BIOPRESERVATION AND BIOBANKING Volume 7, Number 1, 2009 © Mary Ann Liebert, Inc. DOI: 10.1089/bio.2009.0701.abs

The International Society of Biological and Environmental Repositories presents Abstracts from their Annual Meeting

Celebrating a Decade of Growth and Development in International Biorepository Excellence May 12–15, 2009 Portland, Oregon, USA The abstracts that follow demonstrate the broad range of timely issues addressed in the contributed oral and poster presentations at ISBER’s 10th Anniversary Annual meeting.

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ISBER Abstracts

Biospecimen Research BSR1 The Effect of Clinical Tissue Sample Cold Ischaemia Time on Immunohistochemical Analysis: Toward a Panel to Check Tissue Sample Quality 1

C. Womack, 2R. Mager, 3G. Greywoode, 1 M. Revill, 2D. Kerr, and 1N. Gray

experiments and confirm the labile nature of pAKT. However, pAKT is not expressed ubiquitously and the quest for an IHC “QC panel” for a tissue bank continues.

BSR2 Use of sCD40-Ligand and Protein S as Biomarkers for Preanalytical Variations of Biobanked Serum and Plasma Samples

1

AstraZeneca, Macclesfield, Cheshire, United Kingdom, 2University of Oxford, Oxford, United Kingdom, 3John Radcliffe Hospital, Oxford, United Kingdom Background: This study was undertaken as a pilot to ascertain the feasibility of using a panel of immunohistochemical (IHC) biomarkers to assess the suitability of clinical tissue samples acquired by the AstraZeneca Cancer Tissue Bank (CTB) for use in its early cancer drug discovery projects. Methods: Samples of malignant and nonneoplastic tissue were removed from resected colectomy specimens taken from two patients undergoing elective surgery. Sampling to a standard operating procedure began within 15 min of surgical removal (time 0) and was continued at time points 5, 10, 20, 30, 40, 50, and 60 min. Each time point sample was fixed immediately in 10% neutral buffered formalin for 24 h. Following routine processing into paraffin wax, sections were cut and IHC stained using standard methods, with a panel of six loading/activity antibodies: vimentin (3B4), vimentin (V9), pan-phosphotyrosine, phospho p27, phospho AKT (pAKT), and PTEN. Intensity and distribution of staining was assessed by eye. Results: A reduction in cytoplasmic staining for pAKT in the cancer samples from one patient was identified between 20 and 30 min, with no further reduction to 60 min. We demonstrated no difference in IHC staining over time for any marker in the cancer samples from the other patient or any of the non-neoplastic samples. Conclusions: IHC results from one clinical colorectal cancer sample are consistent with previous observations in xenograft and proteomic

F. Betsou and C. Chaigneau Biobanque de Picardie, Salouel, Picardie, France Background: One of the main issues in biobanking is the establishment of standard operating procedures for specimen collection, preparation, and storage to control preanalytical variation. For biological fluids such as serum or plasma, there is currently a lack of sensitive biomarkers for quality control of cryopreservation conditions. In order for a serum biomarker to be used for quality control, it should be ubiquitous and show 100% loss of activity upon inadequate storage conditions and temperature variations. Methods: Immunoenzymatic assays were used to assess the stability of the following serum candidate quality control biomarkers, belonging to the cytokine superfamily: C5a, CD40 Ligand, G-CSF, GM-CSF, CXCL1, CCL1, CD54, IFN-γ, IL-1α, IL-1β, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-16, IL-17, IL-17E, IL-23, IL-27, IL-32α, CXCL10, CXCL11, CCL2, MIF, MIP-1α, MIP-1β, Serpin E1, CCL5, CXCL12, TNF-α, and TREM-1. Chronometric assays were used to assess the stability of the following plasma candidate quality control biomarkers, belonging to the coagulation factors family: TP, TCA, fibrinogen, antithrombin III, D-dimers, protein C, protein S, factor II, factor VII, and factor VIII. Results: Only CD40 ligand in serum showed an on-off response to 24 h storage at 37°C and protein S in plasma showed a degradation response to 9 years storage at −80°C. Conclusions: Biomarkers that have an on-off response to temperature variation could serve as quality indicators for the core processes of

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biobanking, which are the preparation and storage of biological fluids. The identification of such biomarkers in serum samples is needed. This is the first time, to our knowledge, that such a biomarker is described in serum.

BSR4 Optimal Use of Limited Resource Tissues for AIDS Related Cancer Research 1

1

BSR3 Stability of Genomic DNA at Various Storage Conditions B. Anekella, J. Wu, J. Cunanan, L. Kim, T. Kulatunga, and C. Huang Seracare Life Sciences, Gaithersburg, MD, USA Background: Advances in recombinant technology and completion of the Human Genome Project paved the way for identification and detection of genetic markers of disease. Availability of high-quality DNA is essential for incidence and epidemiological studies that in turn lead to new treatments. Therefore, the determination of efficient storage methods is critical to maintain the quality of isolated DNA. Several storage conditions were evaluated to determine the best method to store genomic DNA without compromising quality. Methods: High-quality genomic DNA was extracted from whole blood using the Autopure Workstation. The DNA was dissolved in TE buffer and stored at various conditions: room temperature (RT), 4°C, −20°C, and −80°C. Real time and stress stability studies were performed. DNA quality was evaluated by agarose gel electrophoresis, PCR amplification of an indicator housekeeping gene (β-globin), and SNP assays on various platforms. Results: Genomic DNA aliquots stored at −20°C and −80°C were stable for over 24 months. Multiple freeze-thaw cycles showed no detectable DNA degradation as assessed by agarose gels, PCR amplification, and genotyping. DNA samples stored at 4°C and RT showed varying degrees of evaporation but DNA was stable for up to 12 months at 4°C. At RT, DNA degradation was seen at 9 months. Additional studies are ongoing. Conclusion: Genomic DNA stored at −20°C and −80°C was of good quality, and these samples withstood multiple freeze-thaw cycles. For short-term studies, genomic DNA can be stored at 4°C or even RT without degradation, but samples should be monitored for DNA concentration.

M. McGrath, 2S. Silver, 2J. Orenstein, L. Huysentruyt, 3E. Cesarman, 4A. Chadburn, and 5L. Ayers

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AIDS and Cancer Specimen Resource & University of California, San Francisco, San Francisco, CA, USA, 2AIDS and Cancer Specimen Resource & George Washington University, Washington, DC, USA, 3Weill Cornell Medical College and the AIDS Malignancy Consortium, New York, USA, 4AIDS Malignancy Consortium & Feinberg School of Medicine, Chicago, IL, USA, 5AIDS and Cancer Specimen Resource, Columbus, OH, USA

Background: The AIDS and Cancer Specimen Resource (ACSR) was established 14 years ago with the mission to obtain and provide AIDSrelated cancer specimens to qualified researchers. At that time, diagnosis of Kaposi’s sarcoma (KS) and AIDS-related lymphoma (ARL) required excisional biopsies; hence, tissue for research was plentiful. Currently, cancer diagnoses are performed by fine needle aspirate, hence limiting material available for research. Therefore, the ACSR evaluated novel methods for immunohistochemical and DNA analysis to optimize fixed tissue use. Methods: A total of 220 ARL blocks were stained with lymphocytic markers to validate the protein/antigenic integrity of the cases. A tissue microarray (TMA) was constructed with sections (0.6 μM) for each validated case. Cases (3, 10 μM sections) were processed by Rubicon Genomics (Ann Arbor, MI) for DNA extraction and whole genomic amplification (WGA). DNA quality was then evaluated by PCR with immunoglobulin constant region primers. Results: All ARLs were stained with anti-lymphocyte antibodies. In situ hybridization revealed Epstein–Barr virus internal repeat signals across the spectrum of specimens. WGA yielded 0.2–5.5 μg of DNA after two rounds of amplification from specimens obtained after 1986. Conclusions: Current diagnostic procedures result in small tissue yields. Thus, biorepositories must optimally use long-standing fixed tissues. This study validated the antigenic integrity and DNA extraction techniques for 220 fixed ARL specimens (1981–2007). The ACSR created a novel collection of ARL cases spanning the AIDS

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epidemic for use in both immunohistochemical and molecular studies. These techniques are applicable to other fixed tissue collections.

BSR5 Lung Cancer Tissue Bank at MD Anderson Cancer Center: Role of a Specialized Tissue Bank in a Multidisciplinary Research Program M. Gabriela Raso, C. Behrens, L. Prudkin, L. Solis, M. Nunez, M. Sun, X. Tang, A. Corvalan, J.J. Lee, J. Roth, C. Moran, and I. Wistuba University of Texas, MD Anderson Cancer Center, Houston, TX, USA Introduction: The MD Anderson Thoracic Malignancies Tissue Bank plays an important role in our institutional basic, translational, and clinical research multidisciplinary program in lung cancer. Materials and Methods: We have established a collection of tumor and normal frozen and archival formalin-fixed paraffin-embedded (FFPE) tissues from ~2000 cases from 1997 to the present. We developed institutional databases to manage tissue bank specimens and patients’ clinicopathological information. For molecular biomarkers analysis we have constructed two sets of tissue microarrays (TMAs) utilizing FFPE tissues from 880 lung cancers, and for molecular profiling activities we have extracted DNA/RNA from frozen tissues of 500 tumors. Detailed clinical and pathological information of all these cases, including follow-up, are available. Results: Using TMAs and immunohistochemistry, we examined the expression of 120 proteins in 330 lung cancers, and correlated our findings with tumors’ genetic abnormalities, including mutation and copy number gain of several genes. We correlated the expression of those markers with patients’ clinicopathological characteristics, including recurrence and survival. We have identified multiple markers and several pathways activated in lung cancer (among others, HER family, epithelial mesenchymal transition, nuclear receptors, IGF axis, NF-κB) which associate with patients’ clinical characteristics and tumors’ pathological and genetic properties. DNA and RNA profiling of these tumors is underway. Conclusion: The analysis of well-characterized tissue specimens with annotated clinical

information of patients has provided useful information in the expression of multiple molecular markers in lung cancer and has facilitated the design of novel therapeutic strategies. (Supported by NCI-UT-Lung SPORE and DoD PROSPECT grants.)

