At the International HPLC Conference of the European Compliance Academy
that was held in Heidelberg in spring this year, one lecture (by Dr Manfred
Fischer, Lilly Forschung GmbH, Hamburg) touched on the discussion point
whether the freedoms granted by the Ph.Eur. Monograph 2.2.46 "Chromatographic
Separation Techniques" regarding the adjustment of chromatographic
techniques can generally be transferred to the analytical laboratory.
for adjusting an analytical technique as described in the Ph.Eur. Monograph are quite generous: in HPLC e.g., the column length may vary
by +/-70%, as may the flow rate, and the inner column diameter may
deviate by +/-25% without any need to consider this as a modification relevant
to change control.
Strictly speaking, the regulations laid down in this monograph apply
exclusively to analytical methods listed in pharmacopoeial monographs. So
they cannot simply be transferred to other analytical techniques, e.g.
within the framework of drug product analysis. On the other hand, it is
generally 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-developed
chromatographic methods towards the Ph.Eur. Monograph. There has
been agreement on the fact that one should validate the method and prove by
means of an appropriate robustness test that this method remains in fact
valid over the whole adjustment range of the individual parameters. The robustness test is meant to ensure that slight changes in the
method parameters will not influence the test result during routine
Furthermore, the adjustment of a method has to be checked immediately
before an analytical sequence through a product-specific system
suitability test. By means of this test it has to be proven that the
chromatographic separation technique is really suitable for the analysis in
hand under the current conditions and settings of the day.
From a formal point of view, it remains to say that no revalidation is
necessary in case of a method adjustment, nor is any further internal or
external analysis or approval. In contrast to this, the modification of an
analytical technique is subject to the change control procedure: the method
has to be revalidated, and a notification of change has to be sent to the
Owing to large demand, the Conference "Successful HPLC Management in a GMP-/FDA-Regulated
Environment" is repeated in Barcelona on 31 March - 1 April 2004
together with the ensuing Post-conference Workshop "Validation of Chromatographic Data Systems"
to be held on 2 April 2004. If you would like to view the conference
programme, please click here.
Dr Günter Brendelberger