Centralization of the IARC Biobank: Combining Multiple Sample Collections into a Common Platform

Abstract

The International Agency for Research on Cancer (IARC) is the World Health Organization's (WHO) cancer research agency. The agency conducts research on cancer with worldwide collaborations, adopting a multidisciplinary approach of epidemiology and laboratory-based studies on cancer causes, as well as preventive interventions. The IARC Biobank stores multiple collections of samples and conducts preanalytical services for studies conducted worldwide in support of the research activities. Traditionally, the multiple collections from these studies were managed by the individual research groups in different project-specific databases. In 2010, a program to centralize sample collections into a single platform was initiated by adopting a common database with the introduction of a minimum dataset for sample collections received at IARC. The process involved checking data files, verifying the storage location of samples, conducting data harmonization, and importing or migrating existing data from project-specific spreadsheets and databases into the common database. In addition to the creation of a common biobank database and an up-to-date inventory of IARC's biological resources, a governance structure was established. The creation of the Biobank Steering Committee and the adoption of an access policy is to facilitate and guide the sharing of IARC's resources in a transparent manner, while taking into account Ethical, Legal, and Social Issues.

Introduction

Advances in research employing assays and state-of-the art technologies^1,2 rely on the availability of high-quality samples and data and are driven by the goals of personalized and precision medicine.³ Biobanks play a key role in these developments and have enabled the molecular and genetic analysis of large numbers of samples from population-based studies. However, maintaining biobanks requires management of infrastructure and processes. The adoption of reliable information technology (IT) tools, quality assurance processes, and a robust governance structure with due consideration of Ethical, Legal, and Social Issues (ELSI)⁴ contribute to the success of biobanks.

The International Agency for Research on Cancer (IARC) Biobank is a key infrastructure supporting IARC's mission of promoting cancer research worldwide. IARC adopts a multidisciplinary approach of epidemiology and laboratory-based studies, focusing on genetics, environment and occupation, nutrition and metabolism, and infections.

IARC plays a leading role in developing international biobanking standards and guidelines, particularly in low-resource countries. The “Common Minimum Technical Standards and Protocols for Biological Resource Centers Dedicated to Cancer Research” was published in 2007 as one of the pioneering documents of standard protocols for biobanking. A follow-up publication, the “Common Minimum Technical Standards and Protocols for Biobanks Dedicated to Cancer Research”⁵ was published in 2017 and provides new information on biobanking with specific sections dedicated to ELSI.

IARC's role in international biobanking is furthered by its membership and contribution to international partnerships. Such as memberships of the European and Middle Eastern Society for Biopreservation and Biobanking (ESBB), the Biobanking, BioMolecular resources Research Infrastructure-European Research Infrastructure Consortium (BBMRI-ERIC),⁶ and the International Society for Biological and Environmental Repositories (ISBER). In 2013, IARC established the Low and Middle Income Country (LMIC) Biobank and Cohort Building Network (BCNet),⁷ in partnership with several international organizations, including U.S. National Cancer Institute-Center for Global Health (NCI-CGH). BCNet members benefit from training and technical support for the upgrade or establishment of biobanks.

The IARC Biobank stores samples from population- and disease-based collections, from studies focused on cancer etiology and prevention, including cohort, case–control, and case-only studies (Table 1).^8–15 The samples are divided into three categories (category 1, 2, and 3): category 1 consists of collections originating from ongoing worldwide consortium studies. The main collection in this category is the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is one of the largest population-based studies with more than half a million (521,000) participants (350,000 provided blood samples) recruited from 23 centers across 10 European countries. Other major collections include multicenter case–control studies conducted by IARC in collaboration with local partners on breast cancer in Latin America, human papilloma virus vaccination and cervical screening in Europe and in LMIC, hepatitis B virus vaccination and liver cancer studies in Africa and Asia, and case–control studies on lung, head and neck, and kidney cancer in Europe.

Table 1.

