Since 1996, conductivity testing of Purified Water, Water for Injection (WFI), and Pure Steam has been a requirement for the production and release of these waters according to the United States Pharmacopeia (USP). New changes to chapter <645> came into effect on December 1st, 2008.
There have been virtually no changes to USP <645> since its introduction in 1996. However, last year, the USP Pharmaceutical Water Expert Committee proposed some revisions to chapter <645>. These changes were approved earlier in 2008. They became effective on December 1st, 2008.
There has always been an allowance in USP <645> for the conductivity testing to be performed in line (Stage 1) or off-line (Stage 2 and 3). However, there has been an exponential growth in the use of in-line conductivity (and TOC) measurements due to the cost savings that is realized from real-time testing and real-time release. Also, there is an adverse impact of CO2 on off-line conductivity measurements of high-purity water which results in the true quality of the water being hidden by airborne CO2. As a result, USP <645> has been amended to encourage the use of in-line conductivity testing.
The existing requirements for the meter electronics calibration (0.1 µS/cm using a 0.1% traceable resistor) and cell constant accuracy (±2%) are unchanged and still required. However, an additional “system” calibration has been suggested to improve measurement accuracy.
"In order to increase the measurement accuracy on the conductivity ranges used, which can be large, and to ensure a complete equipment calibration, it is suggested that periodic verification of the entire equipment be performed. This could be done by comparing the conductivity/resistivity values displayed by the measuring equipment with those of an external calibrated conductivity-measuring device. The two non-temperature-compensated conductivity or resistivity values must be equivalent to within ±20% of each other, or at a difference that is acceptable on the basis of product water criticality and/or the water conductivity ranges in which the measurements are taken. The two conductivity sensors should be positioned close enough together to measure the same water sample in the same environmental conditions.
In addition to the verification method performed in non-temperature-compensated mode, a similar verification performed in temperature-compensated mode could be performed to ensure an appropriate accuracy of the equipment when such a mode is used for trending or other purposes." - USP31 Supplement 2
The final change is a new section that has been added to provide a procedure and conductivity test limits for Sterile Water for Injections and Sterile Purified Water, Sterile Water for Irrigation, and Sterile Water for Inhalation. The limits for these waters are <25 µS/cm for containers ≤10mL, and <5 µS/cm for containers >10mL.
There will be a growing demand for complete system calibrations. For the last 15 years, THORNTON has been the leader in conductivity calibration services by providing calibrator, transmitter, sensor, and complete system calibrations. Through the After-Market Service group, we continue to offer a growing selection of CAL 3x and CAL 4x special calibrations.
