ISBER Abstracts

1 Victorian Cancer Biobank, Carlton, Victoria, Australia HT 01. Cost Recovery—Researcher Expectations versus Funding Agency Requirements

Background: In 2006 the Victorian Government funded the establishment of the Victorian Cancer Biobank (VCB) Consortium from four pre-existing tissue banks. As a requirement of the funding, the Consortium agreed to implement a cost recovery schedule to subsidize operational costs, by cost recovering approximately 10% of the grant funding in the first 3 years.

Methods: A modular format, used by other international biobanks, was adapted to suit our operations and fees. The fees were determined by considering the pre-consortium fees, researcher's expectations and the operational cost incurred. A two-tier model was proposed, charging a higher rate for the commercial sector to subsidize the cost of collecting and supplying biospecimens to the academic sector.

Results: The Consortium Committee approved the proposed cost recovery schedule in 2007. From this time the income from cost recovery has increased steadily. However, as 90% of the cost recovery income is generated from biospecimens provided to the academic sector, cost recovery income for 2010 was only 8% of the funding received.

Conclusion: The implementation of a cost recovery schedule did not meet the expectations of all researchers as some previously paid only minimal fees. However, over time, most academic researchers have accepted the need to cost recover. The cost recovery income is nearing the target agreed to in the Business Plan. The VCB is now increasing collaboration with the industry/commercial sector, which should increase the income and exceed the target. This will therefore reduce the dependency on government funding.

1 Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia 2 Health Issues Centre, Melbourne, Victoria, Australia 3 University of Melbourne, Melbourne, Victoria, Australia 4 The Royal Melbourne Hospital, Melbourne, Victoria, Australia 5 University of Tasmania, Hobart, Tasmania, Australia 6 BreastScreen Victoria, Melbourne, Victoria, Australia 7 Breast Cancer Network Australia, Melbourne, Victoria, Australia HT 02. lifepool: A Collaboration between Women and Researchers

Background: lifepool is a large prospective cohort of women on whom health and lifestyle information, mammogram results and health outcome data will be gathered. A subset of participants will provide biospecimens. lifepool will support research into breast cancer and aims to recruit 100,000 women.

BreastScreen Victoria (BSV) is part of the national breast cancer screening program in Australia and a key collaborator in lifepool. Using established BSV contact protocols, women are invited to consider joining lifepool.

Primary aim: To recruit participants while ensuring no negative impact on screening participation rates.

Secondary aim: To determine the recruitment protocol maximizing participation in lifepool.

Methods: lifepool, in partnership with the BSV Consumer Advisory Committee and Health Issues Centre, conducted a series of consultation workshops to test participant information and consent forms (PICF) and recruitment protocols.

Potential impact on participation in the BSV program and clarity of information were explored with women from urban and regional communities. Amended protocols were tested in pilot recruitment projects.

The lifepool project undertakes to inform individual participants about research data of significance to their health, after expert review. The challenge of providing accurate risk disclosure to a healthy population is being addressed with input from a range of legal, insurance and health ethics experts.

Results and Conclusion:

No significant impact on screening participation

1 Novartis, Cambridge, MA HT 03. Novartis Translational Research Initiative: Taking Biobanking to Early Pharmaceutical Research

Background: Use of high quality, well-annotated human biological material will improve understanding of disease mechanisms, validate biomarkers, and identify novel drug targets. It is also a way to de-risk drug discovery projects by testing early hypotheses in relevant disease context. The Novartis Translational Research Initiative was recently launched to facilitate access to strategically valuable human biosamples, to support early research projects and translational research studies.

Methods: Achieving this objective will require a multi-year approach to build capacity and establish processes on specifics of working with human samples. This strategic initiative provides framework and answers to questions such as:

How can research teams propose and implement actionable projects?

Conclusion: This presentation outlines some of the operational, informatics and organizational measures the Novartis team has taken to establish best practices for using human bio-specimens in a multinational pharmaceutical research organization.

1 IRCSS - Gaslini - Genova, Genova, Italy 2 S.C.LAB. DI GENETICA, GENOVA, Italy 3 Centro Parkinson e Disturbi del Movimento, Milano, Italy 4 University of Siena, Siena, Italy 5 University of Padua, Padova, Italy 6 IRCSS - Fondazione Cà Grande - Ospedale Maggiore, Milano, Italy 7 Istituto Besta, Milano, Italy 8 IRCCS - Casa Sollievo della Sofferenza, San Giovanni Rotondo, FOGGIA, Italy 9 Second University of Naples, Napoli, Italy 10 Istituto Besta, Milano, Italy HT 04. TELETHON Network of Genetic Biobanks (TGBN)

Background: TGBN is the first national, coordinated resource of biospecimens from patients affected by genetic diseases. Supported by Telethon Foundation, TGBN interconnects well-qualified Italian biobanks with the aim to support both the biomedical community as well as the donors, patients and their families.

Methods: TGBN operates in a harmonized environment which ensures the privacy protection of and the donor confidentiality, and the quality throughout the entire process of biobanking that includes collection, storage, distribution and related data recording. TGBN collects various types of biological materials: fetal/adult cell lines and tissues, DNA/RNA, blood/plasma samples from approximately 700 different genetic diseases.

Activities and policies are stated in the Charter, which includes ethical guidelines, organization and governance policies, expected benefits and undertaken duties. The governance bodies are represented by the decision-making Network Board and by a consultative Advisory Board composed of legal/ethical experts and a family association representative. Additionally, TGBN can rely on a Coordinator Emeritus and a Telethon Advisor. To achieve its main objectives, TGBN has created a public web-site (www.biobanknetwork.org) and has adopted a common IT-infrastructure, managing all data collection, sample submissions, requests and inventory.

Results: Aggregated data are published in the on-line catalogue. The IT-system manages and monitors the complete in/out workflow of samples which is therefore fully handled and shared online by all Partners.

Conclusion: Samples will be made available to users for research purposes, provided that an adequate portion of the samples derived from individuals affected by undiagnosed and rare diseases are safeguarded to the patients' advantage to allow retrospective analysis.

1 University of Michigan, Ann Arbor, MI HT 05. Tracing the Biorepository Fasciae: The Creation of Metadata Linkages that Reflect the Presence, Use and Application of Biospecimen Repository Inventories in Research

Background: There is growing interest in developing seamless metadata linkages that relate biospecimen inventories with associated external information resources emerging from the use of these specimens. The creation of “metadata”, or data about data, is well established among researchers operating repositories. Metadata also includes “data results” emerging from the use of biospecimens in research such as essays or microscopic examination as well as publications and reports. When these various metadata are maintained in unrelated collections this limits their potential value to the research community.

Methods: This presentation reviews the state of the archival sciences and the multiple databases that catalog the existence of biospecimen inventories, data records and publications that report analysis of biospecimen data. Examples would include models such as the RAND RD-HUB, NACDA, PubMed and the NIGMS Collection. It will also present on emerging tools that help to organize these independent sources of information into an integrated resource.

Results: The potential for integrated systems clearly exists. Examples such as the SWAN biorepository at the University of Michigan show that this process is already being done for individual research projects. New metadata management tools being developed at NACDA show how this process can be extended to multiple collections, housed and maintained at independent sites.

Conclusion: The creation of information resources that reflect not only the presence of biospecimens, but their use and contributions to science offers great promise for the future. It requires a multidisciplinary approach but it will ultimately add considerable marginal value collections in biospecimen repositories.

1 Foundation biobank-suisse, Bern, Switzerland HT 06. Lack of Information about Clinical Biobanking of Biospecimens Used for Biomarker Discovery in Scientific Publications

Background: Biomarkers are an integrated part of personalized medicine and will play an even more important role in the future. Very promising new biomarkers are discovered every year based on research done with human biospecimens. However little is known about the clinical biobanking activities (e.g. transport, storage, processing) with these biomarkers as quality indicators and how it is described in the scientific literature.

Methods: A PubMed search was done with key words “biomarker discovery, human, English.” Open source publication from 2004 and 2009 (excluding reviews and studies not using biospecimens) were analyzed for published information about clinical biobanking of biospecimens used for biomarker discovery.

Results: The number of publications (total/open source) on biomarker discovery increased from 266/31 in 2004 to 742 /94 in 2009. In 2004 51.6% and in 2009 56.4% of open source studies did not have any information on clinical biobanking. If available there was mostly information only on storage or processing. Biobanks as source of biospecimens increase from 16.1% to 26.6%. Tissue was used in about 1/3 of studies; blood/serum in 1/4 in 2004 and 1/3 in 2009, respectively.

Conclusion: To interpret published results on biomarkers discovery information about clinical biobanking are important (garbage in, garbage out). We found that insufficient amount of information - if at all - was provided. There is a call for action to different stakeholders: biobankers should collect the information, researcher should include it in the paper and journal publisher should specifically ask for it.

1 MedLawconsult, The Hague, Zuid-Holland, Netherlands HT 07. Individual Feed-Back from a Cross Cultural Perspective

Background: If individual feed-back of results of research with tissue is the newest hotly debated ELSI issue in biobanking, the question arises which values or interests drive that discussion.

Methods: It will be shown that the debate started in the United States. In Europe several biobanks exist, either population based, or hospital integrated banks using residual tissue, where the issue was not raised and the non individual feed-back policy thus far did not give rise to ethical complications or less enrolment. This can be explained by the European health care systems and associated cultural values, like willingness to contribute to the public good. European health care is solidarity based and tightly regulated as to what doctors are allowed to offer as diagnostic tools. That does not include not validated procedures with uncertain implications for clinical management of the patient. Hence guiding principles logically follow that individual donor feedback is only allowed, when it has validated clinical meaning, can meaningful serve the patient's treatment and would not have been used in the available diagnostic and treatment options of the health care system anyhow. In addition donors generally do not expect priority ranking to access to health care because of their participation in a biobank.

Conclusion: The US health care system is very different and so are some social values. The European values will be defended. The US debate should be imported with considerable caution and the United States might even learn something from the more restrictive European approach.

1 National Institute of Standards and Technology, Charleston, SC ER 01. NIST's Environmental Banking Expansion Efforts in the Pacific Islands Region

Background: The National Institute of Standards and Technology (NIST) has been involved in environmental specimen banking since 1979 through various sponsored programs. Current projects include the National Marine Mammal Tissue Bank (NMMTB), the Seabird Tissue Archival and Monitoring Project (STAMP), and the National Oceanic and Atmospheric Administration's (NOAA) National Status and Trends (NS&T) Mussel Watch Program.

Methods: These existing projects have proven successful in environmental banking producing overwhelming numbers of presentations and publications. Recently, NIST began expanding environmental specimen banking efforts in the Pacific Islands region. Existing banking expansion projects include the NMMTB, the STAMP, and the NS&T Mussel Watch Program. This expansion will increase the number of species available for analysis in NIST's existing specimen bank. The NS&T program currently has four collection sites in the Hawaiian Islands and expansion efforts for the banking component may extend throughout the Hawaiian and Pacific islands. Additionally, new banking projects are also being established in the Pacific Islands including sea turtle and coral banking. Protocols for these new projects will be based on the already existing and successful projects, however these new endeavors present challenges when considering storage location, storage type, sample type, and future analysis.

Conclusion: In addition to the expansion of the marine animal projects, NIST is looking to establish a branch of the Marine Environmental Specimen Bank (Marine ESB) facility in the Pacific Islands region. Additional details about these projects as well as the new NIST partnerships in the US Pacific Region will be discussed.

1 National Institute of Standards and Technology, Charleston, SC ER 02. Monitoring Total Arsenic and Selenium Mass Fractions in Seabird Egg Samples from the Seabird Tissue Archival and Monitoring Project (STAMP)

Background: Environmental specimen banks (ESBs) can be an excellent resource in providing samples for monitoring organic contaminants and trace elements in animals to determine if environmental trends exist.

Methods: The Seabird Tissue Archival and Monitoring Project (STAMP) was developed in 1998–1999 to serve as a systematic, long-term (decadal) ESB program that identifies and tracks anthropogenic contaminants in Alaskan seabirds. Seabird eggs are routinely collected from colonies located throughout Alaska and are archived by the National Institute of Standards and Technology (NIST) in the Marine ESB at the Hollings Marine Laboratory, Charleston, SC.

Results: Total arsenic (As) and selenium (Se) mass fractions were measured in 78 seabird egg samples representing 3 species of seabirds from 2008. Collection sites focused on colonies located in the Norton Sound region as well as two long-term monitoring sites, St. Lazaria Island in the Gulf of Alaska and St. George Island in the Bering Sea. Egg samples were analyzed using collision cell kinetic energy discrimination inductively coupled plasma mass spectrometry (ICP-MS). Total As mass fractions ranged from 0.015 μg/kg to 0.320 μg/kg while the levels of Se ranged from 0.411 μg/kg to1.02 μg/kg. Total As and Se mass fractions were higher in most of the samples collected from the Norton Sound colonies compared to other colonies.

Conclusion: Norton Sound is located in a highly mineralized region of Alaska and is an area of historical gold-mining that continues today and could be a contributing factor to the bioaccumulation of arsenic and selenium in this region.

1 Westmead Institute for Cancer Research, University of Sydney, Westmead, New South Wales, Australia 2 University of Sydney and University of Western Sydney, Westmead, New South Wales, Australia 3 Westmead Hospital, Westmead, New South Wales, Australia HSR 01. Integration of Biobanking Into Multidisciplinary Team Based Cancer Care

Background: Biobanking is now considered a basic tool for oncological research and care and several models have evolved to optimize single-site and multi-site collection of biospecimens. The Gynaecological Oncology Biobank at Westmead functions as part of the Multidisciplinary Care Team (MDT). Multidisciplinary care is an increasingly important component of cancer frameworks, and is recommended in Australian national clinical practice guidelines.

The Westmead Gynaecological Oncology MDT meeting involves surgeons, pathologists, oncologists, radiologists, nurses, representatives from social work, psychology, familial cancer, clinical trials and biobank research staff.

Methods: Patient cases are presented, pathology results and treatment options discussed and a management plan developed. Gynaecological Oncology researchers have participated in MDT meetings for over 10 years with numerous benefits including increased awareness of biobanking and regular contact with surgeons and pathologists ensuring regular biospecimen collection. MDT meetings also provide the opportunity to collect clinical information and gives researchers insight into the complex diagnoses involved in gynecological oncology. Other information gained includes rationale behind chosen chemotherapy regime, discussion of recurrent cases and identification of patients referred to the familial cancer centre.

Conclusion: Involvement of MDTs in research assists in systematic recording of prognostic indicators, and allows co-ordination of clinical trials and clinical research projects involving collection of biospecimens.

Incorporation of research staff into MDTs facilitates participation of clinicians and pathologists in research thereby promoting the benefits of biobanking and expedites translation of results into changes in clinical care. MDT meetings are a conduit for clinicians and research staff to exchange patient information and cooperate for better patient and research outcomes.

1 Westmead Millennium Institute, Westmead, NSW, Australia; 2 University of Sydney, Westmead, New South Wales, Australia; 3 University of Sydney at Westmead Millennium Institute, Westmead, NSW, Australia HSR 02. Development of Tools to Assist Researchers Applying to Australian Breast Cancer Tissue Bank

Background: The Australian Breast Cancer Tissue Bank (BCTB) recruited the first donor in 2006. The first research application was approved in 2008. Since inception we have explored ways to maximize researcher services and have developed strategies to assist applicants whilst simultaneously increasing operational efficiencies.

Methods: Services developed include:

On-line search engine

Results: 1. The on-line search tool allows researchers to enter specific parameters, e.g. grade, hormone receptor status and specimens required. The search engine talks to our real-time central database returning live information. 2. A novel feature is the ability of the search to return snap-shot images extracted from a representative section of tumor material. 3. eBAS allows researchers to submit an EOI which can subsequently be upgraded to full application status, all on-line. The capacity to upload any required documentation is included in the process. eBAS automatically alerts designated BCTB personnel responsible for processing and tracking applications. Reviews are completed and tracked on-line. 4. To best preserve BCTB resources and assist researchers, nucleic acids are extracted within a central processing facility. This allows for automation, standardization and QC of methodology. Standardization allows for direct comparisons between results on downstream tests. 5. A digital image is obtained on every case and then goes through systematic independent pathology review, prior to marking for TMA construction. Images and TMAs are available to researchers.

Conclusion: The BCTB realizes the importance of optimizing services and the measures adopted have received positive feedback from the research community.

1 BioStorage Technologies, Inc., Indianapolis, IN HSR 03. Growing Biorepository Operations to Meet Today's Scientific Needs

Background: The proper storage, tracking and transport of research samples is vital to to pharma and biotech firms who frequently conduct a variety of testing on archived biomaterials. Consequently, temperature-sensitive samples must be maintained in highly specialized and consistent conditions. Therefore, biorepositories – large and small – must develop cost-effective, innovative and streamlined operations that will allow them to meet researchers' long-term needs for improved sample integrity and chain of custody.

Methods: The information presented will emphasize best practices for ensuring the long-term stabilization of samples generated during medical research. The poster will also highlight the demands of adhering to good storage practices. Specific topics that will be covered, include:

Comprehensive sample management for the entire sample lifecycle

Results: To maintain sample integrity for extended periods of time, it requires standardized, secured, and validated processes and procedures. The presenter will examine these challenges, provide practical design guidelines and use real-world case studies that help improve the success of this approach, while looking at sample management from an operational planning perspective.

Conclusion: Without careful consideration for comprehensive sample management, including cold chain logistics, compliant storage, information management and audit trails, researchers risk specimen degradation and the loss of valuable clinical information. This misstep could prove costly not only for today's research initiatives, but for future research needs.

1 Beaumont Hospital, Royal Oak, MI HSR 04. Beaumont BioBank a Progressive Biorepository

Background: Beaumont BioBank is a successful biorepository model which has addressed and achieved the challenging needs of centralizing, collecting, and annotating biospecimens worthy of the specialized demands of translational research. This has been achieved in a community based academic hospital with investment in staff and equipment to pursue the goals of personalized medicine.

Methods: In two and a half years, 1,244 patients have been consented and 34,000 specimens collected, and stored from 28 different clinical investigators. Collections are driven by a clear clinical question and are initiated through a defined process involving an investigator contract and the BioBank staff, the clinical investigator, his/her nursing staff and a scientific committee. Suitable patients are identified in advance, appropriate collection kit(s) assembled and barcoded and consent sought at the most appropriate opportunity. Using direct OR sampling, over 80% of tissue specimens are collected, processed, annotated and placed in the freezer within 30 minutes; average time for plasma and serum samples to be placed in the freezers are 64 and 54 minutes respectively.

Conclusion: Informatics is a key component of the BioBank, BIGR was chosen to barcode, track specimen location, document history, clinical outcomes, integrity factors; time of collection and preservation of all biospecimens. Quality control is integrated into daily operations, histological validation, DNA/RNA concentrations and integrity. Specimen audits are performed to confirm each specimen and chain of custody of samples is monitored through material transfer agreements and informatics documentation. Institutional investment in this standardized biobank model will lead to the successes of genomic driven personalized care.

1 National University Health System, Singapore, Singapore HSR 05. Reducing Cold Ischemia Time for Tissues Banked at NUH-NUS Tissue Repository, Singapore

Background: A project was undertaken to reduce pre-freezing cold ischemia times for banked cancer tissues. The distance between various hospital departments, manpower constraints, and the hospital staff not being properly educated on the importance of ischemia times for tissue quality contributed to the longer baseline time.

Methods: The team comprised of tissue repository staff, surgeons, pathologists, operating theater staff and coordinators from the hospital's Corporate, Planning and Development office. The pre-project workflow was reviewed and periodically refined, with changes implemented in the timing of typing of the histology form to doing away with the gowning up/down of tissue repository staff in operating theater. Along with, a strict check on the elapsed time between specimen excision in operating theater to freezing down in histopathology lab was ensured, both by the OT and tissue repository staff. Finally, specimen photo taking process was shifted out of the operating theater.

Results: At the end of the project in September 2009, the median and mean tissue freezing time had come down to 24 and 28 minutes, respectively, from mean baseline level of 70 minutes. The percent of cases falling within the project goal TAT of 20 min had risen to 37% from the meager baseline level of 4.3%.

Conclusion: The ongoing monitoring of the project has ensured a 29% collection within 20 min in the last three months of 2010 with 63% specimens being frozen down within 30 min. This ensures that high quality tissues are made available for bio medical research across Singapore.

1 Cleveland Clinic, Cleveland, OH HSR 06. The Genomic Medicine Biorepository: Addressing the Challenges of Biobanking for Translational Genomics Research at The Cleveland Clinic

Background: The Genomic Medicine Institute was established in 2005 during a time when no structural, procedural or human-resource infrastructure existed for translational and clinical research in genetics and genomic medicine. The Genomic Medicine Biorepository was established to support studies for the Genomic Medicine Institute and its local, national and international collaborators. Over the last 5 years, many challenges have given rise to innovative solutions.

Methods: The following processes were implemented to address specific challenges: (1) Establishment of a safer method for accessing cryopreserved specimens from the liquid nitrogen freezers using a custom gantry crane system. (2) Redesign of the patient instructions to facilitate the receipt of samples. (3) Incorporation of a laboratory information management system, Labmatrix, for specimen tracking. (4) Implementation of a lymphoblastoid cell line grading system to quantify trends in cell line viability.

Results: (1)We can access heavy racks from liquid nitrogen in a safe, ergonomic fashion. This helps reduce the possibility of work related injuries or loss of samples due to accident. (2) Better instructions have reduced patient stress and cut down on the receipt of improperly packaged samples. (3) Labmatrix provides a secure LIMS that can integrate sample and patient medical information. (4) Grading the ficoll separation has provided useful information regarding trends in pre-analytical conditions that may lend to problems during the cell line initiation process.

Conclusion: Challenges unique to the process of biobanking, especially in the context of non-existent infrastructure, need to be addressed both at the inception of the facility as well as continuously over the course of time.

1 A C Camargo Hospital, Sao Paulo, Brazil HSR 07. Tumor Banking in Brazil within the Context of a Pathology Residency Program: The Experience of the A C Camargo Hospital Biobank

Background: The A C Camargo Hospital Biobank, established in 1997 to provide human tissues for cancer research, is primarily based in the Department of Anatomical Pathology (DAP), which has a 3-year residency program in surgical pathology, which is the only one in Brazil that includes biobanking activities in the resident curriculum.

Methods: We analyzed, from 1998 to 2010, the number of residents enrolled in our residency program, calculating the number of hours each resident performed supervised activities at the frozen section laboratory (FSL), where over 90% of the tissue acquisition takes place, the number of acquisitions over each year and compared the results to quality indicators (tissue representativeness and RNA/DNA quality).

Results: There were 39 residents enrolled in the residency program from 1998 to 2010. Each resident spent 672 hours/year at the FSL. Residents who were enrolled in the residency program during the first years of the biobank activities performed an average of 8 tissue collections per resident per week, whereas residents from the last five years of activity performed an average of 13 tissue collections per resident per week. Sample acquisition by residents did not affect quality indicators.

Conclusion: Pathologists play a key role in biobanking activities, particularly with respect to quality control issues related to the collection of biospecimens. The involvement of pathology residents in tissue banking activities during their residency program contributes to the formation of professionals familiar with the principles and best practices adopted in biobanking activities.

1 LookLeft Group, LLC, Flanders, NY HSR 08. The Next Phase of Biospecimen Management

Background: Due to increasing regulatory scrutiny and the harsh reality that many historical biospecimens have proven to be of insufficient quality to bring significant value, systems that manage biological samples must evolve.

