Towards harmonized biobanking for biomonitoring : a comparison of human biomonitoring-related and clinical biorepositories

Towards Harmonized Biobanking for Biomonitoring: A Comparison of Human Biomonitoring-Related and Clinical Biorepositories Dominik Lermen, 1–3 Frederik Gwinner, 1,3 Martina Bartel-Steinbach, 1,3 Sabine C. Mueller, 1,3 Jens K. Habermann, 2,4 Matharoo-Ball Balwir, 2,5 Elke Smits, 2,6 Ana Virgolino, 3,7 Ulrike Fiddicke, 3,8 Marika Berglund, 3,9 Agneta A ˚kesson, 3,9 Anna Bergstrom, 3,9 Karin Leander, 3,9 Milena Horvat, 3,10 Janja Snoj Tratnik, 3,10 Manuel Posada de la Paz, 3,11 Argelia Castan˜o Calvo, 3,12 Marta Esteban Lo´pez, 3,12 Hagen von Briesen, 1,3 Heiko Zimmermann, 1,3 and Marike Kolossa-Gehring 3,8 Human biomonitoring (HBM) depends on high-quality human samples to identify status and trends in exposure and ensure comparability of results. In this context, much effort has been put into the development of standardized processes and quality assurance for sampling and chemical analysis, while effects of sample storage and shipment on sample quality have been less thoroughly addressed. To characterize the currently applied storage and shipment procedures within the consortium of the European Human Biomonitoring Initiative (HBM4EU), which aims at harmonization of HBM in Europe, a requirement analysis based on data from an online survey was conducted. In addition, the online survey was addressed to professionals in clinical biobanking represented by members of the European, Middle Eastern and African Society for Biopreservation and Biobanking (ESBB) to identify the current state-of-the-art in terms of sample storage and shipment. Results of this survey conducted in these two networks were compared to detect processes with potential for optimization and harmonization. In general, many similarities exist in sample storage and shipment procedures applied by ESBB members and HBM4EU partners and many requirements for ensuring sample quality are already met also by HBM4EU partners. Nevertheless, a need for improvement was identified for individual steps in sample storage, shipment, and related data management with potential impact on sample and data quality for HBM purposes. Based on these findings, recommendations for crucial first steps to further strengthen sample quality, and thus foster advancement in HBM on a pan-European level are given. Keywords: biobanking, harmonization, sample quality, standardization, human biomonitoring, HBM4EU 1 Fraunhofer Institute for Biomedical Engineering IBMT, Biomonitoring & Biobanks, Sulzbach, Germany. 2 European, Middle Eastern & African Society for Biopreservation and Biobanking, Brussels, Belgium. 3 The European Human-Biomonitoring Initiative HBM4EU. 4 University Clinical Center Schleswig-Holstein, University of Luebeck, Translational Surgical Oncology and Biobanking, Luebeck, Germany. 5 Nottingham University Hospital, Translational Research and Nottingham Health Science Biobank (NHSB), Nottingham, United Kingdom. 6 Antwerp University Hospital, University of Antwerp, Division of Medical Director, Edegem, Belgium. 7 Faculdade de Medicina, Instituto de Sau ´de Ambiental, Universidade de Lisboa, Lisboa, Portugal. 8 German Environment Agency (Umweltbundesamt), Berlin, Germany. 9 Institute of Environmental Medicine, Karolinska Institute, Institute of Environmental Medicine (IMM), Stockholm, Sweden. 10 Joz ˇef Stefan Institute, Department of Environmental Sciences, Ljubljana, Slovenia. 11 Institute of Rare Diseases Research, CIBERER, EuroBiobanK, Instituto de Salud Carlos III, Madrid, Spain. 12 Centro Nacional de Sanidad Ambiental CNSA, Instituto de Salud Carlos III, Majadahonda, Spain. ªDominik Lermen et al., 2020; Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms of the Creative Commons Attribution Noncommercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are cited. BIOPRESERVATION AND BIOBANKING Volume 18, Number 2, 2020 Mary Ann Liebert, Inc. DOI: 10.1089/bio.2019.0092 122 Introduction Human biomonitoring, the analysis of human samples for exposure to chemicals and/or their metabolites, provides a scientific basis for risk assessment and, if necessary, the derivation of mitigation measures. At a European scale, comparable and reliable data on human