Questions and Answers on System Suitability Tests (SST) - Part 1

During the ECA Live Online Training “System Suitability Tests (SST) and Troubleshooting for HPLC Methods” on 04 November 2025, a number of interesting and practice-oriented questions were raised by the participants. These questions were answered in writing by the speakers’ team after the event. To share some of the key insights with a broader audience, we have compiled a selection of these Q&As.

Please find below Part 1 of the questions with answers provided by Dr Gerd Jilge. All answers reflect the speaker’s opinion based on his experience. Parts 2 and 3 will be published over the coming months.

Part 1

1.1 – In Ph. Eur. 2.2.46, acceptable system suitability criteria have recently been introduced (e.g. tailing factor). In our laboratory, there is a validated assay method for the finished product in which the tailing factor is not evaluated. Should we start evaluating the Ph. Eur. criteria in addition to the criteria of the established method?
The chapter 2.2.46 describes all relevant SST parameters which can be defined. However, it is recommended to prepare a rationale e.g. for the definition of the respective analytical target profile (ATP) which SST parameters are really relevant for the respective analytical procedure. E.g., if there is no criticality with respect to the separation quality, it is possible not to test the tailing factor, but to apply other SST parameters like chromatographic resolution.
The European Pharmacopoeia Style Guide recommends to use one or more SST parameters as general information.

1.2 – Are the system suitability criteria for ion chromatography the same as those for liquid chromatography?
Yes, the principles are identical.

1.3 – Is system repeatability for residual solvents by gas chromatography evaluated?
System repeatability is generally described in chapter 2.2.46 and can also be applied for gas chromatography. One possibility is to evaluate the system repeatability at the "threshold of toxicological concern". However, it might be also appropriate to define the SST (e.g. for Headspace GC) by using S/N ratio, chromatographic resolution and peak shape (tailing factor).
In case of the "New European Pharmacopoeia Style Guide", chapter 2.2.46 is also referenced in the description for the SST describing gas chromatography.

1.4 – Is it mandatory to evaluate system precision for organic impurities/related substances determined by liquid chromatography, given that there is no relevant reference in the Ph. Eur. (only in the USP)?
In Ph. Eur. system precision is described in a general way. Although it might not be mandatory (acc. Ph. Eur.), system precision is a good SST parameter, especially near the quantitation limit in order to check the variability of the analytical procedure.

1.5 – During the training it was mentioned that, for example, a retention time of 2.0 min ± 0.2 min can be defined, corresponding to a 10% variation in retention time. Would it therefore be acceptable to perform an HPLC identification test with a maximum 10% difference in retention time between the sample and the working standard? If yes, which guideline is applicable?
There is no guideline in place which describes the variability of the retention time, e.g. for identification tests. The example is an approach and the variability should be justified in a rationale (or even ATP).