Methods: While basic location and inventory management functionality is still critical, modern biospecimen management software solutions must be protocol and process driven to enforce best practices for sample collection, annotation and processing. Advanced biospecimen management systems must include functions and features for informed consent management, bioethical and legal controls, and the ability to collect and connect clinical data to biospecimen data. They must be designed as open architecture platforms with flexible data import and export capabilities and enable integration with, and analysis of, public genomics information. They must offer sophisticated ad hoc reporting tools and user defined dashboards.

Results: Connecting the phenotype to the genotype is the fuel for translational research and a cornerstone of personalized medicine. To achieve the value proposition of using data derived from biospecimen analysis to impact clinical diagnostics and therapeutics will require biospecimen management software solutions that meet increasing international data and privacy standards. Audit-worthy quality systems must be in place with documented processes and practices that comply with international regulatory requirements.

Conclusion: While this will require a commitment to change and the cost of change management, companies that successfully enter the next phase of biospecimen management will be best positioned for the era of personalized medicine.

1 Wales Cancer Bank, Cardiff, S Wales, United Kingdom (Great Britain) 2 Velindre Hospital, Cardiff, S Wales, United Kingdom (Great Britain) HSR 09. The Challenge of Keeping Your Biobank Current

Background: Biobank development is an evolutionary process that can only flourish given solid foundations. Initial stages in operational development focus on patient recruitment and sample accrual. The next phase is concerned with ensuring sample integrity and usefulness by consolidating collections and reviewing the use and demand of both samples and data. The number and quality of research projects applying for access to samples becomes an important marker of development and success in biobank growth and one which facilitates the conduct of novel research programs that will ultimately improve the clinical care of patients.

Methods: The Wales Cancer Bank recently conducted such a review after consenting 4,000 cancer patients to donate tissue and blood samples for prospective collection. At the time of review, 38,000 aliquots of biosamples were available and 4,500 aliquots had been used, either for extraction or supply to research groups. The profile of tumor and sample types in the collection was compared to the incoming requests for samples to ascertain whether the collection strategy was sound or whether amendments to the methodology were required. An audit of treatment and follow up data was also conducted and a synopsis of available biosamples with associated clinical data was formulated.

Conclusion: Biobanks, particularly ones collecting prospectively, must not become complacent once set up and running. Regular scrutiny should form part of the operational program to ensure funding is well utilized and sample use is maximised, to uphold the promise made to donors to use their generous donations to further scientific knowledge and clinical treatment.

1 Makerere University College of Health Sciences, Kampala, Uganda 2 University of Nairobi, Nairobi, Kenya 3 The Ohio State University Medical Center, Columbus, OH HSR 10. Global Collaboration for HIV/AIDS Cancer Research: AIDS & Cancer Specimen Resource Biorepositories in East Africa

Background: Biospecimen science and research biorepositories are expanding internationally to provide quality biospecimens for quality research studies. Growth in biorepositories emphasizing biospecimen quality is well underway in the developed world. However, despite the developing world experiencing 70% of the global increase in cancer burden, there is no comparable growth in research contribution.

Methods: Affiliates of the Mid-Region AIDS and Cancer Specimen Resource (ACSR/NCI) have been established at Makerere University (MU), Mulago Hospitals (U-ACSR) and the University of Nairobi (UON), Kenyatta National Hospital (K-ACSR) to initiate cancer biorepositories. Memoranda of understanding (MOU) and material transfer agreements (MTA) were developed for the collaboration between MU and UON pathologists and the Mid-Region ACSR (ACSR/NCI) located at The Ohio State University in Columbus, Ohio. IRB approved ACSR protocols are in place at MU and UON and studies using African biospecimens initiated.

Results: K-ACSR from 2007–2010 collected 128 AIDS associated malignancies and together with U-ACSR provided 536 source blocks of lymphoma to the Sub-Saharan Africa Lymphoma Consortium (SSALC/ACSR/NCI) with 1388 cores placed in 38 tissue microarray (TMA) blocks through 2010. Nine podium and poster presentations from ACSR tissue studies were presented in 2009 and 2010 at international meetings including AORTIC (Africa), ICMAOI (USA) and APECSA (Africa).

Conclusion: Collaborations promote biospecimen science concepts for human tissue archive management to provide research and publication opportunities. African participation in global biospecimen science and quality cancer research uniquely contributes to understanding tumor patterns, interactions among numerous tumorigenic viruses, adverse environments, nutrition and genetics in cancer, particularly HIV/AIDS malignancies.

1 Company, Wuppertal, Deutschland, Germany HSR 11. Alignment of a Research Biobank with Pharma Biomarker Validation

Background: The understanding and treatment of many diseases is severely handicapped by the absence of biomarkers that can be measured in body fluids like blood or urine. To identify and validate biomarkers in pharma research especially in translational medicine excellent clinical material is indispensably needed (e. g. for molecular analyses at mRNA level). To support and empower research, there is a high demand to create utmost 'value' from scarce samples. Compliance to legal requirements is a must, with additional emphasis on socioethical values.

Methods: We analyzed the legal situation in Germany. We then developed a concept for and established a research biobank including both human and animal specimens.

Results: The Research Biobank of Bayer Schering Pharma AG leverages the clinical network driven by the research projects by providing human samples and their clinical data for bioanalytics under strict compliance with legal, ethical, biosafety, biotechnology, data privacy and information technology guidelines.

Conclusion: We favor a collaborative approach to biobanking where both clinicians and researchers contribute their strengths. By combining our respective experiences and accepting mutual cultural differences during partnering as well as clinical realities during the operations phase in order to minimize risks in clinical sample and data collection we were able to accelerate setting up prospective collections as a reliable, convenient, robust and affordable solution. Experiences gained in the build up of a pharma research biobank can be instrumental in further developing best practices. We will present case studies from our indications which include Oncology, Cardiology, and Gynecology.

1 Department of Veterans Affairs, Washington, DC 2 VA Cooperative Studies Program, Boston, MA 3 VA Cooperative Studies Program, West Haven, CT HSR 12. Million Veteran Program (MVP): A Tissue and Data Repository of The Office Of Research and Development, US Department of Veterans Affairs (VA)

Background: The objective of the VA Genomic Medicine Program's MVP is to create a repository to enable genomic investigation and discovery within the VA. This landmark undertaking will enroll as many as 1 million users of the Veterans Healthcare Administration over the next 5–7 years. Subjects will provide informed consent for collection of blood and clinical data, as well as HIPAA authorization for use of these resources by researchers.

Methods: Veterans will be invited primarily via mailings to participate at their local hospital or clinic. Phenotype data will be collected via health and lifestyle surveys at entry and longitudinally via health data extracted directly from electronic medical record of the VA. All subjects will contribute a 10 ml EDTA blood sample that will be shipped overnight to the VA Central Biorepository and processed to extract 10–15 μg of DNA and to store two 1 ml aliquots of plasma and one aliquot of buffy coat. Samples will be stored at −80°C. Phenotype and biosample data and analysis results will be stored in Genomic Information System for Integrated Science (GenISIS) databases and will be made available to researchers in a scientific computing environment.

Results: The protocol was approved by the VA Central IRB. Recruitment began in January 2011 and will be rolled out to 50 VA sites within a year. Work is continuing to complete laboratory automation and GenISIS development.

Conclusion: Collaborative efforts within VA have lead to the launch of MVP, which aims to be one of the largest resources for genomic research.

1 University of Colorado, Anschutz Medical Campus, Aurora, CO HSR 13. Recovery of MicroRNA from Stored Human Peripheral Blood Samples

Background: Recovery of microRNAs (miRs) from tissue samples of many kinds has become an area of increasing interest and importance in recent years.

Methods: We isolated, and then amplified and quantitated, miRs from human peripheral blood samples stored in the University of Colorado Skin Cancer Biorepository to determine if miR recovery was possible and consistent over time in storage. Forty five blood samples from patients with different stages of malignant melanoma were collected in PAX gene RNA tubes and then stored at −80°C prior to RNA preparation. The samples examined had been stored from 4 weeks to 3 years. Total RNA was prepared followed by miR isolation, amplification and quantitation using real time PCR. A widely expressed microRNA, miR221, was as a standard for comparison across samples and storage time. miR221 was recovered from all samples with no differences observed with longer storage time.

Conclusion: These studies show that miRs can be recovered and quantified from human blood samples stored for up to 3 years.

1 A C Camargo Hospital, Sao Paulo, Brazil HSR 14. Educating the Public about Tumor Banking: An Outdoor Cancer Exhibition Organized by the A C Camargo Hospital in Sao Paulo, Brazil

Background: In order to demystify cancer and bring cancer research closer to society, Hospital A C Camargo (with the support of the Sao Paulo Research Foundation-FAPESP and the National Council for Scientific and Technological Development-CNPq) held in public parks of Sao Paulo the exhibition "Cancer: Know and Prevent". The importance of tumor banking was addressed in a panel (of a total of twenty-two) containing entertaining and educational concepts on the subject.

Methods: The rationale for tumor banking and the Biobank infrastructure and workflow were discussed by the A C Camargo Biobank staff with the hospital press office staff for institutional projects and professionals from the art company Pingado Sociedade Ilustrativa, which created a comic strip with easy-to-understand text. This comic was mounted on a 1.20 (wide) × 1.80 (tall) meter panel.

Results: Beginning on May 30, the exhibition toured eight public parks in Sao Paulo during the year 2010. An additional park was included in the schedule for early 2011.

Conclusion: This exhibition provides an additional means of bringing information to the community about the importance of a tumor bank in cancer research.

1 Institute for Heart and Lung Health, Vancouver, BC, Canada 2 Institute for Heart and Lung Research, Vancouver, BC, Canada 3 James Hogg Research Centre, Vancouver, BC, Canada 4 Institute for Heart and Lung Health/University of British Columbia, Vancouver, BC, Canada HSR 15. Protein Extraction and Western Blot Analysis from Formalin Fixed Paraffin Embedded Biobanked Heart Tissue

Background: Immunohistochemical (IHC) staining and Western blot (WB) analysis are established analytical techniques providing complementary information on protein quantity, localization and distribution within tissues. Technical challenges have meant that these methods are generally used in isolation. IHC is typically performed on tissues processed with fixatives such as formalin, which denature proteins such that analysis of the same tissues by Western blotting, which generally assays freshly extracted protein, may not be possible. In certain circumstances, such as in forensic pathology, only formalin fixed tissues are routinely retained for evaluation. In this study, we extracted protein from formalin fixed (FF) and corresponding snap frozen (SF) tissues as well as from formalin fixed paraffin embedded (FFPE) tissues from six archived myocardial samples to evaluate their performance in WB analysis.

Methods: Myocardial tissue samples from six heart transplant cases were obtained from the James Hogg Research Centre Cardiovascular Biobank at St. Paul's Hospital. Protein was extracted from matched SF, FF and FFPE heart samples. Extracted proteins were analyzed by WB for expression of both cytoplasmic and membrane proteins.

Results: Membrane and cytoplasmic proteins were readily detectable in SF samples. Proteins from FFPE samples were detectable more than 60% of the time and FF samples were not detectable.

Conclusion: The results of this study suggest that WB analysis from FFPE human heart tissue can be successful. Optimization of the retrieval of assayable proteins from archived FFPE heart tissues will provide a valuable resource for proteomic analysis, biomarker discovery and validation, and genotype/phenotype studies.

1 Children's Cancer and Leukaemia Group, Leicester, Leicestershire, United Kingdom (Great Britain) 2 Great Ormond Street Hospital for Children NHS Trust, London, United Kingdom (Great Britain) 3 University of Bristol, Bristol, United Kingdom (Great Britain) HSR 16. Data Coordination for a Multi-Centre Tissue Bank: The Children's Cancer and Leukaemia Group (CCLG) Tissue Bank

Background: The CCLG Tissue Bank has been established since 1998. It is a repository of solid tumor specimens and supporting clinical data, designed to facilitate and support childhood cancer research. Frozen, paraffin-embedded tissue and blood samples collected from children (0–16 years old) across multiple sites are locally stored, DNA samples are centrally stored, and all registration and pathological data is centrally managed at the CCLG Coordinating Centre. The datasets collected include patient demographics, pathology reports and clinical follow-up data, as well as monitoring CCLG biological studies through progress reports, sample tracking and publication output.

Methods: The logistics of central data collection for tissue stored and dispatched from multiple sites can be challenging. Processes have been developed to ensure this data is captured and processed efficiently. A database is used to log all patient and tissue registration information, clinical outcome data, progress of CCLG biological studies and specimens dispatched. Electronic anonymized pathology reports for all specimens are available to researchers. Annual progress reports and publications arising from biological studies are logged.

Results: Supporting pathological data on all 10,112 tissue samples registered to date. Clinical follow-up data has been collected on all registered patients with tissue since 2007. All 80 CCLG biological studies have been supported by clinical data and annual progress documented, including research findings.

Conclusion: A comprehensive collection of data on pediatric cancer has been successfully utilized for research, facilitating effective biological and translational research into various childhood cancers.

1 NIH/National Heart, Lung, and Blood Institute, Bethesda, MD 2 SeraCare Life Sciences, Inc., Gaithersburg, MD 3 Information Management Services, Inc., Silver Spring, MD HSR 17. The NHLBI BioLINCC Operational Guidelines: Streamlining the Review of Biospecimen Requests

Background: The NIH National Heart, Lung, and Blood Institute (NHLBI) is the custodian of multiple contemporary and historical biospecimen collections. The NHLBI Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC) has linked over 4.2 million biospecimens (26 collections) to their phenotypic data and established a public website where scientific investigators can view available resources and submit requests online. The availability of an online application process resulted in an increase in biospecimen requests and reviewing applications in a timely manner became challenging. A new streamlined review process was developed to address this issue.

Methods: A review of publicly available best practices was performed to identify core review elements. The core elements were compared to the type and timing of the information collected during a biospecimen request. A multi-disciplinary team was formed to provide technical reviews early in the request process and a workflow established. Expedited review processes were investigated.

Results: The website application form was retooled and a new review tab on the private website was developed for NHLBI, BioLINCC and biorepository staff to document the multi-disciplinary review and post recommendations. The recommendations were distributed to the scientific reviewers and expedited reviews were performed for “low impact” requests. Initial results indicate that the expedited reviews can facilitate the process.

Conclusion: Implementing best practices to facilitate the search and distribution of biospecimens without introducing unnecessary roadblocks is possible using a multi-disciplinary approach and streamlined workflow.

1 Biomatrica, Inc., San Diego, CA HSR 18. Ambient Temperature Stabilization of Genomic DNA in Saliva Samples

Background: Saliva provides an alternative to blood as a biological fluid in research and diagnostic applications. The major advantage of saliva over other biological fluids is the fact that it is non-invasive and can be collected without training. Biomatrica has developed a novel reagent that preserves the integrity of genomic DNA in saliva at room and elevated temperatures for up to 6 months. This makes the saliva/preservative mixture ideal for sample storage and shipping as an alternative to freezers or cold-packs.

Methods: Samples were collected from 4 donors. Three different DNA extraction methods were employed: Column based, (Qiagen), phenol/chloroform, and precipitation. DNA integrity was analyzed on a 0.8% agarose gel and 10% of eluted DNA was loaded on the gel. DNA yield was determined by fluorescence using the Quant-iT™ PicoGreen dsDNA Assay Kit (Invitrogen).

Results: Biomatrica's new saliva formulation is based on in-house developed chemical compounds that are designed to preserve the integrity of DNA in saliva. The new formulation was found to preserve the integrity of DNA in saliva samples when stored at room temperature and elevated temperature for extended periods of time. The formulation was compatible with different DNA isolation methods. The purified DNA did not show intereference with PCR, long range PCR or QPCR.

Conclusion: The new reagent for stabilizing DNA in saliva provides excellent stabilization for up to 6 months, with high quality gDNA as well as high recovery. The quality of the extracted DNA was evaluated in downstream applications such as PCR.

1 CRO (National Cancer Institute), Aviano, Pordenone, Italy HSR 19. Biobanking Management in a Cancer Center

Background: The National Cancer Institute CRO-Biobank represents a long-term source of human biological samples collected at diagnosis and at consecutive therapeutical stages for research purposes. CRO-Biobank is a member of the Italian Network Cancer Biobanks (RIBBO) and participates in the setting up of a European network (BBMRI).

Methods: At present the collection comprises serum, plasma, buffy-coat, tissues and DNA of healthy individuals and cancer patients, which are collected and stored in compliance with quality standards and ethical regulations. The traceability is guaranteed by the "Matrix" system based on a software (Easytrack2D Ver 2.0, Twinhelix) for the managing of sample data; particularly it allows to know the physical location of samples thanks to 2D-barcoded tubes.

CRO Biobank has developed quality control procedures concerning timing and method to obtain optimal freezing, prevention of hot and cold tissue ischemia and accuracy in the OCT embedding process. Tumor or healthy frozen tissues were also evaluated to establish the percentage of necrotic/ fibrotic areas in cryostat histological sections directly obtained from the samples. To warrant the possibility of aliquoting tissue samples, we have also tested the consistency of biomolecular analyses from multiple cryostat sections of the same tissue block obtained at different times.

Conclusion: The major advantages of setting up our Biobank are: first, scientists can readily assess clinical information in conjunction with biological features of samples for research; second, it represents an important tool to provide accurate and high quality linkages with the regional or national cancer registries.

1 Karolinska Institutet Biobank, Stockholm, Sweden HSR 20. Building a New Large-Scale Biobank for Clinical and Epidemiological Research Studies in Sweden

Background: A strategic funding on a national biobank infrastructure as a part of BBMRI.se made it possible to further develop KI Biobank and create a new high throughput facility. The development was driven by three major population based studies, two within cancer with a target of 200 000 people, and LifeGene with a target of half a million people in Sweden.

Methods and Results: We undertook extensive process-mapping to understand how we could increase capacity and where to introduce automation. After a tender process we selected robotic systems for registration and sorting of incoming samples and aliquoting of different sample types into multiple 220 μl fractions and established new processes for DNA extraction. We changed tube format and developed a simple expandable storage strategy. In addition we extended and modified our facility. Big efforts were made to further develop our LIMS system to support the new processes.

Conclusion: After installation and testing we were able to launch the new operation on November 1, just 10 months after starting the new development. Our automated processes have given us the big increase in sample processing capacity we needed to start 3 new large studies. We now need to optimize our processes for stability and to further increase capacity, and this will enable us to take on more large studies and improve the efficiency of our smaller studies. Our next steps are to automate sample retrieval and to identify a cost effective strategy for long term storage.

1 UTHSC, Memphis, TN HSR 21. Facilitation of Biorepository Functions with Pivot™ by Microsoft^® Live Labs™

Background: Pivot is an application intended to simplify viewing and interaction with massive amounts of data in ways that are powerful and informative. Pivot is a data mining system that allows visualization of data that can be sorted, organized, and categorized according to the user's requirements. Pivot is able to filter through images and information seamlessly because the images are in Deep Zoom format (a component of Seadragon Technology). The Whole Slide Imaging (WSI) system creates a digital replica of the entire content of a glass microscope slide that can be displayed on the computer, emulating traditional viewing of a slide with a conventional microscope. Combining these two technologies makes it possible to create a collection of images and associated information that can be used for sorting biorepository samples.

Methods: Digital slide images created by the ScanScope XT scanner (Aperio Technologies, Inc.) are stored in the SVS (ScanScope Virtual Slide) file format. SVS files are TIFF/BigTIFF files. Pivot only accepts JPEG, PNG, and HD photo files. We converted the SVS files to JPEG files using Digital Slide Studio (Aperio) and then entered the JPEG images into a Microsoft Excel based tool that converted the JPEG images to Deep Zoom Image (DZI) files. The DZI files, which enable viewers to zoom in and pan out without loss of significant resolution, were then used to create a Pivot collection.

Conclusion: Pivot can be a useful tool for biorepositories since it offers the capability to sort images based on different parameters.

1 BC Cancer Agency, Victoria, British Columbia, Canada HSR 22. Comparison of Pre-Operative and Post-Operative Consenting Protocols at the British Columbia Cancer Agency Tumour Tissue Repository (BCCA-TTR)

Background: The BCCA-TTR is a cancer biobank that for its first five years of operation has mostly deployed a pre-operative consent protocol. In 2010 the BCCA-TTR began to also deploy a new post-operative consent protocol. Both types of protocols have many benefits to patients and biobanks, however efficiency and outcomes of each protocol may be different.

Methods: The rates of consented, declined and decision unknown outcomes were compared between pre and post-operative consent protocols for 3279 cancer patients referred for potential consent. Subsets of breast and colon cancer patient decision rates were also analyzed.

Results: There was no significant difference in the global rates for consented (+ve) and declined (-ve) using pre or post-operative protocols (97.7% + ve and 2.3% -ve vs ∼95.9% + ve and 4.1% -ve respectively). There was a significant difference in outcomes with respect to decision made (+ve or -ve) versus decision unknown between pre and post-operative protocols (1.8% vs 23.4% of all patients approached, chi-square test, p < 0.0001). Consented and declined rates were similar for both protocols for breast cancer patients but a higher decline rate was observed for colon cancer patients (p = 0.007). The proportion of decision made to decision unknown was higher with the post-operative protocol with breast and colon patients (<3% vs >33%, p < 0.0001.

Conclusion: These data suggest that pre and post-operative consent protocols are equally acceptable overall to cancer patients. However, pre-operative consent may be more acceptable for some subsets and the rate of ‘decision unknown’ is generally increased with the post-operative consent protocol.

1 Fudan University Shanghai Cancer Center, Shanghai, Shanghai, China HSR 23. Value of Morphological Quality Control of a Cancer Tissue Bank

Background: As already well known, pathology is the cornerstone of a tissue bank, where usage of human tissue is an increasing requirement. The morphological information is as critical as the steps of tissue collecting, processing, annotating and preserving. It is of big value to provide morphological information for the researchers. When possible for each case, we are collecting an aliquot of tissue exclusively for morphological quality control.

Methods: An aliquot of a tissue piece during each case of tumor tissue procurement is collected and snap frozen in liquid nitrogen then transferred to −80°C by the end of the day. A frozen section was cut and H&E staining was performed from the aliquots of the tumor tissue. The H&E stained whole section was scanned in whole using the image analyst of Ariol. The tumor percentage of each case is evaluated and the images were stored as a virtual morphological bank. The information including the scanned morphology was provided to researchers along with the research tissue samples.

Results: More precise sample information was provided to the researchers. They could tell how much tumor component is contained in the sample they are analyzing. Through the necessary micro- or macrodissection we could provide the research results representing the goal tissue and therefore the research study would be more precise.

Conclusion: Morphological information would be helpful for investigators to know more about the samples they are using for scientific study.

1 Royal Dutch Academy of arts and Sciences, Amstelveen, Noord Holland, Netherlands HSR 24. From Bio Specimen to Biomarker? The Quickest Way for Discovery of Novel Candidate Biomarkers

Background: The search for biomarkers relies completely on the availability of high quality specimens from living donors as well as autopsy material collected and stored by biobanks.

The diagnosis of neurological disorders is severely hampered by an absence of reliable biomarkers that can be measured in body fluids such as blood, urine and cerebro-spinal fluid (CSF).

Methods: Biomarker discovery copes with extreme data fluctuation due to the huge variability between individuals and the rapid post-mortem changes. We are currently using beta-Amyloid and Tau as candidate biomarkers for Alzheimer's disease (AD) and fronto-temporal lobar degeneration (FTLD). The collected specimens include RNA,DNA and proteins extracted from brain /tissue /body fluids, subsequently correlated to the classical pathological hallmarks of the disorders.

Results: So far we have identified and measured biomarkers in blood and CSF. We conduct the correlating tests for total and phosphorylated tau and Aβ42 in living donors and in rapid autopsy material and then add the results to MRI imaging results to assist in differential diagnostic procedures.

