Federated Biobanking with Corporate Service Unit: The Munich Biobank Alliance Blueprint

Introduction

Being one of the main German biobanking sites, Munich was also among the first to establish collaborations with the European BioBanking and BioMolecular Research Infrastructure (BBMRI), ¹ already in its preparatory phase starting 2008. These interactions also led to founding the local biobank network, launched in October 2010 as the m⁴ Biobank Alliance (BA), funded by the German Federal Ministry of Education and Research as a part of the Munich leading-edge m⁴ Personalized Medicine and Targeted Therapies cluster program. The BA was designed as a structural project, partnering the BioM Biotech Cluster Development GmbH with the Helmholtz Centre Munich (HMGU), the two Institutes for Pathology at the Ludwig-Maximilians-University (LMU) and the Technical University Munich (TUM), as well as the Departments of General and Visceral Surgery at the University of Munich Medical Centre (KUM) and the TUM-Medical Centre Rechts der Isar (MRI). Its objectives were the harmonization and expansion of present biobank activities by creating a biobank network to provide access to a standardized collection of samples and data to promote biomarker research and ultimately the development of personalized medicine and targeted therapies. This biobank network was intended to be used both for in-house research and on a fee-for-service basis for R&D in pharmaceutical and biotech companies, to optimize the use of biosamples and data with the prospect of cofounding enhanced biobanking activities.

Materials and Methods

Establishing a corporate service unit and developing the contractual framework

BioM has already served as the m⁴ consortium's overall coordinator. To keep required investments for founding a central service unit (SU) that would have to incorporate the BA and its standards as low as possible, BioM finally agreed to integrate ongoing activities into its present corporate structure as a new business unit. The established Biosample Service Unit at BioM provided the following:

(1) A central point of contact, comprehensive project development, and management mainly for projects across biobanks with mediation of interests.

(2) Development and update of all common procedural documents as well as common TQM Standards.

(3) Project reporting and public relations for societal acceptance.

The fully developed contractual framework of the cooperation agreement between BioM, acting as a central SU, and cooperating biobanks is based on the approved ethics and privacy policy as its common standard. Its implementation is verified by using the compliance checklist (Supplementary Data S1; Supplementary Data are available online at www.liebertpub.com/bio). This checklist includes document verification and biobank auditing procedures to make sure that TQM adheres to the common standard. Some of the other features are defined interfaces for reporting collection data. Mandatory operational requirements include the availability of aggregated data on the collections, a defined biobank portfolio, and the provision of operational figures (staff, consumables, number, and type of patients included, number of tissues collected per system of indication/organ, composition of archived collections), as well as a dedicated account for third-party (co-)funding of biobank activities.

Once the cooperation agreement is in place and all operational requirements have been met, the SU is able to act on behalf of the biobank and mediate requests and delivery, invoicing all project-related services and cofunding biobanks, drawing on annual reporting and payment. Figure 1 shows the entire workflow in a two-step flow chart, beginning with establishing the cooperation agreement between the SU and biobank. The second step is initiated by a user's request and highlights all documents for formal processes in the framework of the cooperation agreement. These are Project Protocol (Supplementary Data S2), Project Approval (Supplementary Data S3), User Agreement (Supplementary Data S4), and Allocation Note (Template: Supplementary Data S5). It also includes informal processes, that is, any initial user requests and complaints about sample quality. The chart ends at public reporting on projects by the SU based on the project report form (Supplementary Data S6), leading to subsequent requests. Following the color coding (see legend), it also depicts the complementary contribution of each entity (user vs. SU vs. biobank) to the overall process and, therefore, underlines the driving power of the SU.

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FIG. 1.

Biobank Alliance workflow from implementation of contractual framework to project workflow and related documents.

Results

This workflow has been developed from pilot projects, primarily collaborating with research projects of m⁴ consortium members, but going beyond these. Initial market research in 2011 ultimately focused on 23 personal interviews with representatives of companies from the regional biotech/pharmaceutical cluster. Until 2012, this resulted in 24 requests from seven companies. During ongoing marketing activities, personal contact has been established with another 23 companies, including 19 biotech small and medium enterprises and four large pharmaceutical companies, resulting in a total of 19 further requests from 2013 to 2015.

The initial document had been an extensive request form. The BA project soon revealed, however, obstacles to project development should be kept as low as possible. This resulted in informal requests developed by BioM down to the level of a project protocol to be approved by the user and by biobanks. The requests were very varied: regarding sample types, they ranged from providing FFPE or sections from cryoblocks (OCT) to the prospective collection of combined sample sets, such as plasma and tissues; regarding indications, they ranged from common oncological conditions such as colon cancer to rare infectious tropical diseases (chargas).

