Rapid Revision and Implementation of Pharmacopoeial Monographs Concerning 5 Sartan Preparations

Recommendation

Tuesday, 28 May 2024 15.30 - 17.30 h

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Background

Following the publication of the Assessment Report "Nitrosamine impurities in human medicinal products" by the CHMP on 9 July 2020, the decision was made to directly apply the recommendations on the management of nitrosamine impurities outlined in this report to sartan preparations (angiotensin II receptor antagonists with a tetrazole ring). The EMA provided information on this in a news article released on 13 November 2020. The following sartan APIs are involved:

• Candesartan cilexetil
• Irbesartan
• Losartan potassium
• Olmesartan medoxomil
• Valsartan

The "final assessment report" for these 5 sartan preparations, published at the end of February 2021, includes requirements regarding the control of nitrosamine impurities as well as notification deadlines relevant to marketing authorisation.

Changes in the European Pharmacopoeia

The European Pharmacopoeia Commission then initiated a rapid revision procedure to ensure that the information on these sartan preparations in the pharmacopoeia is in line with current regulatory requirements. The monographs for these sartans have been revised accordingly, with the respective following changes:

• Rewording of the section "Production:
  The manufacturer is required to perform a risk assessment with respect to nitrosamine formation and contamination. If this assessment identifies a potential risk of contamination, the manufacturing process must be modified to minimize this risk. Furthermore, a strategy for the detection of nitrosamine contamination and its control must be established. It is also referred to General Chapter 2.5.42. "N-Nitrosamines in active substances" for further guidance (see the EDQM news dated 7 December 2020).
• The section on testing for N-nitrosamines has been deleted.

The 5 updated sartan monographs were not published in "Pharmeuropa" but are available directly from the EDQM website. They will come into effect on 1 April 2021.

In the course of this revision decision, two other General Monographs of the European Pharmacopoeia were also updated (but not within the rapid revision procedure):

• 2034 Substances for pharmaceutical use
• 2619 Pharmaceutical preparations

In these monographs, guidance on risk assessment regarding nitrosamine impurities in APIs and medicinal products has been included. These monographs are published in Pharmeuropa 33.2.