over 90% of resected tumors are 10mm or less would predict the end of prospective breast cancer biobanking.

Methods: The records of the Breast Cancer Registry of Gundersen Health System, La Crosse, Wisconsin were interrogated to determine the size of infiltrating ductal carcinomas surgically removed in 1998 and 2013 at Gundersen Medical Center (ICD-O-3.1 morphological code 8500/3). Within each year tumor sizes were divided into three categories: less than 10mm, 10–29 mm, and greater than 30 mm.

Results: In 1998 103 ductal carcinomas were resected. 18.5% were less than 10mm, 64% were 10-29mm and 17.5% were greater than 30mm. The mean tumor size in each of these categories was 6.2 ± 2.0mm, 16.6 ± 5.6mm and 39.8 ± 12.3mm, respectively. In 2013 143 ductal carcinomas were resected. 26% were less than 10mm, 52% were 10-29mm and 22% were greater than 30mm. The mean tumor size in each of these categories was 6.6 ± 2.3mm, 15.9 ± 4.6mm and 54.8 ± 20.9mm, respectively.

Conclusions: In the 16-year period encompassing 1998 through 2013 there has been so significant shift towards ductal carcinomas being resected at smaller sizes. Consequently, there is no foreseeable end to the prospective biobanking of these tumors. While this conclusion is a positive indicator for the future of biobanking it highlights the limitation of breast cancer screening programs. Such limitation is likely the result of the documented reluctance of a constant proportion of women to participate in screening and the development of tumors in the interval between screens.

HSR-48 Digital Pathology Networking of Biorepositories Supporting the National Cancer Institute's National Clinical Trials Network: A Feasibility Study

Richards W. 1 Barr T. J. 5 7 DeVries S. 2 Ferriere M. 3 Finnigan M. 2 Ganguly A. 4 Haile A. 6 5 Ramirez N. 6 5 Virk S. 7

1 Alliance for Clinical Trials in Oncology, Boston, Massachusetts, United States 2 NRG Oncology, San Francisco, California, United States 3 ECOG-ACRIN, Boston, Massachusetts, United States 4 National Cancer Institute, Bethesda, Maryland, United States 5 COG, Columbus, Ohio, United States 6 SWOG, Columbus, Ohio, United States 7 NCIC CTG, Kingston, Ontario, Canada

Background: Digital pathology is becoming promising in diagnostic medicine due to its ability to represent tissue sections as digital images that can be electronically shared and analyzed by pathologists on computer screens. Recent consolidation of the NCI Clinical Trials Cooperative Group Program into the National Clinical Trials Network (NCTN), and of the Cooperative Group Biospecimen Banks into NCTN Biospecimen Banks, led to harmonized operational and access procedures, and virtual inventory integration via a common biospecimen IT infrastructure. However, critical pathology support of biospecimen banking remains Group-specific and operationally diverse. To further integrate the NCTN biospecimen resource, the Steering Committee of the NCTN Biospecimen Banks has assessed the feasibility of establishing a digital pathology network to virtually connect biorepositories and pathologists, harmonize review procedures and efficiently share images and resources.

Methods: An on-line survey of 153 pathologists identified as providing services supporting NCTN Biospecimen Banks for specimen Q/C was conducted. Pathologists were asked for their current clinical and NCTN utilization of digital microscopy, their perspectives regarding its utility for NCTN activities, the potential of image processing to provide specimen Q/C analysis, and relevance of a digital pathology network linking images and resources across the NCTN groups.

Results: All NCTN Groups and disease specialties were well represented among the 59 pathologists who responded to the survey. Current use of virtual microscopy was more common in respondents' NCTN work (28% > 40% utilization; 14% > 90% utilization), than in their clinical work (None > 30% utilization; 85% < 10% utilization). Across specialties, most respondents were ambivalent as to the optimal method for Q/C or central review, with small numbers preferring either virtual microscopy or glass slides. About 82% of respondents perceived value in using image processing for specimen Q/C analysis. Respondents overwhelmingly indicated that the perceived advantages of a digital pathology network (resource sharing, efficiency, convenience) would be either relevant or somewhat relevant to their NCTN activities.

Conclusions: Digital pathology is well suited to NCTN biospecimen research activity. The collective view of pathologists supporting NCTN Biospecimen Banks indicates that implementing a digital pathology network would be both feasible and relevant.

HSR-49 Biobanking in Saudi Arabia: The CEGMR Biobank Experience

Buhmeida A. Assidi M. Ramadan H. Abuzenadah A. Al-Qahtani M. Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Makkah province, Saudi Arabia

Background: The human genome project has metamorphosed the medical research field toward the emergence of novel technologies that enhanced our understanding of genomic and/or epigenomic roots of diseases. Moreover, individual (epi) genomic variations in terms of diagnosis, prognosis and prediction biomarkers are a driving force making personalized medicine (PM) a mandatory approach to enhance health care services. However, the major PM challenge is the need of large sets of high-quality and fully annotated biospecimens. Therefore, biobanks become a vital core facility to perform advanced research that improved the public health. To nourish this drastic need for annotated biospecimens, thousands of biobanks in developed countries were built and are in the way to international biobanking practices harmonization. In contrast, the developing countries are still struggling to establish such crucial infrastructure for some awareness, technical, ethical and regulatory reasons. In this context, no single working model is launched yet in Kingdom of Saudi Arabia (KSA). The Center of Excellence in Genomic Medicine Research (CEGMR) is a comprehensive biomedical research center devoted to foster innovative biomedical research that alleviates the burden of genetic/cancer diseases in KSA, known by a high rate of consanguinity. The CEGMR Biobank Unit (CBU) has therefore been a major core facility offering a unique access to valuable collections of fully annotated human biospecimens in order to bridge the noticeable gap between clinicians and scientists. This study gives an overview of the CBU experience, current challenges and future plans.

Methods: The CBU was launched in 2008 as a traditional facility where biospecimens were initially manually documented. Since 2013, the CBU has been upgraded through the development of a home-made “Biosearch” software that recorded the major steps of biospecimens processing from collection till release to scientists. However, the lack of awareness among the health care providers remains a major challenge.

Results: More than 10 hospitals are currently providing the CBU with around 11000 biospecimens, which served for more than 100 publications.

Conclusions: Besides an effective awareness program, we will initiate collaborations with international biobanking experts in order to modernize the CBU and get CAP accreditation. Additional 5 nodes all over KSA will be launched soon as a first germ for the Saudi National Biobank.

HSR-50 Finnish Hematology Register and Biobank (FHRB) – a National Platform for Supporting Research in the Field of Hematology

Vesterinen T. 1 Pitkänen K. 1 Porkka K. 2 Strömberg A. 3 Wahlfors T. 4

1 Biobank, Institute for Molecular Medicine Finland (FIMM), Helsinki, Finland 2 Hematology, Helsinki University Central Hospital (HUCH), Helsinki, Finland 3 The Association of Finnish Cancer Patients, Helsinki, Finland 4 Finnish Red Cross Blood Service, Helsinki, Finland

Background: The Finnish Hematology Register and Biobank (FHRB) is a national biobank that provides a resource of well-annotated, high quality samples coupled with wide clinical information to accelerate hematological research. FHRB is owned by the Finnish Association of Hematology (FAH), the Finnish Red Cross Blood Service (FRCBS) and the Institute for Molecular Medicine Finland (FIMM). In Finland, biobanking is seen as an integral part of routine laboratory diagnostics and follow-up of the hematological disorders and the expenses are included in the costs of normal patient care. Patients are also involved in the management of the FHRB biobank.

Methods: Based on informed, broad consent, FHRB collects peripheral blood and bone marrow samples coupled with wide clinical information across Finland from patients with a hematological disorder. Serial samples are collected from each FHRB patient representing different time points in the disease history, from the untreated diagnostic stage to remission, relapse and treatment refractory stages. Along with blood and bone marrow, skin biopsies are collected for germ-line DNA analysis.

Sampling, sample processing and storage are highly standardized and partly centralized. Participating hospitals are responsible for sampling, FRCBS takes care of the sample processing and coding where as FIMM is responsible for sample storage, sample quality control policies, LIMS and sample delivery for research purposes. FAH takes care of collecting clinical information.

Results: At the moment (01/2015), FHRB has recruited 714 patients who have donated 39 450 sample aliquots. FHRB has also created quality control policies to ensure the quality of the samples collected. One percent of bone marrow samples are reviewed biannually. This review includes the physical verification of the vial location and the durability, as well as the verification of the biological quality of the specimen. For this purpose DNA and RNA are extracted and cell viability, division and growth are tested.

Conclusions: FHRB will start accepting sample applications in the spring 2015. The sample collection will be open to all research proposals whether academic, collaborative or industrial, which fulfill the predefined access criteria. The main aim of the FHRB is to maximize the value of its data and biospecimens by facilitating the translation of basic research innovations into clinical care and thus improve outcome of patients with hematological disorders.

HSR-51 The National Cancer Institute Supported Human Biospecimen Repositories

Demchok J. P. NIH, Rockville, Maryland, United States

Human biospecimens are critical in accelerating the development of molecular-based diagnostics and therapeutics for personalized medicine. The National Cancer Institute (NCI) supports (through grants and contract mechanisms) human biospecimen resources that provide quality biospecimens to researchers. NCI division has a unique goal for the collection, storage and distribution of human biospecimens. The goal of the presentation is to describe a variety of human biospecimens resources supported by the NCI.

Division of Cancer Treatment and Diagnosis

Cooperative Human Tissue Network (CHTN)

NCI Clinical Trials Network (NCTN) Biospecimen Banks

Specialized Programs of Research Excellence (SPORE) Biospecimen Cores

The NCI Office of Director

Cancer Centers Specimen Repositories

AIDS and Cancer Specimen Resource

Division of Cancer Biology

The Chernobyl Tissue Bank

International Registry of Werner's Syndrome

Barrett's Esophagus Translational Research Coordinating Center

Division of Cancer Control and Population Science

Cohort and Consortia Biospecimen Registries and Studies

Division of Cancer Epidemiology and Genetics (DCEG)

DCEG Investigator Collections

U.S. Radiologic Technology Study Resource

Alpha Tocopherol, Beta- Carotene Prevention Study Resource

Division of Cancer Prevention:

Prostate, Lung, Colorectal, and Ovarian (PLCO) Trials Biorepository

In conclusion the NCI provides funding for a variety of biospecimen resources for basic, translational, and clinical research. In addition, the NCI hosts a searchable website, The Specimen Resource Locator (SRL) (www.specimens.cancer.gov) that directs scientists to biospecimens that may have potential biospecimens for their research.

HSR-52 Recent Activities of Korea Gynecologic Cancer Bank

Kwon H. 1 2 Kim J. 1 2

1 Obstetrics and Gynecology, Gangnam Severance Hospital, Seoul, Korea (the Republic of) 2 Gangnam Severance Biomedical Research Center, Seoul, Korea (the Republic of)

The Korea Gynecologic Cancer Bank (KGCB) is a nonprofit organization established in 2012 at the College of Medicine, Yonsei University as one of the Research Materials Bank and also one of the Korea National Research Resource Center (KNRRC).

When cancer starts in a woman's reproductive organs, it is called gynecologic cancer.

The three main types of gynecologic cancers are: cervical, ovarian and uterine. (Another four types are placental, vagina, vulvar and the very rare fallopian tube cancer.)

The purpose of the KGCB is to provide investigators with human biospecimens for research projects relating to gynecologic cancer.

Human biospecimens, such as tissue, blood, urine, peritoneal fluid, and saliva have emerged as critical resources for basic and translational research in gynecologic cancer because they are the direct sources of molecular mechanism research used in the initiation of a tumor, and its progression for metastatic disease and resistance for treatment. Many studies heavily depend on the availability of high quality biological materials from patients with gynecologic cancer.

KGCB has also played important roles in the development of gynecologic research by collecting and providing gynecologic cancer biospecimens and genomes. Based on KGCB, we can additionally anticipate construction of research networks and more over improvements in bioscience research. The KGCB currently maintains a collection of 30,774 specimens that have been isolated from Korea gynecologic cancer patients since 2012. The KGCB has distributed approximately 1,883 specimens to many other researcher both at home and abroad.

HSR-53 Korea Gynecologic Cancer Bank – eBiobank System

Kwon H. 1 2 Kim J. 1 2

1 Gangnam Severace Hospital, Seoul, Korea (the Republic of) 2 Gangnam Severance Biomedical Research Center, Seoul, Korea (the Republic of)

KGCB established eBIO BANK System for Integrated management in 2013. The eBIO BANK System of KGCB is a specialized database dedicated to standardization of work, systematization, automated search, researcher, the applicant for newly built apartments, controller's operation savings and thorough biospecimens management, management of clinical specimen position, collecting, storing, and distributing the histological images of human gynecologic cancer specimens. Human gynecologic cancers are extremely heterogeneous in histology and accurate histological classification of gynecologic cancer is the 1^st step for the biomedical research. The heterogeneity may be associated with the tumor's other important molecular and/or clinical characteristics. The researchers are provided with the images of the cancer specimen by the eBIO BANK System of KGCB, using a specified program. They can conveniently examine the histological features of various magnifications and/or get appropriate images for presentation. The eBIO BANK System of KGCB, linked to the main database system of KGCB, will be an important addition to the KGCB's function as the research supporting system.

We can obtain the effect of KGCB's increased external recognition also strengthening competitiveness through this system.

HSR-54 The Scope of Characterization of HIV-2-Sera in Human Specimen Biorepositories

Cha Y. 1 2

1 Chung-Ang University Biomedical Research Institute, Seoul Korea, Korea (the Republic of) 2 Chung-Ang University College of Medicine, Seoul, Korea, Seoul Korea, Korea (the Republic of)

Backgrounds: While the availability of specimens of human immunodeficiency virus type 2 (HIV-2)-infected patients is essential for the validation of in vitro diagnostics, it is not easy to obtain because this type of virus is primarily found in the West Africa. Moreover, the diagnosis can be misleading because antibody cross-reactivity complicates differential diagnosis between HIV-1 and HIV-2 viruses. It is more likely in the resource-limited countries of West Africa because the diagnosis often depends on the two-rapid test diagnostic algorithm. We performed various HIV tests on the specimens of the patients who were diagnosed as HIV-2 infection in Togo to clarify the exact infection status and to characterize the antibody profiles.

Methods: The plasmas were collected and frozen from 17 patients diagnosed as HIV-2 in Togo and transported to Korea. The commercial assays for HIV-1/2 ELISA tests, rapid tests for HIV-1 and HIV-2 and western blot assays were performed on each of the specimen. Because there were no commercial kits available for RNA loading of HIV-2, a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) method was developed to differentiate between HIV-1 and HIV-2 infection.

Results: Among the 17 patients who were diagnosed as HIV-2 in Togo, we found that only 14 patients were truly HIV-2 infected and the rest of the patients were HIV-1 infected. The correct diagnosis could only be confirmed by western blot assays combined with RNA assays because there were strong antibody cross-reactivity between the two viruses in rapid test and/or immunoblot assay. The possibility of co-infection seemed to be very low because only HIV-1 RNA was detected in the three cases.

Conclusions: The scope of characterization of HIV-2-infected patient's specimens should be as extensive as possible to resolve the cross-reactivity with HIV-1 and to rule out the possibility of co-infection, especially for the accurate profiling of the antibodies. Further discussion for the minimum requirement of HIV-2 specimen's proper characterization will be required.

HSR-55 Accessing Large European Prospective Cohorts through the Transnational Biobanking Infrastructure BBMRI-LPC

Törnwall O. 1 2 Johansson M. 3 Simell B. 1 Brennan P. 3 van Ommen G. 4 Perola M. 2 1

1 Institute for Molecular Medicine Finland, FIMM, Helsinki, Finland 2 Dept of Health, National Institute for Health and Welfare, Helsinki, Finland 3 International Agency for Research on Cancer, Lyon, France 4 Leiden University Medical Centre, Leiden, Netherlands

Background: The research of human disease etiology and evaluation of pre-diagnostic biomarkers is dependent on the collections of biospecimens, lifestyle information and prospective clinical data. In 2013, an EU funded multinational BBMRI-LPC project (Biobanking and Biomolecular Resources Research Infrastructure – Large Prospective Cohorts) was established in mission to facilitate networking, harmonization and access to samples and data available in the large follow-up studies in Europe. BBMRI-LPC unites prospective study sets from 17 countries with 20 different cohorts involving over 1 million study participants. The infrastructure, progress and main accomplishments of the BBMRI-LPC project are presented in this work.

