Why is the current system for sourcing samples broken? And what does this mean for researchers who use biosamples? Robert Hewitt, MB BS, PhD, of Biosample Hub, investigates.
The journey for every biospecimen used for medical research is different. It all begins when the sample is donated by an individual and it ends when the sample reaches the research laboratory where it is analysed. Between these two points, there is a wide variety of possible routes, events and timelines, any of which may have the potential to affect the quality of the sample. Because of this it is vitally important that researchers know the provenance details of everyone of the biospecimens they use in their work. Unfortunately, for researchers working in industry, this information is often lacking, and this will affect the reliability of the resulting research they conduct.
Why is this? The reason is that researchers in industry very often obtain biospecimens through the services of a commercial broker. These brokers act as an intermediary between the client in industry and the hospital biobank where the sample was originally collected and preserved. Brokers source the samples that their client require and charge a fee for doing this. They prefer not to allow free and unconditional communication between the researcher and the hospital biobank, because this would risk their own circumvention and potential loss of profits. So, in general, brokers keep the source of their samples to themselves. The result of this is that the researchers may then lack biospecimen provenance information they need.
For the industry scientists who are the end-users of the samples, the provenance information that is important to know includes: (a) sample processing history, (b) information about the donor and their medical history, (c) the geographic origin of the sample which provides information about environment and ethnicity, and (d) previous custodians, which may include one or several commercial brokers.
Even in simple cases there is great potential for variation in sample processing. To take one example: diseased tissue removed during an operation by a surgeon. This type of sample needs to be preserved rapidly to minimise damage caused by anoxia which begins once tissue is separated from its blood supply. The speed with which preservation is started, by cooling and freezing, is highly variable and dependent on the efficiency of the biobank staff.
Another example, is where blood samples need to be processed by fractionation into different components (blood cells, plasma, and serum) and again the efficiency of this process can 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 a particular biobank has obtained appropriate licencing, certification or accreditation, this will give confidence about sample quality and reliability. This includes 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 in danger 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.
Industry scientists need information about the sample donor, including demographic information and medical history. To be sure that this information is correct, it is best for the scientists to be in direct contact with the source biobank. If additional information is required subsequently, for example the response to treatment or survival time, then it will be necessary to get back in touch with the source biobank. All of this is made significantly more difficult if a broker will not comply with a request to reveal the source of the samples.
Knowing the geographic origin of a sample 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 by Medicines Discovery Catapult found that diagnostics SMEs in the UK obtained 75% 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 about 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 USA. 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 option is for companies to develop their own networks of biobanks to supply the samples that they need. In the long term this may be feasible, however in the short term it can be very difficult to find suitable hospital biobanks with the necessary samples in stock. Companies can consult the publicly available biobank directories, 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. This means that for start-up companies and those with urgent sample needs, there is often little alternative but to obtain samples through brokers.
A recently established not-for-profit company provides a possible solution. This company called Biosample Hub provides 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.
Looking ahead, regulatory requirements for the approval of drugs and diagnostics will enforce the need for reliable sample provenance information. For makers of medical devices the European IVDR regulations already require this. In addition to the introduction of new legal and regulatory requirements, there are promising technological developments on the horizon that will help ensure reliable sample provenance information going forward. To take one example, Blockchain with its distributed virtual leger technology offers the potential to track samples with absolute confidence while also protecting patient confidentiality. Given this we can say that prospects for improving biosample provenance in the future look very promising.
About the author
Robert Hewitt, MB BS, PhD, is the founder of Biosample Hub, a new platform that connects Biotech companies looking for samples, with Biobanks that have ethically sourced samples available.