Why the system for biospecimen procurement is broken
Dr Robert Hewitt explains why the need of biospecimen brokers to protect their commercially-sensitive information can result in significant issues for industry end-users and the results of their research.
A biospecimen’s journey from donor to research laboratory can involve wide variety of possible routes, events and timelines, all of which may have the potential to affect the sample quality. For this reason, it is vital for researchers to know the provenance details for all the biospecimens they use. Unfortunately, for researchers in industry, this information is often lacking and this affects the reliability of the resulting research.
The reason is that researchers in industry often obtain biospecimens through a commercial broker. These brokers act as an intermediary between the hospital biobank where the sample was originally collected and preserved and the client in industry. They source the necessary samples for their client and charge a fee for this service; they cannot allow free and unconditional communication between the researcher and the hospital biobank because this would risk their own circumvention and loss of profits. So, in general, brokers conceal the source of their samples with the result that the end-user may lack biospecimen provenance information.
For the industry scientist who is the end-user of the sample, the provenance information that is important to know includes: sample processing history; information about the donor and their medical history; the geographic origin of the sample which provides information about environment and ethnicity; and previous custodians, which may include one or more brokers.
Even in the simplest of cases, there is huge potential for variation in sample processing. For example, take diseased tissue removed by a surgeon – these samples need to be preserved rapidly to minimise damage caused by anoxia that begins once tissue is separated from its blood supply. The speed with which preservation, by cooling and freezing, is started is highly variable and dependent on the efficiency of the biobank team.
To give another example, blood samples need to be processed by fractionation into different components (blood cells, plasma and serum) and the efficiency of this process can again vary between different sources. At the most basic level, knowing the identity of the source biobank allows researchers to decide whether samples are likely to be reliable, based on past experience. If that biobank has obtained appropriate licencing, certification or accreditation, this will provide confidence about sample quality and reliability – for example, licensing by the Human Tissue Authority in the UK, ISO certification (ISO9001 and ISO20387), US CAP Accreditation and CTRNet Certification. Researchers who are unable to assess the reliability of their samples are at risk of producing research that is irreproducible. This is not only a waste of research funding on a huge scale, but it also delays the development of lifesaving therapies.
The industry scientist needs information about the sample donor, including demographic information and medical history. To be sure of this information, it is best for the scientist to be in contact with the source biobank. If additional information is required subsequently, such as the response to treatment or survival time, then it will be necessary to recontact the source biobank. All of this is made much more difficult if a broker refuses to reveal the source of the samples.
In the years ahead, regulatory requirements for the approval of drugs and diagnostics will enforce the need for reliable sample provenance information”
Knowing the geographic origin of a sample or biospecimen is essential because this may provide information about environmental, socio-economic and genetic factors that will help make sense of research findings. This is particularly important because the international sourcing of samples for industry is highly prevalent. In a recent survey, the Medicines Discovery Catapult found that diagnostics small and medium enterprises (SMEs) in the UK obtained 75 percent of their samples from other countries. Part of the reason is that in the UK and other countries in western Europe, there is a high level of concern surrounding the ethics of trade in human tissue, so brokers find it much easier to source samples in other parts of the world, like eastern Europe, Asia and the US. It is important to note that some countries like China, India and Russia have legal restrictions on the export of samples, so another reason to be sure of geographic origin is to avoid the use of illegally sourced samples.
The international sourcing of clinical samples may involve a number of commercial entities operating in different countries, which adds additional degrees of separation between the source and the end-user. It is important for end-users to be aware of this and the possible effect on the reliability of information provided about patient consent and sample provenance.
Information about sample provenance is clearly vital for a range of scientific, ethical and legal reasons, so what can be done to make sure that when industry obtains samples, they always come with reliable provenance information?
One option is for brokers to allow direct communication between the hospital source of samples and the end-user, but to require both parties to sign a contractual agreement to the effect that they will not circumvent the broker; such contracts are indeed being used effectively by several commercial brokers. However, the fact they place restrictions on the freedom of companies and biobanks to form partnerships is not always acceptable to one or other of the potential partners.
Another possibility is for companies to build their own networks of biobanks to supply them with the samples they require. This may be feasible in the long term, but in the short term it is often very difficult to find suitable hospital biobanks with the necessary samples or biospecimens in stock. There are publicly available biobank directories that companies can consult, but these are generally designed with academic researchers in mind and may not indicate whether the biobanks are willing or indeed motivated to work with industry. So, for start-up companies and those with urgent sample needs, there is generally little alternative but to obtain samples through brokers.
Recently established not-for-profit organisation Biosample Hub offers another solution: an online platform dedicated to partnering industry with academic biobanks. The platform includes directories of biobanks, companies and requests as well as networking features to allow members to communicate. So far this has been well received by academic biobanks in western Europe, providing industry with a route to previously inaccessible sources of clinical samples.
In the years ahead, regulatory requirements for the approval of drugs and diagnostics will enforce the need for reliable sample provenance information. Already the European In Vitro Diagnostic Regulation (IVDR) requires this for makers of medical devices. Together with the introduction of new legal and regulatory requirements, there are promising technological developments that will help ensure reliable sample and biospecimen provenance information: for example, the distributed virtual leger technology of blockchain offers the potential to track samples with absolute confidence while still protecting patient confidentiality. Overall, the prospects for improving biosample provenance in the future look very bright.
About the author
Dr Robert Hewitt is the founder of Biosample Hub, a new platform that connects biotech companies looking for samples with biobanks that have ethically sourced samples available.