Analytical Methods: Validate or Qualify?

The terms 'validate' and 'qualify' are both applied to analytical methods, often leading to confusion, so which is the correct term to use? If you consult the dictionary definitions of each word you could probably successfully argue that either of the terms could be applied to the process of demonstrating that a laboratory test method works as it is supposed to. Therefore what we really need is a consistent terminology whereby everyone understands the same thing when these terms are used.

In my experience, there is already quite good agreement but confusion can arise from the slightly different approaches that are taken for test methods for small pharmaceutical molecules compared to large biopharmaceutical molecules. If you have always worked with small molecules, then it is quite likely that you have never applied the term 'qualify' to an analytical test method and are much more likely to apply it to a laboratory instrument. However, in large molecule testing laboratories it is fairly common to 'qualify' methods in early stages of development and 'validate' them in late stage development.

Often, although not always, these early stage methods for large molecules can be quite generic, and they may be referred to as 'platform' methods. At this stage it is not claimed that the test method is completely optimised for the molecule of interest in the expected sample matrix and so when demonstrating its fitness for purpose, the term 'qualify' is felt to be more appropriate.

This is similar to the principle applied in instrument qualification where we are not claiming that all test methods will work on the instrument but that the instrument is fit for use. I think that the approach in computer system validation, as described in the EU GMP Annex 11, is helpful: "The application should be validated; IT infrastructure should be qualified." You can think of the analytical test method like a specifically set up piece of software and an instrument like an operating system. So qualification is for general (supporting) situations and validation is for specific ones.

Whether you agree with the approach of using both terms for analytical test methods depending on the stage of development, or you prefer to always use 'validate' for test methods because 'fit for purpose' covers all stages of development (both approaches seem to be accepted by regulatory authorities), it is still useful to know how the use of the terms has evolved in the pharmaceutical/biopharmaceutical industry so that any confusion can be removed.


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Problems Storing HPLC Water?

The use of water in HPLC mobile phases can be a source of many problems. In this blog post we look at the effects of storage and how to prevent storage related problems.

When you make up fresh mobile phase you probably assign an expiry date based on the fact that you know the solvent mixture will be subject to change over time but what you may not consider is the storage of the solvents prior to mobile phase preparation.

In the case of water, this can have significant detrimental effects on your chromatography. The primary reason is that water is a great solvent. It can absorb contaminants via leaching from the container in which it is stored, and it can also absorb contaminants, such as airborne bacteria, from exposure to the atmosphere. These contaminants are likely to increase the total organic carbon (TOC) in the water which in turn can lead to chromatographic problems such as: noisy and drifting baselines; extra (unexpected) peaks, often referred to as 'ghost' peaks, and in extreme cases problems with retention times and peak shapes.

The extent and impact of these effects will depend on the nature of the HPLC method that you are using. For some methods you may not see any detrimental effects and for others it can be absolutely critical. Contaminants are much more likely to show up, and thus create problems, if you are using UV detection at low wavelengths, in the area of  ~ 210nm, or sensitive mass spectrometry. In these cases it would be worth investigating the effects of water storage and source (e.g., lab purification system vs. bought in bottled water) as part of robustness in method development so that the problem and issues are understood fully before the method is in routine use.

To prevent these problems (or reduce them as much as possible) the following is advised:

• Don't store water, get it fresh before use.
• Discard the first 1-2 litres from the water purification system.
• Use glass containers for water.
• Don't attach plastic tubing to the delivery point of your water purification system.
• Look after your water purification system, maintain it well and don't ignore warning lights!
• For critical methods, investigate the effect of water storage (and source) as part of method development.

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Validation & Transfer of Methods for Biopharmaceutical Analysis

We have decided to split our popular course, 'Validation & Transfer of Methods for Pharmaceutical Analysis', into two versions: one for traditional small molecules - 'Pharmaceutical Analysis'; and another for large molecules - 'Biopharmaceutical Analysis'. Although the content of the two versions will be very similar, this approach will allow use of case studies, scenarios and examples which are tailored to the needs of the learners.

The dates for both versions of the course may be found on the course list page of the MTS website.

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25% Discount on Books

We are offering a 25% discount on our books, 'Validation of Analytical Methods for Pharmaceutical Analysis' and 'An Introduction to HPLC for Pharmaceutical Analysis', as a special end of 2016/beginning of 2017 offer.
Just £22 each (plus shipping if applicable).
Offer ends 31st January 2017.
Visit the MTS website to buy your copies today.

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Course Dates for 2017

The MTS course calendar for 2017 is now available. Click here to view the calendar and visit the course list page on the MTS website for more information on all the available courses.

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