Methods and Results: To achieve its objectives, BBMRI-LPC provides solutions for fair transnational access to samples and data in the European prospective cohorts. Currently, improved harmonization of individual data on lifestyle, environmental and other exposure factors as well as establishing the unified definitions for clinical endpoints are on-going. A web-based cohort catalogue has been established enlisting the BBMRI-LPC sample collections available for access, including 2 EU-wide biobank networks and 18 country specific cohorts. Three open scientific calls aimed for investigators in the EU and associated states have been planned in the course of the BBMRI-LPC-project (ends in Feb 2017). After each call, successful study proposals are selected based on their significance, excellence, innovation, study design and research environment by a competitive peer-reviewed procedure. Successful projects are offered financial support for covering the costs of access and possible data upgrading (genotyping and omics analysis). The 1^st BBMRI-LPC call open from April to July 2014 was targeted to the broad field of common chronic diseases. In total, 9 proposals were received of which 4 focusing on cancer, cardiovascular disease and metabolomics were approved. The 2^nd BBMRI-LPC call is planned to be released in March 2015 and the 3^rd in the autumn of 2015.

Conclusions: In order to map the cohort specific access operations and to determine the bottlenecks and refinement needs, BBMRI-LPC closely monitors and records the call procedures. Based on this, Best Practice for Transnational Access will be established to benefit the future research infrastructures in Europe. Thus, the main deliverable of the BBMRI-LPC will be the improved access process itself.

HSR-56 Strategic Valorization of Normal Breast Cancer Biospecimens and Data to support Biopharmaceutical Research

Mathieson T. 1 Ball L. 2

1 Indiana University Komen Tissue Bank, Indianapolis, Indiana, United States 2 Biostorage Technologies, Indianapolis, Indiana, United States

The Susan G. Komen Tissue Bank at the IU Simon Cancer Center, (KTB), is dedicated to the collection of normal, healthy breast tissue cores and matching blood products from women without breast cancer. To date the KTB has collected breast cores and blood samples from over 4200 healthy volunteer donors. These biospecimens are collected with strict adherence to SOPs and include comprehensive medical annotation and are sent worldwide to researchers who are unravelling the biological implications and causes of breast cancer.

De-identified raw data from much of the breast cancer research involving the normal breast tissue core and blood products samples has been returned to the KTB and is housed on the KTB Virtual Tissue Bank. This Virtual Tissue Bank is made available to investigators to allow them to access data which has already been elucidated from KTB samples.

Pharmaceutical companies, with the power of their research teams and drug pipelines could well benefit from the knowledge housed in these truly normal breast samples, (as opposed to reduction mammoplasty and adjacent normal). It is the vision and plan of the KTB to be partnering with biopharmaceutical companies to provide the normal breast cores and/or blood products for use in breast cancer research.

The presenter will provide a discussion on:

- Reaching out to Pharmaceutical companies to cultivate interest and a mutually beneficial partnership in breast cancer research.

- Increasing the awareness of and encouraging the use of KTB biospecimens while emphasizing the high quality of the samples due to collection and storage methods.

- The content, value, and benefits of the Virtual Tissue Bank, which holds raw data generated from experiments using KTB samples as well as tissue images and tissue donor annotation.

Gains in pharmaceutical research into breast cancer treatment could be greatly hastened by the use of the normal breast cores and blood products housed at the Komen Tissue Bank at Indiana University. Agreements concerning sample use and return of raw data to the Virtual Tissue Bank could to be negotiated in such a way that research in breast cancer is propelled forward and treatment and prevention options are expedited to reduce breast cancer's impact on society.

HSR-57 Banking on Success for Precision Medicine

McQuaid S. 1 5 Peter H. 2 Salto-Tellez M. 2 3 Clark P. 4 James J. 1 2

1 Northern Ireland Biobank & NI Molecular Pathology Laboratory, Queen's University Belfast, Belfast, United Kingdom 2 Centre for Cancer Research & Cell Biology, Queen's University Belfast, Belfast, United Kingdom 3 Northern Ireland Molecular Pathology Laboratory, Queen's University Belfast, Belfast, United Kingdom 4 Northern Ireland Biobank, Queen's University Belfast, Belfast, United Kingdom 5 Tissue Pathology, Belfast Health & Social Care Trust, Belfast, United Kingdom

Background: Biobanking high quality, human tissue samples is recognized as the cornerstone of biomarker discovery and validation. A comprehensive program in molecular pathology and precision medicine should consist of four core components: molecular diagnostics, molecular translational research, digital pathology and biobanking. Integrated services bring benefits for healthcare providers, academia and industry by resource sharing, increased clinical and academic collaboration and technical staff with ‘hybrid’ expertise in clinical activities and research. Biobanks provide a regulated infrastructure for standardized collection of well annotated tissue samples required for biomarker studies undertaken within molecular pathology programs.

Methods and Results: The Northern Ireland Biobank (NIB) is an integral component of the molecular pathology and precision medicine program at Queen's University Belfast (QUB). NIB is functionally aligned with the Northern Ireland Molecular Pathology Laboratory (NIMPL); the capabilities provided as a result cut across conventional biosample procurement, tissue microarray construction, tissue-based hybridization, comprehensive nucleic acid extraction protocols, single-biomarker or PCR-based and high-throughput technologies (including next generation sequencing and gene profiling) with all activities operating to strict quality standards of clinical molecular diagnostics. Digital pathology facilities create digital archives of samples with in-house expertise in image analysis and computer vision technology. Algorithms for pattern recognition are being developed to support and accelerate biomarker discovery and improve the reliability of precision medicine. NIB can tailor collection protocols and help to optimise critical pre-analytical processes such as nucleic acid extraction procedures to facilitate high throughput downstream analyses. In response to the changing face of molecular pathology and translational research requirements NIB can provide samples for detection of circulating tumor cell or DNA, production of primary cell lines or fresh tissue for preclinical ex vivo models

Conclusion: The integrated nature of the Molecular Pathology and Precision Medicine Programme due to alignment of NIB with NIMPL has established an ideal framework for delivery of an unparalleled research program with highly trained staff interchangeable between research and diagnostics to transform the landscape of modern clinical care.

HSR-58 9 Years of Connecting Swiss Biobanks - Towards a Swiss Biobanking Platform

Warth R. 1 Perren A. 2 1

1 Foundation Biobank-Suisse, Bern, Switzerland 2 Institute of Pathology, University of Bern, Bern, Switzerland

The foundation biobank-suisse (BBS) is a collaborative network of biobanks in Switzerland. Since 2005 the network works toward bringing Swiss biobanks together in one platform. The main goals are to support Swiss biobank managers and facilitate for research access to human biospecimens. The BBS foundation will end its operations in 2015 and hand over the main activities to the newly formed Swiss Biobanking Platform.

In a final step the foundations analyzed all projects and documented their outcome. The main focus was on harmonization of standards and the creation of a central database making information about biospecimens available for researchers. The foundation also analyzed business models to sustain financing of biobanks.

Harmonization - The foundation supported the development of nationwide templates for informed consent and patient information for biospecimens, and biobank regulation. The templates are designed to be used in Switzerland and translated in French, German, Italian, and English.

Database – In November 2012 the BBS database contained information about 85000 specimens (80% fresh-frozen, FF) from 35000 patients. The specimens originate to 98% from the Institutes of Pathology in Basel, Bern, and Lausanne collecting FF specimens since 1984, 2003, and 1993, respectively. The database is accessible for research over a web-based interface.

Sustainable Financing – The foundation provides a business model based on revenues collected by the national healthcare system. The model serves to study the financial feasibility and identifies customer segments.

The foundation's activities were financed by private donors, who had the vision to accelerate translational research by connecting biobanks. With the creation of a publically financed Swiss Biobanking Platform including the six largest Swiss research hospitals, the donor's vision has found strong support. The experience gained by the Foundation biobank-suisse in last 9 years shall be a good source of inspiration for the new platform.

HSR-59 Enabling Epidemiological Research by Biobanking of Human Endothelial Progenitor Cells

Kinev A. V. 1 Vershinin V. 2 Il'yasova D. 3

1 Creative Scientist, Inc., Durham, North Carolina, United States 2 Institute of Natural Sciences, Ural Federal University, Yekaterinburg, Russian Federation 3 School of Public Health, Georgia State University, Atlanta, Georgia, United States

Creative Scientist, Inc. develops cell-based assays to assess functional effect of drugs and environmental stressors at a population-wide scale. In this presentation, we will demonstrate the value of population-wide collection of CD31⁺/CD34⁺ circulating endothelial progenitor cells, also called endothelial colony forming cells (ECFCs). ECFCs possess qualities necessary for their successful biobanking and can subsequently be used in the development of high-throughput and high content assays. Specifically, ECFCs show > 90% viability after cryopreservation, robust growth for more than 60 population doubling after the storage, and a responsiveness to a variety of environmental stressors, i.e., ionizing radiation, heavy metals (cadmium), and endocrine disruptors (Bisphenol A).

To enable population-wide analysis of ECFCs' response to environmental stressors we initiated a collection of donor-specific cord blood-derived ECFCs. For this purpose, we adopted a standard operational procedure, which affords (a) successful ECFCs' isolation from small volumes of blood, (b) efficient cell expansion in culture, and (c) high density cryopreservation with a minimal loss of cell viability. We started the biobanking of our first population-wide collection at the School of Public Health at Georgia State University (Atlanta, GA, USA). Our second ECFC collection will be established at the Institute of Natural Sciences at Ural Federal University (Yekaterinburg, Russia). Once established, these collections will help to assess: 1) functional effects of environmental stressors in newborns and pregnant women; 2) effects of early exposure to environmental stressors on developmental and chronic diseases; and 3) the extent of vulnerability of certain population groups to biohazards. The proposed collection of ECFCs will be associated with donor's medical information; it is also intended to reflect population diversity. This presentation will discuss overall logistics of establishing a cell-based biobank as well as biological, medical, and ethical aspect of ECFC biobanking.

HSR-60 Successful Use of Banked Research Biospecimens for Molecularly Driven Clinical Trials

Pasquale N. Amin N. Chadwick D. Roehrl M. H. University Health Network, Toronto, Ontario, Canada

Background: Demand for tissue for enrollment in molecularly driven clinical trials and associated correlative studies is increasing. Since 2001, solid tumor, normal and other diseased tissue has been comprehensively banked for research purposes from excess surgical tissue at Canada's largest academic hospital system, University Health Network (UHN). The purpose of this study was to determine the success rate of fulfilling clinical trials requests using research tissue banked in the UHN Program in Biospecimen Sciences.

Design: Clinical trials requests received from the Correlative Studies Program and other Clinical Trials coordinators at UHN from January, 2012 and December, 2014 were evaluated. Data collection included request date, study name, number of requests received, disease site, tissue requirements, whether banked tissue was available, whether it was deemed suitable by the study pathologist, and, if not banked or suitable, the reason why.

Results: Since 2012, all solid tissue requests for clinical trials have been made to the Program in Biospecimen Sciences. Over the two year study period, there were 1448 requests for tissue. Banked tissue was deemed suitable by the study pathologist for 618 (42.6%) requests received. The main reason that banked tissue was not used was because it was not available. The main reasons for not banking were that the requested tissue was from a clinical biopsy, the tumor was too small, the request was from a disease site that was not banked by our Program (neurological lesions), the surgical specimen came in after hours, or there was only frozen tissue available.

Conclusion: Nearly half of all clinical trial requests for solid tissue at UHN may be fulfilled using research specimens banked from excess surgical tissue. Identifying the reasons that banked tissue is not available will help identify ways to improve research tissue banking rates. Participation in molecularly driven clinical trials represents a valuable opportunity to utilize research biospecimens, preserve tissue in the clinical archive, develop multidisciplinary collaborations and provide revenue to help sustain hospital based biospecimen sciences programs.

HSR-61 Building Shanghai Cancer Biobank Platform for Research

Sun M. 1 Chen H. 1 Qin G. 1 Gu Y. 1 Zhang Z. 1 Ding F. 1 Ni S. 1 Jin H. 2 Xu C. 2 Wu J. 3 Chen H. 3 Li K. 4 Zheng J. 5 Ding G. 5 Xiao J. 6 Wang J. 6 Dai K. 7 Wang J. 7 Zhong L. 7 Zhang J. 8 Yu K. 8 Zhang P. 9 Zhao Y. 9 Wang H. 10 Du X. 1

1 Pathology, Fudan University Shanghai Cancer Center, Shanghai, China 2 Ob&Gyn Hospital Fudan University, Shanghai, China 3 Huashan Hospital, Fudan University, Shanghai, China 4 Zhongshan Hospital Fudan University, Shanghai, China 5 Changhai Hospital of Shanghai, Shanghai, China 6 Shanghai Changzheng Hospital, Shanghai, China 7 The Ninth People's Hospital of Shanghai Jiaotong University School of Medicine, Shanghai, China 8 Shanghai Chest Hospital of ShanghaiJiaotong University School of Medicine, Shanghai, China 9 Shanghai Pulmonary Hospital, Tongji University, Shanghai, Shanghai, China 10 Children's Hospital Fudan University, Shanghai, China

The Shanghai Cancer Biobank Network is composed of 10 hospitals, including Fudan University Shanghai Cancer Center, as project leader hospital; Huashan Hospital Fudan University; Zhongshan Hospital Fudan University; Obstetrics and Gynecology Hospital of Fudan University; Children's Hospital Fudan University; Changhai Hospital of Shanghai; Shanghai Changzheng Hospital; The Ninth People's Hospital of Shanghai Jiaotong University School of Medicine; Shanghai Chest Hospital of Shanghai Jiaotong University School of Medicine; Shanghai Pulmonary Hospital, Tongji University, Shanghai. Each hospital has specific tumor types reflecting their clinical major tasks. Almost all types of common and uncommon malignant tumors are available in this Network. A web site is designed to open all the information needed for potential projects requesting sample. After two years consummating, general standardized SOPs and IC were shared, and relevant training courses were given to the managers and technicians within network. Up to date, samples in this network from 12,500 patients are available for research use. Parallel sample access has reached 12,300 vials for scientists from various research fields. Next, the network will serve as a public biobank platform for cancer research need, nationally and internationally.

HSR-110 A Skin Tissue Oriented Biobank Supporting Disease Research in Dermatology

Beleut M. 1 Seclaman E. 2 Solovan C. 1 Baudis M. 3

1 Dermato-Venereology, University of Medicine and Pharmacy “Victor Babes”, Timisoara, Timisoara, Romania 2 Biochemistry, University of Medicine and Pharmacy “Victor Babes”, Timisoara, Timisoara, Romania 3 Swiss Institute of Bioinformatics, Institute of Molecular Life Science, University of Zurich, Zurich, Switzerland

Background: Biobanks of patients' tissue specimen, corresponding blood samples and associated clinical data are increasingly recognized as major assets in clinical diagnostics and biomedical research. Here, we present the first biobank of skin tissue samples in Romania, established in the frame of a recently funded Swiss-Romanian research program.

Methods: The biobank includes fresh frozen material (skin tissue), extracted genomic DNA, fractionated blood samples and formalin fixed paraffin embedded specimen, supported by an exhaustive database, with focus on skin inflammatory and neoplastic diseases. At present, the fast growing collection contains 187 samples, with full donor authorization (informed consent), based on sufficient information and adequate understanding of both the proposed research and the implications of participation in it, and ethics committee approval for use in research activities. We aim to collect and process participant samples as quickly as possible. Tissue samples consist of biopsy specimens obtained surgically. The samples are collected in clinic setting and the blood is processed within a few hours by local laboratories before low-temperature archiving. For the tissue samples, there is no delay between collection and cryopreservation at −80° C, so that the loss of labile species in the samples does not occur. Our project aims to support external participants both in archiving submissions and through providing material for research studies.

Results: In an accompanying research study performed in collaboration with the University of Zürich, we aim to identify DNA aberrations and gene expression changes typical for different, previously understudied cutaneous pathologies. Another goal is the identification of circulating biomarkers as therapy-responsive and/or therapy-monitoring factors as well as for disease (sub) classification.

Conclusions: We expect our project to both have immediate impact on local, personalized medical care services, as well as on research efforts aimed at diagnostic tool development and the identification of candidate molecules for targeted therapies.

Repository Automation Technology

RAT-62 An Automated Laboratory Workflow for Stool DNA Extraction

Gorman J.A. 1 Erbsen J.S. 1 Harrington S.C. 3 Zschunke M.A. 1 Ice J.L. 3 Nelson M.B. 1 Oldfield K.A. 1 Root J.A. 1 Bolster J.M. Summer 1 Highsmith W.E. 1 2 Thibodeau S.N. 2 Chia N. 3 Cicek M.S.I. 2

1 Biospecimen Accessioning and Processing Laboratory, Biorepository Program, Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA. 2 Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA. 3 Microbiome Program, Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA.

Background: The number of DNA samples tested in research protocols have been exponentially increasing and expanding to sample types other than tissue or whole blood. The ability to perform automated DNA isolation from stool samples and perform microbial genome analysis has become an important service within the biorepository and research space.

