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Cleaning validation of manufacturing equipment involved in pharmaceutical production is an essential factor in GMP. However, it requires complicated and laborious processes such as sampling from the equipment, sample pretreatment, analysis of the compound concerned, and evaluation of the residue amount. Setting the threshold values, which have to be determined taking into consideration various factors such as the effective amount and dosage of the medicine, the size of the production batch, highly sensitive analytical method and a simple method of evaluation.

The Shimadzu Cleaning Validation Support System, Co-Sense for CV is an HPLC application system addressing this demand. The unique system configuration and special software dramatically enhance the efficiency of cleaning validation by automatically conducting all processes from sample concentration to analysis and data processing.

Unique Hardware Configuration

A column-switching technique is used to concentrate the target component within the sample onto the concentration column, then send it to the analysis column for separation and detection. Complex sample pretreatment is therefore unnecessary.

High-sensitivity detection of trace components

Because the target component is concentrated from a large amount of sample, even a trace amount of component can be detected with high sensitivity.

Reliable concentration with any sample solvent

The target component is concentrated while diluting the sample by any desired rate, assuring creation of a clear peak, as well as a high recovery rate regardless of the type of the sample solvent used for extraction. This chromatogram has been obtained using the ethanol solution of isopropylantipyrin (100ng/mL) as a test sample. 1mL of the sample was injected. The sample was diluted by 20 times in water before being introduced into the concentration column. The result showed a high recovery rate for tocopherol acetate at almost 100%.

*1 Cleaning validation is a procedure to verify whether the equipment that has been used (or is to be used) for pharmaceutical manufacturing has been sufficiently washed and cleaned. The purpose of this procedure is the prevention of cross contamination of drugs and contamination by foreign substances. The practical procedure involves quantitation of the residues in the manufacturing equipment (individual units in the manufacturing process) and judgement of the quantitation result against the permissible level. “Residues” in this context include active ingredients and decomposition products of medicines, other additives, and contaminants such as the detergent used for cleaning and dust. Cleaning validation is one of the most important components of pharmaceutical GMP.The “Validation Standards” (April 1996 in Japan) also stipulates cleaning as an item that must be validated.
Cleaning validation is conducted according to the following procedure. 1) Collection of the sample from the manufacturing equipment after cleaning, 2) Sample pretreatment including concentration, 3) Calculating the residual amount through quantitative analysis (HPLC and TOC are the main quantitative analysis methods), 4) Pass/fail judgment through comparison with permissible limits. Cconcentration of many different samples involves laborious procedures. Setting threshold values for result judgement is also a complex procedure. Threshold values must be set for each medicine based on various factors such as effective dosage, administered dosage, size of the production batch, and size of the equipment. Furthermore, threshold values for each medicine must be revised if factors such as the size of the production batch, pharmaceuticals manufactured using the equipment or the instruments used in the manufacture process has been changed.
This system uses a column switching technique to once trap and concentrate target components in the sample in the concentration column, which are then led to the analysis column for separation and detection. This procedure eliminates the need of complex pretreatment even for dilute samples. Furthermore, the dedicated cleaning validation support software automatically conducts all processes from the creation of analysis schedules to the calculation of the amount of residual medicine and pass/fail judgment.