BSR6 Innovative RNA Preservation Technologies for Room Temperature Sample Handling, Storage, and Transport P. Faix, S. de Rozieres, O. Sharron, L. Martin, J. Muller-Cohn, and R. Muller Biomatrica, Inc., San Diego, CA, USA RNA integrity is a critical factor in obtaining meaningful gene expression data. Current methodologies rely on refrigeration of samples during shipment and storage. To address the critical need for alternative sample storage and transport technologies, we have continued to develop a room temperature RNA preservation technology that protects against degradation during dry storage. Our results demonstrate real-time stabilization of purified total RNA for more than 14 months at room temperature and even at 50°C for extended time periods. Recovered samples can be used directly in downstream applications including bioanalyzer and microarray analysis, cDNA synthesis, quantitation analysis (eg, quantitative RT-PCR), reverse transcription, and gel analysis. Results will also be presented using the stabilization technology for the development of a reagent that permits convenient and efficient concentration of dilute, aqueous RNA samples obtained from limited sample types (eg, needle biopsies). Picogram amounts (=10 pg) of purified total RNA in up to 500 μL can be concentrated to only 10 μL with minimal sample loss as compared to conventional methods (ie, alcohol precipitation, SpeedVac®, microcolumns, etc.). RNA integrity is maintained during the concentrating process and the dried sample can be conveniently stored at room temperature for up to 1 week before rehydration and immediate use in downstream assays, including gene expression analysis and other molecular genetics applications. The development of novel RNA stabilization methods and reagents will have a significant impact on biomedical research by eliminating some of the detrimental variables associated with the handling, storage, and transport of labile RNA specimens.

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BSR7

BSR8

Adaptation of Archival Clinical Samples for Genome-Wide Microarray Experiments at the Exon Specific Level by Specialized Protocol Utilizing Random DNA Fragmentation

Assessment of Warm Ischemia Time by Targeted Measures of Transcriptome and Proteome by Cell Line Xenografts with Known Gene Dosage Alterations

G. Hostetter, S. Savage, C. Gooden, J. Carpten, J. Trent, and M. Bittner

G. Hostetter, A. Watanabe, S. Gately, M. Sepulveda, J. Black, and M. Demeure

Translational Genomics Research Institute, Phoenix, AZ, USA

Translational Genomics Research Institute, Phoenix, AZ, USA

Genomic technologies, such as array Comparative Genomic Hybridization (aCGH), offer definitive measures of gene dosage that increasingly are applied to clinical samples. Technical improvements in detector composition and genomic coverage by long-oligonucleotide microarrays offer very sensitive measures at unparalleled genomic resolution. Historically, copy number profiling was performed on large freshfrozen samples where intact DNA could be readily extracted. The genomic analysis of preneoplastic tumors and small biopsies is often limited to DNA processed by formalin-fixing and paraffinembedding (FFPE). Here, we present specialized protocols for the extraction and processing of genomic DNA from FFPE tissues including a DNase processing step to generate randomly fragmented DNA. We show that these protocols are robust for a wide range of FFPE samples, of various tumor types, from various institutions and of 4–11 years archival age. aCGH experiments were performed on eight (8) split-sample pairs (portion fresh/fresh frozen and portion FFPE) of cell lines and colorectal tumor (CRC) samples. For each split-sample type, we show equal detection across the entire genome (HCT116 cells) and exon-specific homozygous loss of SMAD4 (SW480 cells). In addition, we show equal detection of gene-specific alterations in the split CRC samples. Finally, we assess the applicability of aCGH to common FFPE collections by compiling the derivative of log ratio (DLR), a particular sensitive detector of measurement variance, for 216 sequential FFPE sample hybridizations. The majority of samples (93%) showed comparable DLRs as would be expected with DNA from fresh frozen tissue.

Translational applications utilizing fresh frozen tumors require standard collection parameters. Warm ischemic time is a preanalytical variable that significantly affects transcript and protein integrity as sample preservation remains poorly controlled. In order to better understand the effects of warm ischemia in solid tumors, we designed a study utilizing cell line xenografts in nude mice. Here we present data on analyte preparations from mouse xenografts of HCT116, SW480, and SW620 cells. Collection parameters were controlled with aliquots into snap-frozen, RNAlater and 10% buffered formalin at timed intervals of 1, 5, 10, and 30 min. We identified differentially dosed tumor markers using microarray CGH data from highdensity (244K oligonucleotide probes) experiments on fresh cell preparations, including differential dosage data for MYC, SMAD4, MGMT, MYB, and SMAD5. We show methods and tissue amounts needed to ensure equal sample preparation using automated frozen disruption (AFD) to ensure homogeneous sample aliquots. RNA integrity was measured using the Agilent Bioanalyzer 2100 with notation of RIN score (1–10) as well as ratio of 28S:18S ribosomal RNA. The transcripts of differential dosed genes will then be analyzed by expression profiling over the defined post collection ischemia timepoints. Finally, we integrate proteomics measures into the known aCGH and expression profiles discovered to be altered at discrete timepoints that mirror present tumor collection practices. Thus, by experimental design, we have controlled for warm ischemia time so that sample preparations can be analyzed to ensure sample uniformity and biological representativity prior to the various downstream-omic experiments.

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Environmental Repositories

ER2

ER1

Total Arsenic Concentrations in Common Murre (Uria aalge) Eggs Archived in the Marine Environmental Specimen Bank (Marine ESB)

Development of Standard Reference Material (SRM) from the Marine Environmental Specimen Bank 1

A. Moors, 1R. Pugh, 1L. Beddia, 1P. Becker, and 2 B. Porter 1

National Institute of Standards and Technology, Charleston, SC, USA 2 National Institute of Standards and Technology, Gaithersburg, MD, USA The National Institute of Standards and Technology (NIST) maintains the Marine Environmental Specimen Bank (Marine ESB) located at the Hollings Marine Laboratory in Charleston, South Carolina. In addition to banking marine animal samples under cryogenic conditions for long-term storage, the Marine ESB also houses a Standard Reference Material (SRM) Production Facility within the clean room space. SRMs and Control Materials (CMs) made from marine animals are produced as freeze-dried material using a Mill-Rock large capacity lyophilizer or as fresh frozen powder material using a large capacity Palla VM-KT vibrating cryomill. Common mussels (Mytilus edulis) were collected in April 2004 to produce SRM 2978a (freeze-dried) and SRM 1974c (fresh frozen material cryo-homogenized). These mussels were collected in response to the depleting supply of SRM 1974b, and the sold out collections of SRM 2974-Organics in FreezeDried Mussel Tissue and SRM 2978-Mussel Tissue (Organic Contaminants—Raritan Bay, New Jersey). The mussels were shucked, blended, and frozen. Half of the material was freeze-dried and the remainder was cryogenically homogenized. The challenges, details, and results of the two procedures will be described.

R. Pugh, W. Davis, S. Vander Pol, A. Moors, R. Day, and P. Becker National Institute of Standards and Technology (NIST), Charleston, SC, USA The Seabird Tissue Archival and Monitoring Project (STAMP) was developed in 1999 to serve as a systematic, long-term (decades) program to identify and track 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 Environmental Specimen Bank (Marine ESB), Hollings Marine Laboratory, Charleston, SC. Recent results indicated that eggs from common murre (Uria aalge) colonies within Norton Sound have significantly higher mercury levels than other colonies of this species in the Bering Sea. In addition, previous analysis of liver samples collected from ringed seals (Phoca hispida) in Norton Sound, and banked in the Marine ESB, had concentrations of total arsenic on average, 2–3 times greater than the average concentrations found in this and other marine mammal species in Alaska. To determine total arsenic concentrations in seabird eggs, 43 STAMP murre and glaucous gull (Larus hyperboreus) egg samples collected from colonies located throughout the Bering Sea, including within Norton Sound, in 1999, 2000, and 2005, were analyzed using collision cell kinetic energy discrimination-inductively coupled plasma mass spectrometry (ICP-MS). Total arsenic concentrations ranged from 0.060 μg/kg to 0.349 μg/ kg and were higher in the Norton Sound colonies than other colonies in the Bering Sea. 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 mercury in this region.

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Human Specimen Repositories

HSR2 Initiation of the Manchester Cancer Research Centre Biobank: Key Learning Points

HSR1 The Importance of the Proper Description and Definition of Biobanks in Health Research P. Riegman and B. Jong

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J. Rogan, 2G. Ashton, 2D. Johnstone, and 1 N. Clarke

1

Erasmus MC Rotterdam, The Netherlands

The Christie NHS Foundation Trust, Manchester, United Kingdom, 2Paterson Institute for Cancer Research, Manchester, United Kingdom

The high number of samples needed for obtaining highly significant outcomes in health research today forces biobanks to collaborate and therefore to strongly harmonize and in some settings even standardize. This ongoing process anticipates on enabling research groups to work with high-quality samples ready to exchange in cooperation with different institutes on a National and International level. To facilitate this process, tools like guidelines, best practices, network access rules, standards, and codes of conduct to facilitate cross-border exchange were developed. When trying to implement these tools they can become at some point inappropriate for your biobank. This can be the result of (1) the development group not being aware of differences between the different biobanks and (2) the developed tool lacks proper description for what type of biobank it was developed. Nevertheless, further harmonization and standardization are still needed. Actually it is foreseen that further cooperation between the different biobanks would extend the scientific opportunities in healthcare research. Therefore, we need to understand the differences between the different types of biobanks. In the presentation, the differences between clinical-based and population-based biobanks will be highlighted. In addition, the different terms to use and different situations will be presented. These definitions are not only of major importance to biobank managers to understand each other, but also for future users of biobanks and policy makers to understand the potential scientific outcome of certain collections. Furthermore, the juridical community needs to understand the differences in research and collection settings having implications for developing legislation.

Research biobanks are a vital resource in basic and translational scientific research, allowing researchers easy access to high-quality human biological samples. The Manchester Cancer Research Centre (MCRC) has established a Pan-Manchester biobank based at The Christie NHS Foundation Trust site and involving four additional Hospital Trusts across the region. Frozen and formalinfixed tumor and normal tissue, with related blood and urine samples, is collected from patients undergoing cancer surgery. Archives are also mined, particularly where these collections are linked to clinical outcomes. Resource for the biobank has been obtained from various sources, both academic and commercial, and there is great emphasis on linking each sample “six-pack” to related bioinformatics and cancer registries. Challenges faced when setting up a large cancer biobank are varied and complex, and key learning points have been identified from the MCRC Biobank experience. Things considered include effective and early communication with collaborating NHS Trusts, timing of staff recruitment, development of Standard Operating Protocols to produce highquality samples, and the need for an advanced database system to deal with both sample tracking and related informatics. Involvement of key clinical, scientific, managerial, and support staff has been critical at each stage. Learning points from the development of the MCRC Biobank may assist future cancer biobank developments to ensure a robust infrastructure supporting the collection of large numbers of high-quality biological samples, which are easily accessible to researchers.