IARC Sample Collection with Information on Study Design, Date, Sample Origin, and Type

Study title	Design	Start date	Sample nature	Sample origin	Keywords
Mutographs	Case series	2017	Whole blood, buffy coat, plasma, RBCs, frozen tumor tissues	20 countries	Esophageal cancer, kidney cancer, pancreatic cancer, colorectal cancer
Ice-bile	Prevalence	2010	Bile, frozen tissue, paraffin tissue, serum	France	Gallbladder cancer, helicobacter species
K2	Case–control	2008	Buffy coat, DNA, FFPE and frozen slides, lymphocytes, frozen tissue, paraffin tissue, plasma, RBCs, whole blood	Czech Republic, Romania, Serbia	Kidney cancer
HIV case-case Study	Case-case series	2007	DNA, dried blood spot, frozen tissue, paraffin tissue, plasma, whole blood	Kenya, South-Africa	Cervical cancer, human papillomavirus, HIV
Russia multicancers	Case–control	2007	Buffy coat, DNA, FFPE slides, lymphocytes, frozen tissue, plasma, RBCs, whole blood	Russia	Lung and kidney cancers
NPC	Misc	2006	Blood clot, buffy coat, saliva DNA, plasma, serum, RBCs, whole blood	Thailand, Malaysia	NPC, South East Asia
Lymphoma	Misc	2006	Blood clot, buffy coat, plasma, serum, RBCs	Thailand	Lymphoma, South East Asia
Breast	Misc	2006	Buffy coat, plasma, RBCs	Malaysia, Thailand, Singapore	Breast cancer, South East Asia
Pancreatic cancer study	Case–control	2004	Buffy coat, DNA, FFPE and frozen slides, lymphocytes, frozen tissue, paraffin tissue, plasma, RBCs, whole blood	Czech Republic, Slovakia	Pancreatic cancer
GEMINI (GC Iran)	Cohort	2004	Blood spot, buffy coat, hair, nail, plasma, RBCs, whole blood, urine	Asia, Iran	Esophageal cancer, carcinogen exposure, lifestyle factors
ARCAGE	Case–control	2002	Buccal cells, buffy coat, paraffin tissue, plasma, RBCs, frozen tissue, whole blood	Europe, Western	Alcohol-related cancers, genetic susceptibility, upper aerodigestive tract, Western Europe
Cervical cancer	Case series	2000	DNA, dried blood spot, frozen tissue, paraffin tissue	Bhutan, Chile, Georgia, China, Guinea, Iran, Korea, Mongolia, Nepal, Nigeria, Pakistan, Poland	Cervical cancer, human papillomavirus
EPILYMPH	Case–control	2000	Blood clot, bone marrow, buffy coat, plasma, RBCs, serum, whole blood	Europe	Environment, lymphomas
EPIHEALTH	Cohort	1990s	Dried blood spot, hair	Russia	Epidemiological study, tobacco, alcohol, cancer mortality in Siberia
HPV multicenter case–control studies	Case–control	1990s; 2000s	Buffy coat, DNA, exfoliated cells, frozen tissue, serum	Worldwide	HPV, cervical, oral cancers, multicentric study, p53 mutations
HPV prevalence study	Prevalence	1990s; 2000s	Buffy coat, DNA, dried blood spot, exfoliated cells, slides, plasma, RBCs, serum		HPV types, cervical cancers, low- and middle-resource countries
SA-HN (SAS)	Case-control	1998	Buccal cells, buffy coat, plasma, RBCs, frozen tissue	Latin America	UADT, cancers, p53 mutations
INCO-COPERNICUS (CEE)	Case-control	1998	Buccal cells, buffy coat, DNA, plasma, RBCs, frozen tissue, whole blood	Czech Republic, Poland, Romania, Russia, Hungary, Slovakia	Lung, kidney, and UADT cancers
Oral cancer	Case–control	1996	Buffy coat, slides, DNA, exfoliated cells, frozen tissue, paraffin tissue, plasma	Australia, Canada, Cuba, India, Ireland, Italy, Poland, Spain, Sudan	Head and neck cancer, human papillomavirus
EPIC	Cohort	1992	Plasma, serum, RBCs, buffy coat	Europe	Nutrition, cancer, metabolism, genetic factors
IBSCC	Case series	1990	DNA, frozen tissue	Algeria, Argentina, Benin, Bolivia, Brazil, Canada, Chile, Colombia, Cuba, Germany, Guinea, Indonesia, Mali, Panama, Paraguay, Philippines, Poland, Spain, Tanzania, Thailand, Uganda, USA	Cervical cancer, human papillomavirus
GLCS	Case–control	1990s	Serum, plasma	The Gambia	Hepatocellular carcinoma, aflatoxin
WESTNILE study	Cohort	1970s	Serum, plasma, tissue, milk, saliva	West Nile District of Uganda	, Epstein–Barr virus
ESMAESTRAS	Cohort	2006	Serum, plasma, buffy coat, RBCs, urine	Mexico	Nutrition, cancer, metabolism, genetic factors
PROLIFICA	Cohort/case-control	2012	Serum, plasma, buffy coat, urine	Gambia, Senegal	Hepatocellular carcinoma, liver fibrosis, hepatitis B
Interchange	Misc	2013	Buffy coat, FFPE slides and scrolls, frozen tissue, plasma, RBCs, whole blood	Brazil, Argentina, Uruguay	Head and neck
LUN	Misc	2012/2013	Buffy coat, FFPE slides, paraffin tissue, frozen tissue, plasma, RBCs, whole blood	Serbia, Czech Republic, Romania, Poland	Lung cancer
Sally	Misc	2000/2001/2002/2003	Buffy coat, plasma, RBCs	Pakistan, India	Lung and larynx
CAMA	Case-control	2010	Serum	Mexico
PRECAMA	Pilot case-control	2014	Serum, plasma, buffy coat, RBCs, urine	Chile, Colombia, Costa Rica, Mexico	Premenopausal breast cancer

