Professor Jens K Habermann, director of the Interdisciplinary Center for Biobanking-Lübeck, explains the value of hospital-integrated biobanking.
The Interdisciplinary Center for Biobanking-Lübeck (ICB-L) combines more than 40 clinical departments and institutes of the University of Lübeck1 and the University Medical Center Schleswig-Holstein (UKSH),2 Germany, to facilitate the standardised and high-quality collection and processing of biospecimens and associated clinical data. Not only can these be put to use in basic research into certain diseases, they can also serve as a basis for the identification, testing and validation of innovative biomarkers to improve early diagnosis, treatment, prognosis and follow-up, thereby promoting targeted therapy strategies in the context of personalised medicine.
Here, the centre’s director, Professor Jens K Habermann, member of the council of the European, Middle Eastern & African Society for Biopreservation & Biobanking (ESBB),3 outlines the specific challenges and advantages of hospital-integrated biobanks (HIBs) like ICB-L, reflects on how best to ensure the sustainability of biobanks as a whole, and provides his own perspective on the status of biobanking in Europe today.
In what ways can hospital-integrated biobanks be effectively utilised as supporting infrastructure for precision medicine?
Precision medicine comprises the entire patient path from screening via diagnostics, therapy and response monitoring up to prognostication for a single patient. Hereby, treatment decisions will not only rely on clinical routine diagnostics or tests that are currently reimbursed by public healthcare systems. Furthermore, treatment decisions are increasingly based on molecular characteristics of an individual patient. The molecular phenotype is reflected by biomarker compositions in the patient’s tissue and/or body fluids (e.g. blood, urine) and can be elucidated using different omics techniques (e.g. genomics, pharmacogenomics, transcriptomics, proteomics, metabolomics, and/or microbiomics). What all omics techniques have in common is the need for high-quality samples, with each analysis technique having specific requests for sample preparation and quality measures.
Furthermore, high-quality biospecimens need to be accompanied by corresponding clinical data for enabling precision medicine. Both can be provided by hospital-integrated biobanks since HIBs close the infrastructural gap between routine patient care and translational research. Hereby, HIBs obtain, process, and provide high-quality biosamples and corresponding clinical phenotype data in a standardised and timely fashion – intra- and extramural. HIBs can play a fundamental role in returning research results back to the clinic so that the clinician in charge can access actual research results for her/his individual patient for choosing the individually best possible treatment regime. Such scenarios can reach from molecular imaging-based planning for complex surgical interventions to molecular tumour boards in which the interdisciplinary team of physicians considers omics-based systems medicine therapy guidance – the latter scenario being partly established for patients resistant to first or second line therapies at major healthcare providers.
In the broadest sense, HIBs can help to yield the best possible clinical knowledge gain for an individual patient by bridging clinical work with translational research and vice versa.
What specific challenges are involved in successful hospital-integrated biobanking?
The term ‘biobank’ describes a collection of human biological material (e.g. tissue, blood, urine) and analytes thereof (e.g. DNA, RNA, proteins, circulating tumour cells) which are linked to sample- and donor-specific data as well as sociodemographic information about the donor. Depending on the material and data collected, the European, Middle Eastern & African Society for Biopreservation & Biobanking divides different types of biobanks: museum, environmental, population-based, cell culture, therapeutic, and hospital-integrated biobanks. HIBs belong to the most challenging type since sample and data processing has to be implemented into the clinical setting where treatment of patients has the top priority. All processes need to be standardised and quality-assured despite the fact that the clinical setting does vary substantially from one clinical discipline to another, from in- to outpatients, and from individual staff members having different roles and rights along the patient’s clinical path. Hereby, data protection laws, ethical approval and patients’ informed consent (IC) are mandatory and the most sensitive issues to be addressed, but at the same time biobanking cannot interfere with or delay clinical care. For high sample quality, HIBs need to apply state-of-the-art cryotechnology, automated infrastructure, (certified) quality management, quality controls, and – in its own best interest – biospecimen research addressing pre-analytical pitfalls.
All these different areas are highly interdisciplinary and particularly labour- and cost-intensive. It can be easily envisioned that such tasks can only be achieved at a high level through centralised HIBs.
How have you responded to these challenges at ICB-L, and are there any examples of best practice there that could be exported to wider biobanking in Europe?
The Interdisciplinary Center for Biobanking-Lübeck has been established as the central HIB of the University of Lübeck, the UKSH, and the Fraunhofer Institute for Marine Biotechnology (EMB).4 Serving more than 40 clinical disciplines on campus, ICB-L operates on a strict governance concept with internal and external advisory boards, an executive committee, as well as use and access regulations for biobank members and external requests. ICB-L is DIN EN ISO 9001 certified and uses a three-stage broad and generic IC procedure allowing the sharing of samples and data for biomedical research projects with collaborators in academia and industry worldwide.
