19.05.2016 |

LOGFILE No. 32/2016 – The New USP <1231>: Water for Pharmaceutical Purposes


Exclusive Excerpt from the new pdf download The New USP <1231>: Water for Pharmaceutical Purposes

by Fritz Röder


This section has a new structure with the subsections "Heat", "Chemistry" and "UV". In the former version all three procedures were described under the same heading.

Thermal sanitisation

The new version of USP <1231> recommends temperatures ranging from 65 to 80°C for thermal sanitisation. The previous version mentioned standard temperatures of > 80°C. Now, sanitising temperatures that significantly exceed 80°C are not recommended, as these temperatures cause stress to materials and instruments while offering no additional benefit for the control of biofilm formation.

Other guidelines refer to similar temperatures. Table 1 shows the different opinions of the existing bodies:

Recommended sanitising temperatures
USP 1231 65-80 °C
ISPE Guide Volume 4 „Water and Steam" 80 ± 3 °C
FDA Guide to inspections on high purity water systems 65-80 °C
VDI 2083 Sheet No. 13.1 > 80 °C
WHO Technical Report 929 70-80 °C







Table 1: Sanitising temperatures of different guidelines and standards

Only a sanitising temperature of 80°C complies with all guidelines.

Chemical Sanitisation

Chemical methods typically employ ozone, peracetic acid, hydrogen peroxide or combinations thereof. In chemical sanitisation it is important to systematically take into account that biofilms cannot always be deactivated completely. For successful sanitisation it is essential to adequately distribute the disinfectant. Seals and boundary areas with less throughflow are problematic. Depending on the substance, disinfecting agents form strongly reactive peroxides or hydroxyl radicals with oxidative effect.

Sanitising with ozone offers the advantage that applying a 254-nm UV emitter may help eliminate residual ozone and permanently overlay the storage tank with ozone. The emitter is installed in the supply flow, where it destroys the ozone before the water reaches the points of use. The distribution system can be sanitised periodically by deactivating the UV emitter, preferably at daily or weekly intervals. This information is new to the new version of USP <1231>. It is pointed out that the cycle frequency should be selected so as to ensure that a biofilm cannot form at all.

Process validation of these systems requires evidence that disinfectants reach all areas of the system in adequate concentration. This is also true for points of use. Furthermore, not only the presence of the chemical, but also its absence after successful sanitising must be appropriately substantiated.

This section has been amended with the above-mentioned new structure and the additional notes.

UV sanitisation

It is pointed out that UV systems can be used to reduce bacteria, but not as the sole means of sanitising. Their use in combination with other measures is recommended to reduce sanitising frequencies.

Sanitisation procedures

The purpose of sanitisation is to keep biofilm formation at an acceptable level. Regardless of whether chemical or thermal procedures are used, it must be demonstrated that the sanitising method is effective in all system areas. Specifically, this means that in chemical disinfection, evidence for the presence and absence of disinfecting agents must be given. Thermal systems require heat distribution studies. The decisive point is that hard-to-reach areas in the system also be sufficiently sanitised.

Sanitising frequency should also be supported by monitoring and trend data (obtained from Product Quality Review (PQR)). If necessary, additional measures can be derived from these data. In any event, the sanitising interval should be determined in such a way that it ensures that neither alert nor alarm levels are regularly exceeded.


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