FFPE, formalin-fixed paraffin-embedded; HIV, human immunodeficiency virus; HPV, human papilloma virus; IARC, International Agency for Research on Cancer; NPC, nasopharyngeal carcinoma; RBCs, red blood cells; UADT, upper aerodigestive tract.

Category 2 samples are from studies that have fulfilled the primary endpoint and the samples are available for international collaboration. Category 3 samples are human or animal cell lines established at IARC or obtained from collaborators, representing over 13,000 vials.

Prior to the centralization, existing data on the three categories of samples were kept at different places (e.g., biobank and research groups) and in different formats (access, excel, word, and paper documents). The IARC Biobank also accommodates the preanalytical service platform for sample reception, storage, retrieval from storage facilities, aliquoting, DNA extraction and quantification and quality control (QC) on extracted DNA, and worldwide distribution of samples.

The biobank is a good example of a facility that started by providing storage facilities for projects managed by individual groups and evolved into a multiuser resource. Due to an increase in the number of collections, a change in scope and focus of IARC, and demand for the reuse of samples, the IARC Biobank needed to transition into a centralized facility. The resources are managed through a common database developed in-house¹⁶ to enhance data harmonization and guided by international guidelines.

The adoption of the common database facilitated the centralization process. However, there were various challenges to overcome in terms of concept and resources. In this article, we will present the process, challenges, and solutions employed in achieving the centralization, with a view to providing a case study of a not uncommon transition.

Materials and Methods

Organizing the sample collections stored at IARC Biobank

From the early 1970s to the late 1990s, samples were stored in freezers and liquid nitrogen (LN2) tanks located in multiple sites. Located in the research laboratories and in the basement of the main IARC building without any global management system of the storage facilities. The Biological Resource Center (BRC) was constructed in 1995, to host the LN2 tanks for the EPIC samples. An automatic refilling system was installed, with a 7000-L supply tank located outside the building.

