On 9 July 2008, EMEA published a concept paper on the intended creation of a guideline on specifications for related impurities in antibiotics.
The paper refers to antibiotics manufactured by fermentation or semi-synthetic methods (fermentation followed by one or several synthetic steps).
For antibiotics manufactured by chemical synthesis, the corresponding information on how to set specifications for impurities and how to determine limits for reporting, identification and qualification of impurities can be found in quality guidelines and in the European Pharmacopoeia.
In contrast to this, there are no such regulations for antibiotics manufactured by fermentation. In this case, the active ingredient is often formed by a series of similar compounds showing the relevant biological activity. As a result, if the substances are very similar it is difficult to decide whether they are part of the active ingredient or whether they must rather be considered as related impurities. Such related impurities are currently being classified on a case-by-case basis.
This is especially critical, since the impurity profiles of fermentation products and semi-synthetic products are often more complex than the impurity profiles of substances manufactured by means of an exclusively synthetic procedure.
In addition to this, in many cases it proves difficult to develop a suitable analytical method for the assay that features the required specificity and sensitivity and that can be applied both to the closely related substances representing the active ingredient and to the related impurities.
The text also asks the concrete question if some of the monographs on cephalosporins in the European Pharmacopoeia are still up to date.
By elaborating a guideline, a harmonised procedure for setting and assessing specifications for related impurities is meant to be achieved for the products in question.
The complete document can be found here.
Feedback on this concept paper is expected to be received by the end of October 2008.
Dr Günter Brendelberger
On behalf of the European Compliance Academy (ECA)