Quality Management

The quality of biomaterials is of paramount importance for the success of biomedical research.

Under the umbrella of GBN, we are developing standards and solutions for the next generation of biobanking.

An interview with: Michael Kiehntopf

Quality in Biobanking: “The greatest challenge is the standardization of processes in the pre-analytical phase”

Numerous biobanks have been founded both in Germany and internationally in recent years. These contain and make available human biomaterials and the accompanying phenotypic data for biomedical research. To date, there have been no uniform standards available for the processing and storage of these samples.

 

Dr. Kiehntopf, it is clear that 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 organization and infrastructure that are necessary and so can make an important contribution to research. This is apparent alone from the quality of samples, which 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 for procedures to be established 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 of particular importance 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, of importance for sample quality, are already standardized in many biobanks. In some cases the biobanks are certified and some areas, such as internal quality control, 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 an appreciable 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 flow directly into an improvement in workflow and in 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 to therefore promote the availability of collections of samples that are larger in scale and equivalent in qualitative terms for research purposes.

What are the 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 draw up 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. They are currently discussing it and checking on feasibility. We will make the results of this process available to the BBMRI via the GBN, as an input for the European work program. 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. German biobanks can therefore contribute the expertise they have gained in recent years to a large number of national standardization activities and can accelerate the processes considerably so that we will hopefully have a biobank standard of international validity in the not too distant 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. A large number of internal biobank procedures are now well standardized, for example through the introduction of automated procedures, and are subject to direct quality control by the biobank, whereas processes outside of the biobank cannot be directly controlled at present and 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.

Sample collection and transport are often considered to be the greatest uncontrollable problems for the quality of the samples.

That is correct. As already mentioned, the pre-analytical phase has the most factors that impact on quality. It is important that validated and harmonized standards be used for specific sample materials that define process steps that are critical for quality and their control. It is also important that all processes, from sample collection through transport and processing to the storage of the samples in the biobank are comprehensively documented. This is necessary because it is assumed that there may be deviations from agreed standards in the heterogeneous environment of sample collection. However, samples that do not 100% satisfy the defined criteria do not always have to be excluded from use. The quality of a sample is not an absolute. The quality of a sample may be sufficient for a special application, but may be completely unsuitable for a different purpose. Sample quality is thus relative and always has to be assessed against the background of the requirements, for example the measurement of a specific analyte. A knowledge of the exact sample history, or the determination of quality control markers which enable a subsequent statement on the conditions to which the sample has been subjected, is therefore essential. This allows pre-analytical conditions that are not directly controllable to be managed.

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. The QM measures therefore have to be satisfactory for the later usage of the samples. It is assumed that many project partners of a biobank reside in regions that are tightly regulated and are subject to various national and international regulations such as GxP, AMG, MPG or those of the FDA. In such cases the requirements that a QM system must satisfy are clearly defined. Each biobank must evaluate its internal risks and establish corresponding processes. EN ISO 9001 should always be used as the base standard and must then be explicitly extended to meet the additional requirements. A certification or accreditation, with the corresponding certificate to demonstrate the quality level, should always be aimed for. This will provide an excellent basis for meeting the requirements of the international biobank standard that will hopefully specify the requirements in summary form.

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. As a result, in a joint application for research funding for a project involving various groups the resources to be set aside for sample collection have to be sought from the research partners. Since, however, the award of funding for research projects depends increasingly on the length of time for which the samples can be used, as well as the existence of a quality-assured infrastructure for biobanking, the planning of corresponding resources is absolutely essential. 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.

 

PD Dr. 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 Schirrmacher, 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.

The interview was conducted by Wiebke Lesch in March 2016.

Questions?

germanbiobanknode@charite.de

Tel. +49. 30. 450 536 347


Fax +49. 30. 450 753 69 38

BMBF
top
Biobank Directory European Biobank Directory GBN products Download templates, manuals and other materials