I have come across several organizations who have state of the art Water for injection (WFI) generation and distribution plants with on-line conductivity and TOC measurement but continue to rely on off-line measurement and testing in QC labs. It is often a big challenge to convince users, system owners, and the testing team to fully trust online systems. I have been unsuccessful in selling this idea in the past.
While users agree that offline testing is significantly prone to sampling/testing errors and the influence of environment on both TOC and conductivity values, the hesitation is sometimes due to significant differences observed between offline and online measurement. How can we justify these differences to reviewers and regulators is one of the concerns which stop users from migrating to using online measurements.
One should keep in mind that high purity water at ambient temperature absorb CO2 from atmosphere quickly and a sample conductivity can go from 0.05 μS to 2 μS in less than 2 minutes. Similarly, differences of 100-250 ppb between online and offline TOC is not uncommon. Sampling procedure, state of the sampling container, atmospheric contamination and previous samples tested on the offline TOC machine contribute to these differences.
Most regulators are aware of these differences and do not demand or question the differences between online and offline values. Even if they do, there is enough scientific evidence and literature to convince them these are normal, that your systems indeed are operating well, and the low values of conductivity and TOC are not due to poor instrument operation.
One should maximize their investment done in good WFI system and online measurement setup by eliminating offline measurements. Those who do not have online TOC in a biopharmaceutical or parenteral plant, should consider investing in one. Break even on investment can be quick considering the savings from reduced testing setup, sampling efforts, offline TOC machine maintenance, staff training. There is also the non-evident but fairly significant cost of laboratory and OOS investigations.
This article first appeared in the Author’s LinkedIn page on July 18, 2019
Featured image courtesy mt.com