USP <1058> originated at a conference organized by the American Association of Pharmaceutical Scientists (AAPS) in 2003 called
Analytical Instrument Validation. The first thing to bite the dust was 'validation' as the attendees agreed that instruments
are qualified and processes, methods and computer systems are validated. Thus analytical instrument qualification (AIQ) 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 as you will be arguing 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 2004,2 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 to be 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 requirements 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 for chromatography and associated equipment,
instruments and systems.
Positioning AIQ Versus Other Laboratory Quality Checks
A common debate with analysts who do not understand the problem that if we validate an analytical method it does not matter
which instrument we run it on: a chromatograph is a chromatograph 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, rather than after you have bought it and have been
caught by Quality Assurance using it). This establishes that the instrument is fit for use around the operating parameters
that you test against. Some examples are the maximum and minimum pump flow-rates and the wavelength range for the detector.
- 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 chromatograph is not qualified. Again as an example, if the analyte you are
developing a method for has a λmax outside of the wavelength range you have just qualified then you will exceed the qualified detectors working range and should
requalify the detector.
- 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 a system suitability test (SST) to ensure
that the chromatograph and the method work on the day before you have committed the samples for analysis.
- Finally, you may include quality control (QC) and perhaps blank samples to check that the chromatographic analysis results
are OK and give you further 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. Note that the only instrument layer is the instrument
qualification (first stage), which should be performed with measurement instruments such as flow meters that are calibrated
to national or international standards. The remaining three levels of checks are method-specific checks which assume that
the chromatography or instrument is working correctly.
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. However, the problem with <1058> is that it is written from the perspective of the laboratory,
but do you develop and manufacture your own chromatograph instruments? Probably not, so let's look in more detail at the basics
of the instrument qualification process described in <1058> and in doing so we'll revisit the hierarchy of the quality checks
again, but in an expanded form.