MTS Helpdesk

Question:

What is the difference between ‘validating’ and ‘qualifying’ an analytical method and what is the regulatory perspective on this issue?

Answer:

In the pharmaceutical and biopharma industry, both of the terms ‘validate’ and ‘qualify’ may be found applied to the demonstration of the capability of analytical procedures. In my experience, the term ‘qualify’ is more common in biopharma and can sometimes lead to confusion about which is the correct term to use. It is often a surprise to analysts to learn that this term is not used in the main regulatory guidance documents on the topic of analytical procedures, such as ICH Q2(R2) and ICH Q14.

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 procedure 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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A full discussion of analytical procedure lifecycle management is included in our courses, ‘Validation, Verification and Transfer of Methods for Pharmaceutical Analysis‘, and ‘Validation, Verification and Transfer of Methods for Biopharmaceutical Analysis‘.

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