Early in the 2000s, the sample storage facilities were reorganized. A dedicated storage area was allocated to accommodate 40 freezers (−80°C, −40°C, and −20°C) and 9 (30–50 L) LN2 tanks. A basic alarm system to monitor freezer temperature was installed, based on the internal freezer temperature probe and the existing IARC Centralized Technical Management system. Later, the LN2 tanks were transferred to the BRC, creating an LN2 facility of 34 (600-L) tanks (containing almost 3.5 million straws) and 9 smaller tanks. For optimizing LN2 delivery schedule and reducing the related cost, in 2012, the 7000-L supply tank was replaced by a 20,000-L tank.

Over the years, the small tanks were replaced by bigger additional tanks to house new collections. Currently, over 4.3 million blood-derived products, tissue, and cell lines kept in straws and vials are stored in a total of 50 LN2 tanks. In addition, over 900,000 samples are stored in 67 freezers (e.g., blood-derived products, tissues, body fluids, exfoliated cells, and nucleic acids) and at ambient temperature (e.g., dried blood spots on filter paper, hair, nail, formalin-fixed paraffin-embedded blocks, and slides) (see Table 2 for storage conditions). Freezer space is continuously being expanded to cater for growing needs, to cater for adequate backup space to accommodate the heterogeneity in terms of racks and content, and also the increase in breakdowns, which is anticipated with the aging freezer units.

Table 2.

Storage Conditions of Samples Stored Within the IARC Biobank

Type of sample	Storage temperature
Biopsy	−80°C or −196°C
Blood clot	−80°C or −196°C
Bone marrow	−80°C or −196°C
Buccal cells	−80°C or −196°C
Buffy coat	−80°C or −196°C
Cell line	−196°C
Cervical cells	−196°C
Circulating plasma DNA	−20°C
DNA	−20°C
Dried blood spot	RT
FFPE H&E slide	RT
FFPE block	RT
FFPE scrolls	RT
FFPE section	RT
FFPE stained slide	RT
FFPE unstained slide	RT
Feces	−80°C
Frozen H&E slide	RT
Frozen scrolls	RT
Frozen section	RT
Frozen tissue	RT
Frozen unstained slide	RT
Germline DNA	−20°C
Hairs	RT
Leukocytes	−80°C or −196°C
Lymphoblastoid cell line	−196°C
Lymphocytes	−80°C or −196°C
Nails	RT
Normal tissue	−80°C or −196°C
OCT block	−80°C
PBMC	−80°C
Plasma	−80°C or −196°C
Plasma miRNA	−80°C
RNA	−80°C
Red blood cells	−80°C or −196°C
Saliva	RT
Serum	−80°C or −196°C
Tumor tissue	−80°C or −196°C
Urine	−40°C or −80°C
Viable lymphocytes	−196°C
Whole blood	−80°C or −196°C

H&E, hematoxylin and eosin; OCT, optimal cutting temperature; PBMC, peripheral blood mononuclear cell; RT, room temperature.

See Figure 1 and Supplementary Table S1 for geographical distribution of samples by country in the IARC Biobank; a comprehensive list of the collections is available at the IARC Biobank website and in Table 1.

FIG. 1.

Geographic distribution of samples by country in the IARC Biobank. The samples are from ongoing or completed studies conducted worldwide in collaboration with IARC. IARC, International Agency for Research on Cancer.

Establishing the centralized biobank

The centralization program initiated in 2010 involved the reorganization and verification of samples in defined storage locations, the introduction of a common database, and the establishment of a governance structure. The IARC Laboratory Services and Biobank (LSB) Group became the focal point to implement the centralization and manage the changes in line with the strategic direction provided by the Biobank Steering Committee (BSC). The LSB group conducted its biobanking activities in collaboration with the project sample custodians and sample managers, and was supported by the IT department.

The common biobank laboratory information system (SAmple Management for IARC Biobank [SAMI]) was developed in-house and adopted in 2011 to store and manage sample location and movement. The program stores information on sample identifiers, geographical origin, age, sex, sampling date, and links with clinical, epidemiological, and related individual identifications (IDs). Sample IDs and locations were verified for existing collections by comparing extracted data from spreadsheets and project-specific databases with actual storage locations.

