Current Considerations on Pharmaceutical Water Systems and Ozone

Recommendation

17-19 September 2024

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When ozone is used to sanitize storage and distribution systems, its effectiveness must be proven. On the one hand, this is done indirectly by determining the CFU values and, on the other hand, by proving that the ozone concentration is being measured correspondingly in the water system.

For instance, the ISPE Baseline list at least three measuring points for this reason:

• Before the UV system (discharge of the storage tank)
• After the UV system
• In the return flow

The ozone value before UV indicates that during permanent ozonisation, the concentration in the storage tank is sufficient and that the ozone generator is working correctly. After the UV system, permanent measurements are performed during operation to indicate that the ozone is removed. In the return flow of the piping system, measurements are taken to prove that the ozone concentration is sufficient during sanitization of the pipes after the UV lamp.

Experts recommend comparing the values before UV and in the return flow in order to calculate the system's specific half-life period of the ozone. This typically amounts to 15 minutes for polluted systems and can amount to over 60 minutes for very clean systems. For technical reasons, it is necessary to know the half-life period, as the UV system cannot completely break down the ozone and the current ozone measurement technique has a lower detection limit of 5-10 ppb. For critical applications where the water has direct contact with the product, it is mandatory to know the system-specific half-life period of the ozone for a solid risk assessment. In future, this topic will certainly gain importance when cold WFI will be produced and stored in the course of the European Pharmacopoeia Revision. In case that an upgrade to WFI is planned after April 2017, current HPW systems should be reviewed accordingly even today.