Ozone is commonly used in the pharmaceutical industry for disinfecting pharmaceutical-grade water, which is present in process systems, such as washers, autoclaves or secondary water purification systems, and used to clean delicate pharmaceutical manufacturing equipment. High-purity pharmaceutical-grade water followed by distillation forms the base ingredient in the manufacture of ingestible and injectable medical products. According to US Pharmacopoeia (USP) regulations, pharmaceutical-grade water must be validated to demonstrate that it meets certain requirements for ionic and organic chemical purity, and must also be protected from microbial contamination.¹

Ozone is used for microbial disinfection purposes during the sanitization of pharmaceutical-grade water production to disinfect the water network prior to distillation. It is essential that the water is disinfected effectively during this process to ensure the highest quality water and to avoid increased costs during the distillation process. In creating such high-quality water, it is essential to measure the levels of dissolved ozone at various points in the process to ensure that adequate ozone concentrations are present during sanitization and that there is no residual ozone at the point of use.

Ozone monitoring

Ozone is the strongest stand-alone oxidizer currently available for water treatment. One of its largest uses is in the production of pharmaceutical-grade water, where it is dissolved in the water and reacted with bacteria, viruses and other microorganisms to create removable solids of dissolved minerals and to neutralize certain chemicals. During the pharmaceutical manufacturing process, ozone is used to treat pharmaceutical-grade water and water for injection (WFI) to ensure that the water distribution network is sanitary/cleaned. As the ozone-injected water is flushed through the distribution system, disinfection is extremely effective when compared with conventional steam cleaning solutions.

Ozone can also break down pesticides, kill microorganisms and remove unwanted colour, leaving behind no taste, odour and, most importantly, no dangerous chemical residues. Ozone also has a very high oxidation potential and is exceptionally quick-working, enabling pharmaceutical manufacturers to significantly reduce downtime and increase productivity.

Dissolved ozone has traditionally been monitored and controlled using redox analyzers, ultraviolet (UV) spectrophotometers, amperometric or potentiometric electrochemical monitors, colorimeters and sensors that measure the photochemical reaction of ozone with ethylene. However, these instruments can demonstrate significant shortcomings: redox analysers are nonlinear and not sensitive enough to accommodate certain applications, and UV spectrophotometers are expensive and complicated to use, requiring a reference gas, moving parts in the form of solenoid valves and also incorporate optics that may become easily misaligned. Additionally, the UV spectrum of ozone may be confused with that of other compounds present in the water sample being monitored.

The use of amperometric or potentiometric electrochemical monitors can be problematic when monitoring ozone as the instruments are not ozone-specific, produce a very small signal in low-conductivity water and are not efficient in ultra-pure water. Such sensors have proved unreliable and inaccurate as electrodes and membranes are easily fouled, internal solutions may become contaminated and maintenance requires complex disassembly.

An alternative technique, the use of colorimeters, does not offer continuous sample analysis and requires the disposal of contaminated samples. The photochemical approach is also becoming less common because of the need for a continuous supply of reagents and the ability to handle exhaust products.

Alternative technologies

Figure 1

To overcome common issues with colorimetric monitoring techniques, an alternative technology has been developed that enables continuous on-line monitoring and control of ozone systems. This technology, shown in Figure 1, has been designed and proven to meet a variety of monitoring applications, and is capable of measuring dissolved ozone concentrations as low as 0–200 ppb full scale down to 0.5 ppb. While providing the sensitivity needed for demanding applications, such as pharmaceutical-grade water or semiconductor wash water, this technique can also accommodate high-range applications that require 0–20 or 0–200 ppm.

Unlike on-line colorimetric and most amperometric methods, this innovative technology uses a highly selective, membrane-covered polarographic sensor that does not require the addition of chemical reagents. Dissolved ozone readings are easily achieved without measurement interference from other sample components such as residual chlorine. The need for maintenance is also greatly reduced as the technology does not require the use of moving parts, meaning there are no tubing breaks or pumps and motors that burn out. The technology has been designed with the flexibility to enable optional dual measurement capability, and provides both dissolved ozone and pH analogue outputs. Dual analogue outputs can also be configured to track ozone and temperature, ozone and ozone, or ozone and pH for increased process control.

On the go...

Dissolved ozone sensors incorporating this technique are generally installed in a flowcell, with sample piped to the flowcell using 6.35-mm inner diameter sample tubing. The standard flowcell arrangement uses a constant-head overflow system to ensure stable flow and pressure across the sensor, regardless of sample line fluctuations. A low-volume flowcell is used for installations where minimum sample flow is desired, and sample flow and pressure can be carefully controlled.

A standard feature of this alternative technology is a proportional-integral-derivative (PID) control function, which can be configured quickly and easily. To use this function, the primary 4–20 mA output must be assigned for PID control. While not suitable for systems with rapid flow changes requiring compound-loop control, the PID function can handle many stable flow applications.