Membrane Technology for Pharmaceutical Water - How often to sanitise?

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17-19 September 2024

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GMP Compliance and Technology for the Manufacture of Oral Solid Dosage Forms

Both in the production of purified water (PW) and in the production of water for injection (WFI) with membrane technology, reverse osmosis (RO), as the main barrier to impurities of all kinds, plays an essential role. For pharmaceutical use the systems including the RO modules should be hot sanitisable. Chemical sanitisation of RO modules is no longer considered state of the art, because e. g. H2O2 is usually not efficient, especially with Pseudomonas or similar germs. But how often should hot sanitisation be carried out?

Already in the qualification phase of the water system, an initial sanitisation frequency of the system must be determined and confirmed in the performance qualification (PQ).

What frequency should be started with? The simple answer is: as often as necessary, but not more often than necessary to keep the thermal stress on the system as low as possible. This is because sanitisation frequency plays a major role in the lifespan of the components in a water treatment system. Reverse osmosis is usually only one step; RO is often combined with electro-deionisation (EDI) and ultrafiltration (UF), often preceded by softening. Softening can be sanitised more frequently. The resin in these systems is very robust. As the first assembly in the system, the softener is also particularly heavily loaded in the case of microbiologically poor drinking water.

However, the sanitisation of UO, EDI and UF is then not carried out for each component individually, but for the entire assembly together. The EDI module is the most sensitive, cost-intensive component and determines the maximum frequency. To avoid replacing the EDI module more frequently than about every five years, a hot sanitisation frequency of three months has proven to be effective. Thus, one can assume a durability of 100-120 sanitising cycles. This applies at least to approx. 60% of the systems in Central and Northern Europe. If the quality of the feed water used is poorer, a higher frequency may be necessary. The effectiveness of the selected frequency must be confirmed during the one-year PQ phase and subsequent routine monitoring. The cost of PQ is often 20-50% of the total investment cost of the whole water treatment plant. It is difficult to change the frequency during the PQ phase or afterwards, as then high expenses for a prolonged or possibly even repeated PQ may be incurred.