The Good old Days of Chromatography Method Development – were they that good?

I can remember my time as a trainee chromatographer, when method development consisted of making a best guess at a suitable column, then preparing an undocumented standard solution, which was repeatedly injected while “tweaking” instrument conditions until reasonable separation and sensitivity were achieved. Then, documented calibration and spiked-sample preparations would be performed as validation. The resultant data was then assessed, and system suitability requirements were set. 

The problem was that every method developed was fit for purpose because its performance characteristics were based on what had been achieved rather than on what was required. Fortunately, the recent ICH Q14 (method development) and Q2(R2) (method validation) standards aid a full understanding of best practise in development/validation.

Q14 and Q2(R2) complete the ICH application of Quality by Design (QbD) to all aspects of pharmaceutical production as described in previous Q standards. This process has not been quick. Other industries, such as automotive production, were many years ahead of pharmaceuticals in applying QbD.

I think ICH should be applauded for the Analytical Target Profile (ATP) concept described in Q14, in particular, for highlighting that analytical performance requirements must be fully defined before a single injection is made. This ensures that the final method is fit for purpose.

Frank Judge – Consultant Chemist at Butterworth Laboratories