If we consider the stance taken by the regulatory agencies with regard to biosimilar analyses, then the FDA states:“…methods should be scientifically sound, fit for their intended use, and provide results that are reproducible and reliable.” (2).
The EMA states: “Methods used in the characterization studies form an integral part of the quality package and should be appropriately qualified for the purpose of comparability. If applicable, standards and reference materials (e.g. from Ph.Eur., WHO) should be used for method qualification and standardization.” (3)
and the UK MHRA says “Analytical methods need to be sensitive, qualified and sufficiently discriminatory to detect possible differences. Robust data require the application of suitable orthogonal methods.” (4).
From these statements it is clear that there is an expectation that methods used will be fit for purpose but that there is not a need to have release-type levels of controls at this characterization stage (i.e. methods are not required to be validated). This gives flexibility for methods to be optimized for structural characterization purposes whilst at the same time setting up the expectation that these methods will have checks in place to ensure that data obtained can be relied upon. Qualification of relevant methods does allow a measure of the expected experimental range or error and thus can serve to site the data generated in a broader framework of the method’s capabilities.