Cleaning Validation by TOC Analyzer with Easy Wiper

Significance of the Topic

In pharmaceutical manufacturing, cleaning validation is essential to ensure that trace residues of active compounds on equipment surfaces remain within safety and regulatory limits. Total Organic Carbon (TOC) analysis offers a reliable measure of any residual organic material, supporting product quality and patient safety.

Objectives and Study Overview

This application note evaluates a swab sampling–direct combustion method using a quartz glass fiber “Easy Wiper” to quantify residual organic carbon on stainless steel surfaces. While Shimadzu TOC analyzers support three validation approaches—swab sampling with direct combustion, swab sampling with water extraction and TOC analysis, and rinse sampling with TOC analysis—this study focuses on the direct combustion workflow to assess recovery of both water-soluble and insoluble pharmaceutical substances.

Materials and Methods

Six model residues (tranexamic acid, anhydrous caffeine, isopropylantipyrine, nifedipine, a steroid ointment, and vaseline) were prepared at 200 µg C per 5 cm × 5 cm stainless steel plate. Soluble compounds were dissolved in water, insoluble ones in appropriate organic solvents. After drying, each plate was swabbed with an Easy Wiper pre-heated at 600 °C for 15 min and moistened with 200 µL of ultrapure water. Blank swabs from clean plates established the baseline.

Instrumentation Used

• Shimadzu Total Organic Carbon Analyzer TOC-L CPH
• Solid Sample Combustion Unit SSM-5000A with IC circuit bypass and cell-switching valve
• Oxygen carrier gas at 400 mL/min
• Short optical cell configuration
• One-point calibration using 30 µL of 1 % C glucose solution

Main Results and Discussion

Recovery rates for all six substances ranged from 96.7 % to 104 %, demonstrating excellent agreement with the theoretical carbon load (200 µgC). The Easy Wiper eliminated fragment contamination seen with quartz fiber filter papers, and blank-corrected TOC measurements confirmed minimal background interference.

Benefits and Practical Applications of the Method

• Direct combustion eliminates sample extraction steps, reducing analysis time.
• High recovery for both water-soluble and insoluble residues ensures broad applicability.
• Quartz fiber Easy Wiper prevents carry-over of swab fragments, minimizing equipment re-cleaning.
• Simplified workflow increases laboratory throughput and consistency.

Future Trends and Potential Applications

Advancements may include automated swab handling, integration with in-line monitoring for real-time validation, and adaptation to emerging low-carbon detection systems. Expanding the method to environmental or other industrial surfaces could further broaden its utility.

Conclusion

The swab sampling–direct combustion method using the quartz glass fiber Easy Wiper and Shimadzu TOC analyzer offers a robust, accurate, and efficient solution for pharmaceutical cleaning validation, with recovery rates near 100 % and streamlined operation.

Reference

Shimadzu Application News No. O60, Total Organic Carbon Analysis (First Edition: January 2017).