exposure from European Union countries are urgently needed. The European Initiative for Human Biomonitoring (HBM4EU) started work on January 1, 2017, to close data gaps on priority environmental pollutants in the European population and to provide sound scientific data as a basis for policy decisions. HBM4EU, co-funded under Horizon 2020, is a joint project of 30 mainly European countries, the European Environment Agency, and the European Commission. One of the aims of the initiative is the harmonization of preanalytical and analytical processes in human biomonitoring (HBM) across Europe and to increase knowledge transfer between scientists, politicians, stakeholders, and the general public. 1–3 Several European countries have been conducting HBM studies during the last decades, whereas such studies are still lacking in others. Since a full characterization of all substances humans are exposed to is not feasible, studies (e.g., from Germany, France, Spain, Czech Republic, Belgium, and Slovenia) have been covering only a selected number of environmental pollutants at the time. 4 Therefore, previous HBM studies differ largely between individual countries pertaining to the target population, questionnaires, matrices, and analytes. First, endeavors toward the harmonization of HBM research across Europe were made in the projects COPHES and DEMOCOPHES. 5,6 For the first time, samples from 120 mother-child pairs were collected in 17 European countries following a consensus protocol describing harmonized sampling and preparation, common questionnaires, and data analysis among others. Six biomarkers (mercury, creatinine, cotinine, cadmium, phthalate metabolites, and bisphenol A) 4 were analyzed according to standardized protocols and strong quality assurance (QA)/ quality control (QC) measures. A quality assurance unit (QAU) was set up to guarantee the reliability and comparability of analytical results. The QAU implemented an Inter-laboratory Comparison Investigation and External Quality Assessment Schemes (ICI/EQUAS) program involving reference laboratories from all over the world 5,7 Biobanking, the shortand long-term storage of human samples under cryogenic conditions, plays a critical role in the preanalytical phase of HBM studies. In contrast to what has long been happening in medical research, where biobanking and related preanalytical processes have been playing an important role for many years, in HBM, the relevance of using standardized biobanking procedures has only been recognized in the last 10 years. Therefore, a transfer of the well-established methods and standards, which are already in place in medical research, would be beneficial for the emerging field of HBM research. Although several online surveys have been conducted to address missing knowledge on the extent of biobanking in Europe, HBM-specific biobanking activities have not been included so far. 8–10 The HBM4EU initiative comprises important HBM key players in Europe, and hence offers a unique opportunity to gather knowledge on harmonization and optimization needs to improve HBM-related biobanking. In this context, we conducted a requirement analysis regarding sample storage and sample shipment through an online questionnaire addressed to all HBM4EU partners. In addition, the current state-of-the-art methods for sample storage and shipment as applied by professionals in clinical biobanking were assessed by an online questionnaire addressed to members of the European, Middle Eastern and African Society for Biopreservation and Biobanking (ESBB). ESBB provides a scientific network to advance BIOSHARING for a better world through mobilizing, inspiring, and educating the biobank community across Europe, Middle Eastern, and Africa. ESBB is open for everyone interested in all aspects of biobanking and biopreservation of biological resources (human, animal, plant, microbial, and environmental), including biobank management, QA and preanalytics, automation, IT solutions, research and innovation, education, ethical, legal, regulatory, and social issues. Members represent the full spectrum of individuals, academic institutions, and companies, whereas a substantial part of members represents clinical-related biorepositories (ESBB; www.esbb.org). Results of these surveys were used to develop a strategy document for human sample exchange between partners as a deliverable of the HBM4EU project. In this study, we present and discuss the main findings of this HBM4EU deliverable report D7.2 Strategy and Standard Operating Procedures (SOPs) for human sample exchange, including ethical demands. 