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, e.g. in Phase I / Phase II projects. In this context, I also came across the term ECP validation (early clinical phase). They can also be done later shortly before normal validation to have first ideas about how the method is performing and to determine the essential method characteristics. More concretely, method 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, or an alternative must be searched for. It is "work in progress", so to speak. During method 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, an AMQ can also be used to establish the acceptance criteria. The same parameters as in the following validation might be evaluated, but in general, method qualifications are often less complex, which in turn is also the reason for the term “limited validation”. Method qualifications are often also performed during internal method transfers from the development department to the subsequent routine department. A practical example is given in this blog article.

At the early stages of the development, method 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 AMQ at the early stages and continue with validation when it is required for later stages of clinical trials.

Method 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
Method is documented in a (preliminary, e.g. signed by the laboratory manager) method description	Method is available in form of an approved, concrete test instruction
Early phase / development	Before phase III
Voluntary pre-test	Regulatory requirement
Usually no definition of acceptance criteria, only “reporting”	Compliance with previously defined acceptance criteria necessary
High probability for reproducible results	Demonstration of consistent results under controlled conditions
Reduced number of parameters to be checked	Parameters defined by ICH Q2(R1)