Why System Suitability Tests Are Not a Substitute for Analytical Instrument Qualification or Calibration, Part I

Dec 01, 2010

In this two-part article series 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 Pharmacopeia (USP) general chapter 1058 (1058) on AIQ (1). 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. I'll use the ISO 17025 term of calibration to be equivalent to AIQ and discuss the reason why I have taken this approach.


Table I: Selected U.S. good manufacturing practice (GMP) regulations for instruments and equipment
Specifically, I want to discuss the question why SSTs are not a substitute for AIQ for the initial qualification or requalification of a chromatograph (that is, 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. Using SSTs as the sole instrument qualification approach will leave any laboratory exposed to regulatory action or nonconformance 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 compounds 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 visual assessment that things are right.

At the other end of the scale are the formal SSTs described in the pharmacopeias used in pharmaceutical QC laboratories. Here a minimum of 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, and so forth) are objectively compared with predefined specifications defined by the pharmacopeia (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.