Conclusion: Human biobanks play a major role in the collection of large numbers of high quality specimens for biomarker identification. So far, no single biomarker has been found which discriminates between AD and other dementias. Therefore we are aiming at international collaboration between biobanks and harmonization of SOP's to enlarge the panel of valid biomarkers which will substantially increase the sensitivity and specificity of the diagnosis.

1 Komen Tissue Bank, Indianapolis, IN 2 Indiana University School of Medicine, Indianapolis, IN HSR 25. How Do They Do That?

Background: Since Oct of 2007 the Susan G. Komen Tissue Bank at the IU Simon Cancer Center in Indianapolis has collected over 1300 normal breast tissue samples with matching blood, plasma, and DNA from women with no signs of breast cancer. There is currently a waiting list of 500 women willing to give tissue from their healthy breasts to be used in breast cancer research. How does the Komen Tissue Bank achieve this? Why are women lining up to donate? What is a collection day like? How are the samples collected and processed to achieve the highest standards of sample integrity possible? We present a brief journey from the inception of the Komen Tissue Bank through IRB, legal, and logistical challenges to the present day summation of what the Bank holds. A sample collection and processing description is included as well as testimonials from the women who have donated their precious healthy breast tissue to the Bank.

Methods: A breast tissue collection event utilizes up to 80 volunteers to complete the donation process from consent to biopsy. Samples are immediately processed according to strict SOPs.

Results: A typical collection event lasts 7 hours. During this time, samples of breast tissue and matching plasma and serum from 100 donors are collected and processed.

Conclusion: The Komen Tissue Bank is the source for normal breast tissue for breast cancer research. When women are asked to personally contribute to breast cancer research, they generously line up to do so.

1 Marshfield Clinic Research Foundation, Marshfield, WI HSR 26. Creating a Framework for Serial Collection of Residual Clinical Phlebotomy Samples, from Community Consultation to Infrastructure Development

Background: Here we describe the development process for the collection of serial samples using residual clinical specimens from participants in a population based biorepository.

Methods: We identified three groups essential to the definition and implementation of serial sample collection: the participating community, the scientific community, and the infrastructure development team. Initial steps focused on the participating community, with active community engagement from focus groups, community advisory board discussions, and external ethics advisory board consultations. The scientific community was asked to determine the characteristics of a useful sample; we consulted both internal scientists, and sought external scientific advice. To determine the infrastructure development needs, we identified stakeholders from different departments to plan workflows that transition a sample from clinical collection to biorepository storage.

Results: Information from focus groups and advisory committees led to the development of an "opt out" model for incorporation of serial samples; this has resulted in less than 1% of participants requesting removal from the study. Scientist input in serial sample collection helped identify characteristics of a valuable sample including continuous care within the institution, diagnosis of a common condition, age, and overall health of the participant. Stakeholder input identified small changes in workflows that might have the potential to increase sample value, such as fast tracking a sample to a temperature controlled area and tagging potential biorepository samples at the site of initial sample processing.

Conclusion: Collecting additional serial samples from an established cohort can be established only with the input of all affected groups.

1 BioStorage Technologies, Indianapolis, IN HSR 27. Best Practices for the Global Distribution of Specialized Biomaterials Generated in Clinical Trials

Background: The poster will provide attendees with detailed solutions to the intricate processes of global cold chain management of clinical trial samples. Specifically, the poster will highlight various aspects of international transportation and best practices that ensure the on-time and compliant distribution of temperature-sensitive materials.

Methods: To mitigate risk of degradation and ensure compliance, biorepositories must have a broad understanding of the complexities involved in global cold chain management. Using real-world applications and industry case studies, the presenter will give insight into the complexities of cold chain management and highlight strategies biorepositories can implement to ensure on time, compliant transportation of temperature-sensitive clinical trial samples and supplies.

Results: Pharmaceutical and life science assays often require accurate and constant temperature control to acquire meaningful data. As a result, particular attention must be paid to the effects temperature variances have on the stability of biospecimen samples, and how to overcome these hurdles by addressing them in upstream processes. By adhering to best practices for the shipment and storage of temperature-sensitive materials, companies can reduce risk and increase efficiency throughout the development process.

Conclusion: Cold chain logistics is a multifaceted function demanding homogeneous solutions to rising cost concerns, environmental responsibilities, packaging procedures and custom regulations. Without validated, carefully considered planning for the complexities of global cold chain logistics, biorepository operators risk product degradation, and possibly the loss of irreplaceable materials. This pitfall can lead to delayed clinical trials, postponed product launch and ultimately loss of revenue for the trial sponsor.

1 Catholic Health Initiatives, Towson, MD 2 BioFortis, Columbia, MD HSR 28. A Flexible Informatics Framework to Guide the Advancement of Personalized Medicine and Improve Patient Outcome in a Community-Based Healthcare System

Background: In contrast to urban single-site academic hospitals, networks of community-based hospitals enable vast, demographically diverse, biospecimen collection. Catholic Health Initiatives (CHI) is committed to bringing cutting-edge research and treatments to its 73 hospitals in 19 states. Facilitating the advancement and integration of personalized medicine, CHI has established the Center for Translational Research (CTR) comprising of Biorepository, Molecular Diagnostic and Research Laboratories. By engaging CHI physicians and leveraging diagnostic testing infrastructure, CTR has established state-of-the-art Biorepository facilities to enable innovation and advance personalized medicine within their communities.

Methods: Using an IRB approved protocol, CTR collects biospecimens from eligible cancer patients and associated clinical and longitudinal follow-up data for up to 10 years. We describe the collaboration with BioFortis in implementing a Labmatrix-based IT framework that guides data collection, management and exploration of patient and molecular data. HIPAA-compliant Labmatrix meets evolving scientific needs and data exchange standards, and is capable of tracking data from donor consent along with their comprehensive clinical profile, bar-coding, sample collection, processing, storage, shipment and disposal, to specimen usage and assay data.

Conclusion: With a sophisticated security framework, Labmatrix provides standardized data format and collection, by creating forms or providing interfaces to hospital-based EMR systems (HL7 standards) while maintaining and assuring the quality and chain-of-custody of biospecimens. Through Labmatrix, CTR has a robust compliant infrastructure to standardize procedures across the CHI network - linking patient clinical and outcome data with molecular data enabling the translation of biomarker and health data into useful tests to improve patient outcomes and drive innovation.

1 Kaiser Permanente Northwest, Portland, OR HSR 29. Introducing the NW Biobank: A Research Repository at Kaiser Permanente Northwest

Background: The NW Biobank is a multi-modal repository housing legacy research specimens from 37,327 unique subjects and specimens from ∼3,000 prospectively recruited subjects. The NW Biobank is nested within Kaiser Permanente Northwest (KPNW), an integrated health care system with a large, stable membership (∼475,000) and extensive data on members dating back to 1960.

Methods: To pilot-test prospective recruitment, we mailed invitations to 2,000 members asking to use their discarded blood samples in a hypertension study. We also asked current members with a history of breast cancer (3,921 cases) and 2,000 matched controls for samples.

Results: The response rate for the hypertension study was 34%; 82% of respondents consented to participate. For breast cancer, the response rate was 35%, varying between cases (40%) and controls (19%); 90% of respondents consented to participate. Most of the samples in the NW Biobank are from females (86%) and Caucasians (95%). The gender imbalance reflects the recruitment criteria, and women's greater willingness to participate in research. We have more than 10 years of medical history for about 50% of subjects. A major factor affecting future use of legacy specimens is limited informed consent. We are now re-consenting subjects to enable broader data sharing.

Conclusion: We plan to invite all adult KPNW members to participate in the NW Biobank. The high response rate (>30%) and reliable methods for obtaining blood samples integrated into the health plan infrastructure should lead to successful accrual of specimens for future genomic research.

1 Korea National Institute of Health, KCDC, Chungbuk, Republic of Korea NIR 01. Role of National Culture Collection for Pathogens (NCCP) and Pathogen Bank Network in Korea

Background: National Culture Collection for Pathogens (NCCP) is the only national pathogenic resource bank in Korea. NCCP is operated by a governmental agency from 1972. The function focuses on collection, preservation, development and distribution of pathogenic microorganisms isolated from patients with infectious diseases including high-risk pathogens. We affiliated the World Federation of Culture Collection (WFCC) under the name NCCP in 2004.

Methods: According to the international criteria, the NCCP has managed and collected various standardized pathogens by 2009 ISO 9001 requirements, 345 species for 1,131 strains. Currently, NCCP has established the network among 8 unit banks, 3 of which are specialized banks for pathogens isolated clinically and controlled under KNIH, 2 of which are collaborative banks for special pathogens difficult to be collected or managed as tuberculosis and medical fungi, and 3 of which are regional banks for pathogens isolated from the patient's clinical specimen by National University Hospital in Korea. NCCP has provided financial support as well as standard operation protocols (SOPs) for management of unit banks and established the network between central and unit banks.

Conclusion: An informational network was constructed and is operated by Pathogen Information Management System (PIMS), and all information of pathogenic resources can be accessed through the web-site (http://nccp.cdc.go.kr). This provides various information including antibiotic resistance, clinical data, biological character, etc, also linked information from the unit bank. NCCP wants to network internationally with similar biobanks about resource information and management systems.

1 CNIO, Madrid, Spain NIR 02. Spanish National Biobank Network [BBMRI-ERIC.es]: A New Dimension in Biobank Collaborative Networking in Spain

Background: The Spanish National Biobank Network (SpNBBN) is an initiative of the Spanish National Institute of Heath (ISCIII-Ministry of Science and Innovation), ordered and structured to function as a stable instrument of coordination between its various component institutes.

Methods: The main mission focuses on developing a cooperative network of public service, made up of hospital biobanks and other related institutions:

To provide the Scientific Community access to quality sample collections and associated data through a cooperative structure of public service.

Conclusion: Initially, the network is composed of 52 hospital biobanks and another 11 institutions with relevant biobanking activity, mainly as regional biobank network promoters, and the Spanish National DNA Bank, integrating a wide range of biobank and collections types including Pathology Department clinical collections, disease oriented collections and population biobanks, all of them in different formats (solid samples, serum and other blood derivatives, brain banks, DNA banks, etc.)

1 AIDS and Cancer Specimen Resource, Washington, DC 2 University of Miami Miller School of Medicine, Miami, FL 3 Northwestern University-Feinberg School of Medicine, Chicago, IL 4 Joan & Sanford I. Weill Medical College of Cornell University, New York, NY NIR 03. AIDS Epidemic Studies Require Access to Multicenter Biorepository Programs for Comparative Data

Background: Global HIV/AIDS complications reflect local anti-retroviral (ARV) therapy. While ARVs appear to control HIV replication, cancer continues to cause death and has emerged as the major cause of death within the developed world. AIDS-defining cancers such as Kaposi's sarcoma (KS) and non-Hodgkin's lymphoma (NHL) are significantly reduced but non-AIDS defining cancers emerge earlier, occur more commonly than in the non-HIV population, and have overtaken the AIDS-defining cancers as major causes of death. The AIDS and Cancer Specimen Resource (ACSR), established by the National Cancer Institute (NCI) in 1994, contains an inventory of over 400,000 biospecimens from its three major regional biospecimen repositories (RBR), east coast, mid-region and west coast and characterizes the U.S. AIDS epidemic. The goal of this study was to determine if the three RBR biospecimens equally represent the AIDS epidemic in the United States.

Methods: Large multi-RBR biospecimen collections were evaluated in the course of research performed by the ACSR and collaborative investigators: data on 11 different NHL associated biomarker immunophenotypes from 119 cases on an HIV AIDS diffuse large cell B cell lymphoma (DLBCL) tissue microarray (TMA) and >200 blood specimens from two of the RBRs for KSHV seroprevelance.

Results: ACSR RBRs had similar distributions of DLBCL immunophenotypes and the KSHV seroprevalence in the non-KS patients from both the EC and WC collections was identical.

Conclusion: This study suggests that the HIV-infected profile within the United States is homogeneous and without regional bias in the diseases.

1 Foundation biobank-suisse, Bern, Switzerland 2 Fraunhofer Institut für Biomedizinische Technik (IBMT), Potsdam-Golm, Berlin, Germany 3 Stiftung biobank-suisse, Bern, Bern, Switzerland 4 University of Bern, Bern, Switzerland NIR 04. Simultaneous Query of Two Biobank Networks: BBS and CRIP Are Synchronized via Web Services

Background: Both biobank-suisse (BBS; www.biobank-suisse.ch) and the Central Research Infrastructure for molecular pathology (CRIP; www.crip.fraunhofer.de) are biobank networks or meta-biobanks displaying data on biospecimens stored at their partners' hospitals and serving to acquire research projects for them.

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

Results: The coupling of user's log-in and web-based interactive query tools allow for a single sign-on with both BBS's and CRIP's web sites and simultaneous search of both meta-biobanks without affecting their access rules, contractual framework, privacy regimes, workflow, and corporate design. Putting the principle of data sparing into practice, data is transferred only upon a user's focused request. Background operation of web services conveniently enhances the users' query efficiency.

Conclusion: Coupling CRIP and BBS provides a model for networking meta-biobanks (“hubs and spokes”) without impairing their governance, regulatory framework, workflow, and infrastructure.

This work was funded by grant 01EZ1021A from the German Federal Ministry for Education and Research (BMBF).

1 CNIO, Madrid, Spain NIR 05. CNIO Tumour Bank Unit and Spanish National Tumour Bank Network: 2006-2010 Achievements

Background: The CNIO Tumour Bank Unit provides samples and associated data, as well as ethical and documentation support to CNIO Researchers mainly through the Spanish National Tumour Bank Network.

This network was created in September 2000 and currently includes 25 institutions. The biobanks within these institutions are autonomous. The CNIO Tumour Bank maintains collaborations with other biobanks as a part of the Spanish National Biobank Network, and actively participates in research projects in collaboration with different CNIO groups and other external research groups.

Main achievements of the 2006–2010 period:

As a Biological Resource Center, we made possible 233 research projects in the 2006–2010 period, most of them for multicenter cooperative groups, corresponding to 505 requests of tissue. The median impact factor of the 96 supported publications in this period was 6,355.

1 Indian Institute Of Technology Guwahati, India, Guwahati, Assam, India NIR 06. Current Status of Biobanking in India

Background: India is a natural habitat to several thousand species of microbes, plants and animals that constitute about 8% of global biodiversity including 2.9% of the world's threatened species. Therefore, India is recognized as one of the 12 mega-biodiversity hotspot regions in the world.

Among the ten ideas changing the world, listed in Time magazine in March 2009, biobanking is a vital one. Biobanking, an emerging field in India is nationally operated by central government and regionally managed by state governments. The public sector biobanks is comprised of 5 institutions, the National Bureau, gene banks, research institutes, hospitals and universities, which are involved in managing all kinds of biospecimens. Technological advances have made it feasible for India to establish Human DNA Bank in Lucknow as Asia's first and world's second Human DNA Bank for Human identification. Another unique type of biobanking found in India is the “Community Seed Bank”, run and managed by local communities for themselves. Recently, some community seed banks have also been set up in partnership with government owned various plant breeding research institutes.

Conclusion: Though the biobanking sector in India is quite diverse and vast, it lacks organization and coordination for a wider reach and impact. To ameliorate the various problems faced by the biobanking sector in India, currently an initiative has been projected by various institutes, universities and nongovernmental organizations to develop a connection amongst the biobanks for knowledge sharing, sustainable resource management, and a better outlook for future plans to bring forward biobanking in India.

1 Chungnam National University, Daejeon, Republic of Korea NIR 07. Korea Brassica Genome Resource Bank

Background: The purpose of establishing the Korea Brassica Genome Resource Bank is to maintain various genetic resources of the Brassicacea family including the Brassica rapa ssp. pekinensis (Chinese cabbage). These resources will be distributed on request internationally as well as domestically for research purpose. Moreover, the establishment and distribution of the genetic resources will help in strengthening the on-going research on Brassica genetics and genomics in Korea.

1) Distribution of Genetic Resources: Collection of genetic resources of various Brassica and related species with a wide range of traits, will be helpful in crop improvement. The genetic resource of wild species will play an important role for introducing new agronomically-important traits in the cultivated Brassica crops for improving their productivity, quality, and environment sustainability. Besides, mapping populations will be useful for construction of genetic maps, undertaking marker-assisted selection, and gene cloning.

1 Korea National Institute of Health, KCDC, Chungbuk, Republic of Korea NIR 08. Infectious Disease Biomarker Database (IDBD)

Background: For the biotechnological research revival and diagnostic development of infectious diseases, we designed the Infectious Disease Biomarker Database (IDBD, http://biomarker.cdc.go.kr) by web based platform on useful biological contents of biomarkers of pathogens for diagnosis, detection, protection, and characterization of infectious diseases. It supplies information of pathogens and biomarkers, which are the components for modeling and simulation of the infectious diseases and the biological processes. On the other hand, IDBD provides omics to information of biomarkers and the description of pathogens and diseases. It is a community annotation database utilizing collaborative Web 2.0 features and provides a comfortable user interface to enter and improve data on-line. It supports various types of data searches and the application tools to analyze sequence alignment, phylogenetic tree and structural characteristics of the potential and the validated biomarkers.

Methods: At present IDBD integrates 1,826 16s rDNA sequence of the pathogens, 710 of biomarkers for the group with 11 diseases, 79 infectious diseases and 80 pathogens including bacterium, viruses, fungi and parasites. Researchers can use this web site as new information entry in the biotechnology field effectively.

Conclusion: Contents in IDBD are freely accessible open to the general public. Also, we connect biomarker information with pathogenic resource of National Culture Collection for Pathogens (NCCP, http://nccp.cdc.go.kr) to distribution service in Korea National Institute of Health (KNIH).

1 The Research Institute at Nationwide Children's Hospital, Columbus, OH NIR 09. Integrated Workflow for Digital Pathology in a Biospecimen Repository Environment

Background: The increasing demand for more expedient pathology review has led to the expansion of the field of Digital Pathology. The Biomedical Imaging Team (BIT) in the Biopathology Center (BPC), located at The Research Institute at Nationwide Children's Hospital in Columbus, Ohio, has integrated digital pathology into its biorepository's operations. The BPC currently serves as the biorepository for the Children's Oncology Group and the Gynecologic Oncology Group as well as the pediatric division of the Cooperative Human Tissue Network and a Biospecimen Core Resource for The Cancer Genome Atlas (TCGA) project. This integration into banking operations has required the development of specialized applications to support the utilization of this technology.

Methods: The BIT utilizes high-capacity scanners to generate high-quality whole slide images and uses its custom-built VIPER (Virtual Imaging for Pathology Education and Research) application to distribute images and QC review forms to reviewing pathologists. The images are uploaded to the Ohio Super Computer Center (OSC) where they are served to users in the United States and Canada. The OSC provides a reliable high performance computing and communications infrastructure and has allocated 50 terabytes of storage capacity to support digital pathology initiatives at the BPC.

Results: The integration of digital pathology into BPC's workflow has decreased pathology review turnaround times and eliminated shipping costs for many projects. Simplified logistical operations have resulted in an overall increase in operational efficiency.

Conclusion: This disruptive technology is allowing the BPC to overcome many of the disadvantages of traditional glass slide pathology review.

1 Australian Prostate Cancer BioResource, Kelvin Grove, Queensland, Australia NIR 10. Achievements of the Australian Prostate Cancer BioResource: First 5-Year Round of Funding 2004–2009

Background: Funding for the Australian Prostate Cancer BioResource (APCB) network has been renewed by the NHMRC & PCFA for 2010–2014. This funding is to continue the prospective collection of tissue from men with early stage prostate cancer treated by radical surgery for another 5 years to allow 10 year outcome data to start to be accrued.

Methods: Tissue is collected from daVinci robot-assisted laproscopic prostatectomy (RALP) as well as retropubic radical prostatectomy (RRP).

Results: Over the last 5 years 2,894 participants have been recruited with accrual of 1560 (54%) fresh frozen prostate and 1,871 (65%) blood samples. Although collection and processing times can be different between RALP and RRP, histological examination and RNA extraction performed on representative cohorts showed no difference in tissue histology, RNA integrity or gene expression by quantitative RTPCR for several genes between the 2 procedures, thus allowing a larger pool of tissues for distribution. Over the last 3 years, 1,477 tissues have been distributed nationally leading to 6 publications to date. 336 samples from the Brisbane cohort have been used for genotyping in the PRACTICAL genome-wide association studies.

Conclusion: At 5 years, the APCB has a collection of high quality prostate cancer tissues with associated blood samples and clinical and pathological data acquired at diagnosis and surgery. This collection has become an important bioresource for prostate cancer research nationally and internationally. With maturity and accrual of ∼5,500 men by 2014 with 5–8 year clinical follow up it will become an even more significant research resource.

1 Indian Institute of Technology Guwahati, India, Guwahati, Assam, India 2 Institute of Bioresources and Sustainable Development, Imphal, Manipur, India PSR 01. Plant Biorepository Management in North East India – The Nature's Biorepository

Background: North East region (87°32'E to 97°52'E latitude and 21°34'N to 29°50'N latitude) of India is a part of the Vavilovian center of origin for several cultivated important crop plants. Climate of the region ranges from Alpine to tropical, 85% of its landmass is mountainous and inhabited by 87 tribes with rich indigenous knowledge of plants. A preliminary survey showed that despite of richness of plant biodiversity, biobanking and biorepository management in the region has been largely in a state of infancy.

Methods: The region houses more than 500 orchid species, 10% medicinal plants out of 5,000 angiosperms, 91 species of Zingiberaceae with 22 genera and 151 types of citrus. The ethnic community of the hills maintains a unique set of medicinal plants and indigenous health system. To check the genetic erosion of these rich gene pools, on farm conservation practices have been implemented in the hilly regions. Few germplasm banks of orchids and two research centers for orchids as well as citrus are nascent but vital initiative for the management of biorepository.

Conclusion: Several rice research centers maintain a set of more than 50 percent of estimated 10,000 rice landraces of the region and is a spearheading effort towards plant biorepository management.

A recent joint initiative between the Indian Institute of Technology Guwahati and Institute of Bioresources and Sustainable Development, Imphal is expected to strengthen plant biobanking with equitable sharing of potential resources and expertise in efficient management of plant bioresources and develop strategy to advance plant biorepositories in the region.

1 Kaiser Permanente Northern California, Oakland, CA 2 University California San Francisco, San Francisco, CA BSS 01. High-Throughput DNA Extraction and Normalization from Saliva Results in High-Quality DNA for Genotyping and Telomere Analysis

Background: Kaiser Permanente's Research Program on Genes, Environment, and Health is using saliva as a source of DNA for a NIH-funded project that requires genome-wide genotyping and measurement of telomere lengths on DNA samples from 100,000 individuals; the resulting data will be merged with clinical, survey, and environmental information on the same individuals to create a new research database. DNA was extracted and normalized from more than 120,000 biospecimens in 15 months. To our knowledge, this is one of the largest human DNA extraction projects ever attempted, and the largest to extract DNA from saliva.

Methods: Saliva was collected using Oragene® kits and was stored at room temperature for 0-3 years prior to extraction. Specimens were weighed and visually inspected prior to DNA extraction with a magnetic bead kit. DNA samples were quantified by PicoGreen® and normalized to 30ng/uL for telomere length measurement and 10ng/uL for genotyping assays.

Results: 2.5% of saliva biospecimens were excluded from extraction due to particulate matter or low volume. The average DNA yield was 4.86 micrograms per 0.5mL saliva. DNA purity (A(260/280)) ranged from 1.5-1.9.