Methods: The Mayo Clinic Biospecimens Accessioning and Processing (BAP) laboratory is implementing an automated workflow incorporating instruments and software for accurate and timely DNA extraction from stool. The BAP laboratory utilizes a Perkin Elmer Janus liquid handler for accurate aliquoting of stool lysates that are generated using a FastPrep-24 5G bench top homogenizer. DNA is extracted from the stool lysates using the chemagic MSMI instrument and aliquoted into robotic friendly tubes. DNA samples are analyzed for quality and quantity prior to storage in a robotic freezer. Stool samples from ten subjects were aliquoted in quadruplicate for comparison to the MoBio Power Soil DNA Isolation Kit. Stool DNA was amplified targeting V3 and V5 regions of the bacterial 16S subunit and was purified using Agencourt AMPure XP magnetic beads prior to sequencing on a MiSeq instrument.

Results: Implementing an automated solution for stool DNA isolation allows for higher throughput and a more controlled processing environment, leading to better quality control. Genomic DNA recovery from both methods of DNA extraction yielded similar results between methods for each sample analyzed. DNA recovery from 150 mg of stool varied between 10 ng and 5 ug across subject samples. Yields of 16S library prep also show very similar yields between both methods of DNA isolation.

Conclusion: Utilization of automated laboratory systems is a key requirement for a biorepository laboratory. Automation improves throughput, quality, and the efficiency of the laboratory. By minimizing the number of manual processes, specimen integrity remains at its highest.

RAT-63 Standardized Workflow for Bio-Material Requests:

van Iperen E. 1 van Enckevort D. 6 Hulsen T. 4 van Duijn W. 3 van der Reijden J. 3 Terpstra F. 5 Verspaget H. 3 Boiten J. 2 Lansberg P. 2

1 Durrer Center for Cardiovascular Research, Amsterdam, Netherlands 2 CTMM, Eindhoven, Netherlands 3 PSI, Leiden, Netherlands 4 Philips, Eindhoven, Netherlands 5 UMCU, Utrecht, Netherlands 6 University Medical Center Groningen, Groningen, Netherlands

Background: The exchange of samples from biobank/lab to researcher or from hospital/lab to biobank is traditionally administered through e-mails, fax or telephone. This approach lacks a proper track-and-trace and audit trail of specimens, impeding a fast recovery of lost samples. In close collaboration with the Parelsnoer Institute (PSI)*, the TraIT (Translational Research IT) Workflow for requesting and distributing samples was developed. This workflow supports all process steps typically needed in a sample workflow: request of bio-materials from a specific biobank, evaluation and approval of a request, track and trace of the sample during shipment.

Methods: The workflow tool has been developed in collaboration with CSC using the OpenText Business Process Modeling (BPM) platform in a use-case driven approach. The design was based on the rules and recommendations outlined in the existing PSI biobanking protocols and SOPs. The various steps in the workflow are implemented as separate building blocks, and can be customized to the specific needs of any organization or multi-center collaborative network with biobank activities.

Pilot tests were performed in the PSI platform and the PCMM (Prostate Cancer Molecular Medicine) study. End-users from these two evaluated the workflow tool with simulated sample requests. Additionally the Workflow tool was assessed in parallel with the non-automated workflow procedures (telephone, mail, email) using a real-life DNA-sample request from the PSI CVA (Stroke)-Pearl.

Results: The workflow was developed as a cloud based solution to monitor requesting, dispatching, collecting and processing bio-specimens from collections under full control of audit trails. Time constraints can be set and attachments can be added at every step in the workflow (eg. Material Transfer agreement, project proposal). The tool is now hosted in a production environment (Vancis) and is actively used in TraIT projects as well as the PSI platform.

Conclusions: A methodized cloud based workflow application for requesting, dispatching and collecting bio-materials from collections enables the users to work according to a standardized process, improving quality, reliability and accountability. Every process step is logged and location and/or status of the sample can be monitored at any point in the sample exchange process. Phone calls, fax and e-mails, used in the traditional sample logistics workflow, can be eliminated or at least greatly reduced.

Repository Management

RM-64 Development of a Central, Institution-wide Biorepository Emergency Response Plan

Horne E. Sieffert N. Hoover T. Biorepository Regulatory Support, MD Anderson Cancer Center, HOuston, Texas, United States

Background: MD Anderson Cancer Center has maintained a large collection of human research tissue through a federated system that includes an Institutional Tissue Bank (ITB) and more than 28 satellite banks (specialty banks organized by organ or histology that contribute to the ITB) for decades. Hundreds if not thousands of additional departmental and individual investigator-directed biospecimen collections have also existed within this environment, without previous benefit of a central biorepository emergency response plan (CBERP). This placed the institution and its resources at significant risk for loss or damage. Access, retrieval and dissemination of applicable policies, procedures, best practices and internal resources required to create such a plan is difficult. The process requires extensive knowledge, time, training, and can be grossly inefficient. MDACC Biorepository Regulatory Support (BRS) successfully developed and integrated a comprehensive CBERP to fulfill this need.

Methods: Biospecimen-related best practices were integrated with institutional operations and infrastructure (e.g., Environmental Health & Safety, Human Resources, Facilities Management) with the goal to consolidate information and create a comprehensive, central plan for biorepository emergency response planning and management. The collective experience of the biorepository community and internal BRS staff along with key satellite bank partners was also considered, and was crucial in development of this central plan. Next, recognizing that each bank has unique needs, a user-friendly template was created which allowed individuals to customize a plan to fit their needs, while ensuring minimum CBERP requirements were met. The CBERP will be implemented as a pilot within the ITB, followed by implementation across all satellite banks. The final objective will be to adopt the CBERP as institutional policy.

Results: SOP implementation is in progress and policy development is pending. Developments will be shared at the ISBER Annual Meeting.

Conclusion: Implementation of a CBERP is key in ensuring optimal disaster prevention, preparedness, emergency management and recovery of biorepository resources. The protection of biospecimens is not only the responsibility of BRS staff, but that of the institution. Institutions of any size can learn from this model and benefit by merging and aligning departmental functions to create an emergency response plan.

RM-65 Leveraging Technology to Power Biological Sample Intelligence and Research Decision Making

Hart R. 2 Ball L. 1

1 Chief Operating Officer, BioStorage Technologies, Indianapolis, Indiana, United States 2 Director of Technology Solutions, BioStorage Technologies, Indianapolis, Indiana, United States

Having a flexible data integration platform is key to optimizing biospecimen collections and advancing research. Reductions in research funding have made biological samples even more valuable assets to researchers. To leverage the value of these assets, it is important to understand the location of the biospecimen, quality level, donor characteristics, consent status, and to match the biological sample with its respective clinical data in order to fully optimize the sample for future research.

The presenter will provide a case study on data virtualization utilizing a cloud-based platform that is applied to global biospecimen samples. This strategy can lead to more streamlined and integrated biological sample intelligence and improve drug discovery and development time, provide faster solutions, and increase the flexibility in how research and clinical information is delivered. Specific topics to be covered include:

1) the benefits of connecting multiple data networks into a single, secure and easily accessible system

2) how improved sample intelligence can lead to more efficient drug discovery and development

3) the potential cost-savings gained from the integration and virtualization of sample data

4) strategies for expanding sample visibility to improve research sample optimization.

This innovative technology solution has the potential to shorten research timelines, reduce research costs by improving laboratory workflow processes, enhance faster research decision making, and optimize the value of research assets for biopharmaceutical academic and non-profit research.

RM-66 Purchasing Database Software for Implementation into a Biobank

Raymond E. Wesley Research Institute Tissue Bank, Brisbane, Queensland, Australia

After reviewing 16 database options for Biobanking, FreezerPro, by Ruro was purchased in August 2013. Implementation of system began immediately with the data entry of patient and samples information of the past 7 years. In January 2014, FreezerPro has become part of the standard process for the Ventyx Wesley Research Institute Tissue Bank.

RM-67 Can You Characterize Samples in Your Biobank? Sample Annotation Approaches

Wang W. Wu M. Zhou G. Wu Y. Zhao L. Weng X. Key Lab of Environmental and Children's Health, Xinhua Hospital Affiliated to School of Medicine Shanghai Jiaotong University, Shanghai, China

Biological sample without comprehensive description of its characteristics holds little value. Biobanking resource forms the necessary infrastructure for high-quality research, which requires well-annotated samples with associated data. Annotation is to label, index or categorize samples uniquely to target research questions for searching and retrieving resource specifically. Clearly the value of biobanks is not just determined by the quality of the banked samples, but also by the quality of associated data.

Biobanking in China have rapidly accumulated a wealth of biological samples. However one of biggest challenges we face is lacking enough data for annotation, while another challenging issue is heterogeneity of sample annotation across biobanks. We take two different annotation approaches to address these two issues: for cohort study-based sample annotation, it is decentralized collection from multiple hospitals/biobanks, but a well-designed questionnaire is available to guide data collection in a standard format, we thus focus our annotation on data quality review, comparative analysis and evaluation to reduce heterogeneity of annotation across biobanks. Whereas for disease-orientated collection, data setting and quality varies with clinical departments, we focus clinical annotation on disease-specific approach to maximize the availability of clinical data.

We have built a comprehensive workflow for collection and quality management to harmonize collection for birth cohort studies. Data elements and datasets are defined mainly to label and index the samples to be retrieved as batches of samples and/or donors for epidemiological study. Given the differing data elements and formats for clinical annotation, we define data elements and datasets specific to each type of disease and clinical presentation, and lab value as well. The clinical annotation thus mainly aims in helping researchers to retrieve samples and/or subjects by cherry picking method in a more individualized manner of searching and retrieving. We have proved they are workable and best practice approaches in our biobanking practice for sample annotation based on different source. Annotation of sample in this research was supported by STCSM funding (Grant No. 13430710300).

RM-68 An Update on the Evolution and Growth of a Federated System of Repositories at the University of Iowa

Galbraith J. Knudson C. Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States

The years 2013 and 2014 saw the creation of a Federated Biorepository System at the University of Iowa (UI) from a disconnected set of independent facilities. With many early challenges to overcome including the need to win acceptance of the concept and increase utilization, the approach has reached sufficient critical mass to ensure this system will continue to expand.

The Tissue Procurement Core (TPC) acts as a shared facility that interfaces with Pathology, collects and stores specimens, performs QA and distributes specimens for the various repositories across the federation. The tissue specific repositories in the Cancer Center focus on consenting patients, keeping clinical information updated and providing oversight and approval of all research projects using tissues under their IRB approved protocol. This structure allows for customization for each repository while taking advantage of the efficiencies of a centralized process for tissue collection and distribution. The implementation of a common information system further supports this structure and has led to significant standardization of data collection and workflows. The Federated system has promoted “best practices” and largely eliminated redundant efforts for specimen collection and subject consent. The Federation has contributed to NIH programs like TCGA and PDX and has dramatically expanded local utilization of tissues. As one example, the number of cases distributed has grown nearly 400% over the past 2 years while the number of specimens distributed has gown nearly 1500%.

Success of a Federated repository system depends on more than just shared facilities, protocols, communication and informatics; it requires a fundamental paradigm shift and buy-in from leadership within the individual repositories and across the institution. At the UI we have primarily used the positive aspects to garner participation in the Federation but have also used fees as an incentive on occasion (one example is a fee for collection by Surgical Pathology instead of the TPC). The federation continues to evolve and has provided opportunities for enhanced communication, improved efficiency, and expanded teamwork across the formerly dissociated repositories. The presentation will define the current state of the model, discuss the success to date, and pave a pathway through the challenges ahead with an emphasis on sustainability.

RM-69 The Garvan Query Application (GQA): A Comprehensive Search Engine for a Prostate Cancer Biorepository

Tiwari S. 1 Haynes A. 1 Nguyen Q. 1 Hammond G. 2 Kench J. G. 3 1 Horvath L. G. 4 1 Stricker P. D. 5 1

1 Prostate Cancer Research Program, The Kinghorn Cancer Centre/Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia 2 Information Technology, Garvan Institute Of Medical Research, Darlinghurst, Sydney, New South Wales, Australia 3 Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, Sydney, New South Wales, Australia 4 Medical Oncology, The Chris O'Brian Lifehouse, Royal Prince Alfred Hospital, Camperdown, Sydney, New South Wales, Australia 5 St Vincent's Prostate Cancer Center, Darlinghurst, Sydney, New South Wales, Australia

Introduction: CanSto is an in-house bioresource and clinical information database developed by the Garvan Institute of Medical Research, Sydney Australia. It incorporates SPREC (Standard PREanalytical Code) to collate clinical and tissue specimen information on men with prostate cancer. In order to extract clinical and scientific information on over 13,000 men from CanSto, the Garvan Query Application (GQA) was developed. While most databases can only house clinical or biospecimen data, CanSto along with GQA can link these two subsets of information for precise clinico-pathological data. Researchers can ask questions against the CanSto dataset by creating simple or complex query language statements using GQA.

Methods: CanSto consists of six components: patient's clinical information, biospecimen data, reports, arrays, slides and biomarker data. Each component contains unique descriptive datasets, such as treatment history and tissue microarray information. GQA can link these datasets together to produce a table containing the desired information, using SQL (Structured query language) queries. Pre-defined reports/syntax can be used to generate reports for monthly statistics, quality assurance or other common queries and upload data from other databases into CanSto by matching data fields together. It also has the ability to export data from CanSto into a spreadsheet format for further statistical analysis or for other reporting purposes.

GQA has security measures in place that can limit access to confidential information based on the ethical approval agreement and research methodology for each study.

Results: GQA enables researchers to retrieve the desired information from CanSto. It allows the comparison of clinical information with scientific findings obtained from the collected tissue specimens. For example, GQA has matched clinical information with pathologically confirmed cancer containing tissue samples for coring in biomarker discovery. It is also an effective tool to audit for quality control, ensuring completeness of data, to upload mass data, to view editing history and to extract data.

Conclusions: Prostate cancer research aided by CanSto and GQA has resulted in over 80 peer-reviewed publications since its establishment in 1994. The publications have ranged from clinical studies, epigenetic findings, predicting treatment outcomes using novel biomarkers and imaging techniques for prostate cancer diagnosis.

RM-70 Sustainability Metrics in a Cancer Oriented Biobank: Number of Research Projects Requesting Samples, and Value of Research Grants

Campos A. H. Carraro D. M. Soares F. A. Martins V. R. A.C. Camargo Cancer Centr, Sao Paulo, Sao Paulo, Brazil

Background: The A C Camargo Biobank (ACCB) is a 17 year-old Brazilian biobank that provides tissue, blood and macromolecules for cancer research. Over the years, the ACCB has been funded by institutional grants awarded by The State of São Paulo Research Foundation (FAPESP) and the National Counsel of Technological and Scientific Development (CNPQ), by direct investments from the A C Camargo Cancer Center and by cost recovery taxes charged to investigators. Performance metrics are reported annually to assess the value and impact of the ACCB.

Methods: We chose one traditional metric (number of research projects requesting samples) and propose a new one (value of research grants obtained by such projects) to assess the value and impact of the ACCB between 2010–2013. The number of research projects requesting samples was extracted from the ACCB Management System (“Biobank”). Each project was counted only once in each year regardless of the number of times it requested samples, and cross-checked with data from the Institution's Project Submission System (“AcProjects”) and from the Institution's Office of Research and Project Administration.

Results: The number of projects requesting samples to the ACCB increased from 36 in 2010 to 109 in 2013. Overall, they were granted R$ 8,712,356.60 (US$ 3,484,942.64) that were used to purchase material and consumables, equipment, third-party services, costs for transportation and maintenance of activities associated with the project, scholarships, and to cover biobank user fees.

Conclusions: Attention has been given to the different dimensions of biobank sustainability. These dimensions are interconnected and successful sustainability involves a balance between them. The number of projects requesting samples is a useful performance metric (in terms of usability) not only in the economic dimension, but also in the operational and social dimensions. Additionally, since these projects were able to be carried out because they could access samples and annotated data retrospectively, the value of research grants given to projects should also be used as a performance metric of the biobank (even if considered an indirect one). These grants, although not totally invested in the biobank, support important research and training of new researchers, justifying ongoing support from the institution and funding agencies to the biobank.

RM-71 Building an Online Catalog to Standardize and Centralize the Knowledge Base of a Diverse Group of Unique Historical Biospecimen Collections: The NHLBI BioLINCC Program Approach

Adams J. 1 Giffen C. A. 1 Krzystan J. 1 Shea K. 2 Carroll L. 1 Wagner E. 3

1 Information Management Services, Inc., Calverton, Maryland, United States 2 Precision Bioservices, Inc, Frederick, Maryland, United States 3 National Heart, Lung, and Blood Institute, Bethesda, Maryland, United States

Background: The National Heart, Lung, and Blood Institute (NHLBI) established the Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC) to provide online access to its biospecimen and data repositories. Biospecimens stored in the NHLBI Biorepository are linked to their phenotypic data in the Data Repository and made available online through study-specific webpages that provide information on the study, the biospecimen handling, and the material types available. However, each collection also has supplemental information that is used internally for biospecimen management and in determining whether or not requested biospecimens are fit-for-purpose. This information was located in internal archival documents and institutional memory, making access and upkeep inefficient. To address these issues, an online Catalog for public and private use was developed.

