BMK - Biomarkers - 2009
- To review present knowledge of tobacco and smoking-related biomarkers of exposure and effect.
- To organise and conduct periodically inter-laboratory comparisons for selected biomarkers.
- To source and develop reference materials to support biomarker analysis for those biomarkers selected for inter-laboratory comparisons.
The CORESTA Biomarkers Sub-Group (BMK SG) was formed from the Nicotine Uptake Task Force, due to the scientific and regulatory interest in tobacco- and smoking-related biomarkers.
The BMK SG initially focused on the biomarkers of exposure, and has begun to consider biomarkers of effect according to the SG objectives. The current membership of 31 delegates come from the Tobacco Industry and the Contract Laboratories, and represents a wide range of expertise in bioanalysis, synthetic chemistry, clinical research, in vitro models and biostatistics. The BMK SG holds joint meetings with the Product Use Behaviour (PUB) SG (formerly called the Smoking Behavior (TSB) SG) and there is a significant overlap in the membership of the two Sub-Groups. Since its inception, the BMK SG members have:
- Reviewed scientific literature and presented findings from original research, originating from within their own laboratories’ and from external publications, pertaining to the above objectives. For example, urine biomarkers of smoke exposure (nicotine and its metabolites, acrolein and 1,3-butadiene), comparison of 24h and spot urine biomarkers, biomarkers of biological effect (eicosanoids) and the approaches to further identification of biomarkers of biological effect. These scientific discussions have underscored a continued need to develop robust methods and a need to consider additional biomarkers and techniques for evaluation of tobacco products.
- Successfully completed a proficiency test (PT) of hydroxypropyl mercapturic acid (HPMA, a urinary biomarker for acrolein exposure) measurement, involving 12 different laboratories globally. The final report was published in July 2016 on the CORESTA website and as a manuscript entitled "An Inter-Laboratory Comparison for the Urinary Acrolein Biomarker 3-Hydroxypropyl-Mercapturic Acid (3-HPMA)" in Beiträge Tabakforsch. Int. 27(5) (2017) 65–76.
- The need to reduce inter-laboratory variability was recognised and a set of recommendations were proposed. Maintaining sample integrity and adhering to uniform sample handling guidelines were some of the suggestions as means to reduce inter-laboratory variability.
- Initiated a comparison test of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL, a urinary biomarker for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) exposure) through the German External Quality Assessment Scheme (G-EQUAS). The use of an independent external scheme administrator was felt to be beneficial because it imposed uniform costs on all participants, without requiring additional input from CORESTA. It was also recommended that as G-EQUAS already carries our regular ring trials on other commonly used Biomarkers of Exposure to tobacco smoke, this scheme should be used by member laboratories to assess their methods in comparison to other laboratories carrying out similar analyses. This would allow laboratories carrying out analysis on Biomarkers of Exposure to tobacco smoke to demonstrate the quality of their analysis and would support publication of this work, and allow better comparison studies on Biomarkers of Exposure from different laboratories.
- A CORESTA Technical Report "Inter-Laboratory Comparison Test Measuring Total NNAL in Human Urine" was published in November 2018.
- Published a manuscript on urinary biomarkers of exposure:
- ‘Urinary Biomarkers of Exposure to Tobacco Smoke Constituents: A fit for purpose approach’ Biomarkers (2013) 18:467-486. This paper reported on the current state of Biomarkers of Exposure to tobacco smoke and the work carried out to establish their ‘fitness for purpose’ as well as any gaps required to be addressed.
- Initiated a meta-analysis study that established that the population level estimate for smokers can be used as the baseline against which changes in exposure for smokers switching to potentially reduced risk tobacco products and/or following cessation can be compared.
- A CORESTA Technical Report "Meta-Analysis Study to Establish Baseline Levels of COHb and NEQs in Smokers and Non-Smokers" was published in December 2019.
- Members have shared information at the joint Sub-Group meetings on the reference materials for biomarker quantification. This has led to the publichation of Guide No. 20 on the requirements for the certification of analytical reference standards for biomarker studies.
- Members have shared information at the joint Sub-Group meetings on the emerging requirements for good laboratory practice (GLP) with regards to bioanalytical measurements.
In addition to the above actions, members of the Sub-Group jointly drafted a separate definitions paper on aspects of smoking behaviour, including some biomarker definitions that was published:
- ‘Assessing Smoking Behaviour and Tobacco Smoke Exposure: Definitions and Methods’ Beiträge Tabakforsch. Int. 25(8) (2013) 685–699. The aim of this paper being to define and harmonise the terminology associated with smoking behaviour and Biomarkers associated with smoking.
Collectively, the activities of the BMK SG are anticipated to address various scientific issues in the area of tobacco- and smoking-related biomarkers. Further, such knowledge may aid the members in fulfilling regulatory requirements, as appropriate.
In January 2016, the text "as agreed by the Scientitific Commission" was removed from the second objective, and in June 2016 the term "ring trials" was removed as the focus of the group is on proficiency tests. In January 2017, reference to "ring trials" and "proficiency tests" in the objectives was replaced by the term "inter-laboratory comparisons."
Updated December 2019
Reports : Meta-Analysis Study to Establish Baseline Levels of COHb and NEQs in Smokers and Non-Smokers12/2019 Reports : Inter-Laboratory Comparison Test Measuring Total NNAL in Human Urine11/2018 Reports : An Inter-Laboratory Comparison for the Urinary Acrolein Biomarker 3-Hydroxypropyl-Mercapturic Acid (3-HPMA)02/2017 Reports : 3-HPMA Interlaboratory Comparison Study 201207/2016 Guides : No. 20 - Biomarker Studies - Requirements for the Certification of Analytical Reference Standards09/2017