Cleaning Validation

The Code of Federal Regulations Title 21 CFR 211.67 states “Equipment and utensils shall be cleaned, maintained, and sanitised at appropriate intervals to prevent malfunctions or contamination that would alter the safety, identity, strength, quality, or purity of the drug product beyond official or other published requirements.”

Total Organic Carbon (TOC) is a quick, accurate and inexpensive screening protocol for contamination validation of small molecule drugs, peptides, proteins, and cleaning detergents. It can be utilised in conjunction with both CIP (cleaning in place) and COP (cleaning out of place).

The amount of carbon containing contamination is seen as the worst case scenario i.e. where all the carbon content is designated the ‘active’ ingredient, even if this is not the case. Thus rapid detection can be used to ‘salvage’ expensive production runs. If the TOC count is higher than acceptable, the contaminant(s) can be identified and quantified using SGS M-Scan’s extensive range of chromatography/mass spectrometry equipment – see detergents and surfactants, leachates and extractables.

Application areas for aqueous based samples typically include:- ultrapure water (water for injection- (WFI)) sample analysis (<20ppb), pharmaceutical applications (<500ppb), and drinking water (<5ppm).

TOC can be used with all relevant standard sampling methods such as swabs, wipes, rinse, and immersion techniques though the most consistent results are obtained by using a single method. TOC can be operated under full GLP protocols if required.

The Shimadzu Total Organic Carbon Analyser used by SGS M-Scan offers measurement options including:- Total Carbon (TC) with a measurement range of 0~3000mg/L, Inorganic Carbon (IC) with a measurement range of 0~2500mg/L, Total Organic Carbon (TOC) and Non-Purgable Organic Carbon (NPOC) All methods have short analysis times and typically require sample volumes in the 350~20,400µl range .