دورية أكاديمية
Determining recommended acceptable intake limits for N-nitrosamine impurities in pharmaceuticals: Development and application of the Carcinogenic Potency Categorization Approach (CPCA).
| العنوان: | Determining recommended acceptable intake limits for N-nitrosamine impurities in pharmaceuticals: Development and application of the Carcinogenic Potency Categorization Approach (CPCA). |
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| المؤلفون: | Kruhlak NL; US Food and Drug Administration (US FDA), Silver Spring, MD, USA. Electronic address: Naomi.Kruhlak@fda.hhs.gov., Schmidt M; Danish Medicines Agency (DKMA), Copenhagen, Denmark., Froetschl R; Federal Institute for Drugs and Medical Devices (BfArM), Bonn, Germany., Graber S; Swiss Agency for Therapeutic Products (Swissmedic), Bern, Switzerland., Haas B; Federal Institute for Drugs and Medical Devices (BfArM), Bonn, Germany., Horne I; Therapeutic Goods Administration (TGA), Canberra, Australia., Horne S; Pharmaceutical Drugs Directorate, Health Canada, Ottawa, Ontario, Canada., King ST; US Food and Drug Administration (US FDA), Silver Spring, MD, USA., Koval IA; Medicines Evaluation Board (MEB), Utrecht, Netherlands., Kumaran G; US Food and Drug Administration (US FDA), Silver Spring, MD, USA., Langenkamp A; Swiss Agency for Therapeutic Products (Swissmedic), Bern, Switzerland., McGovern TJ; US Food and Drug Administration (US FDA), Silver Spring, MD, USA., Peryea T; US Food and Drug Administration (US FDA), Silver Spring, MD, USA., Sanh A; French National Agency for Medicines and Health Products Safety (ANSM), Saint-Denis, France., Siqueira Ferreira A; Agência Nacional de Vigilância Sanitária (ANVISA), Brasilia, Brazil., van Aerts L; Medicines Evaluation Board (MEB), Utrecht, Netherlands., Vespa A; Pharmaceutical Drugs Directorate, Health Canada, Ottawa, Ontario, Canada., Whomsley R; European Medicines Agency (EMA), Amsterdam, Netherlands. |
| المصدر: | Regulatory toxicology and pharmacology : RTP [Regul Toxicol Pharmacol] 2024 Jun; Vol. 150, pp. 105640. Date of Electronic Publication: 2024 May 14. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 8214983 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1096-0295 (Electronic) Linking ISSN: 02732300 NLM ISO Abbreviation: Regul Toxicol Pharmacol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: <2003>- : Amsterdam : Elsevier Original Publication: New York : Academic Press, [c1981- |
| مواضيع طبية MeSH: | Nitrosamines*/analysis , Nitrosamines*/toxicity , Carcinogens*/analysis , Carcinogens*/toxicity , Drug Contamination*/prevention & control, Humans ; Animals ; Structure-Activity Relationship ; Risk Assessment ; Carcinogenicity Tests |
| مستخلص: | N-Nitrosamine impurities, including nitrosamine drug substance-related impurities (NDSRIs), have challenged pharmaceutical industry and regulators alike and affected the global drug supply over the past 5 years. Nitrosamines are a class of known carcinogens, but NDSRIs have posed additional challenges as many lack empirical data to establish acceptable intake (AI) limits. Read-across analysis from surrogates has been used to identify AI limits in some cases; however, this approach is limited by the availability of robustly-tested surrogates matching the structural features of NDSRIs, which usually contain a diverse array of functional groups. Furthermore, the absence of a surrogate has resulted in conservative AI limits in some cases, posing practical challenges for impurity control. Therefore, a new framework for determining recommended AI limits was urgently needed. Here, the Carcinogenic Potency Categorization Approach (CPCA) and its supporting scientific rationale are presented. The CPCA is a rapidly-applied structure-activity relationship-based method that assigns a nitrosamine to 1 of 5 categories, each with a corresponding AI limit, reflecting predicted carcinogenic potency. The CPCA considers the number and distribution of α-hydrogens at the N-nitroso center and other activating and deactivating structural features of a nitrosamine that affect the α-hydroxylation metabolic activation pathway of carcinogenesis. The CPCA has been adopted internationally by several drug regulatory authorities as a simplified approach and a starting point to determine recommended AI limits for nitrosamines without the need for compound-specific empirical data. Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Published by Elsevier Inc.) |
| فهرسة مساهمة: | Keywords: Acceptable intake (AI) limit; Carcinogenic Potency Categorization Approach (CPCA); Carcinogenic potency; Drug impurity; Drug safety; Mutagenicity; N-Nitrosamine; Nitrosamine drug substance-related impurity (NDSRI); Pharmaceuticals; Regulatory collaboration; Regulatory science; Structure-activity relationship (SAR) |
| المشرفين على المادة: | 0 (Nitrosamines) 0 (Carcinogens) |
| تواريخ الأحداث: | Date Created: 20240516 Date Completed: 20240610 Latest Revision: 20240610 |
| رمز التحديث: | 20240611 |
| DOI: | 10.1016/j.yrtph.2024.105640 |
| PMID: | 38754805 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1096-0295 |
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| DOI: | 10.1016/j.yrtph.2024.105640 |