Quality in Biobanking: "The greatest challenge is the standardization of processes in the pre-analytical phase"
Interview: PD Dr. Dr. Michael Kiehntopf
Dr. Michael Kiehntopf is Head of the Integrated Biobank Jena (IBBJ) and Director of the Institute for Clinical Chemistry and Laboratory Diagnostics of the University Clinic in Jena. Together with Prof. Peter Schirmacher, he co-ordinates project quality management in the German Biobank Node (GBN). His main interests include the establishment and operation of biobanks, and in particular their quality management.
Michael Kiehntopf at the National Biobank Symposium 2015 (Photo: TMF e.V.)
Dr. Kiehntopf, the quality of samples has a substantial influence on the quality of scientific research results. What contribution can biobanking make to the quality of the material used for research?
The complex conditions that have to be satisfied for research today – in particular requirements relating to ethics, data protection, international standards and quality – represent a considerable challenge, not just for individual researchers but also for larger research collectives. Biobanks can provide the necessary organization and infrastructure and make an important contribution to research. The quality of a sample is subject to a variable number of influences, depending on the complexity of the project. To obtain samples that are of high quality it is necessary to establish procedures that insure quality requirements are met, from the collection of samples through their processing, storage, release and transport. The pre-analytical phase, from sample collection through to receipt of the sample by the biobank, is of particular relevance to the quality of the sample. This is especially important for multicenter studies in which a large number of different collection centers may be involved and the sample collection phase often has to satisfy specific requirements that are not under the control of the study personnel.
These procedures are already standardized in many biobanks. In some cases the biobanks are certified and subareas like internal quality control processes are also accredited. The quality of the samples stored is documented in such a way that tracking is possible. Biobanks can therefore provide high-quality samples and thus make a valuable contribution to quality assurance for research results. Biobanks do not just actively provide services, they are increasingly taking on research tasks, e.g., in the validation of process steps or in the development of tools for the assessment of sample quality. The results obtained can directly improve the workflow and influence the selection of samples that have to satisfy defined requirements for special analytical methods. Biobanks also support research by driving forward the urgently required national and international harmonization of processes to improve interoperability between individual biobanks and therefore promote the availability of sample collections for research purposes that are larger in scale and of consistent quality.
What are national and international efforts to harmonize biobank procedures that are relevant to quality?
Efforts are being made to develop and establish internationally standardized and quality-assured procedures for biobanking on a global basis. For this it is first necessary to define generic standards and quality criteria for the implementation and evaluation of biobank procedures. National activities must be matched to international ones for this. This is carried out under the leadership of the German Institute for Standardization (DIN) with the aim of developing an ISO standard specifically for biobanks. The aspects discussed at a national level in the national standards committee (NA 057-06-02AA, working group 2 biobanks/bioresources) flow at an international level into the technical committee ISO/TC 276 Biotechnology, WG/2 Biobanks/Bioresources.
How do German biobanks and the GBN compare to international efforts to harmonize quality management procedures?
GBN bundles German expertise and actively brings it to the European level. Germany is at an advanced stage compared to other European countries. GBN/WP3 is a project that has the aim of developing a comprehensive quality management (QM) approach to biobanking for both liquids and tissue samples, coordinated by Prof. Schirrmacher in Heidelberg and myself. A large number of biobank specialists are working at a national level to develop a practice-oriented QM manual with generic SOPs. To this end we have analyzed those standards that are relevant to biobanks – such as EN ISO 17020, 17025, 15189 and 9001 – and have attempted to summarize them. All applicable legal and regulatory requirements were also integrated. The manual has been made available to the German biobanks who actively participated in the project. We will make the results of this process available to BBMRI via GBN. In parallel, BMRI ERIC, with the assistance of specialists from European and various German biobanks, is evaluating the implementation of CEN standards for targeted sample handling. These have just been published as a standardized method and are on the brink of becoming an ISO standard. Hopefully, we will have a biobank standard of international validity in the near future.
What are the greatest challenges for liquid and tissue biobanking? How will they be tackled?
In my opinion the greatest challenge is the further standardization of processes in the pre-analytical phase in particular, which lie outside of the direct control of biobanks, such as sample collection. These processes can only be standardized, for example, by the issue of SOPs by the biobank. The necessity of developing standardized tools and criteria for the direct determination and evaluation of sample quality is thus a further challenge for biobanks. The identification and establishment of quality control markers (QCMs) can be helpful here. These markers are analytical variables that have a concentration that varies according to one or more biobank process stages. It is important that these quality control markers have a high specificity with regard to pre-analytical influencing factors and are independent of the clinical phenotypes of interest in the study in question. QCMs that are promising have already been identified in a range of studies, but they must still be validated in larger-scale collectives of diseases under real study conditions. A further challenge is for the drafted standards to be used in the biobanks in a harmonized manner since local conditions are frequently very different.
What QM measures would be required by anyone wishing to set up a liquid/tissue biobank today?
The biobank must be set up to meet the demands of the users and offer a long service. Samples that are collected today may be used only several years from now within the framework of a co-operation that has defined quality requirements. The biobank therefore has to meet the quality requirements of a potential user at a later date before the samples are stored.
What arguments can biobank operators use to persuade those persons collecting samples that they maintain high standards throughout the collection process, and how can they support them?
I do not think that they require very much persuasion. There is clear agreement that high-quality samples are required for the use of highly advanced analytical methods and that the pre-analytical stage is the greatest influencing factor. The problem is sometimes that the degree of effort and thus the resources necessary for an optimal and standardized collection of samples are often assessed differently. However, the award of research funding depends increasingly on the length of time for which the amples can be used, as well as the existence of a quality-assured infrastructure. Biobanking has to be viewed in this context as an activity that spans different fields and requires close co-operation and agreement between researchers and the biobank. The overall quality is always the sum of the quality of the sub-processes and the motivation to act is derived from the information on the possible benefits.
Interview done by Wiebke Lesch.