Water purification conductivity measurements play a pivotal role in the industry, not only for regulatory reporting but also for effective process control and maintaining the health of water purification systems. Navigating the regulatory requirements, especially those in USP <645>, can be challenging. Here, we provide a clear guide to understanding USP <645> and present a tool designed to simplify sensor calibration without disrupting the water system, ensuring compliance and operational efficiency.
Conductivity measurements in pharmaceutical waters are critical, not only for reporting purposes but also for process control and understanding the health of the water system and the water it produces. Conductivity is a useful indicator of the ionic health of the water, as it is able to reliably measure ionic contaminants and is therefore utilized throughout the entire water purification process. Regulatory bodies recognize the importance of conductivity measurements, which is why Water for Injection (WFI) conductivity is heavily regulated in every major pharmacopeia.
Understanding regulatory information regarding pure water and WFI is critical when working in the pharmaceutical industry. Decoding pharmacopeias can be challenging and confusing, leading to insecurity and a lack of confidence.
This page can help in navigating the regulatory landscape. While it focuses mostly on USP requirements, it is worth noting that compliance with the USP also means compliance with the EP, JP, CP, and every other major global pharmacopeia as well.
The USP outlines three stages of testing conductivity for bulk waters:
On-line temperature and non-temperature-compensated conductivity are measured. The measured temperature value is rounded down to the next lowest 5°C interval. If the measured conductivity is not greater than the limit outlined in Table 1 of USP<645>, the water meets the requirements of USP <645>.
This stage requires taking a sample and stirring it to equilibrate it to atmospheric CO2. If the conductivity is less than 2.1 μS/cm at 25°C ± 1°C, it passes; if not, move to Stage 3.
Saturate the sample from Stage 2 with potassium chloride (KCl). Measure pH to the nearest 0.1 pH unit. Look up the conductivity limit for that pH in Table 2 in USP <645> or in the table below. If the measured conductivity (from Stage 2) is less than the conductivity limit, it passes. If the measured conductivity exceeds this value or the pH is outside the range of 5.0–7.0, the water does not meet the requirements of USP <645> for conductivity.
Stages 2 and 3 are for off-line testing.
Stage 1 testing is typically preferred, as in-line sensors can be used for this test, eliminating the need for sampling. Today, many water purification systems achieve conductivity levels below the levels outlined in Stage 1, eliminating the need for Stage 2 or Stage 3 testing.
According to the USP, conductivity measurements must be reported as uncompensated readings. No temperature compensation can be used, as each conductivity manufacturer has a proprietary temperature compensation algorithm, and because each algorithm is different, they result in different readings of the same water. To eliminate any bias, uncompensated reporting is required, as uncompensated conductivity requires no measurement adjustment algorithm.
Reporting in-line conductivity readings in accordance with USP requires temperature and conductivity measurements. Modern-day conductivity sensors often have an embedded temperature sensor, eliminating the need for additional temperature sensors.
Understanding calibration requirements of the pharmacopeias can be complicated. Knowledge of the mechanics of a conductivity sensor is required to effectively understand the calibration requirements of the pharmacopeias.
In a conductivity measurement, there are three main components that are responsible for measuring or affecting the conductivity:
The first is the temperature. Conductivity is highly temperature-dependent, so conductivity readings are useless without knowing the water or liquid’s temperature. It is worth noting that using an external temperature sensor is an acceptable method for collecting temperature data, so if a conductivity sensor has an embedded temperature sensor it does not need to be calibrated in this scenario. However, in most cases, an embedded temperature sensor is used to avoid additional equipment.
The second part is the cell constant. This is a multiplier applied to the measurement based on the sensor's electrode geometry. A sensor with a greater volume of water between the electrodes will have lower conductivity, since the electrical current must travel through more liquid. The cell constant allows the sensor to report the conductivity of the water per centimeter or other distance units. This allows two different conductivity sensors with different cell constants to report conductivity values in the same units, allowing readings to be compared.
The third part is the measurement electronics. These are responsible for measuring the resistance between the two electrodes. This resistance is then converted into conductivity, as they are inversely proportional. The measurement electronics can be embedded in the sensor's transmitter for analog sensors or embedded directly in the sensor for digital sensors. The pharmaceutical industry historically used analog sensors; however, many companies are switching to digital sensors for increased accuracy and stability.
In short, water conductivity must be measured accurately using calibrated instrumentation. USP <645> has calibration requirements for both the sensor and the measurement electronics, whether they are embedded in the sensor or in the transmitter.
Temperature and cell constant calibrations are typically done using a reference conductivity sensor for the highest accuracy. Measurement electronics are calibrated using reference electronics. Since the electronics are found in either the transmitter or the sensor, depending on the type of sensor, different methods may be required.
As digital sensors have the electronics mounted within the sensor, to perform an accurate calibration of the measurement electronics the sensor has to be placed in air to prevent any interference from liquid touching the sensor’s electrodes. This can be inconvenient for many water system owners with in-line sensors, as it requires removing the sensor from the process pipe, which can cause a system breach, introduce contamination, and require extensive paperwork. This can be a time-consuming and costly process.
Fortunately, METTLER TOLEDO Thornton has a solution. Utilizing the patented UniCond™ Calibrator, METTLER TOLEDO service technicians can calibrate a UniCond conductivity sensor’s electronics without removing the sensor from the process. The tool isolates the measurement electronics, eliminating any interference from the sensor’s electrodes.
Through METTLER TOLEDO Service, companies can save time and money by avoiding system shutdowns and breaches due to conductivity calibration. Thanks to UniCond sensors and the UniCond Calibrator, having a fully pharmacopeia-compliant conductivity sensor can be easily achieved without disrupting the water system.
You can find more information about USP<645> requirements here:
Jared Culbertson – Global Product Manager - Conductivity
Jared Culbertson holds a B.S. in Chemical Engineering, and has spent 5 years in the biotechnology and pharmaceutical waters industry. Over his time at METTLER TOLEDO Thornton, Jared has managed multiple sensor lines, including conductivity sensors, ozone sensors, pure water pH sensors, and pure water dissolved oxygen sensors. In his current role, he provides support and training for these sensors. Jared is a voting member of the American Society for Testing and Materials on the D19 Water committee.