Security, quality, and monitoring

Access to the storage facilities is controlled and restricted to authorized staff members by badge reader at the entry of storage areas. QC measures are in place, including the checking of the worklists and the samples prepared for extraction, aliquoting, and shipment by a second person to ascertain that the correct samples are being pulled out of LN2. Also, routine QC checks are performed for DNA purity and stability by electrophoresis on agarose gel, immediately after extraction and monthly checking of random samples during storage. The biobank participates in annual proficiency testing schemes that evaluate the performance of DNA extraction and quantification and has obtained excellent results (IBBL Biospecimen Proficiency Testing).

In addition, the LSB group conducted studies to evaluate the impact of preanalytical variations during blood and tissue processing and freezing on the quality of extracted DNA and RNA in the context of studies using standard protocols.^17,18 The majority of samples used for those studies came from the EPIC collection. Although the results were not shared with sample custodians, as the recruitment was completed at the time of the analysis, the results contributed to the modification and confirmed the DNA extraction protocols, which had previously been introduced to increase the number of buffy coat aliquots used for DNA extraction from single straw to two.

Establishing a governance structure

Adopting transparent principles for sharing samples and data for international collaborations is not only a requirement of a publicly funded biobank but also fulfils IARC's goal to promote collaborative cancer research worldwide. In this regard, a governance structure was put in place with the establishment of a BSC. The committee is chaired by a senior scientist, other members include representatives of the research groups, technical and administrative support, and the LSB Group. The committee's roles include ensuring that the IARC Biobank operates in line with international technical and ethical standards, reviewing access requests when necessary, and providing advice to management in terms of strategic development.

A formal Access Policy was adopted to facilitate a transparent process of access, attract potential research collaborations, and provide the opportunity for IARC to share its biological resources at the IARC Biobank website.

Procedures for sample and data access, and material transfer were strengthened with the introduction of policies and standard operating procedures to establish material (and data) transfer agreements in line with international guidelines (IARC,⁵ NCI,¹⁹ and ISBER²⁰) and are published on the IARC Biobank website. Approval by the IARC Ethics committee is sought before the inclusion of samples in research projects.

Results

The reorganization and centralization of the IARC Biobank offered the opportunity to review and upgrade the biobank facilities. It was also possible to prioritize the stored samples based on their value, strengthen the governance structure, and increase the visibility of the IARC Biobank in the international biobanking landscape. Altogether, the creation of the IARC Biobank website in 2011 and the formal Access Policy had a significant impact on the access rate. All requests sent to the IARC Biobank are centralized, referenced, and archived.

The sample re-organization involved the verification and manual checking either of all samples (for critical collections) or 10% of randomly selected samples. When discrepancies occurred among the 10% random samples, a larger proportion of the samples were checked. The process of verification, inventory, and upload into SAMI for samples stored in LN2, in freezers, and at ambient temperature involved three biobank technicians, spending a total of ∼13,500 hours/1 million samples and was conducted over a period of 4 years. The process created the opportunity to (1) rectify discrepancies between the physical location of samples and the record in the original databases, (2) rationalize and gain space in the storage device by filling the gaps left by sample usage, and (3) correctly label all storage containers (racks and boxes) with appropriate, printed labels resistant to cryogenic temperatures.

The freezer temperature monitoring system was upgraded in 2012 to an integrated monitoring system equipped with independent and external sensors that provides real-time temperature records and a reliable alarm reporting. Trained personnel respond to alarms in a timeframe that prevents or minimizes loss or damage to samples. A second layer of backup is provided by on-call duty roster staff members, available 24 hours-a-day, who are called in the event of an emergency requiring intervention. The air conditioning and electrical network were also upgraded to secure the freezer facility in case of power cut. A diesel generator is available in case of major power cut and is tested every year.