Genotyping results on the first 58,000 samples show a sample success rate of >93%. Preliminary telomere length measurement results show a CV of <4% across replicates, indicating high-quality DNA.

Conclusion: DNA extraction from saliva biospecimens at high throughput (more than 2,200 samples per week) results in high-quality DNA samples for use in genotyping and telomere length analyses.

1 Brigham and Women's Hospital, Boston, MA 2 Brigham and Women's Hospital and Harvard School of Public Health, Boston, MA 3 Harvard School or Public Health, Boston, Ma 4 Harvard University, Boston, MA BSS 02. Conservation and Preservation of Biological Specimen: Three Pilot Studies for Evaluating New Biomarker Assays

Background: The Nurses' Health Studies Biomarker Laboratory and Repository has collected biological specimens from over 60,000 study participants over the past two decades. To protect this finite resource, a 3-step piloting process has been mandated, including blinded duplicates (Split), processing method (PM), and within person stability (WPS).

Methods: A split pilot is conducted to confirm that biomarker levels are detectable among participant samples and to quantify laboratory measurement error (i.e., coefficients of variation [CVs] among blinded duplicate participant and quality control pool samples). Second, since participants mailed specimens to the laboratory via overnight mail, a PM pilot is done to determine whether biomarker levels are affected by delays in processing of up to 48 hours. Finally, only a single biomarker measurement is available for most participants, thus, a WPS study is performed to examine the correlation between biomarker measurements in repeated samples, collected 1-2 years apart, which indicates whether a single measurement reasonably represents long-term biomarker levels.

Results: In a 2-year period, 106 split pilots were completed, of which 18 (17%) failed. Among PM pilots, 12 of 36 (33%) failed and, among WPS pilots, 5 of 43 (12%) failed. Assay pass/fail rate varied by preservative (EDTA or Sodium Heparin) type. Specific illustrative examples of the 3 pilots will be shown on the poster.

Conclusion: Evaluation and elimination of assays that performed poorly resulted in substantial cost savings and, more importantly, preserved valuable sample from being used inappropriately.

1 Indiana University School of Medicine, Indianapolis, IN BSS 03. Creating Tissue Macroarrays (Multichambered 9 Well Cassettes) to Perform Large Biomarker Immunohistochemistry Studies. An Efficient Use of Tissue Plus Effective Cost Control for a Tissue Bank Facility

Background: Tissue microarray is a technology that has been in used for the past twelve years. The core specimens on tissue microarrays are 0.6, 1.0, and/or 1.8 mm in diameter. Tissue microarray technology facilitates using multiple tumor tissue samples on one slide for predicting targeted therapy and biomarkers to predict clinical treatment outcomes. It is also a proficient and an easier way to evaluate multiple samples in these high throughput studies.

Methods: We created tissue macroarrays using a 9 well cassette and placed 8 tissues plus one control tissue in one macroarray. The tissue macroarrays have larger tissue sample sizes, about 6 to 7 mm in diameter and about 3 to 4 times the size of a tissue microarray core. This study evaluates the use of tissue macroarrays, which are created in multi-chambered 9 well cassettes, and how they can be used to do large biomarker studies.

Results: Approximately 250 macroarrays have been built in the past ten years. A typical immunohistochemical study usually involves examining 50 cases which requires 7 tissue macroarray. The cost of a 50 case study is usually about US$1250.00 per antibody. In a multiple antibody (biomarker study), 4 to 6 antibodies are evaluated, costing US$7000.00. Using tissue macroarrays, the cost is cut by about US$1,000.00 an antibody.

Conclusion: This is an efficient use of tissue and effective cost control for tissue banks, histology labs, and immunohistochemistry labs. This technology saves on reagents, technical time, histologic supplies and immunohistochemistry antibodies and supplies.

1 van Andel Research Institute, Grand Rapids, MI BSS 04. Neonatal Blood Spot Card Biorepository Sample Processing

Background: The Michigan Department of Community Health has established policies to de-identify and code leftover Newborn Screening samples and store them at the Michigan Neonatal Biobank for possible future ethical IRB approved research use. An innovative analytical tool was developed by the Van Andel Research Institute to manage the Biobank's inventory.

Methods: The software analytical tool photographs the front and back of a blood spot card, determines the area of the blood remaining on the card, calculates the capacity for four core punch sizes, and saves the data with a composite image to the Van Andel Data Repository (VADR). VADR uses a computer controlled camera mounted in a custom lighted hood. The algorithm calculates the blood area by analyzing each pixel's hue and luminosity which is compared to a calculated background luminosity threshold. Small spots of blood and small specks of white in the blood area are eliminated.

Results: The Biobank is able to inventory 2,600 cards per day. Over 300,000 of the four million available cards have been imaged and over one million are being tracked in VADR. Over 6,000 samples from this archive have been used for 19 different research studies.

Conclusion: Using this application with custom algorithms to catalog the cards has increased the speed, accuracy, and consistency of cataloging while making available a digital image and predicted number of punches.

1 Indiana University School of Medicine, Indianapolis, IN 2 Indiana University Simon Cancer Center, Indianapolis, IN 3 Marion County Coroner's Office, Indianapolis, IN 4 Analytical Biological Services, Inc, Wilmington, DE BSS 05. Factors Affecting Gene Expression (RIN Value) and Tissue Histology in Ten Different Human Postmortem Tissues: A Study on Tissue Sample Quality at Four Different Postmortem Time Intervals

Background: Markers of postmortem tissue quality include PMI (postmortem interval), length of refrigeration time, agonal state, and disease state. The postmortem neuropathology field has acquired chemical markers of tissue quality: pH and 28S/18S ratio and now includes RNA quality using a RIN (RNA Integrity Number)value obtained on the Agilent Bioanalyzer. RIN correlates the extent of RNA degradation in the 28S/18S peaks.

Methods: In this autopsy study we evaluated 10 tissues (kidney, liver, heart, lung, pancreas, small intestine, skeletal muscle, bone marrow, skin, and brain) from 4 cases with four different PMIs. We evaluated clinical history, agonal state, PMIs of 10 hours, 12 hours, 16 hours, and greater than 24 hours and body refrigeration time. Histology and RIN values were evaluated.

Results: PMI did not influence RIN values in this study. The length of refrigeration time delayed postmortem autolysis keeping RIN values higher. The medical history and the agonal state were important variables affecting RIN values. A prolonged interval of hypoxemia, (>24 hours), lowered RIN values. Histology predicted the RIN score for most organs, but not in the pancreas and small intestine. The heart and lung tissue had the highest RIN values (7.1 and 5.8 average, respectively) across the four cases.

Conclusion: RIN values in most tissues, except the GI tract, was highly correlated with the clinical medical history and agonal state, and was not influenced by the PMI. Quick refrigeration of the body after death may preserve both post mortem histology and RIN values.

1 SeraCare Life Sciences, Inc., Gaithersburg, MD BSS 06. Stability of Extracted RNA at Various Storage Temperatures and through Multiple Freeze-Thaw Cycles

Background: RNA degradation during storage makes samples unusable for assays including reverse transcription, in vitro translation, differential display, expression-array and expression-chip analysis. RNA degradation during storage results primarily from base hydrolysis of RNA under low pH conditions or divalent cation catalysis. The effects of different storage temperatures and freeze-thaw regimens on RNA stability during storage are investigated.

Methods: Tissue sample RNA was extracted using the Qiagen RNeasy Kit. RNA concentration was adjusted to 300 μg/mL using ultra-pure water. RNA was aliquoted into single-use aliquots and stored at room temperature (RT), 4°C, or −20°C. Samples were tested after 0, 1, 2, 3, 7, 14, and 28 days of storage. Testing, in duplicate, included concentration, ribosomal RNA ratio (28S:18S), and RIN number. Similarly, a subset of samples were placed at either −80°C or −20°C and subjected to ten freeze-thaw cycles.

Results: RNA stored at RT was stable through 7 days, declining in all three test parameters at 14 and 28 days. No declines in RNA concentration, rRNA ratio, or RIN number were observed for RNA stored at 4°C or −20°C. RNA cycled between −20°C or −80°C and RT for 10 freeze-thaw cycles had no concentration or integrity decline.

Conclusion: RNA stored in an appropriate buffer is resistant to degradation under sub-optimal conditions encountered during accidental mishandling or shipping delays. Frozen RNA samples can be thawed multiple times without compromising quality. For short-term studies, RNA can be stored at 4°C or −20°C. RNA at RT showed degradation after 7 days.

1 University of Utah, Salt Lake City, UT 2 Huntsman Cancer Institute, University of Utah, Salt Lake City, UT BSS 07. Genome-Wide Germline Genotypes from Normal Tissue Stored in FFPE Samples

Background: Although large collections of formalin fixed paraffin embedded (FFPE) samples exist, sometimes representing decades of stored samples, they have not typically been considered as a useful resource for studies requiring genome-wide genotyping of normal cells. Normal tissue from such samples, however, would be extremely valuable for generation of genotype data for individuals who cannot otherwise provide a DNA sample.

Methods: In order to determine the value of using FFPE tissue blocks as a source of normal “germline” DNA for genotyping experiments, we assessed the quality and yield of genome wide (GW) genotyping data generated from archived FFPE tissue aged 18–41 years. Grossly uninvolved regions of tissue from prostate cancer cases were identified and DNA was extracted from corresponding punches in the original FFPE tissue block. GW genotyping was performed using the Illumina 610Q platform.

Results: The genotyping call rates for the FFPE samples ranged from 0.873 to 0.989. Additionally, we observed a range of 0.993-0.9998 reproducibility in genotyping calls when we compared results from DNA isolated from whole blood versus normal tissue from FFPE.

Conclusion: Our results indicate that DNA extracted from normal tissue in FFPE (even decades old) provides excellent quality GW genotyping data. Overall, this study provides an innovative solution to procuring GW genotyping data for informative individuals not otherwise available for sampling by using stored FFPE blocks.

1 University of Minnesota, Minneapolis, MN BSS 08. Software for Generation of Multigene Expression Signature Maps at the Protein Level from Digitized Immunohistochemistry Slides

Background: Biorepositories provide essential specimens for discovery and validation of diagnostic, prognostic and predictive biomarkers. Among validation methods, immunohistochemistry (IHC) is optimal for gene expression profiling (GEP) at the protein level in routine clinical samples. However, analytical methods to perform GEP using standard IHC are lacking.

Methods: We developed software that interacts with a whole-slide imaging platform to digitally align slide images to an annotated H&E-stained reference slide, quantify IHC stains in annotated areas, and compute a weighted sum of n-gene expression values. The software provides a tiled display of GEP data (termed a signature map) to reveal heterogeneity within disease areas. For purposes of illustrating software features, we produced a four-gene signature map (representing MKI67, ENO2, CD34 and ACPP gene products) on prostate cancer tissue.

Results: Mean aggressiveness signature score (SS) increased with grade from −1.2 for 3 + 3 tumor areas, indicating non-aggressiveness (negative value due to low expression of aggressiveness genes MKI67, ENO2, and CD34, each with a positively-signed weighting factor, and high expression of non-aggressiveness gene ACPP, with negatively-signed factor), to a mean of 2.1 and 6.9 for 3 + 4 and 4 + 3 areas, respectively.

Differences in the standard deviation of SS were observed by grade (3 + 3 SD = 4.71, 3 + 4 SD = 5.81, 4 + 3 SD = 4.14), suggesting that the standard deviation, as well as other measures of heterogeneity, may also be useful for predicting aggressiveness.

Conclusion: The IHC signature map approach may have broad applicability for validating multigene diagnostic, prognostic and predictive disease classifiers using routine clinical specimens.

1 Cooperative Human Tissue Network (ED), University of Pennsylvania, Philadelphia, PA BSS 09. Effect of High Temperature Thawing on PTEN Enzyme in Human Uterine Tissue

Background: Degradation of proteins during the preparation and storage of tissue lysates is an ongoing challenge in proteomic research. During lysate preparation, enzymes and their substrates are brought into closer proximity thereby increasing the chance of enzymatic modification of the substrate (e.g. dephosphorylation by phosphatases).

Traditionally, enzymatic activity is decreased through the use of protease and phosphatase inhibitors. However, the introduction of these exogenous inhibitors might interfere with downstream analysis. One demonstrated way to inactivate enzymes without the use of chemical inhibitors is to use heat during thawing.

In earlier studies we demonstrated the effectiveness of high temperatures in reducing tyrosine phosphatase activity. In this study, we investigated the inactivation of PTEN enzyme in uterine smooth muscle tissue by comparing high heat thawing with more traditional methods of thawing.

Methods: Frozen uterine smooth muscle samples were thawed in the oven (37°C), on ice (4°C), or at 95°C using the heat Stabilizor T1 from Denator AB. Frozen tissues were used as controls. Tissue lysates were prepared without enzyme inhibitors and PTEN Phosphatase activity was assayed using the pNPP Protein Phosphatase Assay kit.

Results: Our results indicate that in comparison to frozen controls and tissues thawed at 37°C and 4°C, specimens thawed using heat stabilization (95°C) had a significant reduction in PTEN activity.

Conclusion: The use of high temperatures is optimum for thawing tissue by decreasing the amount of enzymatic activity, thereby better preserving the proteome.

1 Catholic Health Initiatives, Towson, MD BSS 10. A Survey of Tissue Specimen Collection Techniques: Impact on Biomarker Data Quality

Background: Prognostic and diagnostic biomarker development is currently hindered by access to high quality, clinically annotated biospecimens. To address this limiting factor for translational research, we established a state-of-the-art biorepository facility to procure clinically annotated biospecimens from remote network locations, and isolate high quality nucleic acids for long-term storage and molecular analysis. We describe here a long-term project comparing methods of sample collection and storage, including stabilization media, on the quality of RNA for genomics research.

Methods: Tissues known for the presence of high and low RNAses (kidney/liver and colon/lung, respectively) were collected as FFPE, fresh, frozen in Liquid Nitrogen (LN2), frozen with stabilization media (RNAlater), and LN2 frozen tissues post-treated with stabilization media (RNAice). Total RNA isolated from all tissues was assessed for quality, and analyzed using expression arrays.

Results: At zero time point, no major differences in RNA quantity were observed due to collection and storage treatments. Further analysis of RNA quality with QC arrays revealed intact RNA free of inhibitors of reverse transcription and PCR amplification, genomic and general DNA contamination. Hierarchical clustering of Oncogene and Tumor Suppressor genes revealed three distinct groups; 1) Fresh, LN2 and RNAice, 2) RNAlater and 3) FFPE suggesting that RNA stabilization treatments may influence gene expression patterns.

Conclusion: Currently, experiments are underway to assess the RNA quality on global gene expression patterns and establish a baseline, to be compared to the RNA quality and gene expression patterns at 6, 12 and 24 month post-collection.

1 SeraCare Life Sciences, Inc., Gaithersburg, MD BSS 11. Genomic DNA as a Quality Indicator for Whole Blood Storage

Background: Whole blood is frequently shipped and stored for clinical trials, R&D efforts, and longitudinal studies. Genomic DNA is then extracted for various molecular biology applications including genotyping, sequencing, and PCR amplification. This study compares yield and quality of DNA extracted from whole blood exposed to varying stress conditions.

Methods: Whole blood was aliquoted and incubated at 4°C for up to two weeks to determine acceptable 4°C holding time. Aliquots were also subjected to three freeze-thaw cycles. White blood cells were counted and DNA was extracted using the Qiagen/Gentra Autopure LS. Extracted DNA was quantitated using the Spectramax spectrophotometer to determine yield, and quality assessed by genomic gel electrophoresis and PCR to the β-globin locus.

Results: Storage of whole blood at 4°C for 7 days had no effect on extracted DNA quality and quantity. Statistically significant declines in DNA yield, ∼25% less DNA, occurred at 14 days; however, the genomic DNA appeared intact by gel electrophoresis and gave acceptable PCR results. In contrast, freeze-thaw cycles dramatically affected DNA yield and quality. One freeze-thaw cycle reduced genomic DNA yield by half, two cycles produced extremely low DNA yields with variable A260/280 ratios; the DNA showed visible smearing by gel electrophoresis, with variable PCR results.

Conclusion: Whole blood can be safely stored or shipped at 4°C for up to 7 days without significant effects on yield or quality of extracted genomic DNA. Freeze-thaws of whole blood significantly affect the extracted DNA quality and quantity.

1 Rutgers University, Piscataway, NJ 2 Chemagen USA, Worcester, MA 3 Hamilton Robotics, Reno, NV BSS 12. High-Throughput Extraction of Compromised Whole Blood Samples for Genetic Analysis: Implementation of the Chemagic STAR in a Genetics Repository

Background: Genetic analysis continues to evolve with the utilization of novel technological approaches that require specific sources of genomic DNA. DNA from whole blood is becoming more important in the biomedical research environment with the introduction of epigenetic analyses. To this end, all whole blood sources of DNA, including compromised samples and archived resources, are critical for analysis. In addition, existing large collections (based on retrospective sampling) require a robust high-throughput approach to maximize the yield of DNA from each sample while retaining the highest quality nucleic acid.

Methods: The unique challenges of extracting DNA from various volumes of compromised and frozen whole blood samples require extraction chemistries and automated solutions that ensure a high level of success with these precious samples. This presentation describes the protocol development and implementation of the chemagic STAR for frozen whole blood samples. The integration of chemagen's bead-based chemistry (with modifications for sample source and volume) with the Hamilton STAR creates a robust workflow that maximizes the yield and quality of compromised blood samples, provides a fully integrated “walk away” workflow that catalogues all DNA stocks, and prepares samples for analytical and functional quality control. This platform is tunable from 1ml to 10ml in single extractions providing the flexibility needed for large biorepository projects where samples are processed across many different collections.

Conclusion: Both analytical and functional analyses are performed on all DNA samples and are described in this presentation to document the quality and downstream utility of this extraction approach.

1 Translational Genomics Research Institute, Phoenix, AZ 2 Van Andel Institute, Grand Rapids, MI BSS 13. Proteomic Analyses of Colorectal Tumors by Electrospray Ionization (LC-ESI) and Split Sample Strategy: Effects of Formalin Fixation and Extraction Methods on Peptide Identification

Background: We have extended high performance discovery-based assays to DNA harvests from formalin-fixed paraffin-embedded (FFPE) tissue collections. Proteomic surveys of solid tumors present challenges in accurate measures of cross-linked and degraded proteins and peptides. Several studies have shown good spectral correlation with fresh frozen (FF) and FFPE tissue samples but are of limited spectra.

Methods: Six colorectal cancer specimens, disparate phenotype by genomic instability, were selected for this multi-tiered comparative study. FFPE scrape macrodissected samples were extracted by Qproteome (Qiagen, Inc) and Liquid Tissue (Expression Pathology, Inc). FF split samples were visualized by 2 ink QC method and histological tumor estimate or obtained by LCM method to include protease inhibitors. FF extractions were performed by Invitrogen kit and by Petritis lab method. A total of 24 protein preparations were analyzed by tandem LC-MS by Orbitrap electrospray ionization (ThermoShandon,Inc).

Results: Tumor content was estimated at 30–60% for scrape macrodissected (FFPE) and FF chipped samples. LCM harvests were >95% tumor and 12,000 to 15,000 cells collected. FF & FFPE aliquots showed similar yield, but much sharper bands in FF gels. Slight variance in the peptides was detected in FF and much larger variance in FFPE.

Conclusion: Discovery-based proteomics in FF preserved solid tumors is highly informative, but requires detailed sample preparation. FFPE samples with high SDS (Qprotoeme kit) may have limited tryptic digest. Heating of the FFPE sample appears to be critical for efficient protein extraction but could further degrade proteins. Our results indicate limited utility for FFPE samples in whole proteome analyses.

1 Rutgers University, Piscataway, NJ 2 Qiagen Inc., Germantown, MD BSS 14. DNA Extraction from Frozen Serum Samples: An Automated Approach for Genetic Analysis Utilizing Qiasymphony Purification and Repli-G Whole Genome Amplification

Background: Tremendous resources are used for the collection of clinical samples in research trials worldwide. Occasionally the analytical criteria for some studies are not well defined based on fiscal and technological uncertainty at the time of project initiation. To this end, there are large numbers of samples stored from various clinical protocols which are currently not considered for mainstream analyses. One example of this is serum and plasma samples which are typically stored for specific analyte interrogation where no other molecular components were collected for additional analyses.

Methods: This presentation describes the use of serum (and plasma) derived from whole blood for DNA based genetic and genomic analyses. Given the low quantity and variable quality of this DNA that is mostly cell free, the method of extraction and validation of nucleic acid following processing is of paramount importance. We will describe a fully automated, high throughput, extraction and amplification workflow for these precious clinical isolates. The details of the protocol and QIAsymphony implementation will be discussed specifically in the context of a biorepository setting. Additionally, every nucleic acid sample is subjected to Repli-g amplification in an automated process to maximize the utility of these biological resources for future analyses.

Conclusion: The technical issues addressed in these protein rich, cell free fractions include but are not limited to: shearing and nicking of gDNA, clotting of samples during the extraction process, low molecular weight DNA retention, and variable amounts of gDNA yields per sample.

1 University of Minnesota, Minneapolis, MN CCP 01. The Biopreservation Core Resource (BioCoR): A Resource Based on the Science of Biospecimen Preservation

The mission of the Biopreservation Core Resource (BioCoR), located at the University of Minnesota, is to advance the science, technology and practice of preservation. BioCoR is not a biorepository/biobank but consists of three distinct resources. The first component consists of a research resource whereby new methods of preserving biospecimens and new technologies to improve biospecimen processing are developed. BioCoR faculty members are actively involved in the development of new methods of preservation, understanding molecular mechanisms of damage, and the development of protocols for specific biospecimens. Secondly, BioCoR has an education resource for educating individuals and institutions on biopreservation. BioCoR offers an annual short course which covers topics such as the scientific basis for preservation, different preservation techniques, facility design, protocol development, as well as quality and regulatory issues in biopreservation. The course is offered on the web in addition to in-class participation. In early 2011, BioCoR faculty provided a webinar entitled, “Quality in Biopreservation” which was endorsed by ISBER and attended by over 120 people. BioCoR's third component is to act as a service resource for those who need assistance in developing biopreservation protocols for specific biospecimens, evaluating existing protocols, and providing literature summaries of the scientific knowledge related to the preservation of specific biospecimens. This third component of BioCoR is especially important since biobanks typically do not have the resources or expertise to develop new protocols and methods of preservation. In summary, BioCoR fills a niche in the field of biobanking that biobanks alone do not serve.

1 Bluechiip Ltd, Scoresby, Victoria, Australia 2 Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia 3 Biobusiness Consulting Inc, Lowell, MA CCP 02. Cryogenic Tracking and Monitoring (bluechiip™) For Hematopoietic Progenitor Cell Biostorage: Comparison of Manual and Automated Technologies

Background: Cryopreservation of hematopoietic progenitor cell (HPCs) at ≤150°C for later use requires HPCs to be stored for several weeks to many years. To ensure quality preservation and interpretation of cellular integrity, HPC material must be appropriately identified, stored, monitored and tracked.

Methods: The MEMS tracking device was attached to five medium sized Baxter cryocyte cryopreservation bags containing saline. The aim of the pilot trial was to assess the ability of MEMS technology to consistently measure cryogenic temperature and compare the MEMS tracking capabilities to current manual methods.

The on-site trial commenced with identification and initial temperature measurement of the bags. The bags were then transferred to cryogenic storage where they underwent freeze-thaw cycles.

Results: Tags on all bags at both room temperature and ≤150°C were successfully verified with no failed reads.

