Centre de Ressources Biologiques-Tumorothèque: Bioresources and Associated Clinical Data Dedicated to Translational Research in Oncology at the Institut de Cancérologie de l’Ouest, France

procedures. Samples stored into the biobank are available for both academic as well as commercial researchers, through a defined access procedure. Currently the bioresources consist in more than 99.500 samples with informed consent and associated clinical data.

The Centre de Ressources Biologiques-Tumorothèque ICO is a biobank integrated in a clinical cancer center (ICO, Institut de Cancérologie de l'Ouest, Saint-Herblain, FR) that collects tissues (snap frozen, FFPE, TMA) and biological (serum, plasma, DNA, RNA, stools, etc) samples from oncology patients and dedicated to translational research. The biobank started its activities in 2002 and is certified NF S 96 900. Activities are framed by a quality management system with established and validated SOPs for all work procedures. Samples stored into the biobank are available for both academic as well as commercial researchers, through a defined access procedure. Currently the bioresources consist in more than 99.500 samples with informed consent and associated clinical data. The Centre de Ressources Biologiques-Tumorothèque ICO originates from the grouping of Tumor Bank of ICO created in 2002 located in Angers (FR) and biobank based at ICO Saint-Herblain (FR) created in 2003. The ICO biobanks initially shared with the University Hospital of Nantes was individualized from 1 st July 2018 and became the CRB-Tumorothèque ICO. Samples are collected at both sites of the cancer center (Saint-Herblain and Angers), and the storage and delivery centralized at the Saint-Herblain site. The management of biocollection activities is carried out as part of a NF S 96 900 certification renewed in December 2018. The CRB-Tumorothèque ICO manages biological collections from multiple cancer types or collected in clinical trials in which ICO participates as a sponsor or through the physicians who are investigators. Eight biocollections entitled: breast-gynecology, genitourinary system, digestive system; nervous system; sarcomas; aero digestive track; endocrinology; hematology are declared and registered under the reference DC-2018-3321.
The CRB-Tumorothèque is composed of three activity sectors: 1) "Tumor Tissue Bank" which collects tissue samples; 2) "biology" sector which collect biological samples and their derivatives other than tissues (e.g. blood, urine); 3) "clinical trials" sector collecting all samples related to clinical research protocols (Figure 1). The main objectives of the CRB-Tumorothèque are to ensure the traceability of all samples and associated processes to make them available to the scientific community for translational research projects.

Steps Recruitment
Patients diagnosed and treated at ICO for an oncologic disease who gave their agreement and have signed off the informed consent are eligible for the CRB-Tumorothèque. Patients are included at all clinical Departments. Biological resources can be also collected from external clinical centers and are couriered by certified transporters to the CRB-Tumorothèque ICO within an adequate period of time according the nature of bioresources.

Collection of bioresources
Each clinical/surgical department of ICO collects biological samples in a uniform way and in a routine clinical care setting. Standard Operating Procedures have been established and validated for all laboratory methods related to the bioresources. Each process used at the CRB-Tumorothèque ICO intregrates: staff education and training, safety procedures, access to the facility, logistics, identification of equipment/device and consumables, temperature control, document control, consent procedures, sample intake, handling, storage and distribution (SOPs), services, non-conformities, audit and management review. All these information/procedures are documented in a quality management system under supervision of the quality manager.
A request form including patient identification, material collected, date and time of the collection, informed consent is joined to the resource. Biological samples without informed consent are not processed.
All biological materials sent to the CRB-Tumorothèque ICO are delivered as fast as possible to guaranty the quality of the biological samples.

Preparation/transformation of bioresources
Biological fluids and derivates, and tissue samples are processed by trained and certified staff through the biopathology department (histopathology and biology departments). Tissue specimens are validated by certified pathologists. Only surplus material is passed to the CRB-Tumorothèque ICO.
Immediately after receipt, samples are registered thanks the TumoroteK software, de-identified and processed according to the corresponding procedures. All steps of the process are documented into TumoroteK system. Tissue samples are stored as frozen or Formalin-Fixed Paraffin-Embedded (FFPE) material. Biological fluids (e.g. urines, stools) and derivates (e.g. plasma, serum, DNA, RNA) are aliquoted and stored at -80°C.
Only trained staff of the CRB-Tumorothèque ICO has access to the databases and the physical collections. In close collaboration with the numeric data center, staff has access to other databases of the ICO cancer center to retrieve clinical data, associated with the patient. The CRB-Tumorothèque ICO is certified NF S 96 900 ("Quality of biological resource centres (BRCs) -Management system of a BRC and quality of biological resources") for the following activities: "Receipt, preparation and provision of cancer biological resources (tissues, fluids) from the tumor bank".

