United States Pharmacopoeia (USP) general chapter 1058 on analytical instrument qualification (AIQ) has finally become official and was released in August 2008 in the first supplement to the USP XXXI (1). In this collumn, I'll revisit this approach to AIQ and discuss the impact that this will have in the regulated spectroscopy laboratory.

R.D. McDowall

In my 2006 column (2), I wrote about the draft USP General Chapter 1058, or USP <1058> on analytical instrument qualification (AIQ). Now that USP <1058> is effective from August 2008, I want to revisit the subject and look in more detail at the approach and the impact this will have on the regulated spectroscopy laboratory.

As a reminder, USP <1058> originated at a conference organized by the AAPS (American Association of Pharmaceutical Scientists) in 2003 entitled "Analytical Instrument Validation." The first thing to bite the dust was "validation" because the attendees agreed that instruments are qualified and processes, methods, and computer systems are validated. Thus, analytical instrument qualification was born. Prior to this it had humble beginnings as simply equipment qualification (EQ). The debate about EQ versus AIQ should be reserved for a bar with copious amounts of alcohol because you will be talking about the same process except the name has changed. Either term means that any instrument is fit for its intended use — nothing more and nothing less.

AAPS published a white paper of the conference in 2004 (3), incorporation as a potential USP general chapter followed in 2005, and review cycles followed until it was finally adopted. It is worth remembering at this point that USP general chapters between <1> and <999> are requirements (you must comply or your product may be deemed adulterated) and those between <1000> and <1999> are informational in nature (alternative approaches are OK if they are justified).

Take care, however. Although <1058> is informational, it implicitly refers to other USP GENERAL CHAPTERS pertinent to specific techniques (for example, <21> Thermometers or <41> Weights and balances that are requirements). Therefore, be warned and careful in your overall approach to qualification.

Potential Problems with USP <1058>

At first sight, USP <1058> seems fine: it appears to be a logical and practical approach to qualification of equipment and instrumentation. It is only when you dig into the details and explore the implications that you find that there are potential problems that could catch you out if you don't think things through and interpret the general chapter sensibly. As we go through this column, I will point out areas that will need special care in your interpretation and approach.

Positioning AIQ versus Other Laboratory Quality Checks

A common debate with analysts who do not understand the problem is that if we validate an analytical method it does not matter which instrument we run it on: a spectrometer is a spectrometer, isn't it? Unfortunately, this is not the case, and a hierarchy of quality checks is described succinctly in <1058>.

The foundation of all quality analytical work is the qualification of the instrument: so you do undertake AIQ first (ideally during the purchase and installation and before you use the instrument). This establishes that the instrument is fit for use around the operating parameters that you test against.

Similar to building a house, the next stage is to develop and validate analytical methods for your work within the parameters you have qualified — don't exceed them, as your instrument is not qualified.

Next, when you apply the method, you'll check that the instrument works before you commit samples for analysis. This could be a balance check versus a known calibrated weight to see correct operation or that a spectral library can identify known standards. This is the equivalent of a system suitability test, or SST, which is typically performed on the day you analyze the samples.

Finally, you will include quality control and perhaps blank samples to check that the instrument readings are OK and give you confidence in the method's operation on the day.

This is shown diagrammatically in the USP chapter as a triangle with AIQ at the base and QC samples at the apex.

So the bottom line is if you don't qualify the instrument or do it incorrectly, all the other work you do is potentially wasted. So that's the easy bit, but the problem with <1058> is that it is written from the perspective of the laboratory. But do you develop and manufacture your own instruments? Probably not, so let's look in more detail at the basics of the instrument qualification process described in <1058>. In doing so, we'll revisit the hierarchy of the quality checks again but in an expanded form.