Conclusion: The MEMS tracking technology demonstrated accurate readings for tracking temperature at ≤150°C. The MEMS technology appears to offer consistent improvements in decreased tracking labor time over manual methods. Secondly, implementation of the MEMS technology reduced the propensity for damage to biostorage containers and handlers alike. Further investigations with larger sample sizes are warranted to investigate application of the MEMS technology for biobanking cryopreservation, in particular reduction of freeze thaw cycles.

1 SeraCare Life Sciences, Inc., Gaithersburg, MD CCP 03. Preserving Functionality and Differentiation of Frozen Peripheral Blood Cell Subsets for Repeatable and Large Scale Immunological Studies

Background: Peripheral blood mononuclear cells (PBMC) are used for immunological monitoring in clinical studies, as primary cells in basic research, and as infection models. Handling and preservation methodologies enable longitudinal studies across multiple sites with greater consistency across PBMC lots. In an ongoing effort, we have further extended our cryopreservation, processing, and media protocols to isolate and maintain functionality and differentiation in cryopreserved PBMC subsets.

Methods: PBMC were collected by leukapheresis; purified cell subsets were isolated using RoboSep Stem Cell Technology. After purification, cells were resuspended in freezing media, frozen in a rate-controlled freezer, and stored in vapor phase liquid nitrogen. Testing included post-thaw cell recovery counts, viability and purity assessments. Fresh and frozen PBMC and lymphocyte cell subsets were tested for proliferation and IFN-γ production. Fresh versus cryopreserved monocytes were tested for differentiation into dendritic cells.

Results: Frozen PBMC, purified monocytes, and T cell subsets all showed viability greater than 85%. Furthermore, frozen PBMC and purified CD3, CD4, and CD8 T cell subsets maintain a similar ability to proliferate and produce IFN-γ in response to specific peptide antigen stimulation when compared to fresh cell subsets. Notably, fresh and frozen purified monocytes were able to differentiate into phenotypic and functional dendritic cells with the capability to stimulate allo-CD3 proliferation.

Conclusion: A combination of upstream and downstream handling conditions, standardized cryopreservation protocols and optimized freezing medium allow cryopreservation of PBMC and cell subset populations and preservation of their functionality capabilities.

1 BioStorage Technologies, Indianapolis, IN CCP 04. The Integrity Study: Measuring the Impact of Sample Preparation Techniques and Storage Temperatures on the Integrity Of DNA

Background: To outline the design of a 24-month longitudinal study that analyzes the impact of storage practice methods in regards to the long-term yield integrity of nucleic acids. The poster will compare the use of various aliquoting schema and storage temperatures and highlight the benefits via an end report employing a failure mode and effects analysis.

Methods: The study analyzes the various storage methods of nucleic acids when comparing extraction yields on fresh sample, frozen pre-extracted samples, and extracted nucleic acids which require freeze/thaw cycles for processing. Various storage temperatures and aliquoting strategies will be evaluated over a 24-month period subsequent to a single patient collection event.

Results: The poster will outline study design and discuss the data to be reported. Various methods and procedures to capture and store samples for future research purposes will be discussed and the plan for measuring the impact of preparation method and temperature on nucleic acid sample integrity will be outlined.

Conclusion: During drug development, clinical trial samples must be securely managed and properly stored to support prospective or retrospective nucleic acid analysis. The goal of the INTEGRITY study is to determine the best method for preparing samples and the best temperature to store samples for future research.

1 National Institute of Hygiene, Caracas, Dtto. Capital, Venezuela CCP 05. Cryopreservation of Cell Lines in the National Institute of Hygiene “Rafael Rangel”

Background: The Cell Culture Department of the National Institute of Hygiene "Rafael Rangel" is responsible to produce, preserve, manage, and maintain 15 cell lines from different sources such as hamster kidney, mosquito larva, human laryngeal carcinoma, dog kidney, rabbit kidney, green monkey kidney, and others, which are used as biological substrate for viral diagnosis, investigation and research, viral vaccines production, and biological products control.

Methods: In response to the needs of providing cell lines, the main objective is to give response of the needs of providing cell lines, the main objective is the preservation of strains without morphological, physiological, and genetic changes. Therefore, the Cell Culture Department maintains and stores cell lines from certified institutions like the American Type Culture Collection (ATCC) and the Center of Disease Control and Prevention (CDC), using freezing medium with 15–20% Fetal Bovine Serum (FBS) and Dimethyl Sulfoxide (DMSO) as cryoprotective agent. The freezing method is with a controlled-rate of freezer that decreases the temperature 1°C per minute. The cell lines are amplified to obtain a sufficient cell suspension to prepare the master and working banks to cover the needs of the Department. To ensure that they are free of contaminants, sterility controls are performed to detect bacteria, fungi, and mycoplasma.

Conclusion: Conservation of the proper cell lines conservation is important to respond the needs of the users, ensuring appropriate quality certification of the cell lines.

1 Singapore Health Services Pte Ltd, Singapore, Singapore CCP 06. Tissue Cryopreservation: Long Term Storage of Tissue Samples in Liquid Nitrogen

Background: Our repository has a collection of frozen gastric cancer with matched normal control tissues dating back to more than a decade ago.

Methods: The samples have been snap frozen and stored in liquid nitrogen (vapor phase). In this study, we set out to determine if the quality of nucleic acids in 2 groups of matched gastric samples have altered significantly during long-term storage. Group A (n = 32) consists of normal and tumor tissues harvested in 2010 whilst Group B (n = 24) comprises samples that were harvested between 1997-98. Nucleic acid concentration and purity are assessed spectrophotometrically based on A260/280 ratio and gel electrophoresis is performed to determine integrity of DNA and RNA.

Results: There is no significant difference in the yield of RNA (p = 0.1748) or DNA (p = 0.3840) from samples in Groups A and B. Similarly, the average A260/280 ratio for RNA in Groups A & B are comparable at 2.05 + 0.075 and 2.07 + 0.06 respectively. For DNA, the average readings are 1.88 + 0.11 for Group A and 1.81 + 0.15 for Group B. Based on the presence of distinct 28S and 18S rRNA bands, gel analysis shows intact RNA in 50% of samples in Group A and 37.4% in Group B. DNA integrity is good with all samples showing a band size of over 12kb for both groups.

Conclusion: Our preliminary data indicates no significant difference in the yield of nucleic acids with prolonged storage. Likewise, the quality of DNA is not affected, although RNA integrity appears to be poorer in older samples.

1 The Research Institute at Nationwide Children's Hospital, Columbus, OH DR 01. Disaster Recovery: An Off-Site Expansion of Biorepository Operations

Background: The Biopathology Center, biorepository for two NCI Cooperative Groups, receives tens of millions of dollars annually from the NIH to conduct scientifically-driven clinically-relevant oncology trials at 500 institutions across the United States. These highly successful programs have vastly improved quality of life and survival of cancer patients and collected invaluable research specimens to allow for decades of high quality medical research. The 20 years worth of biospecimens are the tangible product of hundreds of millions of federal dollars spent during this time.

Methods: The satellite biorepository was constructed to not only allow for growth at the existing site, but to provide redundant storage of biospecimens. To preserve at least a portion of each biospecimen in our repository, we have built a facility geographically separate from the Research Institute campus. Unless the specimen has insufficient material, duplicate aliquots will be sent to the secondary site as insurance against natural disasters, criminal activity, or other catastrophic events. By storing a piece of each tumor at two sites, the risk of completely losing a specimen is greatly reduced.

Results: A build-out of 4,400 square feet of shelled space off-site to accommodate two years of projected growth with the ability to expand into 15,000 additional square feet to accommodate ten years of projected growth.

Conclusion: The Biopathology Center has created a redundant, satellite biorepository to allow for storage of biospecimens in separate locations, each with backup power and 24 hour environmental monitoring. This will reduce the risk of catastrophic loss of specimens.

1 Translational Genomics Research Institute (TGen), Phoenix, AZ 2 Biomatrica, San Diego, CA GRS 01. Dry Storage of Biospecimens for an East Asian Glioma Genome Wide Association Study (GWAS)

Background: An international consortium was formed to collect biospecimens in East Asia from 4,000 glioma and 4,000 control participants to identify genetic variants associated with glioma risk. The study will collect biospecimens supportive of post-GWAS experiments to identify how these genetic variants affect tumor biology. A pilot study was initiated at six sites in four Asian countries to demonstrate performance of biospecimen collection, preservation, and shipment to the Translational Genomics Research Institute (TGen) or a collaborating Chinese laboratory.

Methods: Blood from 10 glioma cases and 10 controls at each site is stabilized (Biomatrica's DNA stable blood) then shipped at ambient temperature. Glioma tissue samples are split for flash freeze (-80°C) or stored at ambient temperature (Biomatrica's DNA guard tissue). Biospecimens are shipped to TGen (USA) or the Chinese lab for quality control assays. A cost analysis of shipping and storage costs for frozen versus ambient temperature biospecimen preservation is in process.

Results: Quality control of biospecimens will be presented, including quality and yield of DNA extracted from blood and tumor samples and H&E analysis of tumor samples. A savings of US$13,330 was estimated for shipping all samples at ambient temperature, while an additional US$10,000 is projected to be saved in storage costs.

Conclusion: It is our expectation that the use of dry storage products for blood and glioma tissue preservation will significantly decrease the cost of biospecimen collection and processing, without a loss of analyte quality. Ambient stabilization of biospecimens for research drastically reduces the risk of failed repository responsibilities.

1 University at Buffalo, Buffalo, NY GRS 02. Room Temperature Preservation of RNA Derived from Clinical Samples

Background: Preservation of RNA at room temperature (RT) offers several advantages from traditional frozen specimens in terms of cost, space and energy. A commercial product (GenTegra) has recently become available that purports to enable RT stabilization of RNA samples in a dessicated matrix. An assessment of the capabilities of this product with regards to RNA integrity of clinical specimens would be of benefit for all biobanks.

Methods: 25 tissue specimens were procured at the time of resection. For every case, the time between receipt and freezing of the tissue specimen was <30 minutes. The tissue from each sample was later sectioned in a cryostat and total RNA recovered. The RNA for each sample was then aliquoted into 5 separate tubes intended for 5 separate purposes: 1) a baseline sample 2) RNA kept at RT for 1 month 3) RNA kept in the GenTegra matrix at RT for 1 month 4) RNA incubated at 37°C for 1 month and 5) RNA kept in the GenTegra matrix at 37°C for 1 month. At the end of 1 month, the samples from each group were assayed on a Bioanalyzer Nanochip and the 28S/18S (rRNA) ratio obtained.

Results: Only 14/25 samples had recordable rRNA ratios. Of these samples, 7% maintained at RT and 71% preserved in the GenTegra matrix had demonstrable rRNA. For those samples incubated at 37°C, no samples in group 4 had demonstrable rRNA vs. 78% of the samples kept in the GenTegra matrix.

Conclusion: Based on rRNA, GenTegra preserves RNA integrity.

1 Institut Bergonié - Université Segalen Bordeaux, Bordeaux cedex, Gironde, France 2 Société IMAGENE, Bordeaux cedex, Gironde, France GRS 03. Negligible Effect of Origin and Extraction Procedure on Stability of Air-Protected DNA Samples Stored at Room Temperature

Background: It has been observed that DNA stability during classical storage procedures may be affected by its degree of purity. We previously showed that dehydrated purified plasmid DNA exhibit remarkable stability at room temperature if efficiently protected from the atmosphere. Here we extend this finding to a variety of genomic DNA samples.

Methods: Genomic DNA samples from human, plants and bacterial cells and tissues purified by several routine procedures are submitted to accelerated stability studies while kept protected from the atmosphere in airtight, laser sealed stainless steel containers. Apparent degradation rates are measured by determining the average fragment size by gel electrophoresis.

Results: Accelerated aging kinetics show some differences among the degradation rates of the samples but there is no apparent correlation between the degradation rates and either the DNA origin or its extraction procedure. Most importantly, a heat-simulated 100 year storage period (simulation conditions being determined from Arrhenius plots) does not lead to any detectable degradation of the samples. Contamination nature, degree, and effects on stability will be further investigated.

Conclusion: Regardless their origin and their procedure of extraction, routinely purified DNA samples can be reliably stored at room temperature when efficiently protected from air. Therefore this "green" procedure does not compromise the quality of the stored samples.

1 Ministry of Health, Brasília, Distrito Federal, Brazil LE 01. Brazilian Official Resolution on the Storage of Human Samples for Future Research: Revised and Updated Version

Background: The necessity for well maintained biospecimens is at the forefront of medical research. Although Brazilian regulation on banking of human biological material for research purposes has been approved few years ago (Resolution 347/2005), it no longer met the current challenges and dilemmas.

Methods: Considering the dynamics of science, the Brazilian Research Ethics Commission undertook the current Resolution update, respecting the ethical, legal and social precepts. The revised document went through an extensive process of Public Consultation during the second half of 2010. The new Brazilian Resolution is the result of a broad national debate involving government, scientists, bioethicists and research subject's representatives.

Results: Diverse aspects received improvements or have been elucidated. For instance, Biobanks and Biorepositories have been clearly distinguished. In Brazil, Biobank shall be understood as an organized collection of human samples and its associated information stored for research purposes, in accordance with pre-approved technical and ethical standards, under responsibility and management of the institution. Alternatively, Biorepository is defined as a collection of human samples derived from a specific research, under institutional responsibility and management by the researcher. For Biobanks, in the country or abroad, the Informed Consent Form must include the following mutually exclusive options for the Brazilian subject's express manifestation regarding the future use of stored samples: I - requirement for new consent and II - new consent waiver.

Conclusion: The new resolution, despite allowing the so-called “broad-consent” to subject's decision, maintains individual rights, in accordance with the guiding principles of the Brazilian system of research ethics review.

1 Ministry of Health of Brazil, Brasília, Distrito Federal, Brazil LE 02. Participatory Construction of National Guidelines for Biorepositories and Biobanks—Brazilian Experience

Background: An international concern is the establishment of a network of biobanks harmonized, respecting the ethical, legal and social precepts of member countries, thus, there is an emerging need for national guidelines on the subject. Brazil does not have specific legislation on this subject, with some laws on matters such as Law 11105/05 – Biosecurity and the Resolution CNS 347/05 - Regulations on Storage and Use of Human Biological Material within Projects Research. This work had an objective to characterize the participatory and democratic construction of the National Guidelines for Biorepositories and Biobanks of Human Biological Material in Research, based on ethical principles of social responsibility, solidarity, respect for persons, beneficence, justice, and care.

Methods: To prepare the document, an interdisciplinary working group was formed considering the following criteria: experience in the operation of biobanks, regional representation, type of biological material conditioning, experts in bioethics, as well as participation in the The National Health Surveillance Agency - Anvisa, for regulatory competence, and the National Commission of Research Ethics -Conep, for social control.

Results: The document, based on ethical, legal and technical precepts, introduces the concepts, activities and purposes of biorepositories and biobanks, the subject's consent, and other aspects permeated by concerns of the appropriate use of information.

Conclusion: The text of the guideline was sent with approval by Ministry of Health of Brazil and publication in the Official Gazette of Brazil and, subsequently, the decision, by the board of directors of the Unified Health System.

1 Royal Dutch Academy of arts and Sciences, Amstelveen, Noord Holland, Netherlands LE 03. Legal and Ethical issues Associated with Informed Consent and Genetic Testing in Human Biobanks—A Persistent Dilemma

Background: Biobanks currently aim at the following objectives: a. Foster research in clinical and basic science. b. Standardization of SOPs. c. Facilitate multi-center concordance studies on genetic risk factors in diseases. d. Standardize the ELSI involved in work with human biospecimens.

Methods: We perform genetic testing for multiple genes and also test cognitive status of the donors, in the early and late stage of the disease, after which we refer them to a clinical genetics lab for results and consultation. This is not done by the biobank itself.

Results: We discovered links between genes and neurological diseases, mutations and families who carry these mutations. We tested for genes involved in Huntington's diseases, the Apo-E gene in AD and chromosome 17-Frontal temporal dementia. Currently we are publishing an inventory of the medico-legal framework and the ethical aspects applied in procurement, management, dissemination, confidentiality, "Financial gain" and genetic testing.

Conclusion: The ethical codes of conduct are significantly different in the various repositories and linkage between genes and diseases has future implications on the international legal and ethical systems. It would be advisable to have a global consensus regarding this issue as some of the genetic testing is done by collaboration between experts in different countries.

1 Universidade da Região de Joinville - UNIVILLE, Joinville, Santa Catarina, Brazil 2 Fundação Antônio Prudente, São Paulo, São Paulo, Brazil 3 Ministry of Health, Brasília, Distrito Federal, Brazil 4 Instituto Nacional de Câncer, Rio de Janeiro, Rio de Janeiro LE 04. Biobanking in Brazil: Present Challenges and Future Directions

Background: The adequacy in the national context of internationally recognized practices for procurement, storage and usage of human biological material is a challenge when establishing a biobank with the purpose of health research. In Brazil, it is common at universities and research centers to establish biorepositories to study a particular disease. Biobanks directed to the systematic collection of human biological samples with the purpose of research are more rare and recent.

Methods: Until 2005, the year of publication of Resolution 347 by the National Health Council (regulating the Use and Storage of Biologic Materials During Research Projects), these activities were covered in specific sections of previous resolutions, such as Resolution 196/96 (Guidelines and Norms Regulating Research Involving Human Subjects). In this paper, we present the issues faced during the establishment of two institutional biobanks (the AC Camargo Hospital Biobank in 1997, and the National Tumor Bank of the Brazilian National Cancer Institute, in 2004), making distinctions on particular topics with practices to be followed by biorepositories, as defined by brazilian regulations on research involving human subjects.

Conclusion: Although both biobanks are intended to collect human biological material for cancer research, we believe that several aspects hereby discussed could be useful for the establishment, in our country, of biobanks with other research purposes.

1 William Beaumont Hospital, Royal Oak, MI LE 05. The Nursing Challenges of Multidisciplinary Biobanking

Background: Beaumont is a large community-based hospital with over 1,000 beds and 58 surgical suites. The Beaumont BioBank was set up in October 2008 to begin to harness the vast amounts of clinical material that could be used in translational research aimed at “personalized medicine”. The BioBank has engaged over 30 principal investigators (PIs) spanning clinical disciplines across the healthcare continuum. This multidisciplinary approach poses major challenges for the research nurses who are at the forefront of the operation.

Methods: We have devised a series of procedures that are adapted to each different collection designed to consent and obtain specimens in the shortest possible time while being fully compliant with HIPPA regulations, Human Investigational Committee, the Code of Ethics of the hospital, patient comfort and informed participation. As an example, when working with surgical specimens, we will identify suitable patients through discussion with the PI's and nursing staff, monitor their scheduling on the OR lists, prepare tailored pre-barcoded specimen collection tubes (RNAlater, OCT, zinc formalin), consent the patient in pre-op and collect blood for plasma, serum and DNA extraction. During the operative procedure, we will be present to collect the surgical specimens as soon as made possible by the surgeon. The specimens are taken directly to the BioBank receiving laboratory and immediately processed, aliquoted, and stored after entry into the BIGR bioinformatics system.

Results: Using this approach, we have consented 586 surgical donors, yielding 1,791 specimens with an average time from excision to freezer of 27.3 minutes.

1 Genetic Alliance, Washington, DC LE 06. Disease Advocacy Organization Perceptions Surrounding Informed Consent—An Exploratory Survey

Background: Disease advocacy organizations (DAO) are actively involved in research initiatives, registries, and biorepositories.

Methods: To gain a better understanding of DAO involvement in research, Genetic Alliance conducted an exploratory survey, and 27 DAOs responded.

Results: More than three-quarters (78%) of DAOs surveyed have conducted research studies, including survey research (86%), biological sample collection (62%), patient registries (52%), and clinical trials (38%). More than half (57%) have submitted their study for IRB review, and respondents reported the IRB process to be easy (15%) or somewhat easy (23%), with only 8% reporting the process to be difficult. When asked about types of consent forms, DAOs were comfortable using a tiered consent (60%), blanket consent (40%), or broad consent (60%). When considering consent for a biobank, broad consent (40%) and blanket consent (40%) were preferred, with only 5% preferring to consent participants for each individual research project. Approximately three-quarters (76%) have conducted studies requiring a consent form, and more than half (57%) consent international donors for research initiatives. When asked what motivates research participation, respondents suggested trust in the organization conducting the research (67%), a close relationship with the researcher conducting the study (67%), and receiving information about current and future research projects (52%) to be key considerations.

Conclusion: DAOs are playing integral roles in research, and it is important to understand their experiences and perceptions surrounding the informed consent process. Education and training opportunities are needed to assist DAOs in navigating the scientific landscape.

1 Department of Veterans Affairs, Washington, DC LE 07. New Regulatory and Policy Developments Impacting Human Specimen Repositories

Background: The increased demand for human specimens for research, powerful new genomic technologies and extensive data sharing raise complex privacy, confidentiality and human subject protection issues. Additionally, the development of a national electronic health information infrastructure raises new privacy and policy challenges for the exchange of information needed for human specimen repositories. These issues have resulted in regulatory and policy changes that may significantly affect biobanking operations.

Methods: This presentation will provide an overview of important new policy and regulatory developments and their implications for biobanking. An analysis of requirements resulting from the Health Information Technology for Economic and Clinical Health Act, changes in the Health Information Portability and Accountability Act Privacy Rule, and policy developments on privacy of electronic health records, consent and authorization for specimen banking will be discussed.

Results: Important regulatory and policy changes affecting biorepositories include changes in the requirements for authorizations for future research use, the sale of protected health information for research, new rules for breach notification, policy discussions of US federal advisory committees on human subjects protections and health information privacy, and other policy developments.

Conclusion: The evolving regulatory landscape is likely to have important implications for specimen repositories. Biobankers will need to follow these developments closely in order to respond to requests for comment when draft regulations and policies are issued and to integrate new requirements into systems for oversight, as well as biobank operations.

1 Fraunhofer IBMT, Potsdam-Golm, Brandenburg, Germany 2 IMG Institut für medizinische Genomforschung Planungsgesellschaft mbH, Vienna, Niederoesterreich, Austria 3 Medizinische Universität Graz, Graz, Steiermark, Austria 4 Universität Mannheim, Mannheim, Baden-Württemberg, Germany NIRO 01. Safeguarding Donors' Personal Rights and Biobank Autonomy in Biobank Networks: The CRIP Privacy Regime

Background: Access to large “clinical cohorts” of human biospecimens and data for research requires trans-institutional query tools and cooperation to build operative infrastructures or “meta biobanks” without impairing biobank autonomy and donors' personal rights.

Methods: The Central Research Infrastructure for molecular pathology (CRIP; www.crip.fraunhofer.de) constitutes a federated ICT architecture of local databases (“Integrative Research Databases”, IRDBs) and a central web server,

- processing pseudonymized data within the IRDBs at CRIP's four partner hospitals Charité Universitätsmedizin Berlin, Klinikum rechts der Isar of TU Munich, Medical University of Graz and Universitätsklinikum Erlangen,

Browsing CRIP, the user specifies his or her search criteria which are automatically transferred (as csv-file) to the partner(s) holding suitable material and data. Re-performing the user's query on their IRDB enables CRIP partners to pick the requested material and data instantly.

Results: Since 2006, CRIP integrates and quarterly updates data focused on specific disease (as extracted from medical records), for which specimens and data are available for research at CRIP's partner hospitals. By the end of 2010, the CRIP database contained data on roughly 1 million cases covering the entire spectrum of diseases.

Conclusion: CRIP provides an established and validated ICT architecture for access to clinical biobanks and a blueprint for meta biobanks and biomedical research infrastructures.