Source of associated data
The demographical information (Gender, age) and clinical information (pathology report, treatment protocols, imaging, biological parameters, clinical follow up, etc) are available upon a specific request to the numeric data center associated with the CRB-Tumorothèque ICO and validation by the scientific advisory board.

Ethics Statement
The activities of the CRB-Tumorothèque ICO are in accordance with the French legislation (especially the law of bioethics, 7th July 2011, and the chapter IV of the Public Health Code that gather all regulations for biobanks). They meet the ethical and regulatory requirements that govern the collection, conservation and use of biological samples for scientific purposes; this includes, according to article L.1243-3 of the Public Health Code, approval of the collection from a competent research ethics committee (CPP, "Comité de protection des personnes" in French) and obligation to respect donor's informed consent in any access request to the samples. In addition, the CRB-Tumorothèque ICO works in respect to the national ethical chart reedited in 2010 [4]. All samples processed by the CRB-Tumorothèque ICO were subject to the donor's agreement and the signing of informed consent. The CRB-Tumorothèque is committed to destroying samples and related information at the request of the donor. Researchers who would like to get access to bioresources available at the CRB Tumorothèque ICO must be compliant with the applicable law regarding their research projects and present legal/ethical authorisations/a pprovals required to the CRB upon request as a condition for granting access. As part of the access process, in addition to assessment of compliance with ethical and legal requirements, requests for assignments and accommodation are analysed on the relevance of scientific projects after validation by the scientific advisory board. All bioresources deposited at CRB-Tumorothèque ICO have been declared to and authorized by the French Research Ministry (Declaration Number: DC-2018-3321). This declaration includes approval by a research ethics committee (CPP).

Constraints
Available bioresources are composed by residual samples from patients who gave their agreement and have signed off the informed consent. External bioresources can be hosted by the CRB-Tumorothèque ICO upon request and validation by the scientific advisory board.

Type of sampling
Biobank including Disease-based samples, longitudinal cohort, sampled in a research protocol.

Anatomical site
Tissues and biological fluids from various tumor types and anatomical site are available.

Disease status of patients/source
Oncological patients.

Clinical characteristics of patients/source
Adult and pediatric tumor samples with full clinical data de-identified before release. Clinical data are associated to each biological sample. Their access requests a specific application to the numeric data center associated with the CRB-Tumorothèque ICO and a validation by the scientific advisory board which serves as a formal Institutional Review Board.

Size of the bioresource
CRB-Tumorothèque ICO is a research infrastructure of the Institut de Cancérologie de l'Ouest dedicated to translational research and all collections are ongoing and have no definite end date. The collections contain currently (January 2020) around 100.000 biological samples originating from different research projects in collaboration with multiple researchers and physicians and are enriched by around 10.000 new samples each year.

Vital state of patients/source
Patients are alive at the time of sample collection. Patients are the source of clinical diagnoses.

Control samples
For tissue samples of the same organ both tumor and tumor-free tissue material macroscopically assessed are collected when possible.

Biospecimen type
CRB-Tumorothèque ICO can provide a large variety of biospecimens including serum, plasma, DNA, RNA, ascites, FFPE and fresh frozen tissues and Tissue Microarrays.

Size of the bioresource
The number of full time employees working at the CRB-Tumorothèque ICO is 10.

Release date
Samples and data are available since the 1 st July 2018 upon request.

Access criteria
For any research group, a formal brief application is required (objectives, short description of samples, methods, data needed, timetable, associated funding) (Figure 1). All applications are reviewed by the governance committees (technical committee of the CRB-Tumorothèque ICO that checks the feasibility of the project on the base of the sample availability and the scientific advisory board that takes the final decision of acceptance after analysis of the scientific relevance, project feasibility and conflicts of interests. Similarly, access to clinical annotations will require a formal application and the validation of the numeric data center as well as the scientific advisory board of ICO. After acceptance, a contract including the ethical chart and the conditions of release will be proposed to the applicants and sign off before sample processing (e.g. conditions of transfer, Figure 1: Organization of the CRB-Tumorothèque ICO and flowchart process. Similar flowchart is required by the numeric data center to get access to clinical annotations. *: http://www.ico-cancer.fr/la-recherche/centre-deressources-biologiques-tumorotheque/; +: validation; -: rejection. storage, use, publication of results, disposal of withdrawn material, and financial aspects). The financial contribution is determined with the applicants and depends on the number and nature of data/samples needed as well as the nature of the contract (e.g. collaboration with shared publication or IP). In all cases, the origin of the materials provided (CRB-Tumorothèque ICO, FR) must be indicated in any communications done by the applicants.

(4) Reuse potential
The reuse by the contracting research group of samples delivered is not permitted without the permission of the CRB-Tumorothèque ICO. Conventionally, samples delivered in excess will be sent back to the CRB-Tumorothèque ICO for traceability and destruction. Tissue and fluid samples stored in multiple aliquots can be used for various projects.