Automated interfaces between hospital information systems and the central HIB software allow automated patient recruitment for clinical trials and research studies. While the HIB software runs fully operational in the militarised zone, using a campus-wide harmonised dataset of more than 2,800 clinical and research parameters, pseudonymised data are selectively transferred through a data custodian to external accessible sample and data query tools such as CRIP,5 the Fraunhofer Metabiobank,6 and the North German Tumor Bank of Colorectal Cancer.7
Together with its biospecimen research agenda, sample process automation, and specialisation on automated nitrogen-based cryo-conservation, ICB-L allows for highest sample quality while guaranteeing a fully closed cooling chain. With its set-up, ICB-L supports therapy guidance in molecular tumour boards and patient recruitment/management of clinical trials.
In summary, ICB-L’s IT infrastructure is set up as a fully operational data integration centre bridging from clinical care, clinical trials and intramural translational research up to international biobank networks and research consortia. Hereby, ICB-L is actively involved in ESBB and is – through the German Biobank Alliance – a partner of BBMRI-ERIC (Biobanking and Biomolecular Resources Research Infrastructure under the European Research Infrastructure Consortium).8 ICB-L has become a test site for cryo-technology and IT solutions and undertakes consulting activities for academic and industry partners regarding HIB-related processes.
Some have questioned the overall sustainability and usefulness of biobanks given the significant resources required to maintain them – how would you respond to this?
Indeed, state-of-the-art HIBs are highly cost intensive. However, billions of euros are spent on biomolecular research in the European Union overall and, in contrast, only a few examples exist where research results could be successfully transferred into clinical use. In line, the rate of FDA-approved tests compared to the multitude of biomarker publications is devastating.
One reason has been the overall low quality of clinical samples provided for translational research. Sample integrity can easily be affected by pre-analytical conditions such as time and temperature. However, about 70% of publications addressing biomarker research do not give information on sample collection and processing. This makes it impossible to judge the quality of the samples and hence the research results obtained by using such samples. Therefore, the International Society for Biological and Environmental Repositories (ISBER)9 has established the SPREC (Standard PREanalytical Code) reporting system for controlling the main pre-analytical factors affecting clinical fluid and solid biospecimens.
There is still no consensus on, for example, processing steps or storage temperatures for every type of sample used for biomarker studies. Therefore, identifying and evaluating pre-analytical influencing factors such as temperature during processing and storage, freeze-thaw-cycles, or manual versus automated processes have become substantial in biospecimen research. Against this background it is commonly understood that the sampling, processing and storage of biological materials need to become more standardised and quality-assured than it has been practised in the past.
As a consequence, biobanking developed into a new innovative discipline. The scientific societies ISBER and ESBB, as well as BBMRI-ERIC, do aim for the harmonisation and interconnectivity of biobank processes for allowing comparable sample quality across biobanks worldwide. Investing in research with samples of questionable quality is wasted money; investing in and sustaining HIBs to obtain high-quality samples and according clinical data will be the only way to identify new clinically relevant biomarkers and to enable precision medicine. As such, HIBs should not only be regarded as cost-intensive research infrastructures but also be considered an integral part of routine healthcare systems. Thus, the sustainability of HIBs should be assured by both research-funding and healthcare revenues.
More widely, how would you assess the biobanking landscape in Europe at present?
Medical advancement can hardly be envisioned without hospital-integrated biobanks; precision medicine will be strongly limited without them. HIBs should therefore be considered as an integral part of today’s and tomorrow’s healthcare and research systems, become established Europe-wide, and not be limited to academic university hospitals. This development is under way and primarily pursued by BBMRI-ERIC and ESBB. However, only a few academic clinical centres have invested in state-of-the-art HIB infrastructure and offer their patients according services today. Therefore, more effort and support is needed to build up a European-wide network of HIBs of comparable quality standards to promote biomedical research and benefit all EU citizens and patients.
Challenges and solutions discussed in this interview will be further addressed at the upcoming Global Biobank Week conference commonly hosted by BBMRI-ERIC, ESBB and ISBER in Stockholm, Sweden, from 13-15 September 2017.10
Professor Jens K Habermann MD, PhD
Interdisciplinary Center for Biobanking-Lübeck (ICB-L)
University of Lübeck & University Clinic Schleswig-Holstein, Campus Lübeck
+49 451 500 40431
This article will appear in issue two of Pan European Networks: Health, which will be published at the end of August.