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HSR3 Identification of Best Practices in the Design of a Pharmaceutical Tissue Bank Informatics System: Business Process Flow Diagrams 1

S. McDonald, 2N. Ilasi, and 1E. Velasco 1

Pfizer Corporation, St. Louis, MO, USA, 2 Pfizer Corporation, Groton, CT, USA

Pfizer’s Tissue Bank, in conjunction with Pfizer’s BioBank, is creating an overarching internal software package to cover all general functions of both research facilities, including sample receipt, reconciliation, processing, storage, and ordering. Business process flow diagrams were developed by the Tissue Bank and Informatics teams as a way of characterizing best practices both within the Bank and in its interactions with key internal and external stakeholders. Besides serving as a blueprint for software development, such process flows are key to the optimization of current procedures and their communication to interested groups. Sharing this knowledge could benefit other biospecimen research repositories (both pharmaceutical and other settings), for comparative purposes or as a guide to successful informatics design. Examples of best practices so highlighted include (1) separate but interconnected workflows for different tissue dispositions and intended uses; (2) procedures for missing or otherwise problematic samples; (3) inclusion of sample quality assurance processing workflow; (4) quality, feasibility, and tracking issues for specimens from an outside source; and (5) optimal communication to customers during the various workflow processes, and subsequent assessment of value-added research impact. Future process improvements through this analysis will focus on these areas and the overall synchronization with the BioBank. We conclude that optimized business process flow diagrams are key to the success of several endeavors in pharmaceutical research tissue banking, including best practice identification and sharing, informatics, and stakeholder communications.

HSR4 New Fixation Technology for Simultaneous Preservation of Morphology and Nucleic Acids in Tissue 1

L. Rainen, 2D. Grölz, 3C. Lenz, 3N. Dettmann, 3 M. Hilker, 3E. Traenert, and 4U. Oelmüller

1

BD/PreAnalytiX GmbH, Franklin Lakes, ND, USA, 2 PreAnalytiX GmbH, Hombrechtikon, Switzerland, 3 QIAGEN, Hilden, Germany, 4PreAnalytiX GmbH, Hilden, Germany

We have developed a new method, the PAXgene® Tissue System (PAX), which simultaneously preserves tissue morphology and stabilizes nucleic acids without the use of formalin. The aim of this study was to compare PAX tissue to formalin-fixed or frozen tissue for morphology, nucleic acid integrity, and performance of DNA/ RNA in PCR/qRT-PCR assays. Tissue specimens were treated with either neutral buffered formalin (NBF), PAX reagents, or frozen in liquid nitrogen. PAX stabilized tissues were then stored at different temperatures for up to 4 weeks. Nucleic acid isolation was performed with PAXgene Tissue Kits. Nucleic acid quality and performance was determined by electrophoretic mobility, real-time qRT-PCR, or qPCR assays. Tissue morphology was assessed with histochemical and immunohistochemical methods. PAX stabilized tissue specimens were stable for 7 days at room temperature and for at least 4 weeks when refrigerated or frozen. PAX stabilized tissue could be embedded in paraffin, processed, and stained using traditional histochemical or immunohistochemical methods. Staining patterns and staining intensity were comparable to NBF tissue. High molecular weight RNA and DNA could be isolated from all forms of PAX stabilized tissue. Integrity, yield, and performance in qRT-PCR of RNA were comparable to the tissue frozen in liquid nitrogen. The PAXgene Tissue System stabilizes molecular content and preserves tissue morphology, enabling both molecular and histochemical testing from the same specimen. For research use only, not for use in diagnostic procedures.

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HSR5 A Bio-Repository Based on Preservation of Postclinical Test Samples K. Furuta, H. Kato, and R. Tsuchiya National Cancer Center Hospital, Tokyo, Japan The goal of this activity has been to establish a hospital data center combining patient medical records, laboratory results, and clinical samples that includes a bio-repository that preserves postclinical test samples. Our basic concept of a postclinical test sample is not as leftover waste, but rather as frozen evidence of a patient’s pathological condition at a particular point. We can decode, if not all, most of the laboratory data from a postclinical test sample. As a result, the bio-repository is able to provide not only the samples, but also potentially all related laboratory data upon requests. Therefore, the bio-repository can be regarded as a valued extension of the integrated data center mentioned above. We established the Bio-Repository at the National Cancer Center Hospital (NCCH) in October 2002, and arranged to provide samples to various concerned parties under strict legal and ethical agreements. To respond to various needs, samples have been stored in as many formats as possible, such as plasma or serum, dried blood spot (DBS), and buffy coat. To date, 158,853 plasma or serum, 26,900 DBS, and 244 buffy coats have been registered for the repository. Although the number of the utilized samples was limited initially, inquiries for sample utilization are now increasing steadily from both research and clinical sources. Further efforts to increase the benefits of the repository and to stress the importance of the postclinical samples are intended.

HSR6 UK Biobank—Application of Industrialization Methodology to the Establishment and Operation of a Biological Sample Processing Facility and Ultra Low Temperature Archive P. Downey UK Biobank Ltd, Manchester, Cheshire, United Kingdom UK Biobank is a large prospective study in the United Kingdom to investigate the role of genetic factors, environmental exposures, and lifestyle in

the causes of major diseases of late and middle age. Extensive data and biological samples are being collected from 500,000 participants aged between 40 and 69 years. UK Biobank collects about 55 mL of blood and 10 mL of urine from each participant, and these are transported overnight by commercial courier to a central processing facility where they are processed to aliquots of urine, plasma, serum, white cells, and red cells and stored in ultralow temperature archives. By the end of the recruitment phase, 15 million sample aliquots will be stored in two geographically separate archives: 9.5 million in a −80°C automated archive and 5.5 million in a manual liquid nitrogen archive at −180°C. Because of the size of the study and the numbers of samples obtained from participants, the protocol stipulates a highly automated approach for the processing and storage of samples. Implementation of the processes, technology, systems, and facilities has followed best practices used in the manufacturing industry to reduce project risk and to build in quality and robustness. The application of techniques from manufacturing engineering to the design and implementation of the UK Biobank sample processing and archiving facility will be discussed.

HSR7 Navigating Human Material Transfer Agreement Processes at the NIH: A New Tool to Help! M. Henderson and C. Bell National Cancer Institute, NIH, DHHS, Bethesda, MD, USA In response to US Congressional recommendations to modify the approval process for use of human biospecimens in research, the National Institutes of Health (NIH) drafted a new Material Transfer Agreement (MTA) policy in 2008. The new policy modifies existing procedures and elevates signature authority required for approval. The changes have resulted in significant delays in transferring specimens for research. Over the past year, we have been working to streamline processes for NIH intramural investigators to allow rapid establishment of MTAs. Key discussions involved NCI and NIH offices, including two Technology Transfer Centers, the Ethics Office, both NCI Institutional Review Boards (SSIRB and CCIRB), and the NIH Office of Human Subjects

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Research. We created an intranet decision-making tool that describes human subjects and technology transfer requirements under various biospecimen transfer scenarios. To use this tool, investigators click through a series of questions related to the biospecimens they wish to transfer. On the basis of those answers, investigators arrive at a Web site detailing the relevant documents needed to obtain approval of the specimen transfer, guidance as to how and to whom the documents should be submitted, as well as descriptions of terms necessary to understand what information is requested. Future directions include working with other NIH offices to develop a web-based application that can serve as a “one stop” site for investigators to request a material transfer and obtain the required approvals rather than the current system of presenting information separately to the various offices that are involved in the approval process.

(3) pH: ALS, 6.44 (range: 5.90–6.87); control, 6.23 (range: 5.83–6.60); and (4) RIN: ALS, 5.9 (range: 2.8–7.0); control, 4.7 (range: 2.2–6.7). Across different brain regions, pH and RIN did not vary significantly. Moreover, by quantitative RT-PCR using primers for three housekeeping genes (amplicons < 160 bp), RNA levels were comparable and reflected RIN values. Although the sample size is small, the best indicators of postmortem brain tissue quality are pH and RIN with higher pH values correlating with higher RNA integrity. Interestingly, neither longer PMI times nor times from death to tissue freezing result in lower pH or RIN values.

HSR9 Evaluation of the Armed Forces Institute of Pathology (AFIP) Tissue Repository 1

J. Eliason, 2S. Wolman, 3N. Pande, and 4 J. Janisse

HSR8 Quality Control Parameters in Postmortem Brain Tissue Derived from Patients with Amyotrophic Lateral Sclerosis 1 3

K. Trevor, 1C. Brown, 1J. Averill, 2A. McKee, E. Deykin, 3D. Rose, 3L. Fiore, and 1A. Prasad

1

Southern Arizona VA Healthcare System, Tucson, AZ, USA, 2Bedford VA Medical Center, Bedford, MA, USA, 3Boston VA Healthcare System, Jamaica Plain, MA, USA The VA Amyotrophic Lateral Sclerosis (ALS) Brain Bank is banking frozen and formalin-fixed postmortem brain and spinal cord specimens from the National Registry of Veterans with ALS cohort. Up to 18 anatomical regions are represented. Essential for research is postmortem tissue quality. Traditional quality indicators include postmortem intervals (PMIs), brain tissue pH (agonal or stress state marker), and RNA quality (RNA Integrity Number, or RIN). These parameters have been compared for 20 frozen (−800°C) brain specimens from ALS subjects (average age: 59 years; range: 22–80 years) and 10 control brain specimens derived from subjects with no known neurological disorders (average age: 61 years; range: 34–75 years). The average parameter values were (1) PMI times to body refrigeration: ALS, 8.6 h (range: 1.3–22.4 h); control, 16.7 h (range: 1–72 h); (2) time from death to tissue freezing: ALS, 39 h (range: 24–72 h); control, 44 h (range: 12–120 h);

1

Michigan Neonatal Biobank, Detroit, MI, USA, George Washington University School of Medicine, Washington, DC, USA, 3Asterand, plc, Detroit, MI, USA, 4Wayne State University, Detroit, MI, USA

2

The AFIP repository comprises 7.8 million cases and over 86 million samples (slides, blocks, and wet tissues). These are stored in two separate collections: (1) the Central Repository (CR) with samples collected from 1917 to the present and (2) the Base Realignment and Closure (BRAC) collection that houses materials from closed military hospitals sent to AFIP since 1992. Our evaluation (in 2008) of the biomedical research potential of these collections employed a disease-based approach, focusing on two common cancers (colorectal and prostate), a rare cancer (synovial sarcoma), and an infectious disease (tuberculosis) for the CR. Approach to the BRAC collection was based on a search for “breast cancer.” In contrast to the three databases storing information for the CR, which have searchable fields for diagnosis, the BRAC database uses free text searches of scanned documents. Thus, successful retrieval of clinical data representing the search criteria was only 69% in BRAC compared with 83% recovery from the CR. The following parameters were analyzed for each collection: (1) accuracy and completeness of the databases; (2) histologic representation of the lesion diagnosed in the databases; (3) size and physical condition of relevant tissue specimens;

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and (4) antigenicity determined by immunohistochemistry. Recovery of samples matching the clinical diagnosis was similarly high for both collections, 89% for the CR samples and 98% for BRAC. The availability of tissue blocks in over 60% of cases and documentation of preserved antigenicity attest to the value of this resource for disease research.

between 7 and 8 at all time points between 0 and 50 months.

