Questions and answers A question-and-answer document is available for marketing authorisation holders on implementing the Article 5(3) CHMP opinion. It covers the following: Outcome of the Article 5(3) referral and its relation to lessons learned exercise from nitrosamines detected in sartansPrinciples, methodology and scope for nitrosamine management in human authorised productsGuidance for establishing and reporting acceptable intake limits derived from implemented approaches: carcinogenic potency categorisation approach (CPCA), read across (SAR) and in vitro (EAT) / in vivo studies.Changes to marketing authorisations and requirements for new applicationsNew approaches for setting nitrosamines limits based on robust scientific knowledge about carcinogenic potency, including the Appendix 1 on acceptable intakes established for N-nitrosamines, Appendix 2 on the carcinogenic potency categorisation approach (CPCA), and Appendix 3 on the enhanced AMES test (EAT) protocol. Questions and answers for marketing authorisation holders/applicants on the CHMP Opinion for the Article 5(3) of Regulation (EC) No 726/2004 referral on nitrosamine impurities in human medicinal products Appendix 1: Acceptable intakes established for N-nitrosamines Appendix 2 : Carcinogenic Potency Categorisation Approach for N-nitrosamines Appendix 3 : Enhanced Ames Test Conditions for N-nitrosamines