This work was funded by grants 01GR0601 and 01GR0701 of the German Federal Ministry for Education and Research (BMBF).

1 Hadassah-Hebrew University Medical Center, Jerusalem, Israel 2 Sheba Medical Center, Tel Hashomer, Israel NIRO 02. Networked Biobanking in Israel: Challenges and Progress

Background: The process of establishing a biobanking network in Israel has taken several years, and functions largely on a personal level among its proponents. This is due to funding limitations and to legal governance limitations – Israel has no laws specific to biobanking activity. Over the last five years, the grass-roots establishment of separately functioning biobanks, has occurred virtually simultaneously, in large teaching hospitals. Institutional review board applications for establishing a biobank require submission of an ethics application with a consent form under the category of "genetic research". Despite its potential, biobanking itself does not constitute genetic research, thus this application category is somewhat problematic. In forming a network, Israel's biobanks face multiple challenges, including harmonization of standard operating procedures, decision-making regarding centralization of certain processes such as forming a common database, and in sharing a common informed consent form. Consent is complicated in that Israel is demographically divided into several religious and ethnic sub-populations.

Methods: We will highlight some of the unique practical and ethical challenges faced by Israel's biobank managers in establishing a functional network.

Results: Using established European and North American models, we propose a unified consent form for biobanking in Israel's academic centers.

Conclusion: Recently, the Israeli government has earmarked funds for a national biobanking network. The mechanism for distribution and overall structure of the network has not been established at the governmental level. It is hoped that active involvement of managers as a team will enhance legal and political discussion of networked biobanking in Israel.

1 BC Cancer Agency, Victoria, BC, Canada 2 Ontario Institute for Cancer Research, Toronto, ON, Canada 3 CancerCare Manitoba, Winnipeg, MB, Canada 4 CHUM Research Institute, Montreal, QB, Canada 5 University of Alberta, Edmonton, AB, Canada 6 Queen's University, Kingston, ON, Canada 7 Canadian Tumour Repository Network, Winnipeg, MB, Canada NIRO 03. Biobank Certification: Development of a Program by the Canadian Tumour Repository Network (Ctrnet)

Background: The mission of CTRNet is to improve acquisition and quality of cancer biospecimens and associated data for research through standardization and improvement of Canadian biobanking processes. CTRNet achieves this mission by creating national standards and harmonization mechanisms to increase the ability of cancer researchers to utilize tumor biobanks. CTRNet continues to focus on developing the necessary infrastructure for high-quality and high-capacity biobanking in support of cancer researchers' increasing biospecimen needs. Two areas of focus in the past year have been: 1) Creation of a Biobank Certification Program; and 2) Development of a Biobank Education Program.

Methods and Results: Biobank experts and translational researchers have recognized the need for better biobank standardization. To address this issue CTRNet is developing a Biobank Certification Program based on three components: 1) Guided self-assessment based on best practice standards; 2) Education on current international Best Practices; 3) External/peer verification that the biobank has undertaken to comply with the standards (through self assessment and education). The certification program also draws on input from Research Ethics Boards (REBs) that have indicated interest in such a process to help ensure confidence in the management of biobanking. CTRNet is also developing a Biobank Education Program to support its certification program and ensure appropriate and optimal accrual and use of cancer research biospecimens.

Conclusion: In addition to the benefits of better biobank standardization and streamlining biobank REB applications, creation of the CTRNet Biobank Certification and Education Programs will lead to increased support, capacity, and capability of translational cancer research.

1 Erasmus MC Rotterdam, Rotterdam, Zuid Holland, Netherlands NIRO 04. The Medical Research Biobanking “My Syndrome”: Its Origin, Consequences and How to Deal with It

Background: The so called “my syndrome” stands for collections of patient material that are not or very difficult to access by external parties and is not well understood. Its mechanisms are even logical, understanding them might give leverage to tip the balance in the right direction.

Methods and Results: Human samples for medical research are often collected within the hospital setting making use of the existing curative and diagnostic pathways. The routine clinical setting is involved in building the collection and the institute puts forward a budget to maintain the biobank. Logically, the ones directly involved in building the collection raise expectations towards their preferred use of the samples. In addition, scientists from the institute know the institute has spent resources to acquire the collection, putting them also in the list of favorable users.

The institute's evaluation of scientific achievement amplifies this effect, but on top has a strong adverse effect on cooperation. The result is that multi-center translational research is not very popular amongst scientists, whereas it would serve innovation of patient care better to strive for the more statistical significant results.

Conclusion: Policy makers and boards of institutes must be made aware of the adverse effects of the current evaluation of scientific achievements and change the rules just a little in favor of cooperation in large consortia.

It would also help if scientists seeking for samples are more prepared to cooperate and/or be prepared to share the acquired data and techniques with the research groups of other institutes.

1 Antwerp University Hospital, Edegem Antwerp, Antwerp, Belgium 2 Free University Brussels, Jette, Vlaams-Brabant, Belgium 3 Ghent University, Gent, Oost-Vlaanderen, Belgium 4 University of Hasselt, Diepenbeek, Limburg, Belgium 5 Catholic University Leuven, Leuven, Vlaams-Brabant, Belgium 6 Center Medical Innovation, Heverlee, Vlaams-Brabant, Belgium NIRO 05. Virtual Biobank as Model for Translational Biomedical Research Collaboration in Flanders

Background: Translational biomedical innovation refers to the research and development of new preventive, diagnostic or therapeutic applications in a patient centered environment. Through this kind of research, strategic basic research is linked to clinical research, which is often bi-directional. An integrated approach which facilitates harmonization between all stakeholders in Flanders will stimulate and improve the position in translational biomedical innovation. The Flemish government established this integration in setting up the Center for Medical Innovation, a strategic research center. The mission of CMI is to support a faster and more efficiënt translation of research findings into the development and application of innovative strategies for prevention, diagnosis and treatment of diseases with medical priority.

Methods: The CMI assembles all stakeholders involved in translational biomedical research into one single virtual platform in Flanders, which in turn functions as an interface with international translational biomedical initiatives. The first activity of CMI is to set up the Flemish biobank project. This virtual biobank infrastructure involves organizational and structural measures that are crucial to connect and support translational research in 5 Clinical Research Centers (Antwerp-Brussels - Ghent - Hasselt - Leuven). Validated and harmonized biobanks with patient samples linked with clinical data will be put in place, reflecting international guidelines and achieving critical mass.

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

1 String of Pearls Initiative, Amsterdam, NH, Netherlands NIRO 06. The Use of the String-of-Pearls Information Models in the Netherlands as Open Standards for Biobank Information Exchange

Background: The String-of-Pearls Initiative (PSI) is a strategic alliance between the eight university medical centers (UMC) in the Netherlands. Established in 2007 the initiative prospectively gathers clinical data and biomaterials from the UMCs. The project's initial focus is upon nine groups of medical conditions, its so-called “pearls.” Together they promote the advance of science, improve patient treatment and encourage the development of new products.

Methods: The gathered data are defined by the PSI Information Model (PIM). It has been developed in the past 3 years to classify and manage more than 2,000 different items of patient data collected for 8 large cohorts. This information model has grown from a straightforward flat file into a well-structured harmonized reference information model.

Results: PIM currently enables scalable, standardized and harmonized collection of clinical data for 8 different institutions participating in PSI. With the increase in structure and terminology in PIM, it became apparent that the real challenges in capturing clinical data lie in bridging gaps between clinicians, IT systems and researchers. Additionally, the PIM was getting large and difficult to assess for physicians who had to agree on its content. Therefore, in 2010 a start was made to describe the content in small pieces called Detailed Clinical Models (DCM). A DCM specifies clinical content and will become an ISO-standard.

Conclusion: Within the String- of-Pearls Initiative standards are created that successfully enable biobank information exchange between 8 institutions. These tools can be applied in other prospective collections.

1 NIDDK/NIH, Bethesda, MD NIRO 07. The NIDDK Central Repositories: An NIH Resource for Research on Diabetes, Endocrine, Digestive, Liver, Kidney, and Urological Diseases

Background: In 2003, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at NIH established data, biosample, and genetic repositories to increase the impact of current and previously funded NIDDK studies by making their data and biospecimens available to the broader scientific community (see www.niddkrepository.org).

Methods: The collected data and samples from over 50 studies allow researchers not involved in the original study to test new hypotheses without new data or biospecimen collection, and they provide the opportunity to pool data across several studies to increase the power of statistical analyses. The NIDDK Central Repositories have three major components: a biosample archive, a genetic sample processing and storage facility, and a data archive/data coordinating center. In addition, through an agreement with the National Center for Biotechnology Information's (NCBI; part of the National Library of Medicine at NIH), GWAS and sequencing data associated with numerous NIDDK studies is housed at the database of Genotypes and Phenotypes (dbGaP; see www.ncbi.nlm.nih.gov/sites/entrez?db=gap) and crosslinked to the associated phenotypic and biosample data. One major focus on the NIDDK Central Repositories is harmonization of data among the many archived studies to facilitate meta-analysis and queries across the studies.

Conclusion: In addition, the Repositories are cooperating with several international cataloguing efforts. Thus, the Repository is adopting the National Cancer Institute's caBIG Common Biorepository Model and has contributed data to the P3G Renal DataSHaPER and the NIH's Office of Rare Diseases Rare Disease-HUB (RD-HUB).

1 BioFortis, Columbia, MD 2 Catalysis Foundation for Health, Emeryville, CA NIRO 08. Critical IT Considerations for an International Large-Scale Tuberculosis Biomarker Discovery Program

Background: Catalysis Foundation for Health (CFH) is a 501(c)(3) non-profit entity dedicated to developing appropriate diagnostics for resource-poor settings.

Methods: Utilizing a grant from the Bill & Melinda Gates Foundation, CFH is currently engaged in a large-scale tuberculosis (TB) biomarker discovery project with a target enrollment of more than 200 human subjects. The study includes the collection of five types of biofluids (blood, urine, exhaled breath condensate (EBC), saliva and sputum) per timepoint over 10 timepoints (0-6 months) for the initial study phase and a data-driven reduction of collection timepoints and samples as the study progresses. In order to execute this 3-year project that spans 3 continents with 2 biofluid collection sites and 2 assay sites, we required a web-accessible database that is capable of collecting patient clinical information, tracking shipments and study data for thousands of samples, and viewing real-time data query results. We hereby describe the implementation details of our informatics infrastructure with Labmatrix, with topics covered such as: 1). standardization of electronic case report forms, prescription drug forms, biofluids and assay results forms, and other workflow-driven information capture, 2). the rationale behind assigning unique & random barcodes to patients and samples, 3). creation of reusable project data queries that can be easily reconfigured for frequent and rapid evaluation of standard and ad-hoc questions, 4). secure exchange of project-related messages and storage of accessory information.

1 Inserm, U 1027 and Université de Toulouse, Toulouse, Midi-Pyrénées, France NIRO 09. BRIF: Bio-Resource Impact Factor. An International Working Group towards An Operational Index to Promote and Recognize Sharing of Biological Samples and Associated Data

Background: There may be obstacles or difficulties to share bioresources. Besides technical and ethical aspects, a major dimension is the recognition of the effort for sharing such resources and of the work involved. The concept of a Bio-Resource Impact Factor (BRIF) has been introduced.

Methods: The main objective of BRIF is to assess and promote the use of bio-resources internationally by creating a link between their initiators/actors and the impact of the scientific discoveries enabled by their use. The concept relies on a quantitative parameter for bio-resource use, similar to the Impact Factor for publications. Such a BRIF would make it possible to document: 1. quantitative use of a bio-resource, 2. research results involving it, 3.scientific and management efforts to set up and make available a valid bio-resource as well as their institution. A working group has been set up, with an online forum http://www.gen2phen.org/groups/brif-bio-resource-impact-factor. Its 95 participants would gain from additional input. The work addresses 5 steps: 1. Creating a bio-resource unique identifier, as digital ID; 2. Standardizing bio-resource acknowledgement in papers; 3. Cataloguing bio-resource data access and sharing policies; 4. Identifying other factors to take into account when calculating the Impact Factor; 5. Prototype testing, involving volunteer bio-resources and the help of journal editors.

Conclusion: Such a system could be used to rationally evaluate bio-resource activities over time. Specificities in data sharing versus biological samples have to be considered. Also, if taken into account in assessing researchers/contributors professional activity, the use of BRIF would promote quality and sharing of Bio-Resources.

1 Washington University School of Medicine, St. Louis, MO QAC 01. Procurement of Human Tissues for Research Banking in the Surgical Pathology Laboratory: Best Practices for the Prioritization of Tissue Sampling

Background: Academic hospitals and medical schools with research tissue repositories often derive many of their internal human specimen acquisitions from their site's surgical pathology service. Typically, such acquisitions come from appropriately consented tissue discards sampled from surgical resections.

Methods: Comprehensive summaries of gross evaluation and dissection practices exist in the literature for surgical specimens, yet these rarely if ever reflect the point of view of biorepositories, who naturally impose coexisting demands on the same tissue resource, and who have interests and objectives which are often distinct from those of diagnostic surgical pathology.

Results: We summarize here a set of best-practice gross pathology guidelines, which reflect our collective experience at Washington University School of Medicine, and which embody the overriding principle that preserving adequate tissue for clinical diagnosis is the highest priority. Essentially, these guidelines are an optimal reconciliation between the needs of diagnostic surgical pathology and the typical objectives of research biorepositories. Because surgical pathology is a complex science with its own organ-specific standards of practice, the involvement of appropriately trained personnel is required for good procurement decisions (i.e. where to take samples from, and how much to take).

Conclusion: Our experience should be helpful to tissue bank directors, and others charged with the procurement of tissues for general research purposes. We believe these principles will facilitate the partnership between surgical pathologists and biorepository directors, and promote both good patient care and strategic, cost-effective tissue banking procurements.

1 National University Hospital, Singapore, Singapore 2 National University Health System, Singapore, Singapore QAC 02. Optimization of Tissue Collection Workflow Helps to Reduce Ischemia Time

Background: The Cardiovascular Tissue Bank in the National University Health System, Singapore, stores leftover tissues removed from adult cardiac surgeries for possible future research with patients' consent and ethical approval from the Institutional Review Board (IRB). Long ischemia time may affect important biomarkers, and it was found to be increased for valves as compared to other specimens, as they usually require pathology review before freezing and storage.

Methods: To reduce ischemia time in the process from tissue excision to freezing, we sought ethical approval from IRB to divide valve specimens in the operating theater, after discussion and agreement of the Department of Pathology. IRB approved that surgeons can cut a piece of tissue for research and biobanking, and the remaining part of the tissue will be sent for pathological and microbiological diagnosis. The piece of tissue for research and biobanking can thus be frozen almost immediately after excision. This protocol also does not exclude the possibility to use banked tissues for further investigations if clinical situation requires.

Results: Valve specimens from 10 patients were collected under the new amended protocol, and the ischemia time of these specimens reduced statistically and significantly from 18.7 ± 16.5 to 2.8 ± 2.5 minutes as compared to the old protocol.

Conclusion: The new workflow of tissue dissection in the operating theater therefore significantly decreased ischemia time. This amendment does not affect clinical outcome and does not compromise patient safety.

1 National Cancer Center Hospital, Tokyo, NA, Japan 2 University of Minnesota, Minneapolis, MN QAC 03. Response of Albumin Solutions to Stresses of Freezing and Thawing and Processing

Background: Fluid biospecimens such as plasma, serum, and urine contain important biomarkers for health and disease. These biospecimens are routinely stored in the frozen state until subsequent analysis. Albumin is a high abundance protein that is routinely used as a urinary biomarker for renal and cardiovascular diseases. Previous studies of the freeze-thaw stability of albumin in urine have been contradictory.

Methods: In order to characterize the freezing response of this protein in a more controlled environment, solutions containing albumin (40 mg/ml) in a NaCl solution were frozen and thawed (repeatedly). Samples were also stressed post thaw by vortexing and heating. Post stress structure of the protein was determined using spectrophotometry and samples were diluted to 0.4 mg/ml prior to analysis using spectrophotometry.

Results: Repeated freeze thaw cycles result in a decrease in the albumin concentration measured. Similarly, vortexing the sample also resulted in a decrease in the albumin concentration measured. Subjecting the samples to heating to 70°C also resulted in a decrease in the albumin concentration measured.

Conclusion: These results suggest that specific specimen handling techniques (repeated freeze-thaw cycles, heating and vortexing) all act is stresses on the protein capable of altering the concentration of albumin measured using standard laboratory methods. Additional studies are needed to determine preservation and processing methods that do not result in alterations in protein content.

1 University of Pittsburgh, Pittsburgh, PA 2 UPMC, Pittsburgh, PA QAC 04. An Immunohistochemical Study Assessing Impact of “Rapid Tissue-Processing” Protocols on Proteomic Tissue Quality

Background: The need for rapid diagnostic assessment had led to the development of new rapid tissue-processing (RTP) methods. Our Anatomic Pathology laboratories RTP machines use high-temperature (95°C) and vacuum to accelerate tissue processing. Since impact of RTP on immunohistochemical (IHC) staining has not been ascertained, this study evaluated impact of RTP on IHC evaluating antibodies with nuclear, cytoplasmic and cell membrane patterns and expression using two different tissues.

Methods: 10 tumor and adjacent normal samples each were collected from kidney and prostate carcinomas; processed using conventional and RTP methods (80 paraffin blocks generated). IHC was performed on kidney samples (Ki67, Pancytokeratin, CD10, CA9, c-Kit) and on prostate samples (Ki67, Pancytokeratin, PSA, AR, CK903). The 400 slides generated were evaluated for intensity/ pattern/ percentage cells staining, using an automated image analysis platform and manual estimation. The data was evaluated to assess for concordance between conventional and RTP processed tissues.

Results: No differences were seen in IHC intensity/patterns between processed with “conventional processed” tissues as compared to RTP processed tissues. The nuclear immunostaining pattern/intensity for Ki67 and AR; the membranous immunostaining pattern/intensity for CD10, CA9 and c-kit; and the cytoplasmic expression/intensity for pancytokeratin, PSA and CK903 were similar in both protocols.

Conclusion: The RTP protocol is useful and accelerated processing with no impact on protein quality at the nuclear, cytoplasmic and cell membrane level. Immunohistochemical staining obtained using RTP is consistent and of high-quality. Therefore, this RTP method can provide faster patient care, with no negative impact on IHC staining.

1 University of Alberta, Edmonton, Alberta, Canada QAC 05. Population Genetic Heterogeneity as a Pre-analytical Variable and its Influence on Gene Expression-Based Classification of Breast Cancers

Background: Distinct gene expression signatures are increasingly accepted as the foundation of the current molecular classification of cancers. Genome wide polymorphism scans in the context of case-control studies have identified disease susceptibility alleles; adjusting for the underlying genetic population heterogeneity (structure) markedly reduces the rates of identification of false positive associations. We therefore hypothesized that population “structure” will influence the differential expression signatures needed to correctly classify the molecular subtypes of breast cancer.

Methods: Gene expression profiles were obtained from the Agilent array platform in 114 invasive primary breast carcinomas in which women had also provided blood for germline single nucleotide polymorphism (SNP) genotyping (Affymetrix-6.0). Unsupervised hierarchical clustering for transcription profiles dichotomized by immunohistochemically defined tumor estrogen receptor status (+/-) were carried out using well established gene signatures from the literature (34 genes) and top ranked 1,700 gene Agilent transcription signature.

Results: Principal component analysis with SNP data identified nine samples as outliers contributing to the population “structure”; remaining samples overlapped with the HapMap Central European population cluster. We identified 210 genes as differentially expressed; belonging to genes in cancer, inflammation, cell death and signaling (1.5-fold difference, T-test p-value ≤ 0.05) between the 105 cases versus the nine outliers. The error rate for misclassifying tumors was high when differential gene expression profiles were used without a priori knowledge about the best set of genes as opposed to the known 34 gene signature.

Conclusion: Population germline genetic heterogeneity was identified as a pre-analytical variable to be controlled in molecular classification of tumor types.

1 William Beaumont Hospital, Royal Oak, MI QAC 06. SPIN: Development of Sample-Specific Protein Integrity Numbers as an Index of Biospecimen Quality

Background: It is widely accepted that variable biorepository specimen handling conditions can significantly alter outcomes of clinical research studies, suggesting the need for a metric for sample analyte protein integrity. In line with the NIH and the OBBR Best Practices, it is vital that the integrity of specimens used for biomarker studies are of the highest standard to ensure validity of the data they generate and confidence in the application of new findings to clinical management. We describe the creation of a program to discover proteins in biorepository samples to assess the integrity of stored specimens for protein-based biomarker studies, similar to the universally accepted quality metric for RNA, the RNA Integrity Number or RIN.

Methods: The study mimics potential variation in preanalytical conditions which may result in proteolysis and other proteome-associated changes and employs surface-enhanced laser desorption time-of-flight mass spectrometry (SELDI-TOF) to assess changes in multiple proteins and peptides in a high-throughput manner. Candidate peaks were selected from SELDI spectra of representative sample types which demonstrated differing but reproducible sensitivity to sub-optimal processing were selected, identified, quantified, and verified by conventional methodology in a series of specimens stored in the BioBank at Beaumont Hospital. We then assigned a relative index which is derived from a ratio of non-stable vs. stable proteins for each sample type in the investigation.

Conclusion: This methodology can be applied to every sample type and, once established and refined, the SPIN could be used by any BioBank without specialized equipment and irrespective of the sample preanalytical collection conditions.

1 Complejo Hospitalario Universitario de Albacete, Albacete, Albacete, Spain 2 Hospital General Universitario de Albacete, Albacete, Albacete, Spain QAC 07. Analysis of the Biomaterials Obtained Using an Extraction Methodology Designed for Optimization of Small Specimens

Background: Clinical samples obtained from the remnants of surgical procedures are sometimes of small size. The small amount of tissue obtained should be carefully managed in order to render enough material for different experimental procedures. We describe a methodology used at our laboratory for that purpose, and we analyze the biomolecules obtained with such procedure.

Methods: Obtained tissue from surgically resected specimens were included in cassettes, embedded in OCT compound, frozen in isopentane and stored at −80°C at the Biobank of the Hospital General Universitario of Albacete, a member of the Spanish National Biobanks Network (RD09/76/47). For tissue processing, the blocks were separated from the cassettes, and ten 30 microns thick slices were obtained with a cryostat. A standardized method for multistep DNA, RNA and protein extraction was used (spin-column technology).

To evaluate our methodology we have used 30 specimens from various sources as skin, larynx, breast and lung cancers. DNA and RNA obtained were analyzed spectrophotometrically and in agarose gels, and proteins were quantified and validated in functional studies.

Results: Inclusion of tissue specimens in cryocassettes was optimal for easily obtaining sections for biomolecules extraction. The material obtained using our protocol was an average of 50 ul DNA at 100 ng/ul, 40 ul RNA at 100 ng/ul and 200 ug protein per sample.

Conclusion: The described methodology permits obtaining enough and well preserved DNA, RNA, and protein from 30 microns thick slices in a single technical process. The method optimizes the use of small tissue specimens stored at a repository when diverse biomaterials are required.

1 Indiana University Purdue University Indianapolis, Indianapolis, IN 2 Indiana University School of Medicine, Indianapolis, IN QAC 08. Quality Control from a Subset of Human Surgical Tissue Specimens from the IU Simon Cancer Center Tissue Bank Collected in 2009–2010. An H&E and RIN Value Assessment

Background: Quality control (QC) of human tissue specimens for research is critical for the development of new bio-markers and their ability to determine clinical trial outcomes. In this study we evaluated 69 samples for both RNA and histology QC measures from the IU Simon Cancer Center Tissue Bank.