11 To the best of our knowledge, a comparison of practices applied in HBM-related and clinical biorepositories was not reported so far. Besides offering insights into differences and similarities, our results may provide ideas and opportunities for harmonizing and optimizing processes in the emerging field of biobanking for HBM purposes. Materials and Methods Survey design A cross-sectional online survey was developed on the web-based platform LimeSurvey. The survey was accessible through a link to the online platform for HBM4EU partners and ESBB members. The cover page of the survey stated the context of the study, asked for participant’s consent to the use of the supplied responses, and confirmed anonymous treatment of participant’s responses. A link to the HBM4EU survey website was disseminated by email to HBM4EU partners by the National Hub Contact Point (NHCP) with a short description of the purpose of the survey, instructions to forward the link to any HBM4EU repository contact not yet addressed, and a deadline for completing the survey within a period of 3 months. A link to the ESBB survey website was distributed through email to ESBB members by the ESBB office, with the same instructions as in the case of the HBM4EU survey. HBM4EU partners and ESBB members were asked to forward the email specifically to the person responsible for the operation of the respective biobank. The survey consisted of 28 closed-form questions in either single-choice (SC) or multiple-response (MR) form, with most questions additionally allowing an open-form (OF) answer by choosing the option ‘‘other’’ and filling in free-form text. The survey was structured into six blocks representing the following topics: Biorepository Background, Legal and Ethical Considerations, Sample Types and Aspects of Sample Storage, Sample Shipment, Data Management, and Quality Management. TOWARDS HARMONIZED BIOBANKING FOR BIOMONITORING 123 The survey addressed to HBM4EU partners was identical to the survey for ESBB members, except for the omission of the block on Biorepository Background, which had already been included in a previous survey (HBM4EU Task 7.1 survey) completed by 43 biobanks participating in HBM4EU. 12 The previous survey was carried out from March to the end of May 2017, the HBM4EU and ESBB surveys were open from September to the end of November 2017. As the study aimed to identify the status quo of HBMrelated biobanks and to compare it with the current state-ofthe-art in biobanking of ESBB members, the block on Sample Types and Aspects of Sample Storage focused on the five matrices most relevant in HBM research (whole blood, plasma, serum, 24-hour urine, and spot urine). Within this block, questions about storage conditions (temperature, containers, and duration) were asked once per individual matrix the participants had stated to store. Data analysis Answers to the survey questions were exported in csv format and read into R (version 3.2.3) for further analysis. Survey results are presented in the results section in tabular form ordered by question blocks. For each question, the type of question (SC, MR, or OF) and the total number of survey participants the question was presented to are noted in the table header. The ratio and percentage (in brackets) of survey participants choosing a given answer are shown in the body of the table. The number of survey participants not providing an answer to a given question is noted under the answer option ‘‘no answer.’’ Results The following sections detail the results extracted from the survey responses. The first section describes completion rates of the survey and the subsequent sections detail the results of the individual question blocks the surveys were composed of. Completion rate Forty-five responses of distinct biobanks were received from HBM4EU partners, out of which 36 were considered valid (seven responses contained answers to less than 30% of the survey questions and two responders did not agree to anonymize publication of their supplied data). The 36 valid responses answered at least 60% of the survey questions (mean completion rate: 83%). Thirty-two out of the 36 valid responses were supplied by biobanks that had already participated in the previous HBM4EU Task 7.1 survey. 