Methods: A Catalog structure with permission-based access to its contents was designed. README files related to each collection, developed during the linkage process, were expanded to include observations and issues encountered during requests. References generated upon specimen intake included information on site collection and storage processes, vial labeling and vial images. These were supplemented with observations and information produced during request fulfillment and QC efforts.

Results: The Catalog structure improved both access and maintenance of biospecimen data. Each collection entry includes a public section which displays basic study information and design, including dates, keywords, NHLBI Division and contact, site information and protocol précis, etc. Additional sections include tabulations of biospecimen types by subject characteristics and visits; biospecimen collection/processing methods and other vial characteristics; vial labeling and other observations; aliquoting schemes; summary Biorepository QC assessments; and observations by BioLINCC analytic staff on key data fields in both the clinical and inventory data.

Conclusions: The BioLINCC online Catalog efficiently provides useful supplemental information to external researchers, but also meets its primary purpose of centralizing the knowledge base across a highly diverse group of unique historical collections in a consistent manner for internal NHLBI, BioLINCC, and Biorepository staff. The Catalog design provides an example of an accessible online method to efficiently maintain reference materials.

RM-72 A Model to Estimate Biobank Inventory Requirements for Canadian Cancer Research

Meredith A. J. 1 Slotty A. 1 Babinszky S. 2 Matzke L. A. 1 2 Watson P. 1 2

1 Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada 2 BC Cancer Agency, Victoria, British Columbia, Canada

Background: In the field of cancer research, 40% of publications report the use of human biospecimens, and many of these are derived from tumor biobanks. Ensuring an adequate supply of such banked samples that are well-annotated and associated with long term outcomes data will be critical in supporting current and future cancer research studies. However, maintaining biorepositories with ongoing and standardized specimen accrual is highly resource intensive. Specimen accrual that does not consider research demand may result in large reserves of underutilized biospecimens that are collected at great expense. This concern is particularly salient for funders who increasingly hesitate to support biobanks, further accentuating long-term sustainability issues. To assess the potential disparity between biospecimen supply and demand, and optimize resource allocation, we have developed an inventory target calculator.

Methods: The inventory target calculator is designed to model tumor biobank utilization and help establish appropriate biospecimen stock targets. Our model incorporates publicly available data on national levels of investment in academic cancer research in Canada, relative to research use of cases described in the publication output of funded investigators. This data is scaled to the regional context of the British Columbia Cancer Agency Tumour Tissue Repository (TTR) by integrating local specimen release and sample utilization data to adjust for the primary intended user base for the biobank. The data is then transformed into projected stock targets by adjusting for several variables intrinsic to biobanking operations and case accrual. These include specimen quality, case reuse, and research selection factors.

Results: Based on our calculator we can now estimate a current stock target of 4500 cases for the TTR, and adjust the relative proportions within the portfolio of cases from different tumor sites, to better support local research needs.

Conclusions: We recognize that this initial model has a number of limitations; it requires extrapolation of research and biobank utilization data, and it does not incorporate biospecimen contributions within the context of a network. However, our calculator represents an important first step to more closely assess and align biospecimen accrual activities with research demand. Creating tangible inventory targets will improve biobank efficiency, sustainability, and may also encourage increased and stable funding.

RM-73 The Strategic Role of Management: Finding a Balance between Heterogeneity and Interoperability across Biobanks

Wang Y. 1 Chen H. 1 Wang W. 2 Guo W. 1 Qian L. 1

1 Shanghai Jiao Tong University School of Medicine, Shanghai, China 2 MOE-Shanghai Key Lab of Children's Environmental Health, Xinhua Hospital, affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China

Biobanking in China, like other parts in the world, faces many challenges. Multiple biobanks have been built within twelve hospitals affiliated to Shanghai Jiaotong University School of Medicine. These biobanks are mainly determined by the specific aims of a research group or overall aim without clear research directions. Operational standards in each biobank are mostly determined on its own. Biobanks are still in early developmental stages and young biobankers often lack skills and experience. Resource heterogeneity across the biobanks is thus unavoidable. Office of Research Management in School of Medicine plays a critical role to coordinate the development of biobanking and professionalism of operation to maximize biobank specimen value with maximizing interoperability of biobanking. However, it is not realistic to demand operational standards and procedures. We thus face a tradeoff between interoperability and heterogeneity. Our efforts turn out to contribute to finding a balance between heterogeneity and interoperability. We develop a stepwise strategy to push for the initial standardization in some aspects, but remain some heterogeneity in other aspects to facilitate realistic development objectives.

We have successfully achieved: (1) By strongly encouraging to implement the same biobank LIMS, we can unify the training and education procures and upgrade the functions to meet common demands; (2) Provide funding support for biobankers to conduct studies on sample stability, pre-analytical variable analysis, best practice to harmonize minimal workflow standards; (3) Establish minimal dataset for the disease diagnosis with lab value common to multiple biobanks; (4) Hold meetings to share challenges, experience and solutions; (5) Set up funding opportunity for clinicians to propose research that specifically requires utilizing banked specimens. Instead of focusing on peer-review publications, the requirements for successful accomplishment of a project must be reflected in biobanking LIMS to evaluate biobanking operation and management, also to perform an appraisal of biobankers' professionalism. In addition, it requires having research data returned to the biobank. We have proved successful procedure in this strategy and approach. We believe this approach has paved the way to further reduce heterogeneity and make it possible to harmonize more down the road (This project was supported by the National “985” Project).

RM-74 Economic Analysis of Position of Biobank Graz in the Research Landscape

Riegler S. Macheiner T. Story P. Bayer M. Sargsyan K. Biobank Graz, Medical University Graz, Graz, Austria

Background: High-quality biospecimens and associated structured data are pivotal for the progress of basic and clinical research in the field of medicine, biotechnology and pharmacy; however, most biobanks are public institutions with high costs. Therefore, long-term financing plays a crucial role in the establishment and maintenance of biobanks and as such, biobanks need to evaluate their economic position as in commercial enterprises. One of many useful tools for such analysis is the Boston Consulting Group (BCG) Analysis.

Method: The BCG analysis helps organizations allocate resources and it is used as an analytical tool in product management, strategic management, and portfolio analysis. The balanced portfolio has stars (high cash flow and high market share) whose high share and high growth assure the future; cash cows that supply funds for that future growth and question marks (innovations) to be converted into stars with the added funds. The poor dogs (low cash flow and market share like an end-of-line model) units should be low.

Results: The most crucial situated properly in the 2D graph of growth and development vs. market share and the cash cows like knowledge transfer, question marks like service and communication center etc. were identified, placed in graph and considered in the development strategy of Biobank Graz.

Discussion: The BCG analysis shows that the Biobank Graz has a strong economic position since there are many innovations and services which can act as Cash Cows for the field of medical research. To secure this position, further innovative developments in sample quality and management as well as cooperations are necessary. Furthermore, the upgrading of IT infrastructure appears pivotal for further innovative development of automation and data management.

RM-75 The Challenges Involved in Setting up Software Solutions in an Interdisciplinary Clinical Biobank, Future Perspectives

Primschitz R. Huppertz B. Sargsyan K. Biobank Graz, Medical University Graz, Graz, Austria

An interdisciplinary clinical biobank is a highly dynamic and this is also true for its software solutions. Not only available state-of-the-art hardware and software technologies are changing dynamically, but the requirements, working processes, data sources, sample types etc. To face the current or even future IT needs in biobanking, it is essential to establish an integrated software environment that is flexible, easy to use and adaptable. So, we need an entire software environment with lowest common denominator as basis.

As a rule, the data structure within database should be stable, even static. However, due to dynamic environment of a biobank such a strict data structure is impossible to maintain. E.g. nearly every new biobank project needs its own database which has a unique data structure. Dynamic databases (all in one) are standard solution for this. These databases need standardized data input which can be reached by interfaces. If there are many different data sources to handle, big effort has to be invested into the process of standardization, either by software or manpower, with serious drawbacks. ‘Human interfaces’ are expensive and time-consuming, while software interfaces which ‘translate’ data from unique data sources are not flexible and have to be reprogramed for each data source or data change. An innovative approach is framework which handles different databases and interfaces. In this setting, databases are created individually as a standalone interface and assembled within a framework. If the data sources, working processes etc. change, it is not necessary to recreate the data interface. It is even possible to gather different databases from different database providers or use other data storage forms. As advantage the graphic user interface simply exchanges data via the framework and not the database directly. Such frameworks are already available, most of which are open source.

These frameworks are supported by big community and industry, so the adaptive work is much cheaper, faster and more efficient in comparison to other technologies. It is relatively simple to keep the framework technology at state-of-the-art standard. The data stored in the different databases is still directly accessible; hence, the entire system stays simple, productive and adaptive. This accessibility is one of the greatest advantages compared to other systems because convenient exit strategy for further technological development or unpredictable events.

RM-76 Utilization of the Kaizen Philosophy for Process Improvement in the BioBank Setting

Larson D. M. Geddes T. Pruetz B. Wilson G. Thibodeau B. Akervall J. BioBank, Beaumont Health System, Rochester Hills, Michigan, United States

Background: Efforts to improve efficiency and reduce costs while maintaining the highest quality of samples collected and patient welfare has sparked the interest of the Beaumont Health System (BHS) BioBank to implement the Kaizen Philosophy. The Kaizen method is a philosophy and practice that focuses on continuous improvement of processes in manufacturing, engineering, business mgmt., or any system including health care. The Kaizen was adopted by BHS in 2012.

Methods: Assigned Kaizen and Biobank team members spent a total of 6 (?) days assessing a wide variety of Biobank processes using the Kaizen methodology. It was determined that the areas of improvement included process of collections between the BioBank and the pre-op, ORs, and Pathology depts. The combined team proposed and tested easily implemented, inexpensive ideas to optimize operational logistics. In addition, time studies were performed on 7 different collections with varying operational workflows to determine time improvement between consent and blood, tissue, urine, and fine needle aspirate collections. Operational Availability Time Studies were run by logging an activity, subtracting scheduled run time from scheduled down time, and dividing the actual run time by the planned time to give the operational availability.

Results: Example 1: With the co-operation of Clin Path, we created a work space in the STAT lab closer to the ORs for quicker processing time of blood and tissue specimens. Example 2: Clin Path allowed the utilization of the pneumatic tube routing system for BioBank specimens; this significantly reduced the time to deliver specimens to the BioBank. Example 3: Future introduction of E-Consent on IPad directly linked to our electronic health record system (EPIC). In the three collections that had repeated logging of activity and time, we calculated a 57%, 79%, and 95% improvement in the operational availability. We also documented circumstances that lead to poor operational availability and made the necessary changes and improved upon efficiency.

Conclusion: The Kaizen project improved performance and complemented the CAP requirements for continuous performance improvement. Value was added to the BioBank operations shortening lead times, improved sample quality, and thus increasing efficiency of our staff. This leads to increased ability to collect more specimens for research and commercial purposes, resulting in an increase in our revenue stream and thus sustainability

RM-77 Wildlife Biomaterial Banking: Quo Vadis?

Labuschagne K. 1 Matlhola N. 1 Kotze A. 2 3

1 Biobank, National Zoological Gardens of South Africa, Pretoria, Gauteng, South Africa 2 Research and Scientific Services, National Zoological Gardens of South Africa, Pretoria, Gauteng, South Africa 3 Genetics Department, University of the Free State, Bloemfontein, Free State, South Africa

Background: Conservation genetics, reproductive technologies, toxicology, pathology, a rapidly increasing list of ‘omic’ studies, and forensic science has necessitated the need and role for optimally managed wildlife biomaterial repositories. In addition, a platform for access to both the national and international scientific communities to contribute to the conservation of South African wildlife biodiversity is critical.

Methods: The NZG Biobank has recently undergone an enormous strategic, operational, as well as management transformation. Evaluations of previously stored biomaterials and methods used were conducted by academics to assess the viability of some of the samples, and recommendations for future collection and storage advised. Sample collection using chain of custody protocols, including e-vouchers and taxonomic verification of species; processing biomaterials following standard operating procedures developed by using Best Practice guidelines; storage of tissues based on sound and emerging research and technologies; and conforming to both legal and ethical considerations: access to biomaterials through a Research Ethics and Scientific committee, sample receipts and material transfer agreements are in use, and national and international import and export permit compliance is adhered to. An analysis of the workflow and data management systems was conducted and it was found that there was a lack of integration and interoperability. This then resulted in the development and implementation of a Biobank Information Management system (BIMS) based on the Specify platform.

Results: The NZG Biobank is currently curating approximately 80 000 biomaterials from > 30 000 individuals, representing 840 different species. Through a changed strategy and management, within 1 year, the NZG Biobank effected a 26% growth. Approximately 2% of the individuals represented have biomaterials stored using the full chain of custody sampling procedure. These samples are invaluable and can be used in forensic cases in court. Two useful tools were developed after implementing the BIMS: an inventory of all the samples in the Biobank, and a workbench for facilitating the cleansing and migration of legacy data on a continuous basis.

Conclusion: With a vision now firmly in place, the NZG Biobank is evolving to a focused collection of germplasm, with emphasis placed on categorized sampling of threatened and protected species, biodiversity conservation, and forensic science.

RM-78 Quality Cost Analysis: Applying the Concept to Biobanks

Abdelhafiz A. S. 1 Aziz S. Abdel 2 Farahat I. G. 1

1 Egyptian National Cancer Institute Biobank, Cairo, Egypt 2 Quality department, Port Said Health Directorate, Ministry of health and population, Port Said, Egypt

Quality and cost are major concerns in biobanks and both are related to sustainability. While quality is related to operational sustainability, cost is related to financial sustainability. Quality costs are costs associated with prevention, detection and correction of defective work. Quality costs include four categories; prevention, appraisal, internal and external failure costs. Failure costs are considered as costs of poor quality while preventive and appraisal costs are considered as costs of good quality

Our aim is to introduce the concept of quality cost analysis as a method for cost control and application of the different types of cost in biobanks

Prevention Costs: Costs of activities developed by the biobank to prevent future losses due to poor quality of samples provided for users. Examples include: staff training costs, identifying specification and evaluation of the suitability of equipment for intended use, scheduled maintenance of equipment, accurate documentation and quality assurance costs.

Appraisal Costs: Costs of activities designed to detect quality problems before samples are delivered to the user and to improve the quality of the product or service. Quality validation tests, regular audits of sample inventory and costs of physical security and temperature maintenance represent some types of appraisal costs.

Failure Costs: which include two subtypes; internal Failure Costs, which arise as a result of loss of the samples before delivery to the user. Such costs may occur as result of equipment breakdowns and can be direct cost of late shipment of samples to users.

External Failure Costs: This type of cost occurs after delivering the product to the users. For the biobank, external failure costs include costs that incur as a result of handling user complaints and may lead to loss of the relationship with target customers. This may necessitates more spending on marketing as a corrective action.

Quality costs analysis can help management to identify quality cost priorities and to avoid unnecessary costs which will be reflected on financial sustainability of biobanks. More focus will be directed on spending on the costs of good quality rather than costs of poor quality.

Quality cost analysis can be a used as one of the performance indicators tools applied in biobanks.

RM-79 Role and Consequences of Principle Investigator (PI) as Biobank Major Stakeholder

Riegman P. Erasmus Medical Center, Rotterdam, Netherlands

It is of course well accepted that those using samples from the biobank are also involved in the biobank as stakeholder. The PI is of major importance for the use of the samples of the biobank. When the biobank performs to expectations the PI will support the biobank in infrastructure and finances.

When finances become low for biobanker and PI a financial challenge seems to arise. The biobank needs to operate cheaper than the PI could organize the needed collection of samples for himself. This in itself forms a threat, because if there the central institutional biobank needs to charge per sample, the PI can simply take over the task (even if the PI is making a judgment error) in an attempt to pay less and perhaps skips a lot of items in the guidelines and best practices.

Another consequence is the difference in willingness to share samples in networks between institutional biobanks. Especially if these networks are not known to PI's. This becomes far more complex when not one PI is the major stakeholder, but more PI's and increases if the PI's do not share the same views in the research field.

An alternative major force was identified in the evaluation of scientific achievement. This force can when cooperation between groups is not needed for survival inhibit cooperation completely. Strangely it is well recognized that high impact translational research is pivotal for innovation of patient care in which strong statistical conclusions based on large numbers of high quality samples are crucial.