HSR11 Establishing Quality Measures in a Cancer Tissue Biobank to Enable Meaningful Results 1

G. Ashton, 2J. Rogan, 2N. Clarke, and 1 C. Womack

HSR10 In Situ Stability of RNA in Blood Samples Stored at −20°C and −70°C in PAXgene Blood RNA Tubes 1

L. Rainen, 2K. Guenther, 3H. Balven-Ross, and 2 R. Wyrich

1

BD/PreAnalytiX GmbH, Franklin Lakes, NJ, USA, PreAnalytiX GmbH, Hilden, Germany, 3QIAGEN GmbH, Hilden, Germany

2

Gene expression analysis in peripheral blood is important in molecular research and diagnostics, and erroneous results can be caused by ex vivo changes of expression patterns. We therefore developed the PAXgene® Blood RNA System, launched in the United States and Europe as an IVD, for the collection of whole blood and the stabilization and purification of total RNA. The PAXgene Blood RNA Tube is widely used to archive specimens for later gene expression analysis. The aim of these ongoing studies is to determine the stability of blood RNA in PAXgene Tubes stored at −20°C and −70°C. For each study, blood was drawn into PAXgene tubes from 10 consented donors. Specimens were stored in situ at either −20°C or −70°C and processed according to the manufacturer’s instructions. Purified RNA was analyzed for integrity using the Agilent Bioanalyzer and tested in CFOS and IL1B qRTPCR assays. Results: There were no significant changes in the relative transcript levels of CFOS or IL1B during in situ storage of whole blood in PAXgene Blood RNA Tubes at either −20°C or −70°C for up to 50 months. Furthermore, no significant loss of RNA integrity was detected in whole blood specimens stored for 50 months at either temperature. Conclusions: Blood can be stored in situ in PAXgene Blood RNA Tubes for at least 50 months at −20°C or −70°C without loss of function in qRT-PCR analysis. Furthermore, supplementary data indicated that mean values for RINs were

1

Paterson Institute for Cancer Research, Manchester, United Kingdom, 2The Christie NHS Foundation Trust, Manchester, United Kingdom

Background: Meaningful analysis of clinical samples depends as much on the integrity of the sample as on a validated assay. Existing routine clinical collection practices suffice for some analyses but not for others. The newly established Manchester Cancer Research Centre (MCRC) Biobank has taken a practical approach to biosample quality. Method: Anecdotal and published evidence gives an indication of the robustness of some biological molecules as they pass from the patient to laboratory for analysis. This emerging biosample science can be applied to prospective collection and storage practices where it can evaluate the likely integrity of archival samples or determine optimal collection conditions both for specimen preservation and clinical safety. We have collected a mixture of archival and prospective samples using standard preservation methods. To ensure that samples released are fit for the specific proposed research purpose, we have adopted a simple approach to biosample quality monitoring. Results: Simple morphological methods are the principal initial quality measure for each sample acquired. These are supported by immunohistological methods that are being developed systematically using samples collected to a protocol incorporating delayed preservation. Integrity of RNA and other molecules are checked using validated methods available elsewhere in the institute. Conclusions: The MCRC Biobank has implemented simple measures to assess biosample quality for research purposes. Sample quality is of fundamental importance and this factor must be combined with ease of and safety during collection.

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HSR12 Unique Design of an Active Sample Management and Biorepository Facility B. Glazer Quintiles Laboratories, Marietta, GA, USA Quintiles Laboratories is a central laboratory supporting clinical trials for the pharmaceutical industry. Samples are received via courier networks; thousands of frozen shippers are received weekly from investigator sites. Each shipper contains 6 pounds of dry ice; the many frozen samples within can have individualized workflows—storage, consolidation, onward shipping, or testing here. Samples must be maintained in a frozen state throughout the entire process. In 2008, we relocated to a new facility. The design plan needed to meet the goals of durability of materials, scalability, facility security, sample integrity, employee health and safety, and optimization of sample flow. CO2 levels, which can spike during the initial receipt process and again at the shipping stage, needed to be within US OSHA regulations. We used innovative design and engineering for our stainless steel processing tables for initial receipt and individual work stations (in a U-shaped configuration with each staff member having an insulated rolling dry ice container sitting on another CO2 exhaust accomplished through ductwork in a concrete trench below the floor). The bench top working area is a combination of solid and perforated stainless steel allowing further exhaust of CO2, which is drawn down and away from the staff at all times so levels remain at a constant low level of ~500 ppm. Spikes are infrequent and generally limited to 200,000 unique individuals within 5 years, which can be linked to a rich source of electronic medical record information.

pathogens from misuse. Information concerning patients affected by infectious diseases is particularly sensitive and special care must be taken to protecting it; in addition, samples are collected for the dual purpose of diagnosis and research, and it often happens that samples originally collected with one intention are later used differently: a specific consent form and special rules for data storing and traceability must be devised. Today, we can register a growing awareness of biobanking issues by national governments, and the rise in the number of funding calls that are being issued will provide the much needed support for the activities of infectious disease biorepositories.

HSR18 Whole-Genome SNP Genotyping of Room Temperature Stored DNA Samples from a Cardiovascular Disease Cohort

HSR17 Challenges in Infectious Disease Biobanking: The Experience of the Biorepository of the National Institute for Infectious Diseases “L. Spallanzani” C. Nisii, F. Carletti, R. Chiappini, D. Khouri, A. Castrogiovanni, F. Petroni, G. Prota, M. Capobianchi, G. Ippolito, and A. Di Caro National Institute for Infectious Diseases “L. Spallanzani,” Rome, Italy The research into improved diagnostic or therapeutic tools for infectious diseases relies on repositories of pathogens and biological samples obtained from infected patients. In addition to the problems common to all biobanks, such repositories are confronted with specific challenges derived from the very nature of the materials that are stored in them. The acute phases of some diseases can be difficult to recognize, resulting in an unbalance in favor of the collection of samples from chronic patients. Traceability is another challenge as in most cases (eg, treated subjects) and multiple samples must be collected from each subject and the clinical information updated every time. The biosafety practices that must be employed when working with infectious materials and the necessity to work under aseptic conditions make standard operating procedures lengthy and increase training requirements and costs. Biosecurity precautions must be in place to protect high-risk live

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M. Hogan, 2S. Murray, 2M. Shaw, H. McMahon, 2K. Goglin, and 1R. Nunez

1

GenVault, Carlsbad, CA, USA, 2Scripps Genomic Medicine, La Jolla, CA, USA

Background: Scripps Genomic Medicine has several ongoing projects that utilize growing sample collections. Since room temperature storage for DNA samples can be useful for sending and receiving samples with outside collaborators and for reducing freezer space, we have conducted a study to compare DNA quality and assay performance between DNA stored in a −20°C freezer and DNA stored using a room temperature (RT) storage system. Methods: Four DNA samples from our cardiovascular disease cohort were stored for 2 weeks at both RT and at 37°C using the GenVault GenTegra system in addition to −20°C. At the conclusion of the test, each sample was evaluated for quality by visual inspection of both genomic DNA and four long-range PCR amplicons (size range 4.8–11 kb) on an agarose gel, and whole-genome genotyping using the Illumina 610 BeadChip. Results: The genomic DNA revealed a 40-kb band for all samples with minimal smearing with no difference in samples stored in at each condition. Visual inspection of the four long-range PCR amplicons across all samples yielded robust products. All samples were successfully genotyped, and DNA quality as assessed by sample call rates, genotype concordance, and standard deviation

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LogR (intensity) ratio were exceptional across all storage conditions. Conclusion: Whole-genome genotyping and long-range PCR assays performed on samples stored using a room temperature storage system performed as good as or better than samples stored at −20°C.

References

HSR19

HSR20

1. Ravid R. Standard operating procedures, ethical and legal regulations in BTB (brain/tissue/bio) banking: what is still missing? Cell Tissue Bank 2008;9(2):121–137. 2. Ravid R, Grinberg LT. How to run a brain bankrevisted. Cell Tissue Bank 2008;9(3):149–150.

The Pitfalls and Practicalities in the Daily Practice of Brain/Tissue/Bio (BTB) Banks for Biomedical Research

Release of New Web Site for Tokyo Metropolitan Geriatric Hospital Autopsy Resource (TMGH-AR)

R. Ravid Netherlands Institute for Neurosciences/ KNAW, Amsterdam, Noord Holland, The Netherlands Introduction: Human Brain/Tissue/Bio Banks (BTB) are a valuable source of adequately collected and preserved specimens of the human body in health and disease; they form an essential bridge between the clinic and basic science which enables translational research. Currently, most banks are still in the process of standardizing and harmonizing the methodological/legal/ ethical guidelines to be used in the procurement and dissemination of human specimens. The gold standard and international SOPs are still in the making. Methods: We hereby propose a golden standard for human specimen repositories: (1) A well-established local Donor program in which consent is obtained for the use of specimens for scientific research. (2) SOPs for tissue procurement, management, preparation, dissemination, and storage for diagnostics and scientific research. (3) Rapid autopsies with a very short postmortem delay and a fresh dissection of tissues. (4) A generally accepted consensus on the clinical and neuropathological criteria. (5) Quality management systems. (6) A code of conduct for the ethical and legal aspects. (7) Adequate safety procedures. In the coming decennia, BTB banks will collect, preserve, and type RNA and DNA extracted from human specimens and identify biomarkers and therapeutic targets. A consensus on the methodological/ethical and legal guidelines is at the moment a top priority; it will guarantee the quality and suitability of the donated samples for high-quality scientific and clinical reseach.

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M. Sawabe, 1T. Arai, 1Y. Saito, 1T. Shimizu, 1 T. Toda, 1S. Murayama, 1M. Tanaka, 1K. Takubo, 2M. Mieno, and 3N. Tanaka

1

Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Itabashi, Tokyo, Japan, 2Jichi Medical University, Shimotsuke, Tochigi, Japan, 3Harvard School of Public Health, Boston, MA, USA

Introduction: To collect human samples, we usually explain the purpose and expected results of planning research to the donors giving blood or other kinds of samples. However, we seldom inform them of the consequences or results of the research. During recent decades, we have been conducting a number of medical researches using TMGH Autopsy Resource. We have now opened its Web site since this April for three reasons: disclosure of research results, proposal for new research collaboration, and communication with the bereaved families who gave us the consent of autopsy. Materials and Methods: TMGH Autopsy Resource comprises clinicopathological database, photos, and paraffin blocks (7500 cases each); frozen tissues and DNA (2000 cases); and frozen sera taken within 2 weeks before death (1800 cases). The brain and spinal cord are registered to “Brain Bank for Aging Research.” The average age at the time of death was 80 years, and a man to women ratio was 1.2. The Act of Autopsy Examination in Japan generally allows the use of autopsy samples for medical education and research. Results: The home pages comprise several pages: introduction of research results, ethical and juristic consideration, communication with the bereaved families, characteristics of TMGH Autopsy Resource, proposal of new collaboration, rule of collaboration program, contributor and

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contact address, and Web links. We have been showing more than 30 research results conducted in the past 5 years. Conclusion: The new Web site provides detailed information of TMGH Autopsy Resource, promotes research collaboration, and improve the ethical framework.

