What's the difference between method qualification and method validation?
Today, we'd like to deal with the question of what is meant by method qualification and clearly distinguish between the two terms method qualification and method validation.
Analytical Method Qualification (AMQ)
Analytical procedures are mandatory for analysis of specific drug substances (DS) and drug products (DP). Qualification of analytical methods simply suggests its suitability for the intended use - as do method validations. Both are steps to check the performance of an analytical method. However, they occur at different times.
Analytical method qualifications are usually performed at the early studies when compared to analytical method validation but can also be done later shortly before normal validation to have first ideas about how the method is performing. More concretely, qualifications should demonstrate that the design of the method per se is working and that reproducible results are obtained for the intended purpose, i.e. that the method is suitable for its application at this time of development. If this is not the case, the method needs to be further optimized. It is "work in progress", so to speak. During qualification it is checked whether the method is fit for its subsequent validation and would be able to meet the validation's criteria with high probability. Thus, it can also be used to establish the acceptance criteria. The same parameters as in the following validation might be evaluated, but in general, qualifications are often less complex. A practical example is given in this blog article.
At the early stages of the development, qualification could be a choice but towards the later stages, validation is mandatory, without which, no application for approval will be accepted.
It is possible (not necessary) for companies to straightway go for the validation and skip the qualification all together. It happens for example, during the development of a generic drug substance, where the chemical equivalence is required to be proven. Because of the cost factor, many companies choose to perform the qualification at the early stages and continue with validation when it is required for later stages of clinical trials.
Qualifications are also known as feasibility studies or pre-validation studies.
Method Validation
Like method qualification, also method validation is a process that confirms the suitability of in-house developed methods for their intended analytical use. Results obtained through the validation are used to judge the quality, reliability and consistency of any analytical method. There are regulatory requirements regarding the parameters to be analysed during validation which may differ according to the type of method. The most important guideline is the ICH Q2(R1). More information about method validation can be found here and here.
To emphasize once again, validation is required by regulatory authorities while qualification is voluntary. In addition, for validation the previously defined acceptance criteria must be met. Thus, the method must already have been fully developed.
| Method qualification |
Method validation |
| Method can be changed | Method is fully developped |
| Early phase / development | Before phase III |
| Voluntary pre-test | Regulatory requirement |
| High probability for reproducible results | Demonstration of consistent results under controlled conditions |
| Reduced amount of parameters to be checked | Parameters defined by ICH Q2(R1) |