PI's do not like even a little risk of not having access to their samples and in the end the PI is distributing the biobanked samples to those the PI chooses to cooperate with and in the way the PI choses to cooperate. Despite all this, there is a lot of good cooperation going on and the scientific survival needs can change such that the field the biobank operates cannot do without cooperation. However, if the access to biobanked samples needs change, do not change the biobank manager, but try to change the PI microenvironment. The facts were determined in the Eurocan Platform project funded by the European Union Seventh Framework Programme FP7 under grant agreement n° 260791 and will be discussed in more detail.

RM-80 The Sustainability Challenge of a Community Hospital-Based Biobank and Core Molecular Laboratory: The Beaumont Experience

Akervall J. Geddes T. Pruetz B. Larson D. M. Wilson G. William Beaumont Hospital (Beaumont Health Systems), Royal Oak, Michigan, United States

Background: The Beaumont Health System BioBank was established in 2008 to collect biospecimens for translational research in an investigator-driven manner. The intention has been to undertake such research in a seamless process that combines high quality biobanking with state-of-the-art laboratory platforms geared towards biospecimen-based research. The original investment was made through philanthropy and grant money from the State of Michigan in combination with institutional support. Pilot studies by PI's are supported by Beaumont Research Institute, and the goal was originally to use such preliminary data to apply for grants. However, grant success rates have been decreasing and we have concluded that a sustainability policy cannot be built on achieving grant expectations.

Methods: To sustain our community hospital-based biobank with an operating budget exceeding $1,000,000 in a financial climate that favors short-term fiscal goals rather than long-term scientific ambitions we have now decided to focus on two areas: 1) Philanthropy and, 2) commercialization of samples and laboratory services. We are currently launching a marketing campaign for the latter and have involved the Beaumont Foundation for the former. Furthermore, to improve our chances for such external financing we went through CAP accreditation, and we are continuously addressing process improvement through kaizen methodology.

Results: Through attracting philanthropic donations based on investigator driven projects, we have secured funding for four major research endeavors as well as two full time employees. Philanthropy has also provided unspecified funds for BioBank use amounting to $150,000. Our commercialization efforts have the potential to secure monies to cover 50% our operating budget and expand our ongoing research effort. However, finalizing legal agreements with companies has been a bottleneck in realizing revenue. Patient concerns have not been an issue.

Conclusions: We conclude that commercialization of specimens is a viable and acceptable pathway to generate revenue for a biobank whilst still fulfilling the ethics of collecting specimens for research. Philanthropy provides an additional avenue for generating funding but, like grants, cannot be depended on as a regular source of money. Harnessing commercial enterprises with improving efficiency and processes will increase specimen collections, increase revenue and underwrite biobank sustainability.

RM-81 The Future of Data Presentation or how Medical University of South Carolina Built an Integrated Data Management System that Allows Different Data Sources to Relate to Common Elements across the Entire Medical University Environment That is Easy to Understand

Morgenweck W. 2 1 Gibbs K. 1

1 Hollings Cancer Center, Charleston, South Carolina, United States 2 Medical University of SC, Charleston, South Carolina, United States

Background: Data today comes in all shapes and sizes and the main responsibility for Information Technology people in the scientific world is to create applications that surpass the expectations of the end users. Developers need to watch and learn from the end users rather than developing systems that seem appropriate to the developer. It is now time that data needs to communicate information clearly and effectively from various sources at the same time. It does not matter where data originates it is becoming more important how it is displayed. Data visualization is a major component to our ever increasing information overload.

Methods: At the Medical University of South Carolina we developed a plug and play system that handles various information systems that adds additional value to the basic Sample Inventory Management Report. These additional information systems include EMR, Clinical Data warehouses, Cancer Registry's commercial vendor systems, HL7 Path reports, REDCap developed by Vanderbilt and even Excel Spreadsheets.

Results: The custom application was developed to meet the needs for a tool to advertise the existence of specimen collections at MUSC to other MUSC researchers and data from select collections have been loaded into the initial release plus data from the Clinical Data Warehouse.

Conclusion: As long as the data can be included as either a document or structured data we interact. The system puts the majorly of the development on the originating data source and uses a common data access layer that needs very little programming. An important aspect of translational research is a simple mechanism that allows Researchers to have access to vast amounts of data in a very simple way.

RM-82 An Alternative Way of Storing Specimen in the Freezer

Woo C. Leong Y. Tan W. Tee S. Chua T. Aw Y. Chong M. Cheng Y. Chow C. Eng C. National University Health Systems (NUHS), Singapore, Singapore, Singapore

Biorepository or biobanks uses a vial/container to store biospecimen at very low temperature for cryopreservation. There are different sized vials for various storage volumes. For fluid specimen such as blood and urine, the size of the vial used is determined by the sample volume collected. However, for solid tissue specimen, such as a sample of excisional biopsy tissue, the choices are limited and often, a larger than required vial would be used. A larger vial usually has a wider opening to allow easy access/deposit of the specimen. The specimen would usually take up less than 10% volume of the storage vials with the remaining as void volume. Void volume takes up space in the freezers/cryotanks. The financial implications are significant as more freezers are needed, higher utility bills and also more space required to house the extra freezers. We have designed a new cryovial which is compatible with the existing vials used to allow easy adoption of the technology in all biobanks.

RM-83 Development of Minimum Information about Biobanking data Sharing 2.0 (MIABIS 2.0) and Application in Dutch Biospecimen Catalogues

van Enckevort D. 6 5 Norlin L. 1 2 Martinez R. Merino 1 2 van Iperen E. 3 Lansberg P. 4 Boiten J. 4 Swertz M. 5 6 Litton J. 1 7

1 Karolinska Institutet, Stockholm, Sweden 2 BBMRI.se, Stockholm, Sweden 3 Durrer Center for Cardiogenetic Research, Amsterdam, Netherlands 4 CTMM, Eindhoven, Netherlands 5 University Groningen, Groningen, Netherlands 6 Genetics, University Medical Center Groningen, Groningen, Netherlands 7 BBMRI-ERIC, Graz, Austria

Introduction: Research into complex and rare diseases requires high quality biological samples. However, it is costly and time consuming to create novel sample collections of appropriate size and quality. At the same time biobanks have large collections that are underutilized, because discoverability and access to the samples is hard. Several catalogues have been published to facilitate the use of biobanks in research, but these catalogues are often incomplete and outdated. In 2013 a working group was formed within BBMRI-ERIC in order to update the MIABIS Minimum Information Model to facilitate the exchange of information between biobanks and research groups using biological samples.

Material & Methods: The working group has revisited the MIABIS recommendation/model and changed it to be more flexible: 1) The model has been split in three core components: biobanks, sample collections, and studies, further detailed in supporting components: sample, participant, omics and rare diseases; 2) The number of elements has been reduced; 3) Data structures have been defined for several elements.

We used an internal voting process following the MoSCoW prioritization to reach consensus.

A reference implementation of a catalogue based on the model has been made with the MOLGENIS software with sample data from the different countries.

Results: The MIABIS 2.0 model has been successfully implemented in several national and international projects: 1) the pre-existing data model of the CTMM-TraIT Biospecimen Study catalogue is an almost 1-to-1 mapping to the MIABIS Participant and Sample modules; 2) BBMRI-NL has successfully converted the data model of its existing catalogue to conform to two of the core modules of MIABIS. Mapping of the existing model onto MIABIS was in general straightforward; 3) The RD-Connect project is implementing MIABIS for the project sample catalogue. Other infrastructures/projects implementing MIABIS are the BiobankCloud, EUDAT, BioMedBridges and IARC.

Discussion: A minimal information model enables interoperability between different systems. MIABIS facilitates automated exchange of information between several systems in the biobanking workflow such as: a) Biobank Information Systems b) catalogues c) workflows for sample shipments. However, other components are needed to unlock the full potential such as a) standardization of terms in ontologies b) globally unique identifiers such as BRIF for biobanks, samples collections and samples.

RM-84 A Successful Strategy Developed by Biobank Graz: A Model for Other University-based Biobanks?

Strahlhofer-Augsten M. 1 Sargsyan K. 1 Bayer M. 1 Lippe I. T. 2 Huppertz B. 1

1 Biobank Graz, Medical University of Graz, Graz, Austria 2 Rectorate, Medical University of Graz, Graz, Austria

Background: The development of new biobanks forces to follow a future oriented, continuous strategy which is steadily controlled and easily workable. The strategy of Biobank Graz was developed in 2009 in cooperation with the vice rector for research and international affairs. It comprised 7 critical success factors: scientific relevance, personnel, infrastructure, management/ethics, business efficiency, added value, international networking. It also included the vision: “Biobank Graz as …

… the most significant, clinical biological resource center within Europe taking a central role in biobanking networks with a focus on Central-Eastern-European countries.

… a pioneer in developing international standards and representing the basis for top class science.

… a catalyst for economic development and innovative health care management.”

Methods/Results: Critical success factors include aims for 3 years describing the fundamental strategic course, and operative aims representing the work packages for the next year. The operative aims arise in the ‘project and activity list’ describing the responsibilities for each work package and the minimal goal to be reached. This list is monitored every quarter to recognize misguided developments in time and to counteract respectively. This list also motivates the staff by showing them to be a key factor for success and further development of Biobank Graz.

To keep the strategy up-to-date and control progress, the strategy is revised every year in a strategy meeting. Since Biobank Graz is a central service facility of Medical University of Graz, the vice rector for research and international affairs I directly involved in critically discussing and respectively adapting the strategy in discussion with CEO and COO plus responsible people of the management team of Biobank Graz. Today the strategy of Biobank Graz comprises five critical success factors: cooperation and competition, resources, management, added value, data protection and ethics. Also the vision is more stringent: “Leader in Biobanking as Hub for Co-opetitive Medical Research”.

Conclusions: Within this time period Biobank Graz has developed to the largest biobank in Europe and became more and more acknowledged. This indicates that a steadily and critically revised strategy leads to success. Meanwhile the strategy of Biobank Graz is used as model for the development of biobanks in other countries and represents a paradigm for a successful strategy.

RM-85 Comparison of Automation Technologies and Manual Storage and Retrieval

Nelson M. B. Lesko J. Klein L. Hahn L. Monroe M. Ellis G. Kwong H. Thompson J. Tree K. Carlson C. Spencer J. Highsmith W. Jr. Bolster J. Summer Thibodeau S. Cicek M. BAP Core Facility, Mayo Clinic, Rochester, Minnesota, United States

Background: The Mayo Clinic Biorepository program Biospecimens Accessioning and Processing (BAP) Laboratory has robotically controlled freezers with a total storage capacity of 4.5 million tubes. In addition, this facility manages over 150 upright −80°C freezers, storing different types of biospecimens. Multiple solutions exist for −80°C storage within the Mayo Clinic Biorepository program, including liquid nitrogen freezers (Vario), standard upright freezers, and automated freezer technology obtained from Brooks and Hamilton Storage Technologies. An extensive evaluation was performed in preparation for our lab move into newly renovated space, replacing aging −80°C freezers and expanding current storage capacity with the best performing and most efficient storage options.

Methods: In order to compare the wide array of freezers used by the Mayo Clinic BAP laboratory, evaluation scores were given to each freezer based on three categories: usability, sample integrity, and overall cost. Usability was determined qualitatively through a questionnaire given to technologists using the freezers installed and quantitatively by timing the BAP standard procedure for pulling samples. Sample integrity metrics focused on average unit temperature levels during varying levels of use. Cost was evaluated in three categories: ongoing costs, startup costs and one-time setup costs.

Results: Mayo Clinic BAP Laboratory determined automated freezer technologies fully integrated with laboratory information management system (LIMS) are best suited to high-throughput storage of BAP standard automation-friendly tubes. Upright freezers have a lower startup cost and, although are installed with fewer risk mitigation factors, can result in faster pull times when FTE per pull is increased where automated freezer pulls cannot be expedited. Automation technology has not yet been developed for sub −100°C storage and liquid nitrogen ready freezers such as the Vario remain the only solution.

Conclusion: The combination of automated and manual storage gives BAP laboratory the flexibility and efficiency to meet the expectations for a variety of biospecimens and their usage. Extensive evaluation and comparison of storage units helped our program to choose the best option for our decommissioning and expansion project. We will continue to evaluate storage units as new technology enters the market and our lab needs change.

RM-86 Operational Efficiencies in Large-scale Remnant Sample Biobanking

Cobb B. L. 1 Harley J. B. 1 2

1 Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States 2 US Department of Veterans Affairs, Cincinnati, Ohio, United States

Introduction: Cincinnati Children's Hospital Medical Center (CCHMC) is one of the largest pediatric hospitals in the United States, with 1,191,880 patient encounters in FY14. The Cincinnati Children's Research Foundation (CCRF) is an integral part of CCHMC and has become the nation's third highest recipient of NIH research funding among pediatric centers. In 2010, CCRF leadership initiated a large-scale remnant sample biorepository. Five years later, we present operational efficiencies realized.

Methods: Leveraged funding: Over $9 million dollars has been committed by CCRF and the University of Cincinnati (UC) to a shared biobank. UC was awarded a grant from the State of Ohio to renovate space at the University of Cincinnati's Reading Road Campus for a biobank laboratory and long-term storage. CCRF has subsequently supported personnel, equipment, and operational expenses.

The election of “remnant sample opt-in” consent: The Cincinnati Biobank manages the ‘Better Outcomes for Children (BOfC)’ project, an institution-wide initiative to collect and store remnant clinical samples for research use. Voluntary participation is offered at the time of registration at virtually all clinical care sites of the hospital. Consenting participants agree to allow their leftover clinical samples to be stored (they have already been collected) and potentially used for future research.

Informatic developments: Signed consent is captured in the electronic medical record (Epic) at the time of registration. Remnant clinical samples are transported to the biobank after a seven-day embargo in the clinical lab. Barcodes identifying clinical lab samples are read by Red Light/Green Light, a custom application used by biobank personnel to determine their consent status. Various automated custom upload functions have been designed to support efficient data transfer to Biomaterial Tracking and Management™ software.

Results: To date, over 148,000 patients/families have consented to BOfC. The Cincinnati Biobank has processed and stored DNA samples from more than 39,000 unique patients and urine samples from over 4,000 unique patients.

Conclusions: Large-scale remnant biobanking may be economical and practical. Efficient compliance and consent is possible with strategies that integrate into existing operations of health care institutions by leveraging routine sample collection and the electronic medical record to serve institutional research and development goals.

RM-87 Second Generation LIMS Implementation for Biorepository Sample Tracking and Data Management

Turner K. D. Riehle D. Tree K. Michael S. Carlson C. Cicek M. Spencer J. Ice J. Thibodeau S. Mayo Clinic, Rochester, Minnesota, United States

Background: Mayo Clinic Biorepository program implemented a vended LIMS solution in 2007. Since the original implementation of the LIMS, changes to laboratory technology and business requirements have resulted in additional customizations. The collective data is forecasting an unstainable increase in cost to maintain these customizations and in addition data has shown the customizations are no longer meeting the needs of the Biorepository.

Methods: To determine our approach for implementation of a solution that meets the changing needs of the Biorepository and to also mitigate the forecasted increase in management costs. A high level analysis of the LabVantage base product was performed which included version 6 and the new functionality being introduced with version 7. The decision was then made to complete a more thorough analysis with LabVantage Consultation Services. This in-depth analysis focused on our customizations and compared them to LabVantage solutions which included a code review and a detailed functional GAP analysis. All solutions were assessed for value and how they could be incorporated into the Biorepository program operations.

Results: The analysis confirmed the vendor's base product solution will meet the current and future needs of the Biorepository program. The value added will result from being able to replace a majority of the customizations and offer the ability to take advantage of new and existing base product functionality which our customizations prevented us from utilizing.

Conclusion: The second generation implementation of LabVantage's base product will reduce the cost to maintain the LIMS system and better position us for the fast changing operation needs of the Biorepository program. The partnership created during the review evaluation will allow us the opportunity to provide suggestions and feedback on the development of new functionality and its timely incorporation into the base product.

RM-88 Biobank Economic Modeling Tool (BEMT): A Cost Recovery Tool for Long-Term Sustainability of Biobanks

Odeh H. M. 1 5 Rao A. 1 Miranda L. 2 Greenman H. 3 McLean J. 4 Memon S. 1 Reed D. 6 Vaught J. 1 5 Moore H. 1

1 Biorepositories and Biospecimen Research Branch (BBRB), National Cancer Institute, NIH, Rockville, Maryland, United States 2 Biobusiness Consulting, Inc., Newburyport, Massachusetts, United States 3 Provia Laboratories, LLC., Littleton, Massachusetts, United States 4 Leidos Biomedical Research, Inc., Rockville, Maryland, United States 5 Kelly Government Solutions, Rockville, Maryland, United States 6 Wrycan, Inc., Cambridge, Massachusetts, United States

Background: Biospecimens are essential for advancing basic and translational research. With the rapid growth of precision medicine and accompanying utilization of biospecimen resources, it is important that biobanks undertake strategic financial planning to ensure long-term sustainability. To support the research community in this effort, the National Cancer Institute's (NCI) Biorepositories and Biospecimen Research Branch (BBRB) has developed the Biobank Economic Modeling Tool (BEMT). This web-based tool is designed to enhance the understanding of the economic considerations involved in operating and maintaining a biobank and thereby assist with long term financial planning and cost recovery.