HSR21 Facilitating Research for the Gastric Cancer Study—Collection and Storage of Biospecimens and Clinical Outcome Data S. Cauberg, D. Bowtell, and A. Boussioutas Peter MacCallum Cancer Centre and University of Melbourne, Western Hos, Melbourne, Victoria, Australia The “Genome-wide expression analysis in gastric cancer study” is an excellent example of how Biobanks enable high-quality research using human tissue while protecting the privacy of donors. Australian National Privacy Principles require written consent from donors before Tissue Banks can obtain medical information. Once written consent is given, samples and clinical information must be de-identified before being passed on to researchers. Over the past 9 years, tissue and/ or blood with accompanying follow-up data has been collected from over 318 donors with gastric or oesophageal adenocarcinoma. Tissues collected from nine Melbourne hospitals, and associated bloods, are processed and stored by the Peter MacCallum Cancer Centre Tissue Bank, which was established in November 1998. In June 2006, Peter Mac joined three other Melbourne Tissue Banks to become one of the founding members of the Victorian Cancer Biobank consortium which continues to support the collection and supply of biospecimens for this study. Capturing clinical data, including outcome data, increases the utility of these biospecimens, as does our unique smaller cohort of donors within this data set, who have provided blood samples at regular intervals from pre-surgery to recurrence. Over 90% of donors enrolled have up-to-date outcome data. Methods for obtaining and storing clinical data, challenges encountered, and some of the findings this valuable resource has facilitated will be presented. This study is supported through funding from the National Health and Medical Research Council.

The Biobank activities are funded by the Victorian Government Department of Innovation, Industry and Regional Development.

HSR22 QIAsafe DNA Tubes for Room-Temperature Archiving of Purified DNA Samples 1

T. Doedt, 2R. Kist, 1D. Heckel, 3S. de Rozieres, 3 R. Muller, and 3J. Muller-Cohn 1

QIAGEN GmbH, Hilden, NRW, USA, 2QIAGEN GmbH, Hilden, NRW, Germany, 3Biomatrica Inc, San Diego, CA, USA As DNA sample collection becomes routine practice, it is crucial to develop convenient and cost-effective technologies for long-term sample maintenance with optimal sample protection. We have continued to develop and evaluate an innovative room temperature DNA storage medium (QIAsafe DNA Tubes and 96-Well Plates) as a useful alternative to cold storage. QIAsafe forms a thermostable barrier around DNA during the drying process, protecting DNA from degradation during shipping or long-term storage at ambient temperatures. Sample recovery requires simple rehydration and DNA is used in downstream applications without additional purification. Here, we compare the performance in downstream analyses of DNA samples stored with QIAsafe DNA at room temperature to samples stored conventionally at −20°C. Results demonstrate the stabilization of DNA for an equivalent of over 30 years under accelerated aging conditions. Recovered samples were subsequently analyzed by real-time PCR, HLA typing, long-fragment amplification, or agarose gel electrophoresis, and exhibited no differences in yield, integrity, or downstream performance between the DNA samples stored at room temperature protected in QIAsafe as compared to samples stored conventionally at −20°C for identical time periods. We conclude that QIAsafe DNA Tubes and 96-Well Plates are well suited for shipping or archiving of DNA at room temperature to protect samples from degradation. QIAsafe DNA Tubes and 96-Well Plates are intended for molecular biology applications. The products are neither intended for the diagnosis, prevention, or treatment of a disease, nor have they been validated for such use either alone or in combination with other products.

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HSR23 Implementing Best Practices for a Statewide Biorepository Network: The BioRepository Alliance of Georgia for Oncology 1 1

HSR24 Variables Affecting Consent Rates at an Established Tumor Bank, the British Columbia Cancer Agency’s Tumour Tissue Repository

J. Giri, 1K. Russell, and 2A. Moore

J. LeBlanc, R. Barnes, and P. Watson

Medical College of Georgia, Augusta, GA, USA, 2 Georgia Cancer Coalition, Atlanta, GA, USA

BC Cancer Agency, Victoria, BC, Canada

The Biorepository Alliance of Georgia for Oncology (BRAG-Onc) has been established with support from the Georgia Cancer Coalition, with the objective of creating a unique repository for research, representative of the diversity of cancer patients in the state. The network is composed of a central bank at the Medical College of Georgia and individual procurement sites that submit specimens for long-term storage to the central hub. The repository network is continuing to evolve, with eight contributing sites at various stages, including two regional nodes with satellites, as well as participants in the NCCCP pilot program. In addition to issues facing individual human biobanks, such as long-term sustainability and appropriate informatics, a statewide repository has additional challenges, some listed below. We will describe the approaches developed for BRAGOnc to address (1) Developing and implementing uniform SOPs, based on BestPractices guidelines, throughout the network. (2) Developing special procurement protocols, to meet the requirements of adverse community of investigators, in particular methods that preserve integrity and quality of various biospecimens for specific molecular technologies and applications; establishing collaborations with research laboratories for this purpose. (c) Developing and documenting quality control measures, especially for tissue collected at various institutions in the network; utilizing web-based digital slide technologies for review of QC slides by Pathologists, and storing QC information. Summary: The BRAG-Onc statewide repository provides a unique opportunity for developing and testing best practices that will be applicable to larger networks and organizations.

Background: The British Columbia Cancer Agency’s Tumor Tissue Repository (TTR) is a provincial biobanking program. One component is a core institutional biobank that has accrued ~2500 cases since 2004. Biobanks provide essential biospecimen resources for the entire spectrum of cancer research. To ensure these resources are available, it is important for biobanks to monitor internal consent rates to verify that effective consent mechanisms are being deployed. Methods: We aimed to answer three questions: (1) does consent rate vary with tumor site; (2) does consent rate differ when offered preoperatively vs. postoperatively; and (3) does consent rate differ with phenotype of the trained consent person? Results: The mean consent rate since inception of the TTR, 96.4% across all cancer types, varied relative to cancer type: breast 95.0%, colorectal 97.4%, ovarian 98.0%, lung 97.8%, and “other” 96.9%. Notably, the consent rate was significantly lower for breast patients vs. colorectal (P = 0.04), ovarian (P = 0.01), and lung patients (P = 0.02). Since the TTR added a postoperative consent protocol, we have observed different consent rates for preoperative (94.0%) vs. postoperative (99.0%) contact. The rate of donors approached for postoperative consent has remained constant at ~5% since establishing a postoperative consent protocol. Our final analysis showed differences between consent decline rates between a Consent Nurse (RN) (2.3%) and Research Coordinator (5.3%). Conclusions: Tumor site, timing of consent, and the type of trained consent person are all variables that impact consent rates. These findings warrant a deeper investigation into each variable, to identify the key differences, and guide our consent processes.

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HSR25

HSR26

Practical Solutions in Biobank Facilitation: The BC Biolibrary Initiative in Canada

Third-Year Report of the Brazilian National Tumour and DNA Bank (BNT) at the Brazilian National Cancer Institute (INCA)

S. Giesz BC BioLibrary, Vancouver, BC, Canada Background: Biobanking focuses on accrual and annotation of biospecimens, but equally critical is the creation of processes for engaging the public before accrual, distributing biospecimens, and cultivating inter-biobank collaborations. Additional focus on the development of synergy between the public and biobanks and these processes will enhance scientific and technological advancement and the translation of discovery to the clinic. Methods: The BC BioLibrary is a novel, province-wide strategy aimed at public engagement in biobanking, facilitating biospecimen, and data acquisition and integration of existing biobanks and research facilities into a functional and accessible framework. Built on evolutionary concepts including repatriation of biospecimen collection back into pathology departments (Biospecimen Collection Units [BCU]), the BC BioLibrary has created a common framework governed and shared by all biobanks independent of institution or health research focus. Results: The BC BioLibrary is embraced by leaders across BC (population 4.4 M) spanning four hospital sites, two health authorities, three funding agencies, and major academic institutions and translational research groups. The first BCU was established in 2008 and has collected >450 biospecimens. This pilot BCU has been used to develop 18 SOPs and ethics board approval for a provincial model. Two of 10 additional planned BCUs will become operational in 2009, expanding the BC BioLibrary into a network. Conclusions: The BC BioLibrary facilitates access to consented, high-quality, annotated biospecimens for biobanks and researchers. By providing a common infrastructure, the model increases efficiency and connection between biobanks and providers, offers a transparent process for donors, and enhances public trust in biobanking.

J.C. Casali-da-Rocha, C. Gustavo Stefanoff, M. Teresa Guedes, P. Camanho, L. Augusto Maltoni, and C. Ferreira Brazilian National Cancer Institute (INCA), Rio de Janeiro, Brazil The BNT initiated in May 2006 at INCA, the major reference center for cancer treatment of Brazil, for recruiting donors and collecting tissue samples. We wanted to establish a national reference Biological Resource Center to stimulate translational cancer research in Brazil. Systematic collection protocols for blood, and paired normal and tumor specimens were implemented at the four INCA hospitals and other collaborative national centers. Specimens are either snap-frozen in liquid nitrogen or RNAlater conserved, and then long-term stored in −80°C freezers until use. The SISBNT software was developed for sample data register and retrieval of clinical and laboratorial information. Internet access of data and query tools are available for researchers in different levels at www.inca.gov.br/bnt. We have already collected 8152 samples, and we expect to collect until the end of the third year over 10,000 samples from more than 2500 patients with a variety of cancer sites. Automatization of sample processes was recently incorporated in the BNT lab practice, including DNA/RNA extraction, blood fractioning, and plate sample preparation procedures. At the third year of continuing activities at the BNT, the processes of recruiting and sample collection were now considered part of the INCA’s hospitals routine. We could get the involvement of care doctors, pathologist, nurses, and administrative team. Future aims include (1) to establish a Latin American network; (2) to establish a database containing clinical follow-up and genetic annotations; and (3) to collect blood from nonaffected population as controls for epidemiological studies. Supported by Swiss Bridge Foundation, FINEP, INCA, FAPERJ.

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HSR27 Trends in Biospecimen Use for Cancer Research Over Two Decades P. Watson, S. Hughes, and R. Barnes BC Cancer Agency, Victoria, BC, Canada Background: Cancer biospecimens hold the key to unlocking the mechanisms of cancer development and progression. For many years biospecimens have been stored for research use. It is clear that these resources are in demand, but there are relatively little data on the change in use. These data are required to make projections for future demand. We hypothesize that the number and type of biospecimens used to support cancer research has changed significantly over the past 20 years. Methods: We set out to answer this question by analyzing biospecimen use reported in all articles published in four cancer research journals: two North American (Cancer Research and Clinical Cancer Research) and two European (British Journal of Cancer and International Journal of Cancer). We analyzed a total of 1228 articles at 5-year intervals (2008, 2003, 1998, 1993, and 1988) for biospecimen utilization, cohort size, type (tissue or blood), and format (frozen or formalin-fixed). Results: Over the 20-year period analyzed, we observed a 10.5% increase in articles using biospecimens (P = 0.5536). Independent of this, we observed a significant increase in the number of biospecimens used per article (median 32–101, P ≤ 0.0001). There were also significant increases in tissue and hematological cohort sizes (medians 35–86 and 24–94, respectively, P ≤ 0.0001). We observed an increase in frozen, FFPE, and blood product cohort sizes and change in demand for the tissue formats. Conclusions: We conclude that the demand for biospecimens for cancer research has increased with changing requirements and larger cohort sizes.