A total of 22 of 43 requests (ca. 51%) clearly surpassed, therefore, the scope of collections within BA framework, for example, explicitly did not include FFPE material from diagnostic archives. Two requests were, however, passed on to the BioM Trials Service Centre and could be implemented as single-purpose collections with individual protocols and ethical approval. Another request could be implemented by hepacult GmbH. Twelve requests (28%) were canceled by BioM because no final project protocol could be achieved, the project had been discontinued by the user, or the quote refused. One request was implemented by a single biobank as scientific cooperation outside BA.

In the BA framework, five projects (12%) could be implemented in total: 2 projects on cryosections, one on various primary epithelial tumors in stock at a single biobank, the other on primary tumors of mammary gland, prostate, head, and neck, glioblastoma, and primary lung carcinoma (NSCLC) across two biobanks. One project on the combined collection of plasma, tumor, and normal tissues in primary lung carcinoma (NSCLC) was also realized across two biobanks. The prospective collection of blood samples and tissues of primary pancreatic, esophageal, and gastric cancer with follow-up data for The Cancer Genome Atlas (TCGA) has been the most challenging project, but proven successful. Although this was implemented as scientific cooperation with a single biobank, the contribution of the SU at BioM for this international project, overcoming administrative hurdles such as the conclusion of the cooperation agreement, has been essential. The following Table gives an overview for the numbers discussed above. It shows additionally that marketing and project management by BioM improved in the second phase of the BA project, with more companies contacted actually placing requests and fewer requests going beyond the scope of m⁴ BA sample/data collection (Table 1).

Although initial revenue could be generated from 3 fee-for-service projects, this revenue did not recover project-related costs. Further evaluation of these costs did not indicate a directly proportional relationship with the number of delivered donors/cases or type/number of samples, for example, the number of sections. This matches the findings from the LPC project ¹⁶ that revealed an overwhelming impact of fixed costs. An initial cost allocation model based on the present cooperation of KUM with hepacult GmbH has been developed, however, including an additional basic fee per project. The full contractual framework as shown above could only be implemented for the cooperation with one newly founded biobank so far.

The overall feedback from these projects indicates recognition of the corporate SU at medical centers/research institutes. BioM Biosample Service gained valuable experience in consulting projects that use human biosamples and medical data, as well as in their development and management. In summary, the BA project has successfully grounded participating biobanks in a common ethics and privacy framework, and in TQM, and it has refined biobanking processes to shaping common standards, clarifying the scope and ownership of these processes.

Discussion

The established workflow shows in general that a central corporate SU does relieve both user and biobank of administrative tasks and project management, simplifying the process of samples/data collection and usage. Each of the three process stakeholders can focus on its core competency: the user on research, the SU on coordination and management, and the biobank on collection/provision of samples and data. Based on a firm contractual framework that ensures compliance and maintenance of common standards (as shown in the Biobank cooperation and qualification section), which is a prerequisite, a central SU can bundle volatile demand, organize requests, and develop projects across biobanks. Thus, it can develop into the integrative power of a biobank network.

However, even for a local type of federated biobanking, BioM as a corporate SU has been struggling with a diversified biobank portfolio and a broad range of public or private stakeholders. Hence, it remains to be seen whether a Biobank Alliance is appropriate for meeting user demands, especially when facing national or even pan-European undertakings to create specialized and, therefore, properly unified biobanking, targeting a single disease such as the Lungscape iBiobank by ETOP. ¹⁷ Moreover, local biotech and pharmaceutical demand for sample/data usage has turned out not to grow as much as indicated by initial market research, and even after three years of business, the development was insufficient for funding the SU. Finally, defining standardized cost-based service fees remains difficult because it depends on how strongly biobank processes are integrated into infrastructures of different purposes: treatment, diagnostics, or research. The higher the level of integration, the trickier is the allocation of fixed costs. The m ⁴ BA model therefore obviously requires a substantial separation of biobanking activities and may be more appropriate for biobanks already formed as separate organizational units with their own budgets, especially in academic institutions.

Whatever the prospect of Biosample Services as an SU at BioM GmbH, the presented outcome of a compiled contractual framework and project workflow and related documents may serve as a blueprint for the effective networking of independent biobanks to promote public–private partnerships in biomedical research. Next steps would require, of course, to broaden the user base by expanding the network across Bavaria or even on a national level. Any implementation of the m⁴ BA Blueprint should be accompanied by more detailed market research. However, at least on a global level, say, drawing on the example of TransHit Biomarkers Inc., finding ways to improve the use of biobanks, ¹⁸ that is, biomaterial sourcing for private biomarker and diagnostics development, can be considered an established business model.

In the context of central biomaterial banks being established at German academic institutions, primarily sustained by public funding through institutional budget and/or research grants, ¹⁹ public interest should support making samples and data available to a broader scientific community. Networking of these kinds of biobanks to effectively support private research and development on a national level would also need an appropriate contractual framework, applying a corporate SU as a driver and provider of comprehensive project development and management. On this level of biobank networking, founding an independent corporate SU would of course require a significant initial investment, leaving the question unanswered of who should ideally afford this economic risk for the purpose of cofounding biobanks.