| | | | | | | | | New pharmacopoeial texts adopted to protect patients’ health | | EDQM
| | During its November session, the European Pharmacopoeia (Ph. Eur.) Commission adopted more than 100 new and revised texts, including new general chapters on the control of N-nitrosamines in active pharmaceutical ingredients (APIs) and on contaminant pyrrolizidine alkaloids (PAs) in herbal products. N-nitrosamines are classified as probable human carcinogens based on animal tests. While they occur at low levels in certain foods, e.g. smoked/cured meat and fish, their presence in medicines has to be avoided and if this is not possible, tightly controlled and limited – only very low amounts are acceptable according to current regulatory requirements. Their detection requires highly sensitive analytical methods. Following the identification of N-nitrosamines in certain antihypertensive medicines containing APIs of the sartan class in 2018 and later on in other APIs and medicines, the EDQM and the Ph. Eur. Commission immediately took a number of measures, in close co-operation with European and international regulators, including the development of analytical methods for their control. The newly adopted general chapter was initially elaborated with the objective of developing validated limit tests for N-nitrosamine impurities in sartan active substances with a tetrazole ring. It provides a toolbox of analytical procedures using different instruments as it was considered important to cover the diverse needs of many quality control laboratories in Europe and worldwide. To further support users in the application of these tests, seven reference standards have been established by the EDQM. When adopting the chapter on Nov. 24, the Ph. Eur. Commission decided to go for an immediate revision to further enhance the text with a framework for the testing of medicinal products. This decision was taken as it has been demonstrated, in the meantime, that other factors than the API can lead to the appearance of N-nitrosamines in medicines, e.g. interactions between the API and excipients used in the formulation, or interactions with the medicine’s primary packaging material, e.g. lidding foils used in the production of blisters. In view of the global use of medicines that have been found to contain nitrosamine impurities, the Ph. Eur. also works with the United States Pharmacopoeia towards convergence to ensure that the public quality standards of the two pharmacopoeias are consistent. While the chapter will be included in Ph. Eur. Supplement 10.6, to be published in July 2021, the EDQM has decided to immediately make the text available to users on its website filling a gap in the public availability of robust and validated analytical procedures for the control of N-nitrosamines.Pyrrolizidine alkaloids (PAs) are nitrogen-containing compounds that occur naturally in plants - several hundred structurally distinct PAs have been found in several thousand different plant species. Many of these plants are common weeds, which can contaminate raw plant materials used for the production of herbal medicinal products. This results in contamination of raw plant materials by PAs, usually at very low levels. PAs have been known for many years for their acute toxic, genotoxic and carcinogenic potential The new general chapter on Contaminant pyrroliozidine alkaloids covers trace analysis of target PAs in herbal drugs, preparations thereof and medicinal products. It does not cover the determination of PAs that occur naturally in plant materials. The chapter represents an important contribution to the safety of herbal medicinal products and the protection of patients’ health. |
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