HSR28 Effects of Specimen Processing and Storage on Whole Blood: Hemolysis and RNA E. Chani, A. Chang, A. Yee, A. Kirimlis, and C. Florez Fisher BioServices, Rockville, MD, USA Hemolysis due to the breakdown of red blood cells is important to the laboratory because it can

have an effect on laboratory results. The effects can be the result of products liberated from the red cells themselves, or due to interferences with laboratory analyzers. The effects of specimen processing and storage on the hemolysis of whole blood specimens collected in SST vacutainers were studied. The hemoglobin content in g/L was calculated using the formula of Kahn et al. by measuring the absorbance of undiluted serum specimens at three different wavelengths. Test results show that proper initial handling of blood collected in SST tubes plays a very important role in assuring clean serum samples. Hemoglobin content increased in improperly handled specimens compared with those handled following the vacutainer manufacturer’s instructions. Storage of centrifuged blood for a period of up to 2 weeks (in 4°C or −20°C) before serum aliquoting did not excessively increase hemoglobin content. Effects of blood collection and storage on the quantity and quality of extracted whole RNA were also studied. RNA was extracted using an ABI 6100 Nucleic Acid PrepStation following manufacturer’s protocol. The quality of RNA specimens was assessed using an Agilent 2100 Bioanalyzer. Test results clearly show the importance of proper sample collection on the quantity and quality of RNA specimens. Improper blood collection decreases the amount of RNA extracted compared with properly collected specimens. Extended storage for up to 5 years at −80°C did not show any adverse effect on the quantity or quality of extracted RNA.

Other Hot Topics HT1 The Next Phase of Sample Management 1 1

B. Chadwick and 2A. Sable-Hunt

LookLeft Group, LLC, Cortlandt Manor, New York, USA, 2Edwards-Hunt Group, Westport, CT, USA

Owing to increasing regulatory scrutiny, the management of biological specimens has evolved from location and inventory management to include informed consent management, bioethics, and the need to connect clinical data to biological specimen data—connecting the phenotype to the genotype is the fuel for translational research. To move to the next phase of sample management will require the combination of advanced software solutions and the modification of standard

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operating processes and work practices. Software solutions for this purpose will not only need to manage the location of every sample, but also need to facilitate access controls, informed consent management, and enable clinical data collection—all in a way that complies with federal regulations around data security and privacy. Although such change will require human, technology, and financial investment, companies that successfully enter the next phase of sample management will be best positioned for the era of personalized medicine.

workflows will provide significant cost savings by reducing reliance on current cold-storage practices for sample storage and transport. Ambient temperature storage also provides a cost-effective solution for secondary offsite backup to adequately ensure valuable sample collections.

HT3 Impact of Compliance and Infrastructure Issues on Validation, Monitoring, and Safe Storage of Biological Samples 1

T. Romig, 1L. Wetherwax, 1K. Manz, 2 C. Barrinuevo, and 2G. Sujo

HT2 Sustainable Sample Management: A Case Study P. Faix, R. Muller, S. de Rozieres, and J. Muller-Cohn Biomatrica, Inc., San Diego, CA, USA Successful biobanking requires effective and efficient sample storage technologies that function to protect the integrity of collected specimens during long-term storage and transport. The challenge is to identify and implement innovative new technologies that enhance sample collection quality and manipulation. A leading academic institution recently completed a successful pilot project to evaluate our platform room temperature storage technology, SampleMatrix, in a concerted effort to reduce energy consumption, achieve sustainability goals, and optimize laboratory space and workflow. Twelve campus laboratories representing a wide range of sizes and research interests were recruited to transfer ~1.0 million candidate samples from −20°C and −80°C freezer storage to room temperature storage. The results of the 6-month pilot project quantifies the benefits achieved within various departmental laboratories and will be used to extrapolate the benefits of adopting SampleMatrix technology to the entire institution. Likewise, the benefits of utilizing room temperature stabilization technology in a biobanking environment can also be derived from the pilot study. SampleMatrix technology can be adapted to robotic platforms and high-throughput work flows due to its ability to accommodate various storage device formats, thereby facilitating efficient sample transfer from existing collections or the creation of new ones. Integration of alternative technologies into biobanking processes and

1

Amgen, Thousand Oaks, California, USA 2PharmBio Inc., Thousand Oaks, California, USA

Developing and maintaining an efficient and robust interface from biological sample management to clinical operations is becoming more difficult as clinical trials expand globally and governing bodies increase regulations over issues such as the protection of patient privacy and consent. The challenges are many; including logistics, regulatory concerns, sample management issues, informatics, and the acquisition of appropriately designed and tested equipments. The authors will present an overview of the compliance issues in this regulated environment and the impact of these issues by focusing on one of the most commonly used pieces of laboratory equipment, the Ultra Low Temperature (ULT) chambers and the biological samples stored within. Detailed results from engineering tests on the performance of four separate manufacturer’s mechanical ULT Chambers will be presented. This included empty chamber, minimally loaded, and full chamber tests. The authors will also put forth recommendations for a minimum standard for the validation and monitoring of these freezers in a regulated environment.

HT4 Innocents Abroad: The Sudden Introduction of a Data Archivist to the Science of BioRepositories J. McNally University of Michigan, Ann Arbor, MI, USA This article provides an overview of the efforts by the National Archive of Computerized Data

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on Aging (NACDA) to gain an understanding of the science and information management skills underlying the organization and preservation of biospecimens within a formal repository. NACDA is the nation’s largest repository of secondary research data on aging, health, and the aging life course. Within its collection of 1600 plus studies over 500 individual surveys contain information, findings, or results from the collection and analysis of biomarkers and biomeasures. With the growing number of federally funded social science based surveys now collecting biospecimens as part of their research design, NACDA has actively sought out opportunities to better understand the science underlying bio-repositories and how their methods intersect with traditional approaches to the archival sciences. Over a 2-year process, NACDA has engaged a number of organizations, meetings, and institutions in the process of managing, preserving, and contributing to our understanding of how biospecimens contribute to our understanding of health, longevity, and the physical world in general. Our core finding is that this process of understanding has only just begun. The article reviews many of the fundamental differences in the approach to information and data management between a bio-repository and a data-repository, but it also identifies many commonalities in terms of challenges, objectives, and the interaction of preservation specialists with the user community. With growing collaborations between the biomedical and the social sciences, the ability to share a common language and understanding of biological data is essential.

Legal and Ethical Issues Related to Repositories LE1 Community Involvement in Ethical Decision Making for the Personalized Medicine Research Project D. Cross and C. McCarty Marshfield Clinic Research Foundation, Marshfield, WI, USA The Personalized Medicine Research Project (PMRP), a population-based biorepository, with ~20,000 individuals has successfully used a community-based approach for guiding biorepository use. This approach consists of a formal

community advisory group (CAG) and a twice yearly newsletter for participants in the PMRP cohort. The CAG’s function is to advise the principal investigator and the institutional IRB regarding ethical and study related issues, and to provide input on the items included in the newsletters. Newsletters provide participants with biannual updates regarding PMRP activities and are a way for participants to voice any concerns. Early in the development of the PMRP, the potential use of samples by industry was discussed. This led to varied responses from the CAG which was translated into a policy of case by case review and a prohibition on “selling” samples without collaboration. The NIH proposed data sharing policy was presented to the CAG and participants via the newsletter. This resulted in a collaborative response from the CAG and the institution to the NIH, and a single PMRP participant opting to stay in the study but not have genetic or phenotypic data shared in national databases. Recently, we have begun the process of incorporating stored clinical tissue samples into the repository. The result has been an overwhelmingly positive response by the community to include all possible tissue samples. By actively engaging the community through advisory boards and regular communication, the PMRP biorepository has effectively maintained the public trust and enthusiasm for this project.

LE2 Making it Easier to Share: Simplifying and Streamlining Biological Material Transfer 1

C. Cormier, 2S. Mohr, and 1J. LaBaer

1

PlasmID Repository/PSI Material Repository, Cambridge, MA, USA, 2Drosophila RNAi Screening Center, Boston, MA, USA In this collaborative high-throughput era, scientists rely on sharing materials to enable the confirmation of published results, to accelerate new discoveries, and to avoid the inefficiency of rebuilding what has already been created. Yet, scientists are increasingly frustrated by the complex and slow process of establishing the material transfer agreements (MTAs) that accompany nearly all transfers. Efforts seeking to streamline the MTA approval process, including the use of standardized language and automated e-mail contact, have not been widely adopted and delays still persist.

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We suggest a new approach that dramatically simplifies and expedites the MTA process. It entails building a network of institutions that approve the terms of transfer for a collection of materials in advance of material requests. Researchers inside the network who request materials receive materials without delay because the institutional signatures are already in place. This approach will unburden technology transfer officers and increase the accessibility of materials to researchers.

LE3 Can the in Minority Used Opt Out Method Survive the Better Known Signed Informed Consent? B. de Jong and P. Riegman Erasmus MC, Rotterdam, The Netherlands Human material biobanks have proven their usefulness many times. Medical research benefits from large collections of well-preserved, documented, and pseudomized or anonymized human residual material supplied by biobanks. The most practical method for all involved to obtain permission from the donor for the use of their residual materials for medical research purposes is the “opt out” system or the comparable “assumed consent.” This “opt out” method asks only the ~1% or less of potential donors opposing the use of their materials for medical research to undertake action, whereas the signed informed consent needs not only for all donors to undertake action, but also personnel to take care of the procedure. The “opt out” method, however, is not the usual procedure in many countries; in addition, it is only known in the clinicalbased biobanks. Therefore, it tends to be forgotten in the description of guidelines and best practices, simply because in the group setting the guidelines or best practices knowledge is not present. If these methods are not described as acceptable methods, the biobank adhering to this system is not compliant to the best practices or guidelines on this point. For those involved in setting up guidelines, we ask to have understanding and attention for this problem. A group with participants from all the types of biobanks and representatives of different (legal) backgrounds should be involved as well as a large sounding board group for comments and avoid “old boys clubs” to initially develop the documents.

