Adjustment versus Modification - Interpretation of the Ph.Eur. Requirements

Adjustment versusModification – Interpretation of the Ph.Eur. Requirements

The possibilitiesfor adjusting an analytical technique as described in the Ph.Eur. Monograph are quite generous: in HPLC e.g., the column length may varyby +/-70%, as may the flow rate, and the inner column diameter maydeviate by +/-25% without any need to consider this as a modification relevantto change control.

Strictly speaking, the regulations laid down in this monograph applyexclusively to analytical methods listed in pharmacopoeial monographs. Sothey cannot simply be transferred to other analytical techniques, e.g.within the framework of drug product analysis. On the other hand, it isgenerally recognised that such a monograph represents the state of the art and knowledge.

It has been discussed whether one can orientate one's own, self-developedchromatographic methods towards the Ph.Eur. Monograph. There hasbeen agreement on the fact that one should validate the method and prove bymeans of an appropriate robustness test that this method remains in factvalid over the whole adjustment range of the individual parameters. The robustness test is meant to ensure that slight changes in themethod parameters will not influence the test result during routineoperation.

Furthermore, the adjustment of a method has to be checked immediatelybefore an analytical sequence through a product-specific systemsuitability test. By means of this test it has to be proven that thechromatographic separation technique is really suitable for the analysis inhand under the current conditions and settings of the day.

From a formal point of view, it remains to say that no revalidation isnecessary in case of a method adjustment, nor is any further internal orexternal analysis or approval. In contrast to this, the modification of ananalytical technique is subject to the change control procedure: the methodhas to be revalidated, and a notification of change has to be sent to theregistration authorities.

Author:
Dr Günter Brendelberger
CONCEPT HEIDELBERG