Why System Suitability Tests Are Not a Substitute for Analytical Instrument Qualification or Calibration (Part 1)

Jun 30, 2010

Can you qualify or calibrate your chromatograph using a system suitability test? No. However, for the doubters amongst you I'll spend the rest of this column and the next one explaining why!

In this two-part column I'll be discussing the role of system suitability tests (SSTs) in the context of analytical instrument qualification (AIQ) and the generation of quality analytical results. I'll look at this first from the perspective of regulatory requirements based upon the United States Pharmacopoeia (USP) general chapter 1058 (<1058>) on AIQ.1 However, as much of this discussion is also good analytical science I will also look at this from the perspective of ISO 17025,2 the interpretation of the ISO 9000 quality management system for testing and calibration laboratories. In this column I'll use the ISO 17025 term of calibration to be equivalent to AIQ and discuss the reason why I have taken this approach.

Specifically, I want to discuss the question why system suitability tests (SSTs) are not a substitute for AIQ for the initial qualification or re-qualification of a chromatograph (i.e., a periodic check or operational qualification) under GMP or calibration under ISO 17025. The reason for this is that there is a common misconception in some laboratories that SSTs can be used to qualify a chromatograph. This is wrong. Furthermore, using SSTs as the sole instrument qualification approach will leave any laboratory exposed to regulatory action or non-conformance as the chromatographs cannot be demonstrated as being fit for their intended purposes. Therefore, we will explore the reasons for this from both the regulatory and quality perspectives.

What is a System Suitability Test?

An SST is simply a check to see if the chromatographic system (instrument modules, column and mobile phase) is capable of undertaking the analysis you require. It is performed immediately before the samples you have prepared in the laboratory are committed for analysis. At it's simplest, an SST is the single injection of a standard solution of reference compound(s) to see if the separation is 'OK'. The only criterion used for assessing if the system is acceptable is a visual check by the chromatographer to assess if the separation is within expected boundaries. However, there are no measurements made: just a simple visual assessment that things are right.

At the other end of the scale are the formal SSTs described in the Pharmacopoeias used in pharmaceutical QC laboratories. Here five replicate injections of a standard are injected and the calculated peak areas and other chromatographic criteria (retention time window, peak shape, peak tailing, resolution between peaks etc.) are objectively compared with predefined specifications defined by the Pharmacopoeia (peak area repeatability) and the laboratory (all other chromatographic criteria). If the SST injections meet all the predefined criteria then the chromatographic system is deemed acceptable and the samples committed for analysis.