The recent recalls of sartan antihypertensives due to the presence of nitrosamines may suggest increased attention from FDA to toxic impurities in drug products from active pharmaceutical ingredients (APIs). Valsartan, Losartan and Irbesartan drug products have recently been recalled due to the presence of the carcinogens N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA) orN-nitroso-N-methyl 4-amino butyric acid (NMBA). These carcinogens were found to be present above the low interim specifications recently established by FDA.
The analytical method used to find these substances will be discussed. The public information about how they got into these drug products, and its implications for the future, will be considered. European Medicines Agency position on nitrosamines will also be presented. This training will provide valuable information to those who plan and conduct cleaning validations and analyses of APIs, as well as pharma company management.
Learning Objectives:
What are toxic impurities
What is trace analysis
What are nitrosoamines
How are nitrosamines formed
How did they get in sartans
What might this mean for other toxic impurities
Areas Covered in the Session :
General Information about the limits for toxic impurities
Handling trace analysis
Structure and properties of NDMA
Structure and properties of NDEA
Structure and properties of NMBA
How are nitrosamines formed?
How did it get in sartans?
Some thoughts on other potential toxic impurities
Who Should Attend:
Quality Departments
Research and Development Departments
Regulatory Affairs Departments
Validation Departments
Everyone involved with Analytical Method Development and Validation
Everyone involved with New Product Selection