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 (BOEs) and then included biomarkers of potential harm (BOPHs). The tobacco product landscape has rapidly evolved and there are a range of novel oral and inhalable tobacco products that are lower on the continuum of risk. However, in the absence of long-term epidemiological studies, well-designed clinical studies will be needed to establish the harm reduction potential of smoke-free products. While BOEs and BOPHs may provide some directional indication, more research is needed to expand the portfolio of biomarkers. Therefore, the SG has recognized the need to identify biomarkers that are closer to smoking-related disease endpoints and are clinically relevant. The objective of these efforts will be to establish guidelines and best practices for utilizing fit-for-purpose biomarkers in studies assessing novel smoke-free products.

The current membership includes scientists from the tobacco industry and 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 SGs.

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 24 h 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.
  • 'Population estimates of biomarkers of exposure to carbon monoxide, nicotine, and NNK in smokers and non-smokers' Qeios, March 2022
• Published a technical report and manuscript on lung biomarkers of potential harm/effect:
  • 'Review of recent lung biomarkers of potential harm/effect for tobacco research' F1000Research (2021), 10:1293. In this review, the published data on lung-related BoPH in human lung disease for potential use in evaluating the effects of tobacco and nicotine products is critically assessed.
• Members have shared information at the joint Sub-Group meetings on the reference materials for biomarker quantification.  This has led to the publication 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.
• Published the Guide No. 29 on the best practices in the application of biomarkers of exposure (BoE) as compliance measures in long-term and epidemiological studies of new nicotine and tobacco products.

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."
In February 2022, the objectives of the SG were amended to fit the revised vision of the group, which is to identify and asses fit-for-purpose biomarkers for tobacco product research.

Updated April 2024