Data integrity in regulated bioanalysis: a summary from the European Bioanalysis Forum Workshop in collaboration with the MHRA.

In this conference report, we summarize the main findings and messages from a workshop on 'Data Integrity'. The workshop was held at the 11th European Bioanalysis Forum Open (EBF) Symposium in Barcelona (21-23 November 2018), in collaboration with the Medicines and Health products Regulatory Agency to provide insight and understanding of regulatory data integrity expectations. The workshop highlighted the importance of engaging with software developers to address the gap between industry's data integrity needs and current system software capabilities.

'Real-world' compensatory behaviour with low nicotine concentration e-liquid: subjective effects and nicotine, acrolein and formaldehyde exposure.

Aims: To compare the effects of (i) high versus low nicotine concentration e-liquid, (ii) fixed versus adjustable power and (iii) the interaction between the two on: (a) vaping behaviour, (b) subjective effects, (c) nicotine intake and (d) exposure to acrolein and formaldehyde in e-cigarette users vaping in their everyday setting.

Design: Counterbalanced, repeated measures with four conditions: (i) low nicotine (6 mg/ml)/fixed power; (ii) low nicotine/adjustable power; (iii) high nicotine (18 mg/ml)/fixed power; and (iv) high nicotine/adjustable power.

Setting: London and the South East, England.

Collaborative Method Performance Study of the Measurement of Nicotine, Its Metabolites, and Total Nicotine Equivalents in Human Urine.

Biomarkers of tobacco exposure have a central role in studies of tobacco use and nicotine intake. The most significant exposure markers are nicotine itself and its metabolites in urine. Therefore, it is important to evaluate the performance of laboratories conducting these biomarker measurements.

E-cigarette puffing patterns associated with high and low nicotine e-liquid strength: effects on toxicant and carcinogen exposure.

Background: Contrary to intuition, use of lower strength nicotine e-liquids might not offer reduced health risk if compensatory puffing behaviour occurs. Compensatory puffing (e.g.

Self-titration by experienced e-cigarette users: blood nicotine delivery and subjective effects.

Rationale: Self-titration is well documented in the tobacco literature. The extent to which e-cigarette users (vapers) self-titrate is unknown.

Objective: This study explored the effects of high and low nicotine strength liquid on puffing topography, nicotine delivery and subjective effects in experienced vapers.

Bioanalysis for plasma protein binding studies in drug discovery and drug development: views and recommendations of the European Bioanalysis Forum.

Plasma protein binding (PPB) is an important parameter for a drug's efficacy and safety that needs to be investigated during each drug-development program. Even though regulatory guidance exists to study the extent of PPB before initiating clinical studies, there are no detailed instructions on how to perform and validate such studies. To explore how PPB studies involving bioanalysis are currently executed in the industry, the European Bioanalysis Forum (EBF) has conducted three surveys among their member companies: PPB studies in drug discovery (Part I); in vitro PPB studies in drug development (Part II); and in vivo PPB studies in drug development.

In-depth study of homogeneity in DBS using two different techniques: results from the EBF DBS-microsampling consortium.

Background: At the start of their work, the European Bioanalysis Forum dried blood spots microsampling consortium did not form a dedicated team to investigate the spot homogeneity. However, two teams performed experiments that produced results relating to sample homogeneity.

Results: The data, which were produced via two different approaches (a radiolabeled and a nonradiolabeled approach), are highly complementary and demonstrate clear effects on sample inhomogeneity due to the substrate type, compound and hematocrit levels.

Recommendations on bioanalytical method stability implications of co-administered and co-formulated drugs by Global CRO Council for Bioanalysis (GCC).

An open letter written by the Global CRO Council for Bioanalysis (GCC) describing the GCC survey results on stability data from co-administered and co-formulated drugs was sent to multiple regulatory authorities on 14 December 2011. This letter and further discussions at different GCC meetings led to subsequent recommendations on this topic of widespread interest within the bioanalytical community over the past 2 years.

Interlaboratory comparability of serum cotinine measurements at smoker and nonsmoker concentration levels: a round-robin study.

Introduction: Cotinine, the primary proximate metabolite of nicotine, is commonly measured as an index of exposure to tobacco in both active users of tobacco and nonsmokers with possible exposure to secondhand smoke (SHS). A number of laboratories have implemented analyses for measuring serum cotinine in recent years, but there have been few interlaboratory comparisons of the results. Among nonsmokers exposed to SHS, the concentration of cotinine in blood can be quite low, and extensive variability in these measurements has been reported in the past.

Changes in environmental tobacco smoke (ETS) exposure over a 20-year period: cross-sectional and longitudinal analyses.

Aims: To examine long-term changes in environmental tobacco smoke (ETS) exposure in British men between 1978 and 2000, using serum cotinine.

Design: Prospective cohort: British Regional Heart Study.

Setting: General practices in 24 towns in England, Wales and Scotland.

Relative bioavailability and pharmacokinetics of two oral formulations of docosahexaenoic acid/eicosapentaenoic acid after multiple-dose administration in healthy volunteers.

Objectives: To assess the comparative pharmacokinetic profile and bioavailability of docosahexaenoic acid (DHA)/eicosapentaenoic acid (EPA) after multiple-dose administration of a new oral formulation (test formulation) and a commercially available reference formulation in healthy subjects.

Methods: Forty-eight healthy subjects received a 28-day oral treatment with DHA/EPA in the form of either the test or the reference product according to an open-label, randomized, parallel-group design. Both formulations were given t.