Methods: A comprehensive online survey was distributed to approximately 450 biobank directors worldwide. The purpose of the survey was to obtain cost and pricing data. Data surveyed included infrastructure and labor costs, funding mechanisms, types of biospecimens, specimen products, and services with pricing. The resulting data was anonymized and used to develop a comprehensive database of the costs associated with developing, maintaining and operating a biobank.

Results: Following the survey, the data from over 100 respondents was used to create a database that supports a novel web-based tool, the BEMT. Users of the tool can perform cost analyses to determine start-up expenses, understand labor and infrastructure requirements, allocate costs based on percent of costs recovered, create fee schedules, and develop financial forecasts.

Conclusions: The BEMT is a publically available web-based financial planning tool for biobanks. Users of the tool will be able to review and compare their own cost and revenue information against anonymized survey data, establish pricing for services and generate a short or long term financial plan for their biobank.

RM-89 An Optimized LIMS Support Infrastructure for the Biorepository

Spencer J. Burt C. Carlson C. Foster T. Michael S. Sorensen-Holmes S. Ice J. Mayo Clinic, Rochester, Minnesota, United States

Background: The LIMS is a critical infrastructure component to any successful biorepository operation which is often underestimated or misunderstood. To successfully safeguard and leverage a LIMS investment, the support infrastructure must include the necessary personnel, tools, and procedures and must provide an efficient, user friendly, method to report issues.

Methods: The Mayo Clinic Research Laboratory Information Management Program has established a support infrastructure model for its current LIMS. The team is a multifunctional group of IT liaisons, developers, software quality assurance and business analyst professionals. The organizational model of this group is a three tier structure with auxiliary service lines. The three support tiers consist of help desk & triage, IT maintenance, and IT engineering. In addition to the three tier structure, various auxiliary teams were formed, specifically, data migration, integration, and reporting teams, to augment the LIMS data management and reporting capabilities. A standard suite of tools are used to track issues throughout all levels of support and auxiliary teams.

Results: The support model allows the program to provide needed support required by the laboratory. This support has been accomplished with minimal increase in team size or additional overhead costs since its original implementation even though the user base has increased 10-fold to over 30 laboratories and 300 users. The tools used to track issues provide invaluable information to forecast projected support needs.

Conclusion: Support infrastructure is critical to the LIMS and cannot be overlooked. As laboratory needs change, the LIMS must be able to adapt and blend with laboratory operations as well as support changes to data management requirements. A properly executed support model, with the correct balance of support activities, can help ensure success of the LIMS investment while minimizing the operational costs to keep it functioning.

RM-90 The Canadian Longitudinal Study on Aging (CLSA): Biorepository Operations and Infrastructure

Naik C. 1 Marcotte C. 1 Brooks N. 2 Arseneau E. 1 DiPietro V. 1 Marchese M. 1 Ivica J. 1 Balion C. 1 2

1 Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, Ontario, Canada 2 Laboratory Medicine, Hamilton Health Sciences, Hamilton, Ontario, Canada

Background: The Canadian Longitudinal Study on Aging (CLSA) is a national longitudinal study established to evaluate the quality of life and health of 50,000 Canadians aged 45 to 85, for at least 20 years. Participants will be contacted every 3 years and will provide data through interviews. Of these, 30,000 will go through a clinical exam and donate blood and urine samples. The Biorepository and Bioanalysis Centre (BBC) manages collection, processing, analysis and storage of the biospecimens.

Methods: Biospecimens are obtained from participants at 11 CLSA Data Collection Sites (DSC) located across Canada. Standard operating procedures (SOPs) have been developed to minimize variation throughout the preanalytical, analytical, and post-analytical processes. Each collection site is equipped with identical processing instrumentation. All consumables purchases are coordinated by the National Coordinating Centre (NCC) to ensure consistency in product and to document and monitor lot number and expiry dates. Approximately 50 mL of blood is collected and a urine sample resulting in 10 types of biospecimens and 42 0.5 mL aliquots. The time from venipuncture to temporary storage at −80°C occurs within a strict two hour window. Included during this time is a complete blood cell count (CBC) analysis. Biospecimens are shipped weekly in cryoshippers to the biorepository in Hamilton, Ontario where they are stored in cryofreezers. All steps are time stamped in our Laboratory Information Management System (LabWare) to allow for quality monitoring of the processes and provide valuable data to assess variation in biomarker data. Environmental monitoring occurs at each DCS, during shipment and within the biorepository.

Results: There are 31 liquid nitrogen freezers (LABS-94K) with a capacity to store 160,000 0.5 mL Matrix cryovials. Humidity controlled GenVaults provide storage for 12,000 GenPlates. The biorepository receives 100 boxes of cryovials as well as 80 GenPlates per week. Technical support and training for the biospecimen collection is also provided to the DCSs by the biorepository staff. Development of LabWare continues for expanded functionality and to provide data for quality assurance purposes.

Conclusions: The CLSA biorepository ensures consistency across all DCSs and captures detailed data to assess biospecimen integrity.

RM-91 Building a Biospecimen Collection Operation – Approach and Lessons Learned

Masunga J. G. Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States

Background: The Cohorts Biorepository currently houses biospecimens and data from large U.S. based study cohorts dating back as far as 40 years. With over 3 million specimens in inventory matched to participant level data, these collections represent an irreplaceable resource for cutting edge biomarker and genomic studies in relation to risk of multiple chronic diseases. Cohort specimens are collected from men and women across the US using specialized collection kits shipped overnight. Previously, we worked with vendors to conduct and manage our sample collection and processing; leading to incompatible data sets, missing information, and unacceptable error rates in the process. In 2013, we began to build an internal collection operation and team to provide direct oversight and ensure more accurate processing, storage and recordation of incoming specimens. We present here our approach to and lessons learned from building a specimen collection enterprise.

Methods: Creating the collections enterprise began with securing a dedicated space to manage the large number of supplies and kits in an organized and work stream based fashion. Next a quality management framework was created to guide the operation, including training schedules, SOP standards, quality assurance SOPs, collection design and cost model standards, and vendor relationships for supplies. Multiple vendors were contacted and interviewed to guarantee supply chain agreements and negotiate best pricing. A key component of internalizing the operation was the customization of the LIMS system to accommodate varied incoming collections. We worked closely with our development team to create an approach to tracking communications with participants, collection kit logistics, and receiving, processing and storing chain of custody data. Operations and data collection was regularly assessed and modified to ensure the use of best practices.

Results and Conclusions: The benefits realized in establishing a biospecimen collection enterprise have made this undertaking very worthwhile. We learned that accounting for delays in project timelines from internal and external factors beyond our control and making appropriate modifications is key to successful project roll-outs. It is also paramount to perform extensive tests before bioinformatics applications are released. Cross training staff on all areas of the operation and evaluating project progress ensures that a project is kept on the right course.

RM-92 The Biobank Information Management System (BIMS) Life Cycle Management and the BIMS Cloud Management Platform (CMP)

Niu M. Zhang l. Scientific research system, Goodwill Information Technology CO., LTD, Beijing, China

The Biobank information management system (BIMS) is one of the most important components for operation of modern biobank. As some contemporary BIMSs focus on the storage management of biological samples, the life-cycle management of biospecimen related to the sample quality management and future application, and the longitudinal information of the sample donors are largely overlooked. Therefore, it is imperative to implement six core issues of BIMS, which include sample source registry, life-cycle management, storage positioning, quality control, data correlation analysis and utilization, and data security & privacy protection.

In the past few years, with strong support from the Beijing Municipal Science & Technology Commission, we have developed a BIMS bearing our notion of “full life-cycle management and quality control” and a cloud management platform (CMP) for longitudinal clinical data collection. This platform adopts the Browser/Server structure, which make it easy to support multiple centers, departments and multiple disciplines, the end users, to get authorized access to the centralized cloud platform by browser. The system can track the sample sources and provide the life-cycle data collection and management highlighting key points of quality management.

Our Full life-cycle management includes some key status: sample temperature information monitored by cold chain preanalytic information base on PREanalytical Code (SPREC) and quality control module tracking the sample delivery process and time cost. In order to ensure the quality, reliability of the input data, and synchronization with SOPs, the BIMS provides the guiding template, logic check, automation operation check, sample traceability, operation process audit, and switch function of operational, to perfect match the actual work flow.

This system will provide solid foundation for the future implementation of longitutinal cloud platform for clinical and scientific researchers.

RM-93 The Development of the National Biobanking Facility for Conservation of South African Biodiversity

Zwane A. A. 1 Bartels P. 2

1 Animal Breeding and Genetics, Agricultural Research Council, Pretoria, Gauteng, South Africa 2 Tshwane University of Technology, Pretoria, Gauteng, South Africa

South Africa (SA) has a number of biomaterial collections that are governed by different departments, institutions and the private sector. Collections include plants, animals, human, insects, microbial, aquacultures and other collections. The open and evolving nature of biobanks has profound ethical, legal and social implications for individual and group autonomy. There are a multitude of aspects that influence the success operations of a biodiversity biobank and include Informed consent, privacy, confidentiality, secondary use of samples over time and quality of samples. Other aspects include return of results, data and benefit sharing with the communities. Complexities also emerge because of increasing international collaborations, and differing national positions. Public consultation and involvement of the communities in running and managing of the Biobanks is still very limited in South Africa. The implementation of international standards in national laws is still problematic. Therefore a structure is needed, whereby all the biobank institutions of South Africa will be coordinated in one body in order to respond to the national biobanking demand. This project is aimed at developing the national biobanking infrastructure for South Africa's biodiversity which will serve as a centralized coordinating structure for all the Biodiversity Biobanks in SA. The South African Center for Biobanking (SACB) will serve as a national imperative which represents a geographically unique resource that should be managed as a national asset to the benefit of biodiversity conservation and biotechnology development. The objective of this initiative is to advance knowledge, awareness and innovation in the conservation and use of South Africa's biodiversity, through securing and making available components of biodiversity, for the benefit and well-being of society. The SACB will therefore provide a comprehensive biomaterials information and sample service to a multi- and trans-disciplinary research and conservation audience regionally and globally.

RM-94 Development and Implementation of a State-of-the-Art Information Technology System for Research Biospecimens and Molecular Derivatives

Alam A. Abi-Saab T. Chadwick D. Roehrl M. H. University Health Network, Toronto, Ontario, Canada

Background: CaTissue Suite, a research specimen database, and Caisis, a clinical annotation tool, have been customized to meet the needs of research specimen BioBanking at the University Health Network (UHN). SAP Business Intelligence technology, a powerful search and reporting tool, was configured to federate data from both systems improve workflow and facilitate concurrent searches and reporting of clinical information on research specimens.

Methods: CaTissue Suite was tailored to enhance the three stages of biobanking: pre-collection, collection and post-collection. As part of the configuration process, more than 12 years of legacy data were cleansed and loaded into caTissue Suite with the corresponding UHN CoPath Pathology report. Caisis was customized so that synoptic and full text reports from the CoPath database were uploaded via a live HL7 feed. SAP technology was used to federate caTissue Suite and Caisis via a web-based user interface.

Results: CaTissue Suite automatically retrieves patient demographics from the hospital's electronic patient record, and allows for documentation of research consent. Specimens can be annotated to include clinical data and research study information. CaTissue displays the various levels of specimen collection, and auto-assigns banked specimens to designated storage locations. Banked specimens can then be distributed to registered research protocols. SAP reports are used before sample collection to track potential fresh tissue cases for distribution to research studies, and after collection to accompany the distributed specimens. Custom searches have also been created that combine pathology data in Caisis such as diagnosis, disease site, TNM staging and molecular profiling results with research specimen data in caTissue Suite.

Conclusion: A state-of-the-art information technology system for research specimens and derivatives has been developed and implemented at UHN. CaTissue Suite tracks collection, storage and distribution of biospecimens, while Caisis contains the associated Pathology report in a searchable format. SAP, which federates caTissue Suite and Caisis, improves and facilitates workflow by combining data from both sources into one report.

RM-109 Integration of Standard Pre-analytical Code with Biobank Management Software FreezerPRO

Liu S. 1 Tang Z. 1 Guo A. 1 Ma B. 1 Shen G. 2

1 Biobank of Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China 2 RURO (Shanghai) Software Limited Company, Shanghai, China

Standard Pre-analytical Code (SPREC) is a useful tool that the ISBER Biospecimen Science Working Group developed for recording the main pre-analytical factors that may have impact on the integrity of sampled clinical fluids and solid biospecimens and their simple derivatives during collection, processing and storage. ISBER releases a SPRECCalc_FLIUD and SPRECCalc_SOLID version encoding by Excel and Access. However, it is separated from Biobank management software and inconvenient for Biobank operators. We integrated the SPREC contents into our Biobank management software FreezerPRO 5.3 (RURO, MD, USA), which include biospecimen collection time, temperature before centrifugation, pre-centrifugation delay time, duration time, speed and temperature of centrifugation, temperature after centrifugation, post-centrifugation delay time. We annotated every biospecimen with SPREC element. Which enhance the ability to manage and track pre-analytical variations impacting biospecimen integrity of high quality tissue samples for research, and the effective and efficient interconnectivity and interoperability between national and international Biobanks.

RM-111 Sustaining a Disease Focused Biobank Using a Dynamic Approach

Salman A. Petrillo S. Lazaris A. Metrakos P. McGill University Health Centre, Montreal, Quebec, Canada

The Liver Disease Biobank (LDB) was initiated based on the need of putting in place a strategic systems medicine program focused on liver disease including non-alcoholic fatty liver disease (NAFLD) and colorectal cancer liver metastasis (CRCLM). Our goal is to support translational and patient-oriented research and therefore requires a dynamic system to respond to those needs, while maintaining all ethical requirements. Although we follow Best Practices (ISBER) in our procurement of biospecimens, the process is a living entity, changing in a structured manner to allow research to flow and not be hindered. The success of our translational projects relies first and foremost that we work with our teams, describing the projects and ensuring our protocols are able to sustain our needs and if not, be able to quickly respond and have the modified protocols in place. For example, in our project studying unique lipid signatures in Colorectal Cancer Liver Metastasis, we require frozen samples that maintain their architectural integrity, similar to FFPE samples; therefore we collect tissue specimens in isopentane at −45°C. Furthermore, our NAFLD/NASH project requires fresh liver tissue to be perfused and immediately processed for organelle isolation. Working together with the surgeons, OR nurses and pathology, we are able to perfuse liver samples and process within 20 minutes of procurement. The success of our Biobank is in its ability to stay on top of the needs of research and evolving technologies, “smart” usage of biospecimens, publications and to cement all of these together collaborations at the local, national and international level. Central to our functionality and integral to our Biobank framework is our ethics structure. We operate with a “mother” protocol, which allows us to consent patients with liver disease and collect specimens. It does not allow research to be performed however it allows for the consent to use the material for research, including genetic analysis and addresses the question of return of results and international collaborations, using an opt-in approach. We then submit “companion” protocols, linked to our mother protocol for each research project. These protocols all pass research review, overseen by our ethics board and do not require any additional consent from participants, as this is covered by the “mother” protocol. This integrated system allows us to perform research in a timely fashion with local institutes/universities and international groups for multi-site studies and team-oriented grants.

Repository Standards

RS-95 A STR-Based Quality Assurance Procedure for the eyeGENE Biorepository

Garafalo A. Parrish R. NDifor V. Goetz K. Reeves M. Yim A. Cooper R. Iano-Fletcher J. Wang X. Tumminia S. National Eye Institute, National Institute of Health, Bethesda, Maryland, United States

Background: Quality assurance and quality control procedures can be challenging, but they are vital to good repository management. The CLIA-certified laboratory of the eyeGENE^® Network receives whole blood for individuals with certain inherited eye conditions, isolates DNA from that blood, banks blood and DNA, and ships aliquots of DNA to genetic diagnostic testing and research laboratories. Clinical genetic test results are returned to the affected individuals, so it is imperative that sample integrity is preserved throughout laboratory processing. This need led to the development of a clinically-validated, short tandem repeat (STR)-based approach, termed Sample Confirmation Testing (SCT), to ensure that no significant laboratory errors occurred during processing.

