The European Pharmacopoeia Commission has revised via a rapid implementation procedure the five “sartan” monographs (Valsartan, Losartan potassium, Candesartan cilexetil, Olmesartan medoximil and Irbesartan); they will enter into force on 1 April 2021 to align them with the CHMP decision on the detection, management and prevention of the presence of N-nitrosamines in “sartan medicinal products” (see EMA news item of 13 November 2020).
Given the changes in these monographs, it is considered that the currently valid CEPs referring to these monographs are already in conformity with the requirements of the monographs and therefore remain valid (i.e. there is no need to demonstrate conformity to the monographs). CEP holders of these concerned substances will therefore not be contacted by the Certification Department, as is the usual procedure following the introduction of a revised monograph.
However, on the basis of the production statements included in the monographs, CEP holders may decide to revise their control strategy for nitrosamine impurities, in which case a request for a minor revision should be made according to the EDQM Guideline on requirements for revision/renewal of Certificates of Suitability to the European Pharmacopoeia monographs (PA/PH/CEP (04) 2, 7R corr), 4.II.2.1 Change in the specification parameters and/or limits of the final substance g) Change of a limit for a mutagenic impurity in the final substance specification according to the principles and limits of the ICH M7 guideline.
CEP holders are reminded of the need to elaborate the revised control strategy following the guidance in ICH M7 and to clearly demonstrate in the request for revision how the new strategy is in accordance with these requirements. In addition, any other changes being made as part of a revised control strategy should also be classified using the EDQM revisions policy document and detailed in the comparative table and the application.