12 The remaining four responses came from HBM4EU-partnered biobanks that had not been reached by the previous survey. Twenty-nine responses of distinct biobanks were received from ESBB members, out of which 28 were valid (one responder did not agree to anonymize publication of their supplied data). The 28 valid responses answered at least 70% of the survey questions (mean completion rate: 92%) (Table 1). Biorepository background Responses to the surveys indicate that the majority of both, biorepositories of HBM4EU and biorepositories of ESBB members who filled in the questionnaire, are hosted by public institutions (Table 2, Q1). HBM-related biorepositories identified by this survey are mostly operating within research institutes, whereas most biorepositories for clinical purposes are based in hospitals, universities, or research institutes (Table 2, Q2). The majority of HBM4EU repositories are operated as a single and individual repository, whereas ESBB members reported to operate mostly centralized biorepositories that store samples from multiple independent projects (Table 2, Q3). The host institution is most commonly offering not only biobanking services but also offers related processes and services ranging from sampling, sample processing, and biobanking to the analysis of samples (Table 2, Q4). A major difference between ESBB and HBM4EU biorepositories is the target population. Based on the aim to reveal the actual exposure and its effects on human health, HBM4EU responses clearly focus on the general population. In contrast, biorepositories of ESBB members participating in the survey mainly target samples from patients or clinical cohorts (Table 2, Q5). As a consequence, the design of their studies also revealed differences. While HBM studies mostly follow a cross-sectional or longitudinal study design, in clinical biorepositories case–control, case-only, and clinical trial studies are equally well represented (Table 2, Q6). Only a very small number of HBM4EU partner biorepositories were members of a biobanking society, for example, of the ESBB and the International Society for Biological and Environmental Repositories (ISBER), or participated in the Biobanking and Biomolecular Resources Research Infrastructure – European Research Infrastructure Consortium (BBMRI-ERIC). To gain insight in clinical biobanking, we addressed the questionnaire to ESBB members. In addition to ESBB, some of the biorepositories responded to also be a member of ISBER and/or BBMRI-ERIC (Table 2, Q7). Legal and ethical considerations The use of human samples for research purposes postulates the prior informed consent of the sample donor. This can be Table 1. Overview of Survey Participation HBM4EU Task 7.1 survey HBM4EU survey ESBB survey Number of responses 43 45 29 Insufficient answers (<30% of questions answered) 0 7 0 Agreement to publication of data lacking 0 2 1 Valid responses 43 36 (32/36 biobanks also surveyed by Task 7.1) 28 ESBB, European, Middle Eastern and African Society for Biopreservation and Biobanking; HBM4EU, European Human Biomonitoring Initiative. 124 LERMEN ET AL. Table 2. Biorepository Background Type of institution Q1—SC HBM4EU (n=36) ESBB (n=28) Public 34/35 (97%) 24/28 (86%) Private 1/35 (3%) 4/28 (14%) Other 0/35 (0%) 0/28 (0%) No answer 1 0 Host institution of the biorepository Q2—MR HBM4EU (n=36) ESBB (n=28) Hospital 5/36 (14%) 13/28 (46%) University 6/36 (17%) 10/28 (36%) Research institute 20/36 (56%) 13/28 (46%) Patient’s association 0/36 (0%) 0/28 (0%) Company 1/36 (3%) 2/28 (7%) Other 8/36 (22%) 1/28 (4%) Organizational format Q3—SC HBM4EU (n=36) ESBB (n=28) Single individual biorepository 23/33 (70%) 4/28 (14%) Centralized biorepository (storing samples from multiple independent projects) 8/33 (24%) 21/28 (75%) Other 2/33 (6%) 3/28 (11%) No answer 3 0 Carried out activities at the facility/biorepository Q4—MR HBM4EU (n=36) ESBB (n=28) Sample collection 30/35 (86%) 23/28 (82%) Sample preparation 26/35 (74%) 25/28 (89%) Storage 34/35 (97%) 28/28 (100%) Sample shipment 24/35 (69%) 25/28 (89%) Analysis 25/35 (71%) 18/28 (64%) Other 3/35 (9%) 4/28 (14%) No answer 1 0 Target population of studies from which samples are stored Q5—MR HBM4EU (n=43, previous survey) ESBB (n=28) General population 42/43 (98%) 11/28 (39%) Clinical population 3/43 (7%) 23/28 (82%) Other 5/43 (12%) 3/28 (11%) Design of studies from which samples are stored Q6—MR HBM4EU (n=43, previous survey) ESBB (n=28) Cross-sectional 17/42 (40%) 12/28 (43%) Longitudinal 24/42 (57%) 17/28 (61%) Case–control 5/42 (12%) 10/28 (36%) Case-only 0/42 (0%) 13/28 (46%) Clinical trial 0/42 (0%) 9/28 (32%) Other 5/42 (12%) 6/28 (21%) No answer 1 0 Is your institution a registered member of a biobanking society or infrastructure? Q7—MR HBM4EU (n=36) ESBB (n=28) ESBB 2/36 (6%) 26/28 (93%) BBMRI-ERIC 3/36 (8%) 10/28 (36%) ISBER 2/36 (6%) 10/28 (36%) Other 3/36 (8%) 5/28 (18%) None 29/36 (81%) 0/28 (0%) Presented are the type of question (SC; MR), the total number of survey participants, as well as ratio and percentage (in brackets) of survey participants choosing a given answer. The number of survey participants not providing an answer is noted under ‘‘no answer.’’ The information marked in bold is the most relevant result. BBMRI-ERIC, the Biobanking and Biomolecular Resources Research Infrastructure – European Research Infrastructure Consortium; ISBER, International Society for Biological and Environmental Repositories; MR, multiple response question; SC, single choice question. 125 either specific and allow only the use of samples for a welldefined set of analysis or can be broad to allow sample usage for a much wider range of analyses, even for such analysis not directly affiliated with the original research question. Results of our survey indicate specific and broad consents to be applied in HBM as well as in medical research. Currently, broad consents seem to be the preferred consent type used by ESBB-affiliated biorepositories (Table 3, Q1, Q2). We further asked which legal and ethical documents are available for the collections. Nearly all ESBB-registered biorepositories reported to have ethical approval forms (86%), informed consent forms (86%), and Material Transfer Agreements (MTAs, 82%), as well as data protection (57%) and biobank approvals (68%) available for the majority of collections. In medical research, MTAs are well-established tools to ensure legally approved sample exchange, as our results confirm (Table 3, Q4). However, only 47% of biorepositories of the HBM4EU consortium reported the use of MTAs. Data protection as well as biobank approvals were also lacking (Table 3, Q3). Sample types and aspects of sample storage Sample types. Since whole blood, plasma, serum, 24-hour urine, and spot urine are often used sample types in HBM, the block on technical storage aspects focused on these sample types. Interestingly, besides collecting other sample types (like e.g., cell isolates, cell lines, and tissues), HBMrelevant sample types have also been collected by surveyed biorepositories in the ESBB community (Table 4, Q1). Furthermore, these samples are usually stored by ESBB biorepositories using similar supplements as HBM4EU biorepositories (EDTA or Na/Li-Heparin for whole blood and plasma samples, no supplement added to serum and urine samples, data not shown). Storage infrastructure. Both surveyed groups still use a wide variety of sample containers (Table 4, Q3). However, not all containers are suited for cryopreservation of samples using liquid nitrogen (LIN) as the cooling agent. Therefore, the use of specific container types indicates widespread sample storage at temperatures above -130C. In clinical Table 3. Legal and Ethical Considerations Type of broad consent Q1—MR HBM4EU (n=43, previous survey) ESBB (n=28) No broad consent 17/43 (40%) 4/27 (15%) Written informed consent 25/43 (58%) 22/27 (81%) Parents’ written consent 17/43 (40%) 10/27 (37%) Oral consent 1/43 (2%) 2/27 (7%) Other 0/43 (0%) 5/27 (19%) No answer 0 1 Type of specific consent Q2—MR HBM4EU (n=43, previous survey) ESBB (n=28) No specific consent 18/43 (42%) 8/25 (32%) Written informed consent 24/43 (56%) 15/25 (60%) Parents’ written consent 15/43 (35%) 