Methods: SCT utilizes the following commercially available kits: Promega PowerPlex^® S5 System, Thermo Scientific Phusion Blood Direct PCR Kit and Qiagen QIAamp DNA Blood Mini Kit. The PowerPlex^® S5 System amplifies four STR loci and amelogenin from extracted DNA. The PowerPlex^® S5 primer set is used with the Phusion Blood Direct PCR Kit to amplify the same loci directly from whole blood. Blood samples that are dried or clotted and cannot be used for direct amplification are first purified with the QIAamp DNA Blood Mini Kit. The purified DNA is then amplified with the PowerPlex^® S5 System. Capillary electrophoresis and fragment analysis are performed, and the STR profile of the blood is compared to the STR profile of the extracted DNA.

Results: SCT has been performed on more than 2,200 of the approximately 5,500 patients in the eyeGENE^® biorepository. Thus far, the number and genetic variation of the loci in the PowerPlex^® S5 System have proven sufficient for the size of the eyeGENE^® biorepository, as no two patients have been observed to share the same STR profile. Of the samples tested, 99.6% match. For the remaining 0.4%, eyeGENE^® and outside laboratory errors were identified and addressed through corrective actions.

Conclusions: The ability to identify potential laboratory errors is essential to the integrity and curation of samples in the eyeGENE^® biorepository. SCT improves the quality of the data returned to affected individuals and the data distributed to researchers using eyeGENE^® samples. By proving its utility, this basic approach serves as a framework that can easily be modified and implemented in similar repositories to improve sample quality and management procedures.

RS-96 Histological Assessment of Tumor Tissue Samples via the Mirror Image Method

Li H. Guo Y. Sun B. Chen K. Tianjin Medical University Cancer Institute & Hospital, Tianjin, China

Background: Human tissue biorepositories have become the key platform for the acceleration of basic and translational biomedical research on cancer in China. The maintenance of sufficient amounts of tumor cells is critical for a wide variety of cancer studies. Ensuring the high quality of frozen stored tissue specimens is a crucial requirement. However, different tumor locations and various methods of tumor tissue removal can lead to variable numbers of tumor cells from banked tissue specimens. Thus, an effective method to assess the tumor cell content is essential for tissue samples in biobanks.

Methods: In the present study, the mirror image method was used to evaluate the amount of tumor cells in stored tumor tissues of six common cancer types, including solid and hollow organ cancers. All tissues were stored in the Tianjin Medical University Cancer Institute and Hospital (TMUCIH). Histological assessment was performed by pathologists who conducted morphological diagnoses of tumor percentage on mirror image sections of frozen stored samples which were stained with hematoxylin and eosin (H&E).

Results: The tumor percentage of solid organ cancers was higher than that of hollow organ cancers (χ² = 17.11, P < 0.0001). Among solid organ cancers, the highest tumor percentage was observed in renal tumor tissues, and likewise esophagus tumor tissues had the highest tumor content among hollow organ cancers (multiple tests, P < 0.05). Three kinds of samples, which showed higher proportion of tumor content under 25%, were stomach, liver, and colorectal cancers, and the proportions were 15.0%, 10.9%, and 10.6% respectively.

Conclusions: The histological assessment based on the review of mirror-image H&E sections offers the most direct and objective judgment. The results can not only be applied to the tissue quality feedback process of biobanks but also guide a wide variety of scientific studies.

RS-97 Utilizing In-house Resources to Correct Inevitable Sample Mix-ups in a Medium Throughput Biorepository: Case Studies

Geddes T. Ketelsen B. Ahmed S. Pruetz B. Larson D. M. Akervall J. Wilson G. BioBank, William Beaumont Hospital (Beaumont Health Systems), Royal Oak, Michigan, United States

Background: It has been reported that there is up to a 1.5% sample identity error rate in biobanks today, and greater than 98% of these errors occur from issues during sample collection. Given the demands on a multidisciplinary approach to sample collection, and despite the rigorous QA/QC measures designed to minimize sample mix-ups in a contemporary biorepository, the potential for mistakes is still a concern. Programs to deal with potential uncertainties are a necessary part of every successful biobanking operation. The Beaumont BioBank and associated Core Molecular Laboratory have developed procedures to address these rare incidents.

Methods: Sample audits are performed regularly as part of the quality control program in the Beaumont BioBank. If a sample's identity is doubted, an investigative process is launched. Discrepancies in sample type and identity are rectified using a flow consisting of inventory history review, qualitative tests, and Agena Bioscience's iPLEX™ Pro Sample ID Panel. Each step of the investigation is recorded and a final report prepared.

Results:

Case 1: Samples with a “serum” sample type were discovered in an aliquot tube designated for “plasma”. A sample history audit suggested they were mislabeled and not in the wrong tube type. A thrombin-clotting test was performed on one of the daughter aliquots and a sample type of plasma was confirmed.

Case 2: Two patients' DNA tubes were labeled with the same sample number. Inventory software sample history audits of all collections in a two week period revealed that one patient was missing DNA sample aliquots. DNA was isolated from FFPE tissues from both patient donors and a sample ID assay confirmed patient/DNA relationships.

Case 3: An unlabeled tissue was discovered from the day's collection. DNA from suspected donor's FFPE tissues was compared to genomic DNA isolated from each donor's blood and tissue/donor identity was confirmed.

Conclusion: With a well-established QA/QC program and associated Core Molecular Laboratory, the Beaumont BioBank can discover sample identity errors and also remedy them through an effective investigational and correctional standard operating procedure (SOP). Through the process of problem identification, documentation, plan of action, and final resolution, samples that are discovered to be of questionable identification during routine audits can be confidently and correctly identified leading to certain rectification and resulting in added value.

RS-98 Quality Control and Internal Audits of Electronic Biospecimen Data by the Biopathology Center (BPC) at Nationwide Children's Hospital

Noyes L. Ramirez N. Nationwide Children, Columbus, Ohio, United States

Background: The BPC houses numerous biorepositories (including those of the COG, the GOG, and SWOG) and has a robust electronic Specimen Tracking and Reporting System (STARS) for biospecimen inventory management. BPC team members utilize STARS at each stage of biospecimen handling processes and are responsible for data entry into the system. Data entry still relies heavily on manual input, leading to potential for error. The quality and accuracy of biospecimen data is as equally important as the corresponding physical specimen – assuring this quality means an active effort towards regular verification of entered data to ensure correctness and completeness.

Methods: The BPC has a process defined to compare received paperwork with entered specimen data for specimens received using a specialized Quality Control (QC) Screen in STARS. Errors found are tracked in a log and returned (“QC Returns”) to the applicable individual for verification and correction. In addition, the built-in reporting functionality of STARS allows for specialized report creation to target specific data. These reports can then be used to identify potential errors in data entry and trigger necessary follow-up. These exercises are a portion of the overall BPC Quality Management Program.

Results: QC Returns are used as a Quality Indicator and the number and type are reviewed, quarterly. Appropriate corrective actions are taken to reduce the errors being made in data entry. Internal audit reports have been defined and can be used to catch common errors indicative of incomplete or incorrect data entry. When run on a regular basis, they could allow for a system of regular data correction and could lead to development of Quality Indicators stemming from internal audit data.

Conclusion: Checks and balances must persist even after physical handling of any biospecimen is complete to ensure continued data integrity. Finding efficient, yet effective means for data verification continue to be a challenge as they require a dedicated and pointed effort. Moving forward, the BPC aims to integrate these activities into the current workflow so that they can be completed on a timely and consistent manner.

RS-99 Quality Control for Metabolic Diseases Biobank: Storage Stability of Two Important Cytokine Biomarkers of Diabetes in Human Serum

Zhang Y. Lu H. Pan X. Wang C. Jia W. Shanghai 6th people, Shanghai, China

Background: The sensitivities of different biomarkers of metabolic disease were crucial for metabolic disease biobank. It is the biobank's duty to give professional advice to researchers on the storage conditions follow their research aim. In this research, two very important biomarkers for diabetes were tested on their storage stability in different temperature and time to get the best storage conditions for each of the biomarker.

Methods: The serum sample of 10 diabetes patients and 10 healthy volunteers were collected and storage in room temperature (about 20°C), 4°C,-20°C and −80°C for six months to evaluate the stability of adiponectin and FGF21 in serum. The samples were submitted for 10 consecutive analyses at intervals of 3 days for room temperature, 1week, 2weeks and 6 consecutive analyses at intervals of 1 month for 4°C,-20°C and −80°C. Adiponectin and FGF21 were tested by ELISA at each check point.

Results: Adiponectin was quite stable under all temperature conditions. However, the concentration of FGF21 changed significantly after 2 weeks of storage under room temperature and 4°C. It was stable under −20°C and −80°C for 6 months.

Conclusions: For different biomarkers, the storage stability can be very different. Therefore, the biobank must know which biomarkers will be evaluated and the storage time. Then choose the best storage temperature to balance efficiency and the quality of samples. This study will give evidence-based guidelines on the storage of serum samples for metabolic disease biobank.

RS-100 Assessment of ID Integrity with ABO Blood Typing from Questionnaire to Genomic Data in Japanese Biobank: ToMMo

Kudo H. Minegishi N. Nishijima I. Terakawa T. Nobukuni T. Yamaguchi-Kabata Y. Saito S. Ogishima S. Katsuoka F. Nagasaki M. Yasuda J. Yamamoto M. Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan

The biobank of Tohoku Medical Megabank Organization (ToMMo) was established for storing biological specimen and health data from 150,000 participants of community-based and family-based prospective cohort studies in districts where the residents suffered heavy damage from the Great East Japan Earthquake and Tsunami in 2011. We have collected >1,000,000 samples from 70,000 participants. In order to examine the accuracy of handling in our biobank, we have analyzed the consistency of the cohort and genomic information.

In our whole-genome sequencing data of 1,070 participants, and the 10,000 SNP array based analysis, we found 2 and 26 cases of gender-mismatch with the cohort questionnaire, respectively. Therefore, we re-extracted genomic DNA from backup buffy coat stocks of each sample, validated them using the different SNP array or short tandem repeat (STR) analysis and corrected 2 of 2 and 15 of 26 mismatch cases, respectively. There are several methods to validate that multiple DNA samples are originated from identical participants. However, it is difficult to confirm whether or not IDs of genomic data are consistent with IDs of participants donating their blood and health information.

While gender-matching test has high specificity, it is only 50% sensitivity. Thus, we planned to use ABO blood type information to check ID-integrity, questions on ABO blood type have been included in cohort questionnaire, and we have been testing RBC blood type, which is checking surface antigens of RBC, routinely. In Japan, ABO blood types of pregnant women are written in the maternity record books, and >98% of our participants knew and filled their own ABO blood types in their questionnaire forms. We performed PCR-based analysis for ABO blood typing, as well as STR analysis and showed that the handling of remaining 11 cases in biobank had been cleared the doubt. By tracing handling steps of error cases in laboratory management information system (LIMS), we discovered actual error steps, and found other 17 ID-error samples, which share the same error steps with above samples. Of these 17 error samples, we estimated that 10 samples could be traced by ABO genotyping but not by gender-matching test. In consequence, error rate in handling 11,070 samples in our biobank was estimated as 0.30%. The information of ABO blood type should be useful for detecting errors in biobanking procedures.

RS-101 Estimation of Cell-type Composition in Peripheral Blood Mononuclear Cells Improves Quality of OMICS Data in Biobank Research.

Shiwa Y. 1 Furukawa R. 1 Ohmomo H. 2 Ono K. 2 Satoh M 1 5 Hitomi J. 3 7 Sobue K. 4 6 Hachiya T. 1 2 Shimizu A. 2

1 Division of Biobank and Data Management, Iwate Tohoku Medical Megabank Organization, Iwate Medical University, Iwate, Japan 2 Biomedical Information Analysis, Iwate Tohoku Medical Megabank Organization, Iwate Medical University, Iwate, Japan 3 Deputy Executive Director, Iwate Tohoku Medical Megabank Organization, Iwate Medical University, Iwate, Japan 4 Executive Director, Iwate Tohoku Medical Megabank Organization, Iwate Medical University, Iwate, Japan 5 Division of Biomedical Information Analysis, Iwate Medical University, Iwate, Japan 6 Department of Neuroscience, Institute for Biomedical Science, Iwate Medical University, Iwate, Japan 7 Department of Anatomy, School of Medicine, Iwate Medical University, Iwate, Japan

Background: Recent epigenome-wide association studies (EWAS) have elucidated the associations between epigenetic variation and disease risk such as rheumatoid arthritis, cardiovascular disease, and skin disease. In order to perform EWAS using samples collected in large-scale biobanks, there is a need of strict quality assurance and quality control for the stability of the samples. As for most existing large-scale biobanks, whole-blood samples had been transported at a low temperature (2–8°C). However, the effect of shipping at a low temperature on DNA methylation profile has yet to be addressed. In this study, we evaluated the effect of cold storage on DNA methylation profile of peripheral blood.

Methods: Three 7 mL tubes of whole-blood samples were collected from 16 healthy subjects (ten males and six females). Two of the three tubes were immediately processed to the isolation of buffy coats and DNA (Ctrl1 and Ctrl2 conditions). The remaining one tube was stored at 4°C for 24 hours followed by the isolation of buffy coats and DNA (4°C-24h condition). We measured genome-wide DNA methylation profiles of the extracted DNA using the Infinium HumanMethylation450 BeadChip and compared the profiles between conditions.

Results: No significant difference in the DNA yield and DNA quality were detected between conditions. A quantile-quantile (Q-Q) plots comparing the Ctrl1 and Ctrl2 showed little systematic bias between technical replicates, whereas a QQ-plot comparing the 4°C-24h and Ctrl1 conditions revealed that there certainly exists systematic bias in DNA methylation profile due to the storage at a low temperature. The cell-type composition in whole-blood estimated from DNA methylation profiles using a statistical method indicated that the proportion of granulocytes was significantly increased under the 4°C-24h condition. This trend was confirmed by flow cytometry. Using a linear regression model with an explanatory variable related to cell proportion of granulocytes, we successfully decreased the systematic bias under the 4°C-24h condition.

Conclusions: The change of cell-type compositions of whole-blood due to cold storage is a major factor of systematic bias in DNA methylation profiles.

RS-102 Effect of Duration of Ex Vivo Ischemia Time on RNA Quality in Biobanked Human Renal Cell Carcinoma Tissue

Cong X. Sun H. Liu T. Wang L. Liu Y. Tissue Bank, China-Japan union hospital of Jjilin University, Changchun, Jilin, China

Background: RNA degradation is a major problem in tissue banking, and the effects of the ex vivo ischemia time and transport conditions on RNA integrity and gene expression were not well understood.

Methods: At surgery, fresh kidney cancer tissues from five patients were cut into pieces and snap frozen. Additional fresh tissue pieces were (i) left at room temperature, (ii) kept on ice, or (iii) placed in normal saline before being snap frozen after 0.5, 1, 2, or 4 h. RNA integrity was determined by microchip electrophoresis, and gene expression was analyzed by Real-time PCR.

Results: RNA remained intact after 4 h on ice, whereas degradation was found in tissues left at room temperature or in saline. The expression of hypoxia-regulated genes HIF-1a and HMOX1 increased at three different transport conditions. Stress response gene FOS and JUN increased significantly after 0.5–2 h of ischemia. With respect to anti-apoptotic genes, BCL2 and BAG1 remained stable on ice after 4h, BCL2 was stable while BAG1 increased at 4h at room temperature and a slight upregulation was noted at 2h in 0.9%NaCl. In contrast, EGFR and MMP-9 expression levels remained basically stable after 4 h of exposure to different conditions.

Conclusions: Fresh human cancer tissue samples should be transported on ice before biobanking to avoid a major reduction in RNA integrity. Ischemia time and storage conditions affected expression of genes in certain functional pathways.

RS-103 Defining an Efficient, Effective Process for Standard Operating Procedures Increases the Level of Quality in Mayo Clinic Biorepository Program

Kwong H.K. 1 Speltz M.L. 1 2 Root R.M. 1 2 Bolster S. 1 2 Werner D.A. 3 Flotte T.J. 2 3 Highsmith W.E. 1 3 Thibodeau S.N. 3 Cicek M.S. 1 3

1 Biospecimens Accessioning and Processing Core Laboratory, Biorepository Program, Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA 2 Pathology Research Core Laboratory, Biorepository Program, Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA 3 Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA

Background: The Mayo Clinic Biorepository Program provides laboratory services including specimen accessioning, processing, nucleic acid extraction, tissue based services, specimen tracking, shipping, and storage in a highly integrated core laboratory vital to basic, translational and epidemiological research. The number of processes, personnel, and storage specimens within the Mayo Clinic Biorepository Program has increased substantially over the past few years due to implementation of automation and offering new service lines. There is an expectation within the program that laboratory personnel would perform the processes correctly and consistently to maintain the best specimen quality. Due to the rapidly changing processes and procedures, a vigilant effort was needed to ensure procedures were in place and appropriate training was conducted prior to implementation. Additionally, the laboratories relocated in summer of 2014 requiring procedure updates, equipment and process validations, and training documentation.

