By Erik Steinfelder, Biobanking Market Development Director at Thermo Fisher Scientific
From hidden repositories, secreted deep in the basements of universities and hospitals, to the emergence of collaborative powerhouses driving ground-breaking therapies, biobanks have come a long way in the past 30 years.
Biobanks were originally created as vast repositories of information for population studies, disease research and more recently, genomics and personalised medicine research. Chances are that if a patient had any kind of surgery in the past few years, there will be a piece of them frozen in a biobank. These libraries were originally established to preserve samples in case future technology might provide insight for disease cause or cure. Samples were frozen and loosely categorised for use at an unknown future point. Modern biobanks are far from the freezer farms of the past. Instead, they are now viewed as critical knowledge assets, containing vast collections of human tissue and designed for sharing knowledge among researchers.
With their collection of high-quality samples, biobanks are important enablers of research, helping scientists understand diseases and propel the discovery of novel therapeutics. Biobanks can play an essential role in driving evidence-based care and personalised medicine but only if they are leveraged to their true potential. To move beyond the traditional sample storage model, biobanks need to become dynamic institutions that respond to the shifting research landscape, incorporating the ethics, policies and governance necessary to protect these valuable sources of insight.
Biobanks were born from a plethora of needs, opportunities and functions and this has created a siloed structure. Each organisation has historically created its own set of working standards but this comes at a price to the ultimate beneficiary – the patient. Collaboration is the key to future success. The true purpose of a biobank must be to share data, to further research and keep the patient at the heart of all decisions.
Key laboratory technologies have advanced in recent years, supporting biobanks as they become research enablers, and providing the non-negotiable bedrock of safe and secure sample storage. Developments in cold storage technology and laboratory consumables are helping biobanks protect and track samples to maintain integrity and viability, as well as fulfil their potential through efficiency and productivity improvements.
With success criteria focused on therapeutic outcomes, forward-looking biobanks are now adopting fresh strategic, regulatory and technological approaches to become valuable service providers.
The importance of cross-collaboration
Time and effort are needed to create and maintain a biobank. Many have been established over decades, involve thousands of samples and require ongoing investment in both time and money. Understandably, biobank owners want to protect what they have built but this has encouraged siloed biobank construction and ongoing management. This approach is exacerbated by the need to navigate and comply with complex policies, such as the 2018 European general data protection regulation (GDPR).
Although the biobank industry is well-established, the growing trend towards cross-collaboration is still in its infancy and when many of the older banks were first created, it was to store what was currently available, in isolation, without much understanding of how the information might be useful in the future. Since the technology was not available to elucidate understanding, a research aim could not be articulated from the outset. Of course, this cannot be the approach of the future. Biobanks need to have a strategic purpose or they risk holding samples with unexplored potential, unable to contribute to scientific breakthroughs.
The siloed approach needs to be resigned to the history books. The purpose of a biobank is to benefit patients and to further research and discovery but the value of high-quality datasets is negated if they can’t be accessed or shared. A recent report in Nature Biotechnology highlighted that 81% of biomedical researchers are constrained by the inadequate quality and quantity of biospecimens and 80% of companies find it difficult to access materials.1 Access issues can lead to funders removing investment and if donors cannot see biobanks contributing to the society, blood, urine or tissue donation may as well decline. Without funding and human material contributions, biobanks simply cannot survive.
Forward-looking biobanks are now embracing a new paradigm that rewards a collaborative approach and sees them take a new role of a service provider. Some of the most successful biobanks are taking a lead in advancing precision medicine, collaborating with other biobanks, academia, policymakers and pharmaceutical manufacturers towards a common goal of novel and effective drug discovery.
This approach is already bearing fruit. The €28.7 million ConcePTION project2 is a mass population study using largescale sampling to reduce uncertainty around the use of medication during pregnancy and breastfeeding. Started in 2019 and running until 2024, ConcePTION has already published papers on the transfer of medication to breastmilk and on pregnancy and foetal outcomes in women with multiple sclerosis.
The 1 Million Genome3 project is another example of collaboration, aiming to give cross-border access to a million genomes by 2022. Already, 24 European Union countries are involved in building, amalgamating and standardising the database, with the hope that centralised access will drive disease prevention and more personalised therapies.
Embracing global collaboration will provide insight into drug efficacy on more diverse populations, rather than the US and European skew that is often seen in clinical trials. Biobanks are already taking a more central and global role in the discovery of vaccines and therapies, as demonstrated during the Covid-19 pandemic. The expedited discovery and production of Covid-19 vaccines and the widespread availability of effective therapies are in no small part due to the availability of thousands of biobank samples.
Adapting to regulatory requirements
To enable effective collaboration, regulation is critical, and researchers must be assured of sample quality, traceability and reliability.
For many years, there have been no regulations regarding the collection, processing and storage of samples. Instead, biobanks have employed their own best practices, striving to protect their valuable assets and give assurance to the researchers who use them, but, until recently, standardisation was not a goal within reach.