5/25 (20%) Oral consent 0/43 (0%) 1/25 (4%) Other 0/43 (0%) 5/25 (20%) No answer 0 3 Which of the following documents are available Q3—MR HBM4EU (n=43, previous survey) ESBB (n=28) Ethics approval 42/43 (98%) 24/28 (86%) Informed consent 42/43 (98%) 24/28 (86%) Data protection approval 0/43 (0%) 16/28 (57%) Biobank approval 0/43 (0%) 19/28 (68%) Material transfer agreement 20/43 (47%) 23/28 (82%) Other 0/43 (0%) 7/28 (25%) Are terms and conditions for authorized sample usage defined in an MTA? Q4—SC HBM4EU (n=36) ESBB (n=28) No 11/32 (34%) 2/27 (7%) Yes 17/32 (53%) 22/27 (81%) Other 4/32 (13%) 3/27 (11%) No answer 4 1 Presented are the type of question (SC; MR), the total number of survey participants, as well as ratio and percentage (in brackets) of survey participants choosing a given answer. The number of survey participants not providing an answer is noted under ‘‘no answer.’’ The information marked in bold is the most relevant result. MTA, Material Transfer Agreement. 126 LERMEN ET AL. Table 4. Sample Types and Aspects of Sample Storage What type of biological samples/matrix do you store? Q1—MR HBM4EU (n=36) ESBB (n=28) Whole blood 24/34 (71%) 16/26 (62%) Plasma 24/34 (71%) 21/26 (81%) Serum 21/34 (62%) 19/26 (73%) Urine (24 hours) 8/34 (24%) 11/26 (42%) Urine (spot sample) 23/34 (68%) 9/26 (35%) Other 11/34 (32%) 20/26 (77%) No answer 2 2 How long are your samples stored? Q2—MR HBM4EU (n=36) ESBB (n=28) No storage 0/35 (0%) 1/27 (4%) Short-term storage 10/35 (29%) 7/27 (26%) Long-term storage 33/35 (94%) 26/27 (96%) Other 1/35 (3%) 1/27 (4%) No answer 1 1 What type(s) of sample container(s) do you use? (only shown to participants storing HBM-relevant samples) Q3—MR HBM4EU (n=34) ESBB (n=21) Cryo-vials 13/32 (41%) 15/20 (75%) Falcon/Corning tubes 10/32 (31%) 3/20 (15%) Glass tubes/vials 4/32 (13%) 1/20 (5%) Plates 1/32 (3%) 0/20 (0%) Plastic bags/containers 3/32 (9%) 0/20 (0%) Sterile containers 6/32 (19%) 5/20 (25%) Straws 0/32 (0%) 2/20 (10%) Tubes of type Eppendorf 8/32 (25%) 2/20 (10%) Vacutainer 8/32 (25%) 5/20 (25%) Other 5/32 (16%) 6/20 (30%) No answer 2 1 At what temperature are samples stored for short-term storage? (only shown to participants short-term storing HBM-relevant samples) Q4—MR HBM4EU (n=25) ESBB (n=16) Not applicable 4/25 (16%) 1/16 (6%) Room temperature 1/25 (4%) 2/16 (12%) Refrigerator +4C5/25 (20%) 3/16 (19%) Freezer -20C13/25 (52%) 5/16 (31%) Freezer -80C9/25 (36%) 13/16 (81%) LIN, gas phase 0/25 (0%) 4/16 (25%) LIN, liquid phase 1/25 (4%) 1/16 (6%) Other 1/25 (4%) 1/16 (6%) At what temperature are samples stored for long-term storage? (only shown to participants long-term storing HBM-relevant samples) Q5—MR HBM4EU (n=32) ESBB (n=16) Not applicable 0/32 (0%) 1/16 (6%) Room temperature 0/32 (0%) 0/16 (0%) Refrigerator +4C 0/32 (0%) 0/16 (0%) Freezer -20C12/32 (38%) 2/16 (12%) Freezer -80C23/32 (72%) 16/16 (100%) LIN, gas phase 2/32 (6%) 5/16 (31%) LIN, liquid phase 2/32 (6%) 4/16 (25%) Other 2/32 (6%) 0/16 (0%) (continued) 127 biobanking, the use of cryovials is much more common than in HBM-related biobanking. Long-term storage is of great importance for the HBM4EU consortium as well as for the ESBB community (Table 4, Q2). Within the HBM4EU initiative, most partners (72%) use electrical freezers for long-term storage at -80C for at least one sample type (Table 4, Q5). Nevertheless, long-term storage at -20Cis also very prominent (38%). The latter is less common in ESBB biorepositories (12%), who all use electrical freezers at -80C for storage of at least one sample type. Thirty-one percent of ESBB biorepositories additionally operate LINbased infrastructures for long-term storage, which allow storage of samples at temperatures below -130C, while the percentage of HBM4EU biorepositories capable of storage in LIN-based systems below -130C is low (6%). Sample labeling. Barcodes printed on cryo-compatible labels are widely applied in clinical as well as in HBM biobanking. However, handwritten labels are still used by almost a third of the surveyed HBM4EU-affiliated biorepositories (Table 4, Q6). Pseudonymization is a procedure by which the most identifying fields within a data record are replaced by one or more artificial identifiers, or pseudonyms. The purpose is to render the data record