LE4 The Biobanks of Human Genetic Samples and Justice Principle (Ethical Issue) L. Siede Argentina Parliament, Ciudad de Buenos Aires, Argentina The complex Globalization paradigm requires us to redefine the relationships between researchers and its citizens, the state, and the marketplace that are established from repositories as a scientific tool. Human genetic samples have meaningful values for different emergent social actors who play roles in a determined society to make history where relationships of power are reproduced. If we privilege the justice principle, then conflicts of interest and tensions arise between the public and private sector and among individuals and the community. If the owner has rights to their sample and if the human genetic sample has a price, then who has the right to set it? Methods: Apply Ethics. Propose to establish clear rules which refer to public policy as an irreplaceable domain of protection and an affirmation of the whole population’s interests, more than any associated motivation seeking to regulate the economy that benefits private enterprise.

LE5 Ethical and Legal Issues in Postmortem Human Brain/Tissue/Bio (BTB) Banking R. Ravid Netherlands Institute for Neurosciences/KNAW, Amstelveen, Noord-Holland, The Netherlands The use of postmortem human specimens in research is currently the focus of international public and professional concern and is a major issue in bioethics in general. Brain banks, tissue banks, and Biobanks (BTB banks) are a vital source of specimens and grow in sophisticated techniques that can be applied on postmortem specimens increases the pressure from the scientific community and the Bio industry on BTB banks. The most pressing medicolegal and ethical issues involved in brain/tissue/bio banking include (1) tissue procurement; (2) tissue management; (3) tissue dissemination; (4) confidentiality; (5) genetic testing;

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(6) “financial gain”; and (7) safety measures. At present, there is no consensus for these issues. The lack of uniformity prevents the exchange of specimens and wide use and share of common facilities. The differences in policy making and the lack of consensus on commercialization are detrimental for the use of specimens for basic, clinical research, and use by biotechnologies. Conclusions: On the basis of the huge variety of specimens stored in different repositories and the enormous differences in medicolegal systems and ethics regulations in different banks, we strongly recommend putting more efforts in harmonization and standardization of the currently used procedures and the legal and ethical codes of conduct. A well-functioning international network of BTB banks should be recognized as an entity that possesses the legal and ethical approach needed for the procurement and distribution of donated tissues for scientific research.

Reference 1. Ravid R. Ethical and legal regulations in BTB (brain/tissue/bio) banking: what is still missing? Cell Tissue Bank 2008;9(2):121–137.

LE6 Postoperative Consenting For Tissue Banking: A Singapore Perspective R. Singh NUH, Singapore, Singapore Postoperative or postsurgical consenting for the research use of leftover surgically excised tissues was introduced for samples collected by the NUH-NUS Tissue Repository in 2006, following approval by the local IRB. Since this time, postoperative consenting has been carried out in cases where preoperative consenting was either difficult or impossible, as for example in patients who were admitted on the day of operation and patients undergoing emergency surgery. Between January 2006 and June 2008, a total of 299 patients were approached for postoperative consent and 34 declined (11.4%). Over the same period, 1299 patients were approached for preoperative consent and only 78 cases declined (6%). The decline rate for postoperative consenting was slightly higher, but in general, we find that this new approach has been well received by patients. One advantage of

postoperative consenting is that it avoids consenting patients whose operations do not yield useful tissue: Of the 1299 patients approached for preoperative consent, the operations only yielded useful tissue in 720 cases (55%). In contrast, of the 229 patients approached for postoperative consent, the operations yielded useful tissue in 299 cases (100%). Another advantage is of course that postoperative consent makes it possible to obtain research samples from a significant subset of patients for whom preoperative consenting is impossible.

LE7 Exploring the Need for a Universal Standardization of Good Storage Practices J. Mills BioStorage Technologies, Indianapolis, IN, USA Even though trial samples are critical to product research and development and donor programs, they are often handled precariously while in storage and transit. At various phases in development, biomaterials are handled by a number of storage and transit locations, including docks and airports. Coupled with the lack of conformity in industry standards for specimen handling and storage, providing “Good” storage at this point is relative as there is no standard for comparison. As the pharma and biotech world migrate toward more outsourcing, storage and specimen management will need to be scrutinized with the same level of integrity, transparency, and compliance. As with GLP, GMP, GCP, and GTP, there is a need to develop standards of Good Storage Practice (GSP) against which specimen management is audited and measured. As the rest of the regulated environment has evolved so has the importance of sample management to therapeutics. Specimen management therefore needs to be held to the same standards as other GXP environments. Although ISBER has initiated the process by instituting various measurement practices, the speaker will present a forward-looking perspective on the need to broaden regulation to all regulatory bodies across the globe. The following topics will be discussed: (1) Standards for temperature monitoring and mapping; (2) Standards for specimen transport; (3) Standards for health and safety in biorepositories; (4) Business continuity planning and testing; (5) Patient consent management

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(relevant to sample inventory); (6) Standards for data capture and flow; and (7) Equipment mapping and maintenance.

protection of subjects and ethical conduct of repository research.

LE9 LE8 National Institutes of Health (NIH) Efforts to Address Legal and Ethical Challenges Related to Human Specimen Repositories M. Bledsoe and A. Rives

Paperless Electronic Consenting and Biorepositories: The M.D. Anderson Experience E. Cushenberry and S. Hamilton University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

National Institutes of Health, Bethesda, MD, USA Background: Although the availability of human specimens and data present tremendous opportunities for research, there are significant legal and ethical challenges associated with broad sharing of these materials. In the United States, the use of human specimens and data may be governed by the Common Rule, the FDA human subjects regulations, and the Health Insurance Portability and Accountability Act Privacy Rule. However, there is no comprehensive federal policy that covers the full range of repository activities. Furthermore, there are inconsistencies among federal regulations and policies and they do not address some important ethical issues. Methods: The NIH Clinical Research Policy Analysis and Coordination Program (CRpac) is addressing these issues in various ways and plans to obtain input from stakeholders in repository research, including ISBER members. Results: The CRpac program has launched some efforts to address the legal and ethical challenges associated with human specimen repositories. These include the development of a draft policy framework that would apply to all NIH-supported repositories. In addition, a task force involving the regulatory and funding agencies within the Department of Health and Human Services has been established to explore the inconsistencies among federal regulations and policies related to specimen repositories. Finally, tools have been developed to help researchers, IRBs, and institutions understand how the various regulations and policies apply to human specimen repositories. Conclusions: Efforts of the CRpac program to address the legal and ethical issues associated with human specimen repositories should help facilitate repository research while promoting the

Background: The Tissue Procurement and Banking Facility (TPBF) at M.D. Anderson Cancer Center (MDACC) is a well-established NCI Cancer Center Support Grant (CCSG)-supported core facility that provides access to all basic science, translational, and clinical investigators to human tissues that have been removed by therapeutic resection or biopsy. Since 2003, 1800–2000 new and returning patients consent monthly to the Institutional Review Board (IRB)-approved Institutional Banking Protocol to facilitate tissue and/or body fluid collection. Methods: Discrepancies between the manually entered consent statuses in the consent database and the corresponding hard-copy consent forms resulted in an audit of the entire consent database. All recorded consents used by the TPBF were verified from the hard-copy source document (n = 8911) or those consents recorded in the database as invalid. Upon completion of the audit, the Institutional Banking Protocol consent process was restructured with development and implementation of a paperless electronic consent. Results and Conclusions: Specimens from patients without documented consent were destroyed (n = 21, 0.24%) based on the results of the audit. Since the paperless electronic system was put in place, the annualized number of cases collected based on the second quarter of 2007 was 4380, representing an increase of about 300 cases. From April 2007 to July 2008, 32,839 (95.57%) patients consented to the collection and storage of residual tissue and/or body fluid under the Institutional Banking Protocol. Patient responses to the Institutional Banking Protocol have now become a standard part of the electronic medical record including documentation of the actual consenting process.

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National and International Biobanking Networks NIN1 The Australasian Biospecimen Network Tissue Specimen Locator—Challenges Associated with the Development and Maintenance of a National Tissue Database 1

A. Matusan, 1L. Devereux, 2D. Catchpoole, 3 J. Creaney, 4A. deFazio, 5M. Fleming, 6C. Schmidt, 5H. Thorne, and 7N. Zeps

1

Australasian Biospecimen Network, Melbourne, Victoria, Australia, 2Children’s Hospital at Westmead, Westmead, New South Wales, Australia, 3University of Western Australia, Perth, Western Australia, Australia, 4University of Sydney at Westmead Millenium Institute, Westmead, New South Wales, Australia, 5Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia, 6Queensland Institute of Medical Research, Brisbane, Queensland, Australia, 7 St John of God Hospital, Subiaco, Western Australia, Australia ABN-Oncology, a subgroup of the Australasian Biospecimen Network, is an association of Australian Tissue Banks that collect biospecimens across a broad range of cancer types for cancer research. One of the aims of ABN-Oncology was the development of a Web-based specimen locator search page to create a single point of contact for researcher enquiries. The “Tissue Specimen Locator” (TSL) allows cancer researchers to search a national database for biospecimens stored in banks across the country that are available for research. This facility allows biorepositories to retain custodianship of specimens while increasing researcher awareness of individual biobanks. The TSL “went live” in 2006 (www.abrn.net/abnweb/OncologySearchPage.aspx). The TSL uses three categories: “Primary Cancer Type,” “Broad Morphology,” and “Sample Type” to search a database periodically updated with information from seven remote tissue banks across four states within Australia, and returns a results page indicating how many samples fitting their criteria are available and at which bank. The TSL has the scope to allow other tissue banks to join the network, and enables comprehensive management of all initial inquiries and requests from researchers. The ABN-Oncology has encountered a number of challenges associated with the development

and running of the TSL, including (1) the disparate nature of the remote tissue bank databases, (2) hospital firewalls designed to protect patient confidentiality, (3) data integrity, and (4) useability of the web interface. The ABN is now working to address these challenges following the feedback of both users/researchers and member tissue banks.

NIN2 The All-Ireland Cancer Biobank and Informatics Network: Controlling Quality in the First Phase 1

B. Mee, 2A. O’Grady, 2C. Heeney, 2E. Kay, 3 G. Callagy, and 1E. Gaffney

1

St James’s Hospital, Dublin, Ireland, 2Beaumont Hospital, Dublin, Ireland, 3University College Hospital Galway, Galway, Ireland

Introduction: The first phase of the all-Ireland cancer biobank network commenced in August 2008, following a Vodafone Ireland Foundation award. This enabled start-up of the cancer biobank at St. James’s Hospital (SJH), using the same honest broker approach and SOPs as Beaumont Hospital (BH). Methods: Vodafone is funding a biobank scientist to develop the SJH cancer biobank and begin the network. Consent, SOPs, QA, and logistics have been implemented as developed during the buyin phase. Grand round presentations and constant communication with researchers, senior management, and medical staff have gained enthusiastic support for the new hospital facility. Regular discussions are held with BH and University College Hospital Galway UCHG biobank personnel. The open source database CAISIS is being developed as the network database. Because sample quality ultimately depends on intact functioning of all links from patient consent to sample access, performing QC (RNA, DNA, proteins) is mandatory. Results: We are quantifying the approximate degradation of genetic material caused by assessable variables, for example, time and temperature. Currently, we are comparing the quantity and quality of RNA, DNA, and proteins in colon cancer specimens that arrived promptly with those from specimens subject to transport delays. The data will help us communicate to operating theatre staff how sample quality is enhanced by timely specimen delivery for biobanking.