Methods: The IU Simon Cancer Center Tissue Bank is a centralized tissue procurement resource established to collect high quality tissue for basic clinical and translational research, collecting approximately 550 clinical cases per year using an informed consent and HIPAA signed document. All tissues are collected and processed in liquid nitrogen within 30 minutes of removal. The tissue samples are sliced and diced into 100 to 150 mg sample size. Each sample is placed into individual 2ml cryovials. Two representative samples are placed in 10% neutral buffered formalin. Two investigators QC the slides by microscopy to evaluate the following: percent of tumor, percent of necrosis, percent of fibrosis/inflammation, and percent of normal adjacent tissue. RNA was extracted using the Purescript RNA isolation kit (Gentra).

Results: Fifty-four of 69 cases passed both histology and RNA (RIN value) QC. Of the 15 cases that did not pass our QC criteria, 13 cases did not pass the histology QC due to lack of tumor content (below 50%) in the sample, while the remaining 2 cases failed the RNA QC. Seventy-eight percent of samples passed our QC measures.

Conclusion: The results were consistent with the existing literature on tissue quality control in human surgical tissue specimens.

1 Victorian Cancer Biobank, Carlton, Victoria, Australia 2 Cancer Trials Australia, Parkville, Victoria, Australia 3 Peter McCallum Cancer Institute, Melbourne, Victoria, Australia QAC 09. Proof-of-Concept Study to Establish Biomarker Translational Development in Victoria—Clinical Validation of Existing, Known Biomarkers in Colorectal Specimens Held Across Sites of the Victorian Cancer Biobank (VCB)

Background: Biospecimens held by the VCB were independently assayed for quality and uniformity across sites using a range of biomarkers often used in research.

Methods: Immunoassays were used to analyze plasma and serum samples for CEA, CA19.9 and C3a-des Arg.

The quality and amount of soluble DNA present in serum, plasma and that extracted from paraffin embedded tissue was determined by detection of BRAF and KRAS gene mutations. PBMCs were assessed for viability on resurrection, and proliferation on exposure to known mitogens. Extracting RNA and determining its integrity evaluated quality of frozen tissues. Tissue microarray blocks were prepared and percentage tumour in each core was measured. Immunohistochemistry was used to detect the EGFR protein on cell membranes, and CISH was used to measure EGFR gene amplification.

Results: Serum and plasma sample quality was high across all sites. PBMCs quality was consistent although cell recovery and viability was lower than in published studies. RNA extracted from frozen colorectal samples was of a quality suitable for gene expression analysis using qRT-PCR, with 35% suitable for microarray analysis. Tissue microarrays showed moderate to weak staining for EGFR protein but adequate signal strength for EGFR gene amplification. Sufficient, good quality DNA was extracted from tumor samples for mutation detection and microsatellite instability analysis. DNA extracted from serum was in low amounts and poor quality.

Conclusion: The results suggest that the SOPs used by all sites provided biospecimens of a quality suitable for the broad range of biomarker assays conducted in this study.

1 Korea National Research Resource Center, Seoul Women's University, Nowon-gu, Seoul, South Korea QAC 10. Introduction of KNRRC Best Practice Guidelines

Background: The increasing demands on resource centers for authenticated, reliable research resources and associated information have paralleled the growth of scientific technology fields. This is why the Organization for Economic Cooperation and Development (OECD) and international cooperative groups (CABRI, WFCC, ISBER, IPGRI, GBRCN, etc.) recommend establishing and implementing standardized operation procedures (SOPs) considering the size and economic standing of resource centers. Recently it demands compliance with national legislation, rules and regulations for the safe and secure operation of research resources from bioterrorism and ecosystem disruption. KNRRC has been developing Best Practice Guidelines from management of general resource centers to resource centers dealing with specific resources.

Methods: The first four KNRRC Best Practice Guidelines deal with General Management and Security-Safety Management, bacteria, seed, and zebrafish. These guidelines are based on procedures used by research resource centers belonging to KNRRC and preexisting guidelines (OECD, 2007: ISBER, 2008: WFCC, 2010). Each guideline consists of terms, flow diagrams outlining processes, procedures, documentation forms, and references. KNRRC guidelines will be updated to include recent developments and changes to provide basic quality management guidance for research resource centers.

Conclusion: These four guidelines will be posted on KNRRC (www.knrrc.or.kr) and ANRRC (Asian Network of Research Resource Centers, www.anrrc.org). KNRRC suggests that every resource center share the preexisting guidelines to provide authenticated resources in a short time period.

1 Paterson Institute for Cancer Research, Manchester, United Kingdom (Great Britain) 2 The Christie NHS Foundation Trust, Manchester, United Kingdom (Great Britain) 3 The University of Manchester, Manchester, United Kingdom (Great Britain) QAC 11. Ensuring the Quality of Tissue Bank Specimens Through Robust Quality Assessment Procedures

Background: The key to good quality results from banked tissue samples is dependant not only on processing, but also by ensuring specimens are adequately classified in terms of tumor grade and stage as well as percentage tumour contained in each tissue sample.

Methods: At the MCRC Biobank, quality is assessed on H&Es by reporting; grade, percentage tumor, necrosis & stroma. To assess the quality of the frozen specimens, a chip is cut from the frozen sample, and cryosectioned. This method ensures the frozen specimen can be assessed for quality without embedding the whole sample in OCT, which might impact on downstream analysis.

Results: Results show a significant difference between FFPE quality assessed samples and frozen samples from the same patient. Comparison of two matched FFPE samples also shows that there can be significant variation. When compared to a whole frozen sample in OCT, the chip method performs well, although does have the potential to be unrepresentative. Comparison of RNA quality between the OCT embedded vs no OCT, shows no significant impact on the quality of RNA.

Conclusion: The results indicate the importance of completing a quality assessment on each piece of tissue collected for biobanking so that researchers have confidence in the procured sample. Assessing frozen samples is also vital, however the method chosen for assessing the quality of frozen samples should be judged on a project specific basis depending on the researcher's requirements.

1 Imperial College London, London, United Kingdom (Great Britain) 2 Institute of Endocrinology and Metabolism, Kiev, Ukraine 3 Russian Academy of Medical Sciences, Obninsk, Kaluga, Russian Federation QAC 12. The Effect of Long-Term Storage on RNA Quality and Ensuring Fitness for Purpose

Background: Long-term storage of tissue is integral to tissue banking. This study assesses whether storage time impacts RNA quality and suggests additional quality standards.

Methods: RNA was extracted from 12 FFPE and 432 fresh-frozen thyroid tissue blocks that had been stored from <6 months to >9 years in two Institutes. RNA integrity was assessed using an Agilent Bioanalyzer and assigned a RIN from 0 (poor) to 10 (excellent). RT-PCR for different sized amplimers of the housekeeping gene hydroxymethylbilane synthase was used to associate RIN with amplimer size.

Results: Storage time and RIN (frozen blocks): There was no relationship between RIN and storage time. Mean RINs were 7.8 after storage for <2 years and 7.4 after >9 years storage. Forty-nine samples had undergone a thaw/refreeze cycle following a freezer failure and produced RINs <3. RIN and amplimer size: For frozen samples, 1022 bp amplimers were found in all samples with RIN >8.0 (n = 10) and 87% of samples with RIN 5–7.9 (n = 16). 584 bp amplimers were found in all cases with RIN <3.0. For FFPE samples, all RINs were <3 (n = 12) but the maximum amplimer size was 237 bp (58% of samples).

Conclusion: These results strongly suggest that storing frozen tissues in –80°C freezers does not result in the degradation of intact RNA over a 10-year period. Degraded RNA with RINs <3 are still amenable to RT-PCR provided the tissue was stored as frozen, but less so if extracted from FFPE blocks.

1 Indiana University School of Medicine, Indianapolis, IN 2 Komen Tissue Bank, Indianapolis, IN QAC 13. DNA Quality Control Using PCR

Background: The Susan G. Komen for the Cure® Tissue Bank at the IU Simon Cancer Center collects breast tissue, DNA, serum and plasma from healthy volunteer female donors without breast cancer. These specimens can then be used for a wide array of experiments, including serving as a “normal” control in breast cancer experiments. DNA is extracted from whole blood samples and stored until requested for an experiment. Because the DNA is stored long-term, it is necessary to perform quality control tests to be sure the integrity of the molecule is maintained during storage.

Methods: Initially, a Standard Operating Procedure developed by the Canadian Tumour Repository Network (CTRNet) (SOP, 2008) was utilized. This protocol employs PCR for the β-globin gene to show that the DNA has not been degraded while in storage. Using multiple primer sets, the quality of the DNA is rated on a scale of very good to poor. PCR products, using primers from the CTRNet SOP, showed multiple bands, suggesting that the primers are not optimal. Primer sets were re-designed targeting four different sized fragments of the β-globin gene (235bp, 523bp, 989bp, 1363bp) spanning exons and introns. PCR was performed using Fermentas reagents. The PCR products were then run on a DNA gel using the FlashGel system from Lonza.

Results: After redesigning the primers and optimizing the PCR conditions, single products are observed. Preliminary results suggest that the DNA has not been degraded over the time period studied.

Conclusion: Current storage protocols appear adequate to protect DNA integrity.

1 University of Rome La Sapienza, Roma, Italy 2 IRCCS San Raffaele Pisana, Rome, Italy 3 University of Rome “Tor Vergata”, Rome, Italy QAC 14. RFID as a New ICT Tool to Monitor Specimen Life Cycle and Quality Control in a Biobank

Background: Biospecimen quality is crucial for translational research, representing one of the main obstacles to experimental activities. Beside the quality of samples, preanalytical variations render the results derived from specimen of different biobanks and, often, within the same biobank incomparable. Specimens collected along the years should be managed with a heterogeneous lifecycle. Hence, we propose to collect detailed data concerning the whole lifecycle of each stored sample, from collection to refrigeration, employing RFID technology.

Methods: We describe the processing chain of blood biosamples, operating at BioBIM, focusing on technological assessment of RFID tag and performance testing of temperature and biological effects on sample maintenance. All samples underwent automated preanalytical processing.

Results: We developed a pilot study on a fragment of the lifecycle, namely by modeling the storage between the pre-analytics and before the analytics that usually are not traced by automated tools because they typically include manual handling. By adopting RFID devices we have measured the possible critical time delays.

Conclusion: We were able to record detailed information about the storage phases and a fully documented specimens' lifecycle. This will allow us to promote and tune-up the best practices in biobanking because: a) it will be possible to classify sample features with a sharper resolution, which allows future utilization of stored material, b) cost-effective policies can be adopted in processing, storing, and selecting specimens, c) after using each aliquot, we can study the lifecycle of the specimen with a possible feedback on the procedures.

Partially supported by Grant ACCWP3/1b

1 Coriell Institute for Medical Research, Camden, NJ QAC 15. What Characterization Is Necessary to Determine Pluripotency of Human iPSC?

Background: With the advent of induced pluripotent stem cell (iPSC) technology, many iPSC lines are being produced from a variety of starting materials using a variety of reprogramming approaches. The Stem Cell Biobank at Coriell Cell Repositories has been characterizing human iPSC submitted by various investigators prior to distribution through our web catalog (http://ccr.coriell.org).

Methods: Pluripotency can be assessed by a variety of methods, including assessment of surface marker expression, gene expression, directed differentiation, embryoid body formation and teratoma formation. Currently, the gold standard to determine the pluripotency of an iPSC line is the teratoma formation assay, which assesses the ability of the line to produce differentiated cells derived from each of the three primary germ layers in vivo. Directed differentiation assays involve in vitro culturing of iPSC in complex media formulations for extended periods of time, followed by assessment of lineage commitment. These are time-consuming and costly assays. We are interested in determining what minimum characterization can be used as a surrogate for in vivo pluripotency. Using a collection of human iPSC lines submitted to the NIGMS Repository at Coriell, we surveyed embryoid body formation, followed by mRNA expression analysis. Genes representing multiple cell lineages from each of the three primary germ layers were assayed using quantitative PCR.

Conclusion: This information was examined in the context of the result of both in vitro differentiation assays and teratoma formation. We will present the analysis of these data as they pertain to assessing iPSC pluripotency in a biobank setting.

1 Canadian BioSample Repository, Edmonton, Alberta, Canada QAC 16. Biobank Operation Costs Analysis Based on Freezer Power Consumption

Background: Biobanking is an industry with many costs, often the highest costs being facility operation. The Canadian Bio-Sample Repository (CBSR), similar to other biobanks, is conscious about the costs associated with running its facilities. A major cost is the electrical power consumption. This paper summarizes the study of the real electricity consumption of commercially available ultra low temperature (ULT) freezers operating at the CBSR.

Methods: The power consumptions of the freezers were determined using the power calculation formulae. First, the mean voltage from the outlet was determined to be quite stable. Next, the current was measured and logged using an LEM Heme Analyst 2000 to read the magnetic flux of each power cord, after its magnetic shields were removed. The current was measured on multiple freezers for periods of 6 and 12 hours, depending on the availability of the freezer. These periods are adequate for determining the steady state operation current of a freezer as well as finding its current draw while bringing samples down to temperature. After analyzing the collected data, the power consumption and cost associated were calculated for a So-Low ULT freezer (2.54 kW) and Nu-Aire ULT freezers (1.49 kW). The freezers are also analyzed based on their hourly and average daily performance.

Results: The use of efficient compressors and better insulation can reduce the power consumed by ULT freezers. Comparing different brands of freezers, this study shows a difference of almost 40% in hourly consumption rate, which has a large impact on the overall operation cost of a biobank.

1 Korea National Institute of Health, Cheongwon-gun, Chungcheongbuk-do, South Korea 2 Asan Medical Center, University of Ulsan College of Mecine, Seoul, South Korea QAC 17. Comparative Quality Assessment of Optimal Cutting Temperature (OCT)-Embedded Tissues with Fresh Frozen Tissues

Background: Optimal cutting temperature (OCT) compound is widely used for cryo-embedding of surgical tissues mainly for histopathology examination. But, OCT-embedded tissues have been avoided by researchers on translational studies due to the possibility that polyethylene glycol in OCT may interfere with biological analytes.

Methods: In this study, we designed to evaluate the integrity of DNA, RNA and proteins from OCT- embedded tissues by simple quality check (e.g.,OD ratio, RIN value, fragmentation and protein extraction) and practical methods (e.g., PCR, chip analysis and proteomic approaches with mass spectrometry). Also we compared two different workflows (fresh frozen vs OCT) on biobanking processes, such as repeated exposures at working temperature, in terms of consistency of sample quality.

Results: We used 150 solid tissues from different cancers and related control regions. OCT compound has been displayed supposedly inert and didn't affect the DNA and RNA integrity of the samples. PCR and chip analyses of DNA from OCT embedded tissues showed that any interference effect was not observed. We showed the OCT-embedded tissues were applicable to generate reasonable quality of proteomic data. However, the fresh frozen method was better than OCT method for subsequent steps of the proteomic analysis in terms of the numbers of matched spectrum and score of identification.

Conclusion: Our results suggest that OCT method can replace the fresh frozen preservation method. Advantages of OCT method (e.g., pre-aliquoting is not necessary prior to storage and repeatable distribution with histopathology data) with our findings will be helpful in maximizing the quality and efficiency of tissue biobanks.

1 Canadian BioSample Repository, Edmonton, Canada 2 University of Alberta, Edmonton, Canada RAT 01. A Novel Foil Cutter and Cryotube Separating Tool

Background: Biobanking is a growing industry with high value potential. At the Canadian BioSample Repository (CBSR), simple and inexpensive tools are utilized to reduce processing time and lower operation costs. The present paper summarizes the design, modelling, fabrication and testing of a sealing foil cutting and cryotube separation tool.

Methods: A metal tool prototype was developed after a comprehensive design verification using Computer Aided Design methods. The tool is designed to separate cryotubes that are sealed en-masse in an 8 by 12 matrix of 96. This is performed by pyramid-shaped tips of the tool puncturing the spaces between every four tubes, and ultra-thin blades cutting between every two of the tubes. The spacing of the blades in the prototype was based on the ANSI/SBS standards. The tool was manufactured from a 440C grade stainless steel material using a Wire EDM machine. A clear acrylic housing was also made to protect the tool and allow a secure grip. After the prototype was made, it was tested using two brands of cryotubes (Nunc, Matrical), and a variety of foils (Abgene, Axygen and Agilent). These experiments resulted in optimal aluminum foil cutting and cryotube combination. Using this new tool, the sealing and cutting process can be up to 20 times faster.

Conclusion: The tool testing experiments showed reliable foil cutting and tube separation results. While the current metal tool is capable of cutting the heat sealed foils and separating the tubes, polymeric devices will be manufactured in the near future, which will be significantly less costly.

1 University of Alberta - Canadian Biosample Repository, Edmonton, Alberta, Canada RAT 02. Low-Cost Automated Vision System for Biosample Processing

Background: Manual processing of centrifuged blood is used to separate plasma, nucleated blood cells and red blood cells. It is a laborious and potentially hazardous procedure, and is ideal for automated processing. Current vision systems used to measure sample volume are costly, closed systems, requiring advanced training. We developed a robust, low-cost, easy to use, automated vision system which, when linked to an automated pipettor, maximizes recovery, and minimizes contamination, of all layers of centrifuged blood.

Methods: The vision system is built around a low-cost web cam and RoboRealm™ software. The software allows simple creation and customization of image processing algorithms and interfacing with robotic controllers. Using a known distance to a sample and the web cam field-of-view, we could analyze samples for layer volumes. We isolated results by averaging multiple images and tested accuracy by first using dyes, then centrifuged blood in vacutainer tubes.

Results: We tuned image contrast to optimize recognition of blood. We then performed two trials of 11 blood samples at volumes between 0.5 mL and 10 mL contained in 10 mL EDTA vacutainer tubes (Becton Dickinson, New Jersey, USA). Image acquisition and processing time is under 15s, with a tube read failure rate of less than 5%. Accuracy, when compared to standard measurement, is within ± 0.05 ml.

Conclusion: Results show that this low-cost vision system is capable of improving the speed, reliability, and reproducibility of fraction collection. This system effectively measures the layer levels for centrifuged blood sample tubes while ensuring consistent processing of large numbers of samples.

1 The Research Institute at Nationwide Children's Hospital, Columbus, OH RAT 03. Transitioning from Traditional Pathology to Virtual Microscopy (VM) and the Creation of a Digital Histopathology Reference Library

Background: The Biopathology Center (BPC) Biomedical Imaging Team (BIT) at The Research Institute at Nationwide Children's Hospital provides imaging services for the Children's Oncology Group, the Gynecologic Oncology Group, the pediatric division of the Cooperative Human Tissue Network and The Cancer Genome Atlas (TCGA) program.

Methods: The BIT utilizes seven high capacity Aperio XT scanners, one Aperio OS and one Nanozoomer NDP 2.0 scanner to generate high-quality images from archived glass slides in the biorepository. A partnership between the BIT and the Ohio Supercomputer Center (OSC) facilitates the long-term storage and sharing of images. The BIT utilizes its custom-designed VIPER system (Virtual Imaging for Pathology Education and Research) to distribute digital images and QC review forms to pathologists and other researchers. The OSC provides a reliable high performance computing and communications infrastructure and has allocated 50 terabytes of storage to support digital pathology initiatives.

Results: To date the BIT has generated nearly 72,000 images with 14,000 of these images coming from 74 different studies as part of the digital archive project. Each of these archives studies has an average of 189 images, which could serve as a tool to research pathogenomonic findings for the different disease types.

Conclusion: The introduction of whole slide images not only provides the opportunity to create a valuable resource and educational tool but also provide the means for integration of pathology with other healthcare information systems.

1 Vanderbilt, Nashville, TN RAT 04. From 0 to 100,000 + : Automation in the Vanderbilt DNA Resources Core

Background: The Vanderbilt Center for Human Genetics DNA Resources Core manages the BioVU repository of over 100,000 human DNA samples as well as an equal number of specimens in other, smaller collections. The BioVU sample workflow was designed to leverage automation for DNA extraction, quality metrics, and storage and to enable that automation for the smaller scale projects. BioVU required rapid implementation of key, high-throughput, initial steps (DNA Extraction and quantitation) with the ability to bring other systems online in progression (volume checking, small volume extraction, automated storage and retrieval).

Methods: A combination of commercially available solutions coordinated by a LIMS allows a minimum of staff to process over 50,000 new samples a year and fulfill retrieval requests for the banked DNA.

Results: Over 100,000 BioVU DNA samples have been accepted and processed through the DNA Resources Core system. The samples have been successfully assayed in downstream applications ranging from individual SNP genotyping protocols to whole exome sequencing and genome wide association studies.

Conclusion: The automated workflow designed for the BioVU repository meets its requirements, allows the incorporation of additional platforms as those requirements evolve, and benefits other Core projects.

1 SAIC-Frederick, Inc., Frederick, MD 2 National Cancer Institute, Bethesda, MD RAT 05. High-Throughput DNA and RNA Extraction and Processing Strategy Implemention by the Division of Cancer Epidemiology and Genetics' (DCEG) Dedicated DNA Extraction and Sample Handling Laboratory Can Yield Increases in Processing Efficiency and Savings

Background: The DNA Extraction and Sample Handling Laboratory (DESL) is a dedicated service laboratory providing nucleic acid extraction, quantitation and pre-qualification for downstream applications to the Division of Cancer Epidemiology and Genetics (DCEG) of the U.S. National Cancer Institute. Its mission is to support research efforts of DCEG investigators that need to have genomic DNA extracted and pre-qualified for genotyping from various specimen types (e.g., buccal cells, blood-derived products and tissues) and to deliver that DNA to the Division's Core Genotyping Facility (CGF) or other laboratories for analyses. To increase its efficiency in providing these services, DESL has integrated automation into its quantitation, normalization, pre-qualification and cataloging tasks.

Methods: Most recently, DESL evaluated eight different technologies to automate extractions from larger sample volumes (1-10 mls) that could be integrated with its existing platforms. As a result of this effort, DESL identified a product made by Promega that could perform the extractions with reagents that are stable at room temperature for extended periods of time, produce high molecular weight DNA that reduces the need for phenol chloroform extractions and can be operated in a high-throughput capacity.

Conclusion: By implementing these new technologies, DESL was able to increase its daily sample extraction throughput while significantly reducing costs. Our results demonstrate that integration of automated nucleic acid extraction procedures with pre-qualification steps can provide a rapid and consistent delivery system that could be modeled for any medium to large-scale repository supporting genomic studies.

1 Artificial Intelligence In Medicine, Toronto, Ontario, Canada 2 Medical University of South Carolina, Charleston, SC RAT 06. Hollings Cancer Center's Experience with the caBig Common Biorepository Model for Data Sharing

Background: In mid-2009 the Hollings Cancer Institute (Charleston, SC), with the assistance of Artificial Intelligence In Medicine Inc. (Toronto, Canada) undertook the challenge of connecting its existing biospecimen repository management system with the Cancer Bioinformatics Grid (caBIG) via the Common Biorepository Model (CBM) and software components available from the National Cancer Institute's (NCI).This poster describes the motivation and objectives of the project, connection architecture, the steps involved, technical challenges and solutions, and the effort involved in mapping data elements and values from the local controlled vocabulary to the CBM terminology. The poster also discusses challenges related to the on-going maintenance and upkeep of the grid presence.

This poster will be of interest to those who wish to integrate existing research biospecimen databases with the cancer bioinformatics grid.

Conclusion: Exposing biospecimen information on the grid can lead to renewed collaboration and accelerate research activities but requires, among other things, attention to operational policies, procedures, and data sharing agreements between institutions.