To standardize the information received with the new collections that are shipped to IARC from international sites, the Minimum Dataset (MDS) was developed. The MDS was used to capture the different preanalytical processing conditions that could affect downstream analysis in the samples (Table 3). The “Common Minimum Technical Standards and Protocols for Biobanks Dedicated to Cancer Research” (2017) provided recommendations and guidelines for the MDS. The recommended MDS is being adopted for new collections, received at IARC, as many of the older collections do not have the required information related to preanalytical processing conditions. Samples were uploaded in SAMI with the available data and no collection of noncompliance with the new MDS was discarded.

Table 3.

Minimum and Recommended “Dataset” for IARC Biobank

	Definition	Explanation
1	Study details
1.1	Study ID	Textural string depicting the unique ID or acronym for the sample collection or study. This is the same code used for SAMI.
1.2	Study name	Textural string of letters denoting the name of the study in English. This is the same name used for SAMI.
1.3	Description/objective	Textural string of letters describing the sample collection or study aim (max. 200 characters).
1.4	IARC group	Textural string of letters denoting the IARC group acronym.
1.5	Responsible/IARC principal investigator	Textural string of letters denoting the name of the sample collection responsible or principal investigator. This is the same mentioned for SAMI.
1.6	Sample manager	Textural string of letters denoting the name of the sample manager or contact person and e-mail address.
1.7	Study design	Can be one of several, for example, case–control study and prospective study.
1.8	Cancer type or disease	Can be one of several, for example, lung cancer, and diabetes.
2	Collaborators details
2.1	Contact person (collaborator)	Textural string of letters denoting the name of the contact person for the sample collection or study.
2.2^a	Contact phone	Phone of the “Contact person,” including international call prefix.
2.3	Contact e-mail	E-mail address of the “Contact person.”
2.4	Contact institution and department	Department, or corresponding (e.g., division), of affiliation of the “Contact person.”
2.5^a	Contact address	Street name and street number or PO box of the “Contact person.”
2.6	Contact country	The two-letter code in format following ISO standard (3166 alpha2) for the country of the contact person.
3	Collection details
3.1	Collection start	Date in SAMI time format specifying when the sample collection starts (DD-MON-YYYY).
3.2^a	Collection end	Date in SAMI time format specifying when the sample collection ends, if applicable (DD-MON-YYYY).
3.3	Collection centers	List of centers involved in the study.
4	Ethical, legal, and social issues.
4.1	Ethical approval	Date and reference of the ethical approval specifying if it is IARC EC or not (for samples collected in consortium, provide information for individual sites/countries).
4.2	Informed consent	Informed consent available or not, provided or not (provide copies for the biobank archives).
4.3	Material transfer agreement	Material transfer agreement or signed with MOU with IARC.
5	Individuals data
5.1^a	Planned sampled individuals	Number of individuals with biological samples planned for the study (obtainable from approved study proposal).
5.2^a	Planned total individuals	Total number of individuals planned for the study (obtainable from approved study proposal).
5.3	Sex ratio	Textural string of letters denoting the sex of the sample donors. Can be several values (male/female).
5.4	Age of individual participant	Age of study participants.
5.5	Age group	Age group of study participants.
5.6	Origin	Country and center of origin.
5.7^a	Disease status	Healthy or diseased patient (case or control).
6	Biospecimen (information will be provided in the submitted study protocol)