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Comment: In identifying causes of individual sample genetic material degradation, QC will enable us to optimize sample quality. This will lead to the re-evaluation and improvement of logistics, SOPs, and specimen handling in the three hospitals.

NIN3 Biorepository for an International Research Registry for Sjogren’s Syndrome—Lessons Learned 1

Y. DeSouza, 1T.E. Daniels, 1J.S. Greenspan, 2 S. Challacombe, 3S. Daverio, 1D. Drury, 4 Y. Dong, 2L. Fernandes-Naglik, 5K. Fujimoto, 3 A. Heidenreich, 2B. Jacobs, 6S.P. Kreutzmann, 3 V. Kambo, 5T. Kawanami, 3H. Lanfranchi, 4 M. Li, 6A.M. Manniche, 2M. Mistry, 6 M. Schiødt, 5S. Sugai, 5H. Umehara, 1 E. Wong, 4Q. Wu, and 4Y. Zhao 1

University of California, San Francisco, San Francisco, CA, USA, 2King’s College, London, UK, 3University of Buenos Aires, Buenos Aires, Argentina, 4Peking Union Medical College, Beijing, China, 5Kanazawa Medical University, Kanazawa, Japan, 6Copenhagen University Hospital, Glostrup, Denmark The Sjögren’s International Collaborative Clinical Alliance (SICCA) Biorepository supports the first international registry for Sjögren’s syndrome. One goal of this project is to develop and maintain a biorepository of specimens collected from all participants and to develop a plan to distribute the specimens and relevant clinical data to qualified investigators. This presentation will describe the collection, processing, storage, and shipment of specimens within this registry, and the challenges inherent in International collaborations. These include IRB review and approval, shipment of samples to the United States, communications between groups and cultural issues. To ensure biospecimen integrity, a well-defined quality QA and QC program was developed to control for preanalytical variables that could be introduced during the collection, processing, storage, and shipment process. The QA Program of the SICCA Biorepository is an ongoing process that requires daily attention by all staff at all sites. Examples of some of the components of the repository QA program are equipment maintenance and repair records, training records of staff,

record keeping, specimen identification, labeling, and maintaining and updating SOP manuals. The QA and QC program of the SICCA Biorepository will be discussed. The research groups involved in the registry are located in Argentina, China, Denmark, Japan, United Kingdom, and the United States. This work is supported by NIH Contract # N01-DE-32636.

NIN4 Establishing a Global Biobank Infrastructure at AstraZeneca 1

C. Womack and 2B. Dahllof

1

AstraZeneca, Macclesfield, United Kingdom, 2 AstraZeneca, Molndal, Sweden

Background: Human tissue–based research supported by human biological sample (HBS) biobanking is well established at local AstraZeneca (AZ) sites. A coordinated global AZ biobank infrastructure was established in 2008. Methods: Following planned global review of existing biobanking processes at AZ and specific option appraisal for biobanking infrastructure, in 2008 it was recommended that each research and development (R&D) site implement a single biobank with an accountable site head. This is now complete and 11 site biobanks collectively form a global biobank with a separate leader accountable to a sponsor and high-level steering group. The global biobank will secure legal and ethical compliance; harmonize processes and tools; provide physical biobanking facilities; give input to policies and processes; optimize sample use; and identify and share best practice. Results: The R&D sites are in culturally diverse locations to enable global infrastructure development. The site biobank heads have clear goals and accountabilities and lead task forces in the following specific areas: supplier management; clinical strategies for biobanking; ethical and legal policy and positioning; optimizing use of HBS; infrastructure; information technology coordination and strategies; and processes, standard operating procedures, and internal guidelines. Conclusions: Building on local experience, a global corporate biobank is enabling the application of consistent legal and ethical standards, coordinated acquisition, collective storage, and optimizing the human tissue resource respecting the wishes of those who have so generously donated.

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NIN5 Establishment of a Pulmonary Biobank Consortium (PBC) 1 5

C. Villena, 2F. Pozo, 3J. Albert Barberà, 4J. Gea, G. Peces-Barba, 6E. Monsó, 7 T. Rosell, 8J. Rello, 9 A. Esteban, 10J. Cortijo, 11S. Jaume, and 12 A. Agustí

1

Spanish Respiratory Research Network (CIBERES), Palma de Mallorca, Balearic Islands, Spain, 2Hospital Universitario 12 Octubre. CIBERES, Madrid, Spain, 3IDIBAPS-Hospital Clinic. University of Barcelona, CIBERES, Barcelona, Spain, 4Hospital del Mar, Fundación IMIM, CIBERES, Barcelona, Spain, 5Fundación Jiménez Díaz-CAPIO, CIBERES, Madrid, Spain, 6Hospital Germans Trias i Pujol. IGTP.CIBERES, Badalona, Spain, 7Hospital Universitario de Bellvitge. CIBERES, Hospitalet de Llobregat, Barcelona, Spain, 8Joan XXIII University Hospital. CIBERES, Tarragona, Spain, 9Hospital Universitario Getafe. CIBERES, Getafe, Madrid, Spain, 10University of Valencia, University General Hospital Consortium.CIBERES, Valencia, Spain, 11 Hospital Universitario Son Dureta. Fundación Caubet-Cimera, CIBERES, Palma de Mallorca, Spain, 12 Hospital Clínic, Universitat de Barcelona, CIBERES, Barcelona, Spain Pulmonary Biobank Consortium is an initiative of Spanish Respiratory Research Network (CIBERES) in order to provide lung tissue and associated biological samples (sputum, bronchoalveolar lavage, concentrated exhaled, serum, plasma, and blood) with appropriate clinical information to be used by national and international researchers. Lung tissue samples are obtained in collaboration with thoracic surgeons, pathologists, and pneumologists of each hospital in the first 30–45 min from lung resection. Other biological samples and clinical information are acquired during routine clinical assistance. The clinical information registered with the specimens includes lung function test (spirometry, diffusion, volumes, and blood gases), smoking history, anthropometric data, clinical diagnosis, indication for surgery, past 30 days treatment, hemogram, TAC image, and diagnosis. The scientific coordination is centralized with the support of an informatics platform on-line. This platform is a database and a management tool which controls the location of samples and helps to select the best samples for each research project. The

distribution of the samples and the activities of the Pulmonary Biobank Consortium are regulated by an external scientific committee and an external ethical committee. So far, this initiative is supported by 10 research groups in Spain, each of which collects and stores samples. Moreover, we are in process to include more institutions. We started our activity in the first months of 2008, and at the end of 2009 we expect to collect about 10,000 samples from 700 donors.

NIN6 Victorian Cancer Biobank: Providing Fresh Tissue from Operating Theatre to Research Laboratory in 4 h 1

3

A. Thompson, 1Z. Squire, 2S. Cauberg, C. Murone, 4M. Chapman, and 5P. Mamers 1

Victorian Cancer Biobank, Carlton, Victoria, Australia, 2Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia, 3Austin Hospital, Heidelberg, Victoria, Australia, 4Royal Melbourne Hospital, Parkville, Victoria, Australia, 5Southern Health, Bentleigh East, Victoria, Australia The Victorian Cancer Biobank (Biobank) is a large-scale tissue-banking facility built on the expertise of four Consortium member tissue banks. The Biobank’s unique operational model integrates a multisite collection system with a centrally managed application process that streamlines access to biospecimens by researchers in academia and industry, within Australia and internationally. An extensive collection network of 19 public and private hospitals enables the Biobank to support multicenter clinical and translational research projects. At each site, staff can consent donors for tissue for future research and collaborate with clinicians to collect tissue for clinical trial protocols. In addition to supporting clinical research and providing archival material from cryostorage, the collection network also enables fresh tissue to be supplied throughout metropolitan Melbourne to researchers who were previously isolated from the hospital setting. The timely delivery of fresh tissue requires careful planning and coordination. Tissue bank staff monitors surgical lists and notifies researchers of potentially suitable specimens that may become available. Specimens obtained are placed in culture media on ice and delivered by medical courier within 4 h of surgery. Since January 2008, the

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Biobank has been supplying fresh tissue and the demand has steadily increased with 439 specimens being provided to researchers across 12 tumor streams in the first 12 months. Only material from donors who have given explicit consent for the generation of cell lines from their blood and tissue is supplied.

of our NSCLC cases. However, tumor cell content was lower, especially in squamous cell carcinoma histology. The difference found in tumor cell content between squamous cell carcinoma and adenocarcinoma reflects the morphological heterogeneity of NSCLC. Supported by NCI-UTLung SPORE and DoD PROSPECT grants.

Quality Assurance and Control

QAC2

QAC1

Rapid Cytology Smears for Immediate Quality Assessment Improves Quality of Lesional Tissue Submitted to the Human Tissue Repository

Importance of Histopathology Quality Control of Non-Small Cell Lung Cancer Tissue Specimens for DNA/RNA Extraction and Profiling Analysis M. Gabriela Raso, A. Corvalan, C. Behrens, A. Basey, G. Mendoza, J. Roth, C. Moran, and I. Wistuba University of Texas M.D. Anderson Cancer Center, Houston, TX, USA Introduction: High-throughput molecular profiling technologies require good quality tumor tissue samples. To achieve these high standards in our tissue bank, we have in place a series of quality control activities, including detailed pathology analysis in frozen tissue specimens. Materials and Methods: From more than 1500 primary non–small cell lung cancer (NSCLC) tumor frozen tissue samples collected from 1997 to 2007, we selected a subset of 492 cases stored in liquid nitrogen vapor phase. DNA and RNA were extracted and quantified using a bioanalyzer system (Agilent). Before DNA/RNA extraction, we performed a detailed histopathology quality control of the frozen tissues to assess percentage of tumor tissue, tumor cells, normal tissue, necrosis, fibrosis, and inflammation. Results: Tumor >70% was present in 82% of the NSCLC specimens. Tumor cell content >50% was present in 64% (n = 284 cases) of NSCLCs, being 68% in adenocarcinomas (n = 211 cases) and 54% (n = 73 cases) in squamous cell carcinomas. Thirty-eight percent of adenocarcinomas and 48% of squamous cell carcinomas showed 100% tumor tissue content. About 10%–30% of normal parenchyma was present in 43% of both histologies. From 311 tumor samples in which RNA integrity number (RIN) was obtained, RIN > 8 was found in 26% and RIN > 5 in 51%. Conclusion: The required minimum standard for tumor content (>70%) was achieved in most

J. Glass University of New Mexico Department of Pathology, Albuquerque, NM, USA Background: Our study evaluated using rapid cytology smears to improve the quality of lesional tissue submitted to the UNM human tissue repository (immediate QA). Methods: At the time of tissue collection, a small (90% necrosis. Blocks were considered less than optimal (LTO), if they contained