Does Your Biosample Pre-analytical Process Measure Up?

Posted by Debra A. Barnes, Ph.D. on Jun 24, 2014 10:53:00 AM

In our previous blogs, we've discussed some challenges and issues associated with biobank samples, particularly the variations in collection and handling procedures (pre-analytical variables) that can significantly influence various downstream analyses or applications.  Many studies and discussions have focused on  this particular matter. To this end, I am excited to share and discuss some of the recent updates from several groups in the biobanking community.


Processing tissue samples

The National Cancer Institutes’ Biorepositories and Biospecimen Research Branch (NCI BBRB; formerly the Office of Biorepositories and Biospecimen Research, or OBBR) has made the first of a series of Biospecimen Evidence-Based Practices (BEBPs) available. This first entry in the series focuses on best practices in the collection, processing, and preservation of surgical tissue. The BBRB introduced the series and explained the rationale for their approach in a brief report by K. B. Engel, J. Vaught, & H.M. Moore, in the April 2014 issue of Biopreservation and Biobanking.

This is only the most recent of three developments in biospecimen science that focus specifically on the issue of pre-analytical variability. The other two breakthroughs are: the Biospecimen Reporting for Improved Study Quality (BRISQ)1, established in 2011 by the NCI BBRB, for reporting data on pre-analytical sample handling; and the Sample PREanalytical Code (SPREQ) from the International Society of Biological and Environmental Repositories ( ISBER), which defines classification codes and interfaces with the BRISQ (ISBER published version 2.0 in 20122). More about these two breakthroughs later.

It was recognized long ago that promoting the use of a single set of SOPs is simply not practical, as these procedures are generally customized to the requirements of the institution.  However, a uniform approach for the evaluation and validation of specimen collection, processing, handling, and storage is needed.  Without controls for pre-analytical variability, biospecimen-based research can lead to identification of irrelevant biomarkers and a waste of time and resources. As mentioned in their report, Engel et al note that “the question of whether SOPs are developed upon the current state of the science or ritual alone often escapes discussion.”

Biobanking sample management process

The NCI’s BBRB series involves an innovative approach to establishing best practices while retaining flexibility needed for customization of procedures for institutional needs. The BBRB is issuing step-by-step procedural guidelines, and each step is annotated with citations and summaries from the supporting literature.  The guidelines present the optimal procedure and also outline acceptable alternatives if the optimal procedure is not available. According to BBRB, the intent is not to re-invent the wheel, but to augment existing best practices in specimen handling by adding additional detail. 

The first of these evidence-based practices for biospecimen collection and freezing, “Snap Freezing of Post-Surgical Tissue Biospecimens,” is now posted on the BBRB website and new evidence-based practices will be posted as they become available.

Collecting sample and preparing pre-analytical sample types

This approach to best practices follows the BBRB’s innovative structure for reporting specimen-related data, the BRISQ, published in 20112. Biospecimen handling is not uniformly reported in published research, and the BRISQ provides a means of standardizing the reporting of biospecimen-related data, by organizing data elements into three tiers (according to the importance of the information). The BRISQ  is easily translated into an online entity, but is only intended to guide the structure of the reporting of biospecimen-related data.  NCI did not address uniform terminology, however, for this, ISBER stepped into the gap.

Processing sample with proper sample temperature

The ISBER Biospecimen Science Working Group developed the first version of the Sample PREanalytical Code (SPREC) in 2009 and in 2012 issued version 2.03. SPREC provides a seven-element structure for the classification of pre-analytic quality parameters of the biospecimens typically used in human health and medical research, and apply to all mammalian specimens.  The seven elements are: sample type, type of primary container, time period between collection and processing, first centrifugation (if applicable), second centrifugation (if applicable), time period between centrifugation and storage, and type of long-term storage.  For each element, a classification code is defined, so that the seven elements are strung together into a “Pre-analytical barcode”   Version 2.0 maintained the codes of the initial version, but includes additional codes to cover a greater range of variables in sample handling and processing.  For version 2.0, ISBER also defined an interface for the BRISQ, and provided a protocol for implementing SPREC in biobanks4.

ISBER and the BBRB have not only made progress in addressing these issues, but their recommendations are compatible and complimentary!  The question now is, are these advances and innovations being implemented? Are there any additional pre-analytic quality parameters you've come across that applies specifically to your area of study? 

For those who are working with many sample types for various end uses, below is a nice infoposter that illustrates optimal sample storage temperature based on your end-use of the sample. You can also refer to this blog article to learn how you can maintain biosample integrity by minmizing sample freeze/thaw cycle.

Biobank sample storage temperature infoposter

Download InfoPoster


1Engel, K. B.; Vaught, J. & Moore, H. M. (2014). National Cancer Institute evidence-based practices:  A novel approach to pre-analytical standardization. Biopreservation and Biobanking, 12(2):148–150.

2Moore, H. M.; Kelly, A. B.;  Jewell , S. D.; McShane, L. M. & Clark, D. P. et al. (2011). Biospecimen reporting for improved study quality (BRISQ). [BRISQ was published simultaneously in three journals: Biopreservation and Biobanking, 9(1): 57–70; Journal of Proteome Research 10(8):3429-3438; and Cancer Cytopathology 119(2): 92–102] and can also be accessed through the BBRB website at

3Lehmann, S.; Guadagni, F.; Moore, H. M.; Ashton, G. & Barnes, M. et al. (2012). Standard preanalytical coding for biospecimens: Review and Implementation of the Sample PREanalytical Code (SPREC). Biopreservation and Biobanking, 10 (4): 366–374.

4Nussbeck, S. Y.; Betsou, E. E.; Betsou, F. Guadagni, F. Lehmann, S.; & Umbach, N. Is there a protocol for using the SPREC? Biopreservation and Biobanking, 11(5): 260–266.