BackgroundEuropean Medicines Agency (EMA) outlines criterion for validation of bioanalytical assay applied under Good Clinical Laboratory Practice (GCLP) within clinical studies. The validation is performed once and does not inevitably ensures comparable reliability over long duration of assay’s applicability. To address this hurdle, the investigator-driven ‘Labelling of Enalapril from Neonates up to Adolescents’ project (LENA) adapted quality system comparable to industry. A comprehensive set of quality measures was applied to ensure reliability of monthly quantified paediatric samples over duration of 31 months.MethodsA 3-step quality approach analysing the calibration standards (CS), quality controls (QCs) and incurred sample reanalysis (ISR) was used to established reliability of unknown samples. Unknown concentrations were reported only if results of known CS (11 levels) and QCs were within the predefined limits. A maximum deviation of ±15% was acceptable at all five QCs level. ISR was conducted for randomly selected paediatric samples to monitor the assay’s performance over time. The acceptable%difference was ±20% for at least 67% of the ISR according to international guidelines. 1,2Results38 analytical runs were conducted for two drugs (enalapril/enalaprilat) from February 2016 to August 2018. Calibration curve evaluation accounted for exclusion of four enalapril and five enalaprilat runs. Additional investigation of QCs resulted in further exclusion of two enalapril and one enalaprilat runs. Within 32 valid runs 820, QCs were measured for enalapril and enalaprilat. 94% enalapril and 89% enalaprilat QCs were within limits (±15%). This set ensured reliable determination of 1262 LENA paediatric study samples. 93 and 104 incurred samples for enalapril and enalaprilat were reanalysed. ISR for enalapril (70%) and enalaprilat (67%) was also within guidelines.1,2ConclusionThe analysis of bioanalytical data ensured the reliability of reported unknown concentrations. It ensured consistent and reliable pharmacokinetic data from first to the last LENA study patient.ReferencesGuideline on bioanalytical method validation. European Medicines Agency, London, UK ( 2011).Guidance for Industry Bioanalytical Method Validation. US Department of Health and Human Services, US FDA, Rockville, MD, USA ( 2018).Disclosure(s)Mohsin Ali, Jutta Tins, Bjoern B Burckhardt declare that there is no conflict of interest. The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007–2013) under grant agreement n°602295 (LENA)
Corrigendum to: Assessment of Bioanalytical Method Validation Data Utilizing Heteroscedastic Seven-Point Linear Calibration Curves by EZSTATSG1 Customized Microsoft Excel Template