This changed in 2018 with the introduction of the first global standard for biobanks. The ISO 203874 standard provides general requirements for biobanks to ensure competence, impartiality and operating consistency, as well as quality control in respect to the biological material and data that they hold. Naturally, adopting best-practice and ensuring compliance takes time and although biobanks are shifting to adopt ISO 20387 practices, this has been a slow process. Currently, only two biobanks and one US veterinary biobank are ISO 20387-accredited.
In the fragmented and diverse biobank industry, it can be hard to find the quality and traceability guarantees needed to ensure research can be replicated reliably. As ISO 20387 is more widely adopted, it will surely become a prerequisite when biotechnology and pharmaceutical manufacturers choose their biobank partners. In the highly regulated biotechnology and pharmaceutical industries, accreditation provides confidence and helps to fast-track approvals. Researchers expect high-quality samples that have been stored under reliable storage conditions and that are supported by the accurate data needed to confirm this. Compliance with the ISO 20387 standard will provide this assurance and biobanks that cannot demonstrate it will be at a disadvantage.
Ethical and legal considerations in biobanking
Biobanks must also play an important ethical and legal role in protecting samples. Certainly, blood, urine and tissue samples should be accessible to those who have a right to use them, but patients must be confident that their samples are being used only for purposes for which they have given consent. Consent compliance is crucial for a biobank’s long-term prospects. Clear and transparent policies protect patients and give future donors confidence and peace of mind, which can lead to increasing donor numbers. This part of the ethics arena is clear: straightforward consent statements and compliance with those rules create a failsafe framework, protecting both the individual and biobank.
Ethics become more ambiguous when it comes to sharing research findings. Incidental findings can provide both beneficial and detrimental insight for patients and, in the case of genetic research, can extend to family members. Biobanks must decide whether to disclose this information and make it clear at collection whether the donor may receive further learnings related to their tissue samples.
Technology is advancing at great speed; blood, urine and tissue samples may be used in future years to uncover information that we can only imagine today. Technological advances are revealing insights into diseases at rapidly increasing rates and cheaper personalised medicine is becoming a reality. Boundaries and guidelines must be established with donors now so that they can choose whether to receive this future information, however vague the potential may seem today.
The colorectal cancer cohort (CRC-Cohort) project5, developed through the EU-funded ADOPT BBMRI-ERIC collaborative, has involved the collection of data from 25 different biobanks across Europe. Over 10,000 samples have been collected from 12 different countries with the aim to share important clinical, genetic and treatment data from colon cancer samples. Biobanks are compensated for their contribution by gaining access to this larger dataset and this project is fast becoming the blueprint for effective collection, storage and sharing of sample data. Privacy is ensured for each patient according to the conditions that they signed up to and through this project, it is hoped that patients will benefit from faster diagnosis and more personalised therapies based on their cancer profile.
Driving sample quality and integrity through advanced cold storage
From the creation of the first biobanks, safe and secure storage has been a non-negotiable baseline. Even the simplest biobanks were built to maintain samples, to prevent degradation and ensure sample identification. Samples are extremely valuable and in many cases, irreplaceable; collecting samples and the surrounding incidental and genomic data is time-consuming and costly. Cryogenic freezers are key to protecting tissue quality and integrity, particularly in living cells.
Advances in modern cold storage technology have changed the landscape for biobanks, increasing efficiencies and bringing another level to integrity and quality preservation. ISO 20387 standards are driving the selection of certain qualities in cold storage technology, offering confidence to investors and funding bodies, as well as the researchers using the samples.
Cryogenic freezers that are easy to program and monitor provide peace-of-mind and save considerable time, but it is the inner working of the cold storage system that will deliver the biggest benefit.6 Specially designed air handling systems and liquid nitrogen injections can work in tandem for precise temperature control and uniformity throughout the samples. Liquid nitrogen also offers consistent temperature control, even in power outages, safeguarding sample integrity. Indexed storage systems enable fast and efficient sample retrieval and integration with analytical systems. Pharmaceutical companies may stipulate days rather than weeks for sample retrieval and, often, only a heavily automated retrieval system can handle these demands.
Laboratory consumables can have a huge impact on the effectiveness of cold storage technology, and ultimately, on sample integrity and quality. Cryostorage vials and sample tubes serve a critical role in tissue protection as the first line of defence between the sample and its surrounding environment, and they must be compatible with the storage type and temperature. For living cells, storage temperatures need to reach around -200°C, which is cold enough to stop enzyme function, and containers must be robust enough to withstand these temperatures without becoming brittle or damaged. Vial and tube seals must also be robust and able to withstand the storage duration, preventing contamination, damage and concentration changes due to evaporation. Sample containers must be designed with sound engineering principles, since they may need to undergo multiple handling processes and numerous capping and decapping cycles as they move in and out of storage. As such, they must be designed to cope with these stresses, while still achieving and maintaining a tight seal.
Cryostorage consumables also have a role to play in sample identification. Two-dimensional barcodes keep track of every sample, even in a bank of millions. Consistent, easy-to-read, high-quality barcode formats must be used to withstand extreme temperature and the test of time, ensuring that samples can be tracked wherever they are in the system, even if they are accidentally dropped or damaged.