6.1	Biospecimen type	Textural string of letters denoting the type of sample collection. Can be one or several: serum, urine, solid tissue, whole blood, DNA/RNA (in that case, precise the original sample) or another product derived from a human being.
6.2	Anatomical site: organ of origin or site of blood draw	Blood: venous bleed from the arm, finger prick.
		Bodily fluids: mouth, pancreas.
		Frozen and fixed tissues: liver, lung.
		Exfoliated cells: mouth, cervix.
6.3	Collection mechanism: how the biospecimens were obtained	Blood: blood draw, spotting blood.
		Bodily fluids: urine excretion, expectoration, puncture.
		Frozen and fixed tissues: surgery, biopsy, puncture.
		Exfoliated cells: brush, spatula, mouthwash.
6.4	Type of stabilization	The initial process by which biospecimens were stabilized during collection:
		Blood: EDTA, heparin, drying.
		Bodily fluids: additives, preservatives, on ice.
		Frozen and fixed tissues: fixation type and time+preservatives, on ice, snap-freezing.
		Exfoliated cells: additives, preservatives, on ice.
6.5^a	Type of container	The type of sample container:
		Blood: cryotube, vacutainer, straw, Whatman paper.
		Bodily fluids: cryotube, bottle.
		Frozen and fixed tissues: cryotube, slide.
		Exfoliated cells: cryotube, bottle, vial.
6.6^a	Biospecimen size	Size, volume, or concentration of the biospecimen: for example, μL, μg, mL, mg.
7	Preservation and storage (information will be provided in the submitted study protocol)
7.1^a	Delay to preservation	Time between biospecimen collection, centrifugation or processing if necessary, and (cryo)preservation.
7.1^a	Delay to preservation	Warm ischemia time for tissue: period between the circulatory arrest and beginning of the cold storage.
7.2^a	Temperature before preservation	Storage temperature before centrifugation if necessary and (cryo)preservation.
7.3	Type of long-term preservation	The process by which the biospecimens were sustained after collection:
		Blood: freezing, fridge, kept at ambient temperature.
		Bodily fluids: storage at ambient temperature, freezer.
		Frozen and fixed tissues: fixation, freezing.
		Exfoliated cells: kept at ambient temperature, drying, freezing.
7.4^a	Constitution of preservative	The makeup of any formulation used to maintain the biospecimens in a nonreactive state.
		Blood: 10 U.S. Pharmacopeia heparin units/mL.
		Bodily fluids: sodium azide, sodium carbonate.
		Frozen and fixed tissues: 10% neutral-buffered formalin, RNAlater.
7.5^a	Storage temperature for short-term storage	The temperature or range thereof at which the biospecimens are kept until distribution/analysis: for example: −80°C, −20°C to +25°C.
7.6^a	Storage duration	The time or range thereof between biospecimen acquisition and distribution or analysis: for example, short term, long term, 8 days, 5–7 years.
7.7	Storage temperature for long-term storage	Can be several values.
8	Shipment (receipt of samples at IARC)
8.1	Date of deposition	Date in SAMI time format specifying when the sample collection arrives (DD-MON-YYYY).
8.2^a	Number of shipments	Number of biospecimens shipments expected.
8.3^a	Date of shipments	Date or period when the next batches are sent.
8.4	Shipment conditions	Temperature during biospecimens transfer.
9	Categories of data collected
9.1	Epidemiological and survey data (e.g., age, sex, exposure, anthropometric data, reproductive history, physical activity, tobacco status, alcohol consumption, occupational history, socioeconomic status, and previous illness)
		Available or not?
		Which kind of data?
		Where are data kept?
		Who manage data?
9.2	Clinical data (e.g., main diagnosis, disease status of patients, vital state of patients, clinical diagnosis, and pathology diagnosis).
		Available or not?
		Which kind of data?
		Where are data kept?
		Who manage data?
9.3	Follow-up data (e.g., disease development, relapse, and death).
		Available or not?
		Which kind of data?
		Where are data kept?
		Who manage data?

