Sampling Error of TOC swab in Pharmaceutical Cleaning Verification

Area of Science:

• Pharmaceutical Manufacturing
• Analytical Chemistry
• Patient Safety

Background:

• Cleaning verification is crucial in pharmaceutical manufacturing to prevent cross-contamination.
• Total organic carbon (TOC) swabbing is a common method for this verification.
• Previous studies explored factors influencing TOC swab methods, but sampling error in real-world conditions remains under-quantified.

Purpose of the Study:

• To quantify the sampling error associated with TOC swabbing in pharmaceutical manufacturing.
• To investigate the impact of various factors (analysts, concentration, steel finish/position, swab area estimation) on drug product recovery variability.
• To highlight the implications of sampling error on limit of detection (LOD) calculations.

Main Methods:

• Simulation of actual sampling situations to assess TOC swab performance.
• Investigation of variability in drug product recovery based on different analysts, concentrations, steel finishes, and positions.
• Analysis of the impact of estimated swab area on TOC results and LOD.

Main Results:

• Sampling error significantly contributes to the variation observed in TOC results.
• Laboratory-estimated swab areas increased the limit of detection (LOD) by 60%.
• For tank-estimated areas, high heteroscedasticity prevented LOD determination.

Conclusions:

• The sampling error in TOC swabbing introduces substantial variability, affecting the reliability of cleaning verification.
• Current methods for estimating swab area can lead to increased LOD, potentially compromising patient safety.
• Further research and discussion on TOC sampling error are essential for improving pharmaceutical cleaning verification processes.