Business strategies and partnerships strengthen biobank operations
As biobanks transition from siloed repositories to service providers, they need a strategic approach. From manufacturing to marketing, the purpose and goal need to be consistent if biobanks are to deliver consistent messages and differentiate their service from that of their competitors.7 At the heart of these messages must be the drive to improve patient healthcare and lead development and medical breakthroughs. How each biobank does this will be particular to each. To deliver high-quality samples and services that achieve a clear purpose, biobanks need to focus on a distinct goal. Gone are the days when biobanks can collect samples today and think about the purpose later.
In a survey of German researchers in 2019, Klingler8 found that 57% stated high-quality samples as the most important consideration when selecting a biobank. Although this is clearly important, biobanks must also consider a variety of other characteristics to differentiate their offering from other providers. Speed of data or sample access, technological advantages, tissue types, and sample sizes all play key roles in developing points of difference. Biobanks that can demonstrate a clear chain of custody and therefore, complete traceability of samples throughout storage, transport and use will certainly provide confidence to scientists relying on those samples to drive research breakthroughts. Traceability depends on robust, connected and integrated data systems that can track samples from intake throughout their life cycle.
Biobanks operate in one sphere of clinical discovery, but their connections reach out to multi-faceted sectors. Industry experts can provide insight into the wider context of tissue sample collection and use and the market for this service. Technology providers can often take an end-to-end view, working with pharmaceutical and biotechnology businesses and academics across a range of research and manufacturing specialisms. This cross-organisation understanding can help all partners find a solution that can benefit everyone involved. Industry experts can help future-proof operations and safeguard against the unknown, such as fluctuations in the economy, government budget boosts and cuts, new technological innovations, and societal shifts.
As biobanks head towards standardisation and ISO 20387 accreditation, industry experts can deliver crucial insight that might be difficult to obtain from internal stakeholders, and even provide validated equipment and workflows that can demonstrate compliance. Industry expertise has been clearly utilised during the response to Covid-19. As many organisations scaled operations to include vaccine cold storage solutions, experts were on-hand to guide decisions such as sizing, temperature regulation and handling requirements.
Navigating the shift towards a collaborative future
Biobanks have an important role to play in the future development of novel therapies, particularly as society shifts towards a personalised approach to medicine. They already hold the key to understanding the cause and treatment of many diseases, and as many more change their processes and strategies to take a forward-thinking, service-led approach, the value contained within these precious repositories increases.
The Covid-19 pandemic has shown us the critical need for collaboration. In sharing best practice, knowledge and data, many industries have rapidly expanded into new territories to deliver treatment in unprecedented timescales and it has been the collaboration of a network of experts that has enabled this. With the enormous global investment in cold storage for the distribution and storage of the Covid-19 vaccine, a new infrastructure is now in place, one that could lay the foundation for the safe distribution and delivery of the therapeutics of tomorrow.
To fulfil their purpose in improving patient healthcare, and leading development and medical breakthroughs, biobanks need to continue their journey to become service providers. They must demonstrate sample integrity and quality assurance to their customers, and ISO 20387 accreditation is the first milestone on this journey. The technology and consumables already exist to protect samples, track inventories and provide peace-of-mind to all stakeholders, but to achieve new regulatory standards and continue to deliver the sample quality and integrity that researchers demand, biobanks must embrace collaboration. Biotechnology, pharmaceutical, academic, and other industry and technology experts already have specialised knowledge in their fields. By absorbing and applying that knowledge, biobanks can navigate the technological, regulatory and business challenges they need to overcome to achieve their goals.
Volume 22, Issue 2 – Spring 2021
Erik Steinfelder joined Thermo Fisher Scientific in 2008. In his position as Biobank Commercial Leader EMEA, he went on to head the complete biobank portfolio activities. Between August 2017 and January 2020 Steinfelder was Director-General of BBMRI-ERIC, a research infrastructure that brings together the main players from the biobanking field to boost biomedical research. In February 2020 he returned to Thermo Fisher Scientific as Biobanking Market Development Director.
- Nat Biotechnology 38, 1005 (2020). https://doi.org/10.1038/s41587-020-0678-x
- Conception, Biobanking breast milk and blood. https://www.imi-conception.eu/biobank/
- European Commission, European ‘1+ Million Genomes’ Initiative. https://ec.europa.eu/digital-single-market/en/european-1-million-genomes-initiative
- ISO 20387:2018 Biotechnology — Biobanking — General requirements for biobanking. https://www.iso.org/standard/67888.html
- BBMRI-ERIC, COLORECTAL CANCER COHORT – ADOPT BBMRI-ERIC. https://www.bbmri-eric.eu/scientific-collaboration/colorectal-cancer-cohort
- Hubel A. et al. (2014) Storage of Human Biospecimens: Selection of the Optimal Storage Temperature. Biopreservation and BiobankingVol. 12, No. 3. Published Online: 23 Jun 2014. https://doi.org/10.1089/bio.2013.0084
- Hill T. (2000) Order-winners and Qualifiers. In: Manufacturing Strategy. Palgrave, London
- Klingler C. (2019) Evaluating the German Biobank Node as Coordinating Institution of the German Biobank Alliance: Engaging with Stakeholders via Survey Research In: Biopreservation and Biobanking