Risk assessment report of potential impurities in cetirizine dihydrochloride

•Implementation of an assessment for unexpected impurities arising in drug synthesis.•Different ways impurities of Cetirizine dihydrochloride can arise are depicted.•Reaction matrices help to understand side products in synthesis. Recently, the European Medicines Agency (EMA) and the U.S. Food and D...

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Bibliographic Details
Published in:Journal of pharmaceutical and biomedical analysis Vol. 189; p. 113425
Main Authors: Leistner, Adrian, Haerling, Stephan, Kreher, Joerg-Detlef, Becker, Ivonne, Jung, Dirk, Holzgrabe, Ulrike
Format: Journal Article
Language:English
Published: Elsevier B.V 10-09-2020
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Summary:•Implementation of an assessment for unexpected impurities arising in drug synthesis.•Different ways impurities of Cetirizine dihydrochloride can arise are depicted.•Reaction matrices help to understand side products in synthesis. Recently, the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) had reported on “unexpected” impurities in a couple of sartans, ranitidine, and metformin. These events led to a lot of discussion with regard to the risk assessment for the production process itself. Most of these discussions covered the field of nitrosamine impurities only, but that would be too short-sighted. One should expand that scope. It is impossible to synthesize a 100 % pure compound which holds true for all active pharmaceutical ingredients (APIs). Different synthetic routes result in different impurity profiles. Therefore, pharmacopoeias try to consider all possible impurities that can arise from different drug synthesis routes in one a single monograph for impurity assessment. However, API manufacturers cannot simply rely on the impurity profile reported in pharmacopoeias for the production of a high-quality product. They have to implement a whole risk assessment to rate the presence of impurities in the API. Here, a strategy to evaluate and minimize the load of potential risks of impurities during the manufacturing process of the drug substance cetirizine dihydrochloride within the frame of a detailed risk assessment report is demonstrated.
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ISSN:0731-7085
1873-264X
DOI:10.1016/j.jpba.2020.113425