Lesson Learnt from Recall of Valsartan and Other Angiotensin II Receptor Blocker Drugs Containing NDMA and NDEA Impurities

Autor: Ziyaur Rahman, Areeg Anwer Ali, Shailesh Kumar Buha, Naseem A. Charoo
Rok vydání: 2019
Předmět:
Drug
Angiotensin receptor
Drug Industry
Drug Compounding
media_common.quotation_subject
Pharmaceutical Science
02 engineering and technology
Aquatic Science
Pharmacology
030226 pharmacology & pharmacy
Dimethylnitrosamine
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
N-Nitrosodimethylamine
Drug Discovery
medicine
Humans
Diethylnitrosamine
Drug Recalls
Ecology
Evolution
Behavior and Systematics
Carcinogen
media_common
Pharmaceutical industry
Active ingredient
Ecology
United States Food and Drug Administration
business.industry
General Medicine
Processes of change
021001 nanoscience & nanotechnology
United States
Valsartan
chemistry
Patient Safety
Drug Contamination
0210 nano-technology
business
Angiotensin II Type 1 Receptor Blockers
Agronomy and Crop Science
Mutagens
medicine.drug
Zdroj: AAPS PharmSciTech. 20
ISSN: 1530-9932
DOI: 10.1208/s12249-019-1376-1
Popis: The presence of N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) impurities in angiotensin II receptor blocker (ARB) drugs containing tetrazole ring has triggered worldwide product recalls. The purpose of this article is to identify the potential gap area in current pharmaceutical industry practice that might have led to the NMDA and NDEA impurities escaping the drug manufacturer's and FDA's attention. The impact of process change was not adequately assessed by the manufacturer of contaminated APIs (active pharmaceutical ingredients), and potential for generation of mutagenic or other toxic impurities was not considered. The safety and risk associated with a chemical synthetic process was also not evaluated. This is primarily due to current industry practice which focuses on controlling the impurities above reporting threshold. ICH Q3A and FDA guidance on genotoxic and carcinogenic impurities in drug substances and products need to be integrated so that the ICH Q3A decision tree (attachment 3) begins by checking whether the synthetic process has been evaluated for the potential to generate toxic impurities. The compliance with ICH Q3A limits should be carried out only after the process has been determined to be safe without the risk of generating mutagenic and carcinogenic impurities.
Databáze: OpenAIRE
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