Items are optional, but highly recommended.

ID, individual identification; MOU, Memorandum of Understanding; SAMI, Sample Management for IARC Biobank.

Discussion

Before the centralization, samples were stored by individual research groups and managed using a variety of IT systems specific to their projects and downstream applications. This meant that harmonization between databases would require extra steps to standardize datasets and the lack of a uniform biobank platform was a challenge for adherence to best practice principles and international guidelines.

Centralization created the opportunity to organize the samples and associated data, create a common platform and protocols, develop a catalogue of available resources, and encourage adherence to best practice principles and guidelines.

Three important benefits resulted from this work; first, the centralized storage facilities are maintained under the best possible conditions, where it is easy to monitor and maintain a stable and secure environment.

Second, the common MDS and documentation of the preanalytical processing information obtained for samples stored at IARC will facilitate harmonization and interoperability between sample collections and associated database.

Third, incorporating the heterogeneous sample collections into a global catalogue will facilitate the search for information on IARC-based collections and available resources to maximize the utility and visibility of available resources. This is in line with IARC's goal to promote international cancer research collaboration (http://internet.iarc.fr/). During this exercise, equipment replacement, upgrading the facilities, and recommendation of 10%–15% backup system were identified as urgent need for the biobank's sustainability due to the high proportion of aging and obsolete equipment. As a result of this work, funds were allocated in 2015 for the acquisition of new cold storage units to support existing collections and cater for expansion with adequate provision for backup facilities.

Three challenges had to be dealt with during reorganization of the IARC Biobank. First, in the sample management IT, the system had to provide the functions to annotate, archive, track, and manage the diverse collections, sample types, and associated data. It had to be compatible with existing IT platforms. Due to the difficulty in finding a fit-for-purpose commercial system, an in-house system (SAMI) was developed. The IT tools (Oracle software, i.e., database and application server, and dedicated servers) were already available in-house; thus, the improvement and upgrading of SAMI are performed locally at minimal extra cost.

Second, the existing project-specific databases lacked standard items, which are available in the Minimum Information About BIobank data Sharing (MIABIS), a minimum dataset for sharing biobank samples, information, and data.²¹ Thus, for data harmonization between different databases, the data in the existing databases had to be standardized before migration and/or importation into SAMI, and this was time-consuming.

The third challenge concerned the acquisition of complete information on preanalytical variables from the clinical or field sites where samples are collected. The biobank is distant from the sites and preprocessed biological materials are shipped to IARC either frozen or in preservative depending on the sample type and the project protocol. The full adoption of the MDS requirement poses a challenge and requires close collaboration between the biobank, the principal investigators, and recruitment centers to ensure compliance.

A key objective of the reorganization is to increase access and usage of IARC's resources. In this regard, the central management of access requests for category 2 and 3 collections to enable the biobank to monitor requests. This has resulted in an increase in response to requests for cell lines and the establishment of new collaborations. Specifically, in 5 years (since 2013), the IARC Biobank has provided samples for a total of seven requests for category 2 and 3 samples; six of them were for cell lines resulting in 1.4 requests/year. This compared to four requests from 2004 to 2012, that is, 0.44 requests/year.

Access to category 1 samples is sought through the respective steering committee, which maintains the record.

The IARC Biobank is set up to benefit from participation in global catalogues such as the one established by the BBMRI-ERIC,⁶ of which IARC is a member (with observer status). It is anticipated that this collaboration will continue to increase the utility of IARC stored samples.

In conclusion, a centralized biobank platform was created to address the fragmentation of data and information for stored samples and produce harmonized data sets with the potential for interoperability with related platforms and databases. The creation of a centralized biobank platform, which provides core services to support IARC's research and international collaborative studies, would not have been possible without the collaboration of the key stakeholders: the principal investigators, sample custodians, sample managers, BSC, LSB, IT department, and support from IARC management.

Continuous upgrading of the procedures and protocols ensures that the biobank maintains a high level of quality and provides the opportunity for staff training and on-site training for international collaborators, and for students enrolled in a biobank masters course at the Catholic University, Lyon.

Footnotes

Acknowledgments

IARC Biobank Steering Committee: Dr. Rolando Herrero, Dr. Rosita Accardi-Gheit, Dr. Gary Clifford, Ms. Elisabeth Françon, Dr. Ausrele Kesminiene, Dr. James McKay, Dr. Sabina Rinaldi, Dr. Augustin Scalbert, Dr. Ghislaine Scélo, Dr. Eduardo Seleiro, and Dr. Jiri Zavadil.

The authors would like to thank Dr. Catherine Voegele for her expertise and assistance in the development of SAMI and Lucile Alteyrac for her expertise and daily support for the development and upgradation of SAMI.

Author Disclosure Statement

No conflicting financial interests exist.

Supplementary Material

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