Methods: The Quality Specialists in the Mayo Clinic Biorepository Program defined a process which is modeled after the Mayo Clinic Department of Laboratory Medicine and Pathology for creating, updating, reviewing, and inactivating Standard Operating Procedures. This process ensures all documents are written in a standardized format, are reviewed and approved, and are stored and retrievable. This process also defines the steps required for notification and training of personnel affected by new, revised, reviewed, and inactivated documents.

Results: Over 900 documents have been created utilizing the defined document process since 2012, and each document has been maintained through annual review since 2013. In preparation for the laboratory relocation, 245 validation documents were created and completed, 125 procedures and forms were updated, and training of personnel were documented. The implementation of Standard Operating Procedures has allowed for consistent performance, thus decreasing the chance for error and improving the quality of the specimens in the Mayo Clinic Biorepository Program.

Conclusion: Utilizing the defined document process of creating and maintaining Standard Operating Procedures helped build the foundation of quality in the Mayo Clinic Biorepository Program. It has also enhanced effectiveness and efficiency of laboratory operations and provided confidence to customers and others about the consistent performance of the laboratory.

RS-104 Robust Quality Control and Continuous Surveillance of Laboratory Processing Methods

Mathay C. 1 Colson B. 2 Betsou F. 1

1 Biorefinery, Integrated BioBank of Luxembourg, Luxembourg, Luxembourg 2 QuoData, Dresden, Germany

Continuous quality control of a processing method permits to survey its performance in terms of the yield and the quality attributes of the sample output. Quality control also permits to detect trends in the method's performance, such as decreases in DNA extraction yields. Here, the processing methods “DNA extraction from blood” and “RNA extraction from blood” (PAXgene-stabilized) are shown as examples where we continuously monitor DNA and RNA extraction yields and purity over time. For samples which are processed by the same method, the measurement data (e.g. DNA concentration, DNA ratio 260/280) and information about the measurement (e.g. date, operator, device, technique, etc.) are uploaded in the software mqVAL (QuoData). We use the statistical standard ISO 13528 with Q/Hampel adaptation because it is the most robust: outliers don't need to be removed before the upload in the program mqVAL. The statistical approach known as Q/Hampel uses the Q method for the calculation of the robust standard deviation STDEV together with the Hampel estimator for the calculation of the robust location parameter, both being highly insensitive to outliers. Once data are uploaded, mqVAL calculates the mean, standard deviations and all other statistical key values and shows the control charts which present the mean value as the “center line” and the corresponding warning (mean + /− 2STDEV) and control limits (mean + /− 3STDEV). Once the control charts are established, all the results of an extraction run are compared to the corresponding control chart and results should fall within the range mean + /− 1STDEV in the majority of cases. If for example all samples of a extraction run show lower DNA yields than mean – 1STDEV, then action is taken in order to identify the cause of this decrease. This form of data surveillance permits to confirm consistency in the quantity and quality of the product and to monitor the performance of a processing method.

RS-105 Minimal Technical Requirements for Biobanking Capacities

Sargsyan K. Huppertz B. Macheiner T. Bayer M. Biobank Graz, Medical University Graz, Graz, Austria

There is a wide functioning network of biobanks in CEE connected to Biobank Graz since 2008. In one of projects funded by Austrian Development Agency, the COO of Biobank Graz consulted the Minister of Health and Research of Serbian Republic of Bosnia and Herzegovina in terms of strategic development of medical research. Under this umbrella a position paper for minimal requirements of building a biobank in emerging counties was developed. The most challenging part of it was the part of technical requirements.

Following sectors of space requirements was discussed:

- Sector FFPE storage

- Sector ≥ −150°C storage

- Sector −80°C storage

- Sector tissue work place

- Sector blood work place

- Sector PC working place

Following important technical aspects were considered for all sectors:

- cooling sources

- minimum temperature

- maximum temperature

- lighting conditions

- workplace

- storage system

- documentation stock

- ventilation requirements

- atmospheric moisture

- interior equipment (electrical lines, wall cover quality etc.)

- fire safety

- floor barring capacity

- building control technology

- etc.

A solid concept for technical requirements was developed, and an architecture team was commissioned to develop a building concept. The construction of the biobank is on-going.

RS-106 Bio-Sample Thermal Protection: Thermal Excursions of Cryogenically Frozen Vials in Various Cryobox Configurations during Transient Warming Events and Best Practices to Stay Below Tg

Salvetti M. Fink J. Stira M. Croquette E. Walsh C. Rowland J. Life Science, Brooks Automation, Chelmsford, Massachusetts, United States

Background: Many biological samples are stored at cryogenic temperatures (i.e. temperatures below −150°C) to preserve their viability. Normally, these samples are stored in individual vials and then placed into cryoboxes. The cryoboxes are typically stored in liquid nitrogen vapor-phase freezers. The underlying assumption for storing below -150°C is that biological samples show highly reduced degradation and metabolic activity while below Tg (the glass transition temperature). However, every time a cryobox is manipulated or temporarily removed from an LN2 freezer the samples experience thermal excursions and risk harming the samples by inadvertently crossing the Tg threshold. Understanding individual sample warming is complicated, because individual vials in the cryobox do not warm equally and at the same rate. Their temperature variations and rate of change are dependent on several factors, such as their location inside the cryobox, proximity to surrounding vials, vial size and volume of the sample.

Method: The aim of this paper is to provide supporting data to characterize the thermal excursions experienced by vials contained inside various typologies of cryoboxes in varying configurations during typical transient temperature events. Specifically, we focus our attention to the frequent cold chain steps consisting of accessing single vials from a cryobox in long-term storage and transporting the whole cryobox at ambient temperature or in a dry ice (-80°C) environment. We will also discuss thermal inertia effects contributing to vial temperature increase after the cryobox is placed back in the LN2 freezer environment.

Result: In general, the warm-up rates experienced by biological samples in vials stored in cryoboxes depend on the thermal energy exchanged with the surrounding environment via radiative, convective and conductive heat transfer. The magnitude of the heat transfer is driven by multiple factors: the warmer environment temperature and the overall time of exposure, the size and shape of the vials, the cryobox typology and relative population, the type of handling (manual or automated), etc.

Conclusion: This paper will rationalize all the above factors and present experimental measurements showing typical expected warm up rates of various vial and cryobox configurations. As a result, best practice time constants for handling cryoboxes without exposing the individual biological samples to excessive thermal excursions above Tg are suggested.

RS-107 Unexpected Intratumoral Necrosis in Kidney Tumors: Quality Assessment Microscopic Evaluation of Samples That Grossly Appeared Viable

Judd A. Schultz F. Bocklage T. U New Mexico School of Medicine, Albuquerque, New Mexico, United States

Background: Tumor banks often prospectively collect surgical specimens that are resected for treatment purposes. In the Pathology Grossing Suite, a pathologist or pathologist's assistant will select grossly viable tumor tissue for subsequent banking. However, gross inspection may underestimate the amount of necrosis present in such a sample. A necrotic sample is suboptimal for banking. We sought to determine the necrosis frequency, heterogeneity per case and incidence within tumor types in specimens grossly considered 100% viable by experts in pathology.

Methods: An experienced pathologist's assistant or senior surgical pathologist visually inspected all kidney tumors and subsequently cut a piece of tumor for banking (maximum size: 2.5 cm). All tumor specimens were considered grossly 100% viable. The specimens were rapidly divided by Repository technologists equally into frozen and FFPE aliquots. A single H&E section was prepared from each FFPE block. One senior surgical pathologist (the tissue bank medical director) assessed the sections for: 1) percent necrotic tumor and 2) confirmation of the diagnosis. The data were subjected to statistical analysis.

Results: One hundred forty nine tumors were sampled with 1-13 FFPE blocks prepared per patient tumor with a mean of 2.76 and median of 2. The 149 tumors comprised the following number of blocks: 238 clear cell renal cell carcinoma, 25 chromophobe carcinoma, 17 papillary carcinoma, 6 renal cell carcinoma NOS, 2 sarcomatoid RCC, 36 urothelial carcinoma, 22 Wilm's tumor, and 36 oncocytoma. Twenty six cases (17.4%) showed necrosis on microscopic review. The overall mean amount of necrosis per case that exhibited necrosis was 39.8% with a range of 5–100%. Number of slides per case with necrosis ranged from 1-7 with a mean/median per case of 2.42/2. Welch Two Sample t-tests were performed. The kidney tumor type most likely to exhibit necrosis on subsequent microscopic exam was higher grade and/or large clear cell carcinoma. Clear cell RCC was significantly more often necrotic than papillary RCC (p - 0.002) but not chromophobe carcinoma.

Conclusions: In general, experts at gross pathology are able to select completely histologically viable tumor for banking 83% of the time. Although less than optimal for evaluation, even tumors with necrosis averaged approximately 60% viable tumor; thus gross inspection, while imperfect, does enable collection of adequate amounts of viable kidney tumor, no matter what type.

RS-108 The Biospecimen Research Database, a Literature and SOP Resource for the Biobanking Community

Moore H. 2 Engel K. B. 1 Bass B. P. 3 Greytak S. 3 Guan P. 2 Keen J. 2 Kigonya P. 4 Klinger C. 4 Lander W. B. 4 Lolla L. 4 Qi L. 4 Shive C. 4 Singh S. 4 Tabor D. 4 Wu S. 4

1 Preferred Scientific Group, Arlington, Virginia, United States 2 Biorepositories and Biospecimen Research Branch, National Cancer Institute, Rockville, Maryland, United States 3 Kelly Government Solutions, Rockville, Maryland, United States 4 Leidos Biomedical Research Inc., Rockville, Maryland, United States

The Biospecimen Research Database (BRD; http://biospecimens.cancer.gov/brd) is a public database developed and maintained by the National Cancer Institute's Biorepositories and Biospecimen Research Branch (BBRB). Expert curations of 2200 articles on human Biospecimen Science are currently available. The BRD has recently expanded to include Standard Operating Procedures (SOPs) relating to collection, preservation, processing, and storage of human biospecimens. We encourage the ISBER community's contributions to this new SOP library. SOP entries are organized in a hierarchy consisting of three tiers: (1) SOPs that are established protocols; (2) Biospecimen Evidence-based Practices (BEBP) (procedural guidelines developed using literature evidence); and (3) Expert-vetted, evidence-based guidelines vetted by a panel of experts in the field. Sets of related SOPs are assembled in Compendiums, and both SOPs and Compendiums are version-controlled and downloadable. Additional improvements include (i) a dynamic homepage; (ii) keyword search for both literature curations and SOP documents that allows inquiries of specific genes and biomarkers; (iii) user commenting on individual literature curations, SOP entries, and Compendiums; and (iv) a linkout to BRD curations from NCBI's PubMed. New papers are added daily and a “Suggest a New Paper” feature is available to all users. Feedback is welcome, and we encourage submission of SOPs from your lab or institution for inclusion in the BRD at biospecimens@mail.nih.gov .

RS-112 Preparing your Biorepository for CAP Accreditation

Pruetz B. Geddes T. Larson D. M. Farwell M. Manier T. Thibodeau B. Akervall J. Wilson G. BioBank, Beaumont Health System, Royal Oak, Michigan, United States

Background: Competency and sound processes are essential to the quality and research behind any Biorepository. There are “Good Practice” guidelines throughout organizations to assist a new or established laboratory on how to collect and store biospecimens by following standard operating procedures (SOPs). Beyond these SOPs, additional factors for an accredited facility must include a quality management plan, quality assurance/control program, safety, IT, and facility oversight.

Process: Applying to the Biorepository Accreditation Program (BAP) and breaking down the necessary components from the personalized checklist helps organize your facility for the CAP inspection. Assigning leaders to champion specific processes will help divide the responsibilities of the accreditation. Obvious requirements include handling, collection, storage, and quality of samples. Additional BAP requirements include administrative oversight of employees, information technology and security, institutional review and human subject protection. CAP places general laboratory standards to the biorepository program, in the essence of having safe work practices, developing a chemical hygiene plan, instilling competency and education, maintaining standardization checklists across your facility as well as measuring and charting metrics throughout your processes. Another key piece is to secure funding that surrounds the accreditation and any ancillary equipment that may have to be purchased to meet the standards.

Results: Accreditation is granted after the onsite inspection is completed and any deficiencies are corrected, according to the inspector's summation report. Accreditation is for three years providing certain CAP standards are upheld. Self-inspections are required during year 2 and 3, and another onsite inspection occurs during the fourth year.

Conclusion: CAP accreditation gives assurance to biospecimen quality and oversight to human subject research. An established system will reflect positively on the utilization and accuracy of the samples when research and distribution is accomplished. Maintenance of the CAP accreditation takes commitment and resources, but it is a daily reminder of the standards that are necessary for moving investigator-driven biomarker research forward towards personalized medicine.

Biodiversity/Environmental/Microbial Repositories

BEM-7 Biodiversity/Environmental Microbial Repository Network in Developing Countries-Nigeria in Focus

Onuoha P. C. Diagnosis/Biobanking, Patdomado Divine Diagnostic Services, Ipaja Alimosho, Lagos, Nigeria

Biodiversity/Environmental Microbial Repository Network in Developing countries cannot be over emphasized. These countries are poor and under developed thus experiencing low diversification and poor repository activity with all its benefits, thus affects research and lowers the economy adversely. Microbes are very important for our existence. Scientists have proven that human content is 10% and 90% is microbes. Research have confirm that there are over 5-7 million microbes exist but only 1.7-2 million has been identified. Genetic studies have also proved that microbial diversification in developing countries tend to contribute greatly to certain ill health like obesity, infertility as we cannot change our genetic makeup but can adjust it with behavior and technological application. Use of some natural plants as extracts by scientists in bacteria identification during research is an evident of Microbial diversification. In developing countries Microbe diversity is versatile from positive to negative hence they are found everywhere. Positively, in drug discoveries, stem cell regeneration, food production involving nitrifying and purifying microbes, treatment of some diseases such as gastritis and colitis with clostridium deficile. Negatively in disease condition like human immunodeficiency virus, ebola, tuberculosis, leprosy, staphylllococus, some fungi has created opportunity for research and broader diversity thus improving repository network. Although, in Nigeria, so many problems such as poverty, terrorism, deforestation, poor environmental and ecosystem management, poor agricultural practices, over population, political instability, lack of infrastructure, substandard storage facility, lack of trained personnel, lack of awareness and publicity, absence of point of reference and controls, deviation, no validation, lack or poor data correlation have been pulling down the microbial diversity and repository network in the developing countries, but with lean and six sigma application, a lot will be achieved if we consult, analyze and implement with effective management, quality control and assurance especially in storage by using ultra refrigerators, resource sharing, clinical research on human subjects, ecosystem maintenance, certification and confidentiality, microbial date standard repository-(mDSR), coding, avoid exotic agents, provide consumable, plan cost recoveries, personal hygiene continuous networking through various medium and partnership.

BEM-8 The Conservation of our Endangered Animals, Plants and Ecosystems Is One of the Greatest Environmental Challenges Facing Georgia Today

Nadiradze K. BioBanking and Embryo Cryopreservation, Association for Farmers Rights Defense, AFRD, Tbilisi, Georgia

The conservation of our endangered animals, plants and ecosystems is one of the greatest environmental challenges facing Georgia today as Climate change is climbing up to the research agenda of Association for Farmers Rights Defense, AFRD as extreme weather has raised questions in public discourse about the role of anthropogenic warming and concerns about its future impacts; slowdowns in emerging economies and the impact of climate change on conservation of Agro Biodiversity as Global warming, global population increase explosion in global food demand and the pressure on land, energy crisis, environmental degradation, threats to agro biodiversity, all these changes and trends are challenging our understanding of the modern challenges for creation biobanks in Georgia of endanger species of plants (in vitro, in vivo, in situ, ex-situ, in farm and on farm, also germplasm collection). The key reason for our historically high extinction rates is habitat degradation and loss, initially from over-grazing and clearing for agriculture, and more recently from the clearing of native vegetation for urban development. Innovative approaches are needed to tackle the challenge of balancing development needs, while also conserving biodiversity for the future. Biobanking is a market-based scheme that provides a streamlined biodiversity assessment process for development, a rigorous and credible scheme as well as an opportunity for rural landowners to generate income by managing land for conservation. Biobanks generated by Farmers and landowners who commit to enhance and protect biodiversity values on their land through a biobanking agreement. AFRD have just launched a training manuals aimed at farmer groups, extension staff and project managers who are implementing agro Biodiversity conservation on farm and in farm. The project outlines a framework for providing resource-poor communities' access to the biobanking methodologies for identification of most threatened breeds, species and varieties of plants and animals, also bees and poultry. The aim of this project is how explore Farmers capacity and involvement in identification of loss biodiversity and meaning of biobanks.