less identifying. The pseudonym allows tracking back of data to its origins, which distinguishes pseudonymization from anonymization where all person-related data that could allow backtracking have been purged. Survey responses indicate that sample labels are either anonymized or pseudonymized in both communities, HBM4EU and ESBB (Table 4, Q7). Sample shipment HBM4EU partners and ESBB members have been shipping nonregulated and/or samples that are classified as category B samples (Diagnostic specimens, assigned to UN 3373) most frequently (Table 5, Q1). To inform the receiver before shipment is well established in both surveyed communities (Table 5, Q3). The sample transfer protocol (manifest) serves as a control sheet and gives a detailed summary of all samples to be shipped. In the ESBB community, 87.5% of surveyed biorepositories send a manifest to prospective sample recipients, whereas only 59% of HBM4EU-partnered biobanks use manifests (Table 5, Q4). Where manifests are used, HBM4EU partners and ESBB members do, however, include a comparable degree of detail (Table 5, Q5). An important parameter for assuring the sample quality is the recording (logging) of the temperature during sample shipment. Although some biorepositories of both communities log the temperature either at sending and reception or continuously, still 54% of responding ESBB members and 65% of HBM4EU partners do not log shipment temperature at all (Table 5, Q6). Data management The majority of both interviewed communities already use a data management system—either by a homemade solution or a database with respective management software (Table 6, Q1). Most of the HBM4EU partners (54%) use homemade solutions (e.g., Excel sheets) for the documentation of sample-linked data, whereas the majority of ESBB members (75%) store these data in professional databases. Aside from the technical implementation of sample management systems, the degree of detail stored about a sample’s history is an important parameter as well. Table 6, Q2, displays the percentage to which individual sample history items are collected and stored by surveyed HBM4EU and ESBB biorepositories. Currently, the sampling year, the date of sample receipt at the repository, the source of the sample, and the storage temperature are consistently stored by most surveyed biobanks. A very high proportion of surveyed ESBB biorepositories reported to record all of the items on sample history included in the survey question (for details see Table 6, Q2). A more differentiated picture emerges in HBM biobanking, where individual aspects with high relevance for QA (e.g., total storage duration, thaw and Table 4. (Continued) Design of the primarily used sample label Q6—SC HBM4EU (n=36) ESBB (n=28) Handwritten 11/36 (31%) 2/28 (7%) Registration number 12/36 (33%) 5/28 (18%) 1D barcode 10/36 (28%) 12/28 (43%) Data matrix 2/36 (6%) 6/28 (21%) QR code 1/36 (3%) 2/28 (7%) Other 0/36 (0%) 1/28 (4%) Sample label ensures data protection/privacy through . Q7—SC HBM4EU (n=36) ESBB (n=28) Anonymization 20/33 (61%) 12/28 (43%) Pseudonymization 13/33 (39%) 14/28 (50%) Other 0/33 (0%) 2/28 (7%) No answer 3 0 Presented are the type of question (SC; MR), the total number of survey participants, as well as ratio and percentage (in brackets) of survey participants choosing a given answer. The number of survey participants not providing an answer is noted under ‘‘no answer.’’ The information marked in bold is the most relevant result. 1D, one dimensional; HBM, human biomonitoring; LIN, liquid nitrogen. 128 LERMEN ET AL. Table 5. Sample Shipment What type of samples do you regularly exchange with other institutions? Q1—MR HBM4EU (n=36) ESBB (n=28) Nonregulated samples 16/30 (53%) 12/24 (50%) Category B samples 16/30 (53%) 14/24 (58%) Category A samples 1/30 (3%) 2/24 (8%) Other 1/30 (3%) 1/24 (4%) No answer 6 4 What packaging do you use? Q2—MR HBM4EU (n=36) ESBB (n=28) Compliant with PI 620 1/24 (4%) 3/21 (14%) Compliant with PI 650 12/24 (50%) 14/21 (67%) Compliant with PI 650 light 1/24 (4%) 4/21 (19%) Compliant with PI 959 1/24 (4%) 4/21 (19%) Regular parcel 8/24 (33%) 7/21 (33%) Other 3/24 (13%) 2/21 (10%) No answer 12 7 Do you inform the recipient before sample shipment? Q3—SC HBM4EU (n=36) ESBB (n=28) Yes 