Recent studies have revealed that multiple variables in Total Organic Carbon (TOC) swab testing significantly increase sampling errors, which can severely affect cleaning validation results commonly used in the pharmaceutical industry. TOC swabs are a standard method for cleaning validation in pharmaceutical production, but their test results often exhibit high variability. Sampling error has been identified as a key cause of this variability.
A research team from Novo Nordisk and the Technical University of Denmark employed Monte Carlo simulation to quantitatively analyze sampling errors in real-world TOC swab sampling scenarios. They considered factors such as operator differences, residue concentration variation, stainless steel surface finish, sampling locations, and the estimated swab coverage area to build a comprehensive sampling error model. This simulation incorporated extensive laboratory experimental data and image analyses of blue dye-marked areas both in the lab and on old production tanks.
The researchers used the Limit of Detection (LOD) to determine recovery rates—the lowest analyte concentration detectable consistently at a 95% confidence level. Their findings showed that sampling errors cause significant fluctuations in TOC test results. When all variables were considered together, the LOD in laboratory settings was 2.4 times higher than that based solely on the TOC analytical method. Due to high heteroscedasticity (variance), the team was unable to define an LOD for the estimated sampling areas on production tanks.
Further analysis identified sampling area uncertainty as the dominant factor influencing sampling errors. The research team emphasized that precise control of sampling area is critical in practical applications to reduce errors and improve the accuracy and reproducibility of cleaning validation results.
In summary, this study provides important insights for optimizing TOC cleaning validation sampling methods in the pharmaceutical industry. It highlights the need for strict operational protocols and precise area control during sampling to ensure scientific rigor and regulatory compliance in cleaning validation.