12.09.2023 | LOGFILE Feature 34/2023

Excerpt from the GMP Compliance Adviser, chapter 5.E.3: Monitoring of Parameters and Water Quality

Monitoring of Parameters and Water Quality

Monitoring of Parameters and Water Quality

The monitoring of critical parameters is largely automated and is part of the plant control system. In the event of a critical system alarm (e.g. TOC outside of tolerance limits), the control system also performs the system shutdown or the transition to a safe operation mode.

Nevertheless, the system should also be monitored by personnel since the automated control system cannot monitor all components or evaluate trends.

  • Consumable materials (e.g. regeneration salt)

  • Plant status and measured values

  • Logs (e.g. alarms)

  • Operating noise and leaks in the system

  • Certain parameters which are monitored in the automation scheme

The monitoring of water quality essentially comprises two aspects: online sensor technology and offline analyses in the laboratory.

The scope of the online measurements is determined as part of the design. It is then necessary to decide:

  • which sensors are to be installed,

  • which sensors are GMP-relevant, and

  • which sensors, if any, are to be used for release purposes.

A special characteristic of water is that at least some quality parameters can be measured in real time with the help of online analytical technology (conductivity, TOC) according to the monograph. A genuine PAT system is therefore possible here and has been common practice for years. Nevertheless, the formal release of the water can only be done when the data from the offline analyses are also available.

Online monitoring and recording of water system parameters should include at least the following:

  • Temperature during treatment

  • Conductivity after treatment

  • Production flow rate of the generating plant

  • Temperature in the return flow of the loop

  • Conductivity in the return flow of the loop

  • Pressure in the return flow of the loop (if the minimum flow is ensured via pressure monitoring)

  • Fill level in the storage tank

  • UV intensity of UV lamps

  • Volume flow/flow velocity in the return flow pipe

  • TOC measurement in the return flow

In addition to the online monitoring, a water system is sampled offline (sample point). The samples are used to investigate the following quality parameters, which are prescribed in the pharmacopoeia monographs

Bioburden & endotoxins if applicable

  • Source water (1st stage of treatment)

  • Water from the treatment itself (before and after essential treatment steps)

  • Product water (sampling point in the plant and at all points of use)


Wet chemical tests (nitrate, calcium, aluminum or similar)

  • Product water; not all points of use have to be checked individually. USP <1231> Section 6.2.1 can be used as a rationale: here it is mentioned that chemical impurities are basically homogeneously distributed in water.

It is important that the quality maintenance program (consisting of surveillance and monitoring) is assessed and evaluated in its entirety. This evaluation and any resulting measures should be included in the PQR in the form of a report.

Fritz Röder


Fritz Röder
Site Account Engineer, Merck Healthcare KGaA
E-Mail: roederfritz@googlemail.com


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