1 Erasmus MC, Rotterdam, South Holland, Netherlands RIF 01. A Shared Biobank Management System for the Erasmus MC Tissue Bank—Implementation Experiences

Background: Upon participation in the Dutch Pearl String Initiative (PSI) the quality of the Erasmus MC Tissue Bank data registration needed improvement beyond the capabilities and quality requirements of the current self-developed system. This included an audit trail on all changes made to the database identifying the operator, date and time. A customized system was needed but the costs could not be covered by the tissue bank alone. A call to Erasmus MC biobanks was brought out for joining the acquirement of a shared biobank management system. With five Erasmus MC biobanks (three clinical and two population based) and with financial support of PSI, the search, purchase, and implementation was undertaken for a suitable system that could cope with the specific requirements of each biobank. We have reported our experiences.

Methods: The consortium of five Erasmus MC biobanks was formed and after a search and discussing earlier experiences, one vendor was chosen. The Erasmus MC Purchase Department supervised the negotiations and purchase. The Erasmus MC Informatics Department was involved in setting up each biobank's requirements, system integration within the Erasmus MC environment, data migration and coupling to specific LIMS. User manuals were prepared, system tests and training of personnel were performed.

Results & Conclusion: Biobanks without the supplies for acquiring a dedicated biobank management system themselves may do so with sharing a system with others. Further advantages are sharing of experiences and supporting infrastructure, disadvantages are increased complexities of the system due to each biobank's requirements and the implementation course.

1 Translational Genomics Research Institute, Phoenix, AZ 2 Maricopa Integrated Health System, Phoenix, AZ 3 CRP Henri Tudor, Luxembourg, Luxembourg 4 Integrated BioBank of Luxembourg, Luxembourg, Luxembourg 5 Van Andel Institute, Grand Rapids, MI RIF 02. Bio4D: An Advanced Biospecimen Management Software Solution for Biobanking and Clinical Research

Background: Biospecimen collection and analysis is an increasingly critical component of translational biomedical research. Heightened requirements for tracking of regulatory, ethical and legal, clinical, and biospecimen quality data elements are critical to the value and usability of the biospecimens. The Translational Genomics Research Institute (TGen) in partnership with the Integrated BioBank of Luxembourg and Henri Tudor designed and created Bio4D to comply with these expanding data element requirements in biobanking and to facilitate standardized biospecimen collection and processing.

Methods: Bio4D provides tracking of biospecimens from the point of biospecimen collection kit formulation, shipment of kits to the collection site, and delivery and accessioning into the biobank. The Bio4D approach provides a thorough systems management approach to capture the sample lifecycle that is user defined with informative querying and analysis capabilities. The Arizona Burn Center, TGen's research partner, uses Bio4D to assist in the tracking and analysis of biospecimens to identify microflora that colonize and infect burn wounds and to characterize their role in wound healing.

Results: Bio4D facilitates a robust beginning-to-end collection, processing, storage, distribution and re-use management of biospecimens, and annotated data for research. Bio4D's capability to track and monitor the lifecycle of biospecimens in real time has shown to improve operational efficiencies and quality of research outcomes.

Conclusion: Bio4D offers a robust workflow-based management of biospecimens and data:

- Kit production and distribution

1 Australasian Biospecimen Network, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia 2 The University of Oxford, Oxford, Oxfordshire, United Kingdom (Great Britain) 3 Jim's Computer Services (Williamstown), Newport, Victoria, Australia 4 The Children's Hospital at Westmead, Westmead, NSW, Australia 5 University of Western Australia, Nedlands, Western Australia, Australia 6 University of Sydney at Westmead Millenium Institute, Sydney, New South Wales, Australia 7 Queensland Institute of Medical Research, Brisbane, Queensland, Australia 8 kConFab, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia 9 Saint John of God Hospital, Subiaco, Western Australia, Australia RIF 03. Networking Oncology Biobanks Through the Use of the Australasian Biospecimen Network Tissue Specimen Locator Version 2: An Opportunity for Researchers and Biobanks Alike

Background: The Australasian Biospecimen Network-Oncology (ABN-Onc) is funded by the Australian National Health and Medical Research Council and comprises eight biobanks that collect biospecimens for cancer research. Recently, the ABN-Onc upgraded its web-based specimen locator search page which allows researchers to interrogate a national database for available biospecimens (www.abrn.net/abnweb/OncologySearchPage.aspx).

Methods: The Tissue Specimen Locator (TSL2) project was undertaken following researcher/user feedback collected via questionnaire and telephone interview, and significant database changes made at contributing biobanks. The TSL2 uses three categories; ‘Primary Cancer Site’, ‘Broad Morphology’ and ‘Type of Sample’ to search a database periodically updated with information extracted from biobanks. A results page is generated indicating the number of samples that fit the search criteria, the biobank at which they are located, and the date of the most recent biobank data extraction.

Results: The ABN-Onc project manager worked with pathologists, IT consultants and biobanks to:

improve the user interface;

Conclusion: The TSL2 enables comprehensive management of all initial enquiries and requests from researchers, while enabling biobanks to retain custodianship of specimens. These improvements facilitate the process for new oncology biobanks to list their collections on the TSL2, increasing and promoting access to biospecimens for oncology research.

1 Information Management Services, Inc., Silver Spring, MD 2 Heart, Lung, and Blood Institute, Bethesda, MD RIF 04. Repository Informatics: Using Open Source IT Solutions to Facilitate the Search and Distribution of Biospecimens in the NHLBI BioLINCC Program

Background: The NHLBI Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC) is an NHLBI research resource which provides a single point-of-access to an aggregate of clinical data from more than 70 historical research studies and more than 4.6 million banked biospecimens dating from more than 30 years ago to the present. To streamline the search and distribution of the biospecimens, NHLBI needed a web application that linked the study data, biospecimen inventory, and supported request and specimen distribution workflow.

Methods: Information Management Services, Inc. developed the website using open source software including Django, a high-level Python Web framework that encourages rapid development and a PostgreSQL database that provides enterprise level performance in managing the study and processing data. The database is linked to the repository's Biological Specimen Inventory (BSI) system for accessing biospecimen data. The website provides a search interface, user registration and login, request forms for data/specimen distribution, and support for the NHLBI review and approval process.

Results: Since BioLINCC's inception in September 2008, over 18,000 biospecimens have been approved and shipped from the NHLBI repository as a result of a website request. The BioLINCC web application has streamlined the NHLBI and biorepository workflow providing researchers with better access to the biospecimens.

Conclusion: The creation of an informatics system to support the BioLINCC distribution of biospecimens streamlines the search, request and application review process for NHLBI. The system was implemented using an open source technology stack to reduce costs and simplify interoperability with existing data systems.

1 Washington University School of Medicine, Saint Louis, MO RIF 05. caTissue Suite 1.2: An Open-Access, Feature-Rich Tool For Biospecimen Annotation and Data Sharing

Background: Advances in molecular technologies and clinical trial design have mandated new requirements for the operation of biorepostories. caTissue Suite is a caBIG^TM application designed to manage the complexities of biospecimen annotation data.

Methods: caTissue uses a web browser to store and retrieve data from a database. Its open program interface (API) permits customized access to all of the application's features, and data integration from other data systems. The application supports role-based access to administrative functions, biospecimen accessioning, and investigator queries. Enhancements in caTissue Suite v1.2 include text-based quick search, advanced query sharing, editable collection protocol definitions, configuration of containers based on specimen type, and customizable specimen label generation. A new “Bulk Operations” feature allows CSV-formatted data upload using predefined data templates and facilitates migration of legacy data sets. Significant performance, memory, and general usability enhancements have also been added.

Results: caTissue Suite is sufficiently scalable and configurable for broad deployment across biorepostories of varying size and function. Numerous institutions have adopted the application and are using it in their daily operations. A caBIG^TM supported, web-based “Knowledge Center” (https://cabig-kc.nci.nih.gov/Biospecimen/KC) provides on-going application support via discussion forums, technical and user guides, training tools, and webinars.

Conclusion: caTissue Suite is a freely available, fully supported, open-access software application for biospecimen data management. Use of caTissue Suite by several NCI Cancer Centers and other biospecimen resource groups is providing a rapid and facilitated path toward standardizing biospecimen informatics and promoting biospecimen data sharing both nationally and globally.

1 Georgia Health Sciences University (Medical College of Georgia), Augusta, GA RIF 06. Using the Cancer Registry to Annotate Biospecimens for Research

Background: The utility of a cancer biorepository for research depends on the quality of specimens as well as accuracy and completeness of accompanying information. In addition to detailed documentation of procurement, storage conditions and inventory status, demographic and clinical information about the patients represented in the repository is essential for broad research use. Obtaining clinical information from diverse sources can be very challenging for research biorepositories. A wealth of information is routinely collected by Cancer Registries using standardized format, data fields and vocabularies. We tested the feasibility of using a hospital Cancer Registry for annotation of biospecimens, by creating a link between the registry and repository databases.

Methods and Results: We are using the TissueMetrix web-accessible software application for biorepository management (AIM Inc.) and the Cancer Registry software is METRIQ (Elekta). We selected initially 70 data fields from the Cancer Registry, determined validation criteria for matching, and created a new form in TissueMetrix to capture the registry derived data. An interface between the two databases has been successfully implemented and thoroughly tested, with automated monthly updates.

Conclusion: We demonstrated the feasibility of using a Cancer Registry as an important source for annotation of biospecimens. This approach provides convenient access to information pre-filtered for relevance to cancer, for patients represented in both the repository and cancer registry databases. Our plans are to develop a similar approach to utilize Cancer Registries for annotation of biospecimens in a statewide network, the BioRepository Alliance of Georgia for Oncology (BRAG-Onc).

1 Booz Allen Hamilton, Rockville, MD 2 Sapient Government Services, Arlington, VA 3 SapientNitro, Arlington, VA 4 National Cancer Institute - CBIIT, Rockville, MD RIF 07. The Common Biorepository Model: A Standard for Sharing Information on Biorepository Collections

Background: In support of the U.S. National Cancer Institute's (NCI) Best Practices for Biospecimen Resources the Common Biorepository Model (CBM) has been developed to share up-to-date, summary-level biospecimen inventory information via the cancer Bioinformatics Grid (caBIG®) infrastructure. This enables academic and commercial researchers to identify potential partnering biorepositories from a network of reporting sites who may have appropriate specimen collections.

Methods: The CBM Service consists of: thirteen pieces of information required to describe a specimen collection; a list of diagnoses that span cancer, cardiac, diabetic, and rare diseases in a prescribed vocabulary; grid service files and an example database to be used for data mapping. Once each biorepository maps their data to the CBM and exposes de-identified information about their collections via the service, the information can be queried and updated in a periodic, automated manner controlled by each biorepository without the need for manual reporting.

Results: Over 14 biorepository management software vendors have participated in this initiative. CBM services established on the grid today: The University of Colorado connecting their in-house developed system; Hollings Cancer Center, partnering with AIM, Inc.; and Washington University in St Louis using caTissue Suite.

Conclusion: CBM service grid nodes may be queried by individual researchers via tools using the caBIG® infrastructure. One such tool will be the updated NCI Specimen Resource Locator: an easy-to-use web interface to query and get the latest inventory information from biorepositories via CBM services, or through other more manual updates each biorepository provides.

1 Stiftung biobank-suisse, Bern, Vaud 2 Swiss Working Group for Clinical Cancer Research, Berne, Bern, Switzerland 3 Swiss Group for Clinical Cancer Research, Berne, Bern, Switzerland RIF 08. Merging Biomedical Data from Diverse Sources into the CAISIS Database

Background: Biobank-suisse (BBS) is a network of Swiss biobanks. BBS members share resources and publish information about biospecimens available to researchers on the BBS web site. BBS promotes the merger of biomedical data into a medical record accompanying the biospecimens.

Methods: BBS investigated the situation in Switzerland to propose a process which can be used to merge biomedical data from different IT systems into the CAISIS database system. CAISIS is an application to maintain biomedical records and includes a module to manage biobanks. Based on the experience gained during the integration of data from eight different data sources BBS developed a procedure and selected appropriate software. A three-step transformation process evolved: a) Data analysis in MS-Access; b) Data conversion in FLOWHEATER; c) Upload to MS-SQL server. A key role in this process plays the FLOWHEATER application, which serves as workbench with tools to normalize data, perform string/arithmetic operations, and establish connections between the data fields of the source and target data base. The graphical interface allows the data manager to establish rapidly all steps required for import into the CAISIS database. The steps are documented in an XML file, which can be reloaded to change the settings or perform an update.

Conclusion: The new process allows BBS to merge biomedical data from different sources into the CAISIS database. For this process BBS provides a FLOWHEATER tutorial on http://www.biobank-suisse.ch. This should be a valuable tool for biobanks, which plan to migrate to CAISIS or want to establish a data feed with automated scheduled execution.

1 University of Texas M. D. Anderson Cancer Center, Houston, TX RIF 09. caTissue – Adopt vs. Adapt: The MD Anderson Experience

Background: In 2004 the National Cancer Institute (NCI) started the cancer Biomedical Informatics Grid (caBIG). Its mission for data sharing includes providing information technology to share biospecimens. Currently, caBIG supports two strategies for sharing biospecimen details via caGrid: (1) adopting the caBIG product caTissue as an enterprise tissue informatics solution with grid connection tools or (2) adapting institutional or 3rd party applications to create an individualized connection to caGRID.

Methods: The University of Texas M. D. Anderson Cancer Center (MDACC) compared the adopt versus adapt strategy for their federated system of 27 tissue banks. This analysis included a comparison between caTissue and an institutional product, TissueStation, with respect to system features, system functionality, and feasibility of alignment with the MDACC internal strategy of a services oriented architecture (SOA). Challenges posed by the evolution of NCI grid connections strategies were noted.

Results: The review identified the adapt strategy as preferred based on requirements in MDACC workflow, the heterogeneity of needs across our large biospecimen banking community, ease of incorporation of human tissue protections into TissueStation, and opportunities for integration with other software systems and research data repositories at the institution using SOA. Instability in the caGrid connection tools to be supported by NIH with consideration of an HL7 Services Aware Interoperability Framework (HL7-SAIF) solution also played a role.

Conclusion: MDACC will continue with an adapt strategy. It will forge caBIG connections as needed in anticipation of a decision by NIH on which grid connection solution will be supported.

1 University of Texas M. D. Anderson Cancer Center, Houston, TX RIF 10. Managing Change in Informatics to Support Federated Tissue Banking at MD Anderson

Background: The MD Anderson Cancer Center (MDACC) has evolved from a system of independent biospecimen banks into a federated system of tissue banks. The Institutional Tissue Bank is the executive bank for the 26 satellite banks, each of which focuses either on an organ system, a disease or target population, or a tissue type. In 2007, an internally developed tissue informatics system, TissueStation, was introduced as an enterprise solution to (1) facilitate enforcement of regulatory compliance, (2) meet standards set by NIH Office of Biorepositories and Biospecimen Research (OBBR) and caBIG, (3) provide for an honest broker system, (4) integrate tissue, clinical, and research data, and (5) support the federated structure. A steering committee was formed to oversee the process of managing change in the deployment of TissueStation.

Methods: Procedures for migration were established, including documents requirements analysis for customizations, review and clean-up of legacy data, testing, migration, and post-migration review. A method for prioritizing banks was established. Impact of OBBR/caBIG compatibility requirements for funded research was noted as a driving force for some migrations. Migration cost per bank has ranged US$300–US$500K.

Results: Since 2007, 21 of 27 banks are using TissueStation at least prospectively, and by mid-2012, 27 of 27 banks will be fully migrated. Some negative customer feed-back can be attributed to increased complexity and oversight in tissue banking regulations, and an increase in data requirements in order to be OBBR/caBIG compliant. Key factors in acceptance are joint requirements analysis, optimal workflow design changes, and opportunities in data integration.

1 BioFortis, Columbia, MD RIF 11. Using Labmatrix for Managing Aspects of a Large-Scale Medical Sequencing Initiative at the NHGRI

Background: The NHGRI is currently engaged in a large-scale genomics study focused on cardiovascular disease that is intended as a pilot for investigating the use of whole genome sequencing as a clinical research tool.

Methods: This clinical study is recruiting approximately 1000 individuals to include persons across a full range of risk for developing coronary heart disease, as well as those with frank coronary artery disease. From each study participant, about thirty biospecimens are accessioned and banked. Direct sequencing data from functional regions of 300–400 candidate genes involved with certain cardiovascular features will be generated and interpreted in the context of clinical data and research laboratory data generated from these biospecimens. The study has an eventual goal of releasing study data publicly. We describe the IT infrastructure and workflow processes utilized to facilitate management of study participation, clinical data, and biospecimens, with a strong emphasis on maintaining the individual privacy of study subjects.

1 IRCCS San Raffaele Pisana, Roma, Italy 2 Integrated Biobank of Luxembourg, Luxembourg, Luxembourg 3 University of Rome La Sapienza, Rome, Italy RIF 12. A Software Tool for Labeling with the Standard PREanalytical Code (SPREC): Effective Exchanging and Searching Specimens

Background: The ISBER Biospecimen Science Working Group has recently released a “Standard PREanalytical Code” (SPREC) aimed at providing an easy-to-implement labeling standard documenting the main preanalytical factors of biospecimens and their derivatives.

Methods: At the San Raffaele BioBIM we have developed, in collaboration with Olomedia s.r.l., a software tool useful both for output and input SPREC code associated to a specimen. A demo output prototype will be publicly available at our Institutional websites. Basic information concerning preanalytical data are selected from the SPREC tables and the SPREC code is generated together with the corresponding bar code. In a working environment the SPREC generator is intended to be connected to the LIS/BIS in the originating Organization, where the input data are loaded from the database and translated into the SPREC code, printing labels with both the human-readable, and barcoded format. The barcode provides the receiver Organization a fast and reliable communication medium to upload the data documenting the specimen into their LIS/BIS. This approach allows biobanks to share a fully automated data transfer without manual writing or reading, provided that the Laboratories exchanging specimens share the SPREC coding.

Conclusion: Additional advantages turn out if a federated database with a collection of SPREC codes (which do not encapsulate any personal data) are searched in order to find out whether and where the specimens for a given study are available. This possibility of a preliminary check would allow a researcher to select the best material to carry out a planned experiment.

1 Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia 2 Victorian Partnership for Advanced Computing, Carlton South, Victoria, Australia 3 Victorian Cancer Biobank, Carlton, Victoria, Australia RIF 13. Overcoming Challenges Encountered in Creating a Centralized Digital Slide Repository

Background: The Victorian Cancer Biobank (Biobank) is a not-for-profit consortium of tissue banks, supported by the Cancer Council Victoria and the Victorian State Government. Member banks are located in four hospitals across Melbourne, Australia. In 2009, the consortium implemented a centralized digital slide repository using the Aperio Scanscope digital imaging system in conjunction with the Victorian Partnership for Advanced Computing (VPAC) to manage the network.

Methods: Scanning systems are located at each site with images scanned and stored locally, but viewable centrally with appropriate permissions. There is only one server copy of the software housed at VPAC which is accessed remotely by the four sites via a secure connection. Some reduced functionality has been experienced due to the complex configuration required to ensure that the privacy of information is maintained. This includes images being stored locally rather than centrally and a loss in the ability to transfer and copy images using the spectrum software. Bandwidth issues have also been encountered with the multisite setup. A temporary solution has been developed by VPAC to overcome these issues while Aperio is investigating a more permanent solution.

Conclusion: The benefits associated with implementing a centralized digital slide repository using the Aperio Scanscope digital imaging system across various sites, far outweigh the obstacles encountered so far. This setup has proved to be both cost and time effective. Information privacy and improved software functionality have been largely attained with the collaborative efforts of VPAC, Aperio and the information technology representatives at each of the biobank member sites.

1 IMS, Silver Spring, MD 2 Seracare Life Sciences, Inc, Gaithersburg, MD 3 Heart, Lung, and Blood Institute, Bethesda, MD 4 Information Management Services, Inc., Silver Spring, MD RIF 14. Adding SPREC Encoding to Existing Repository Databases

Background: The NHLBI extramural repository currently stores 4.6 million biospecimens dating from more than 30 years ago to the present. To enhance searches of the collection NHLBI adopted the Standard PREanalytical Coding (SPREC) for biospecimens to provide traceability of pre-analytical variations. SPREC is a seven element combination of characterization codes which stores details on pre-analytical sample processing.

Methods: The NHLBI repository inventory utilizes the Biological Specimen Inventory (BSI) system, which has an established data coding system. The implementation challenge was incorporating the SPREC encoding both as searchable data and as an input field. Existing BSI codes had to be mapped to SPREC codes and data validation functions had to be developed to verify input data.

Results: System modifications for input verification were more complex than originally anticipated. Mapping of BSI data to SPREC codes was achieved in a straightforward manner; however the use of a SPREC field for data input created ambiguities in the data translations. BSI data integrity checks also had to be modified to provide cross-code verification of BSI and SPREC data during input.

Conclusion: Having pre-analytical variables available to researchers on newly acquired and archived specimens will allow researchers to evaluate the utility of the specimens in the collection for their research needs. SPREC is an excellent method to store this data in a standardized manner. However, implementation of data integrity checks is essential to ensure the relationship between the internal data and SPREC data remains in a valid state.

1 The Research Institute at Nationwide Children's Hospital, Columbus, OH RIF 15. An Informatics Biospecimen Software Suite to Enhance Cancer Cooperative Group Information Management

Background: The importance of biospecimen submission, accessioning, processing and distribution continues to be a significant topic within biospecimen management and informatics disciplines. The Office of Biospecimen and Biorepositories Research and the International Society for Biological and Environmental Repositories accentuate the need for high-quality specimens and the ability for informatics to manage a specimen throughout the lifecycle.

The Biopathology Center, biorepository for two NCI Cooperative Groups, has developed a suite of informatics applications to provide tracking of specimens, ordering biospecimen kits transporting specimens and monitor institutions submitting specimens.

Methods: The technology utilized is the most recent versions of SQL Server (2008), Reporting Services, Language Integrated Query (LINQ), and NET framework 3.5. Kit Management, an application within the suite, was created to increase the ability for over 500 Cooperative Group institutions to order kits via a web-based interface and allow fulfillment of the kit request. The next application, Specimen Tracking and Reporting System, is an enterprise application designed to harmonize multiple data sources, track a specimen's life cycle & chain of custody, promote best practices in laboratory workflow and integration based on the Common Biorepository Model. The Institutional Performance Monitoring System was designed to monitor institutional specimen submission, per protocol, for specimen quantity and quality.

Results: The suite is invaluable in eliminating the problem of information fragmentation, enhancing specimen awareness, and increasing performance while adhering to best practices.

Conclusion: The suite is in production and is continuously enhanced to meet best practices and to support the Common Biorepository Model established by NCI.

1 NIH, Rockville, MD 2 BioFortis, Columbia, MD RIF 16. A Collaborative Translational Informatics Environment at the NCI

Background: Translational research programs have been created to provide a better understanding of disease susceptibilities and pathway mechanisms. These programs require integration and analysis of multiple disparate data sets that come from different sources such as the hospital and pathology/molecular laboratories.

Methods: At the NIH, a subset of the patients treated at the Clinical Center consent into various Institutes' research protocols. Here we describe how NCI investigators utilize a centralized database system that 1.) securely stores, annotates, curates, and tracks information such as patient data, clinical phenotypes, biospecimen & derivatives data, and experimental research data, 2.) communicates clinical and research information with the NCI Clinical Data Registry and BTRIS systems, 3.) enables collaborative exchange and sharing of information amongst research groups, and 4.) provides an intuitive environment for investigators to query and review their collected data with minimal need for direct IT support.