29/30 (97%) 24/24 (100%) No 1/30 (3%) 0/24 (0%) No answer 6 4 Do you send an electronic manifest to the recipient before sample shipment? Q4—SC HBM4EU (n=36) ESBB (n=28) Yes 16/27 (59%) 21/24 (87.5%) No 11/27 (41%) 3/24 (12.5%) No answer 9 4 What information does this manifest include? (only participants answering Q4 with yes) Q5—MR HBM4EU (n=16) ESBB (n=21) Name and contact details of shipper 15/16 (94%) 19/20 (95%) Name and contact details of recipient 13/16 (81%) 17/20 (85%) Shipping temperature 10/16 (62%) 15/20 (75%) Date of sample shipment 14/16 (88%) 18/20 (90%) Biological substance category 9/16 (56%) 11/20 (55%) Sample type 15/16 (94%) 20/20 (100%) Sample ID 13/16 (81%) 20/20 (100%) Sample volume 12/16 (75%) 19/20 (95%) Type of sample container 5/16 (31%) 10/20 (50%) Number of samples and/or aliquots 15/16 (94%) 19/20 (95%) Prior informed consent 2/16 (12%) 5/20 (25%) Material transfer agreement 6/16 (38%) 11/20 (55%) Other 1/16 (6%) 1/20 (5%) No answer 0 1 How do you log sample temperature when shipping samples Q6—MR HBM4EU (n=36) ESBB (n=28) No logging 20/31 (65%) 14/26 (54%) Continuous logging 7/31 (23%) 9/26 (35%) Logging at sending and reception 6/31 (19%) 6/26 (23%) No answer 5 2 Presented are the type of question (SC; MR), the total number of survey participants, as well as ratio and percentage (in brackets) of survey participants choosing a given answer. The number of survey participants not providing an answer is noted under ‘‘no answer.’’ The information marked in bold is the most relevant result. 129 Table 6. Data Management What data management system for documentation of withdrawal/adding of samples do you use? Q1—SC HBM4EU (n=36) ESBB (n=28) Homemade solution (e.g., Excel sheets) 19/35 (54%) 7/28 (25%) Database and respective management software 12/35 (34%) 21/28 (75%) No data management system 4/35 (11%) 0/28 (0%) No answer 1 0 What information about a stored samples history do you record? Q2—MR HBM4EU (n=36) ESBB (n=28) No information 1/35 (3%) 0/28 (0%) Source of the sample 27/35 (77%) 24/28 (86%) Date of sample receipt at the repository 29/35 (83%) 28/28 (100%) Date of sample shipment from the repository 16/35 (46%) 24/28 (86%) Total storage duration 18/35 (51%) 22/28 (79%) Sampling year/sampling period 31/35 (89%) 22/28 (79%) Person in charge 20/35 (57%) 18/28 (64%) Storage temperature 25/35 (71%) 26/28 (93%) Thaw and refreezing cycles 8/35 (23%) 20/28 (71%) Subaliquots 15/35 (43%) 21/28 (75%) Deviations (e.g., interruption of cooling chain) 11/35 (31%) 18/28 (64%) Other 2/35 (6%) 4/28 (14%) No answer 1 0 Presented are the type of question (SC; MR), the total number of survey participants, as well as ratio and percentage (in brackets) of survey participants choosing a given answer. The number of survey participants not providing an answer is noted under ‘‘no answer.’’ The information marked in bold is the most relevant result. Table 7. Quality Management Is your institution certified, accredited, or otherwise qualified in a quality management system? Q1—SC HBM4EU (n=36) ESBB (n=28) No 18/34 (53%) 12/28 (43%) Yes 16/34 (47%) 16/28 (57%) No answer 2 0 Please specify according to which norm(s)/systems your institution is certified/accredited or otherwise qualified (only shown to participants answering Q1 with yes) Q1A—OF HBM4EU (n=16) ESBB (n=16) ISO 9001 8/16 (50%) 12/16 (75%) ISO 17025 9/16 (56%) 2/16 (13%) GCP/GLP 0/16 (0%) 5/16 (31%) ISO 15189 1/16 (6%) 2/16 (13%) NFS 96–900 1/16 (6%) 1/16 (6%) ISO 15025 1/16 (6%) 0/16 (0%) ISO 14001 0/16 (0%) 1/16 (6%) ISO 18001 0/16 (0%) 1/16 (6%) For which activities has a quality management system been established (only shown to participants answering Q1 with yes) Q2—MR HBM4EU (n=16) ESBB (n=16) Sampling 8/14 (57%) 13/16 (81%) Distribution 4/14 (29%) 11/16 (69%) Shipment 4/14 (29%) 12/16 (75%) Data management/IT 6/14 (43%) 12/16 (75%) Processing 11/14 (79%) 15/16 (94%) Infrastructure 6/14 (43%) 13/16 (81%) Storage 13/14 (93%) 16/16 (100%) No answer 2 0 Presented are the type of question (SC; OF; MR), the total number of survey participants, as well as ratio and percentage (in brackets) of survey participants choosing a given answer. The number of survey participants not providing an answer is noted under ‘‘no answer.’’ OF, open-form question. 130