The standard curves plot absorbance units (AUs) versus wavelengths. Detergent residual analysis looks for compounds which readily absorb ultraviolet and visible light, most often detergents. Devices are extracted in a known volume of purified water and analyzed with a UV/VIS spectrophotometer.

Validating the extraction

In most instances, the team must validate the extraction procedure for each device and contaminant. In some cases, devices or contaminants may be grouped into “families” which have similar characteristics. Appropriate justification for these groupings must be included in the validation file. Then the extraction validation is performed on each family.

Extraction techniques are validated with spike recoveries, or exhaustive extractions, or both. Spike recovery uses positive controls with a known level of contamination. These controls are created by spiking clean devices with a known amount of target contaminant. Only one extraction is needed to establish recovery efficiency. Spike recovery shows the removal efficiency of each contaminant tested, but it can get complicated as the number of contaminants on a device increases.

The exhaustive extraction technique uses positive controls which contain an unknown level of contamination. These “real-life” positive controls are created by exposing devices to the regular manufacturing operations but not the cleaning process being validated. Positive controls for exhaustive extractions require repetitive extractions to establish recovery efficiency. The method provides “real-life” data but may not demonstrate adequate removal of every possible contaminant.

The exhaustive-extraction method lets manufacturers establish precleaning levels of the target compounds, an important step in establishing limits for residual analysis. After establishing the precleaning levels, clean devices are tested to show a percent reduction of residual manufacturing materials. This percent reduction is an indication of the effectiveness of a cleaning process.

Total organic carbon analysis

TOC analysis is a relatively straightforward process for validating a cleaning method and performing routine monitoring of residual levels once the validation is complete. TOC is also a sensitive analytical method with detection capabilities in the parts-per-billion (ppb) range. Residuals are extracted from the devices in a known amount of purified water, and the extract is analyzed on a TOC instrument. The extraction ratio must be controlled for accurate analytical results. If too much water is used, the residue may not be detectable even though it is present. If too little water is used, the residue may not be adequately removed from the device.

A common TOC method begins by acidifying the device extract to purge inorganic carbon. The organic carbon is oxidized with sodium persulfate at 100C to form carbon dioxide. The resulting carbon dioxide is purged from the solution and quantified using a non-dispersive infrared detector. The resulting mass of carbon dioxide is proportional to the mass of TOC in the sample which is interpreted and reported as the total organic carbon extracted from the device.

For TOC to be a suitable analytical technique, users must first establish that the target compounds contain a significant amount of organic carbon. Also, it must be possible to oxidize the carbon present under the test conditions, and the target compounds must be water soluble. Even some essentially insoluble organic target compounds may be removed by water extraction and analyzed by TOC. The analysis will not detect inorganic contamination.