N-nitrosamines as "special case" leachables in a metered dose inhaler drug product.

N-nitrosamines are chemical entities, some of which are considered to be possible human carcinogens, which can be found at trace levels in some types of foods, tobacco smoke, certain cosmetics, and certain types of rubber. N-nitrosamines are of regulatory concern as leachables in inhalation drug products, particularly metered dose inhalers, which incorporate rubber seals into their container closure systems. The United States Food and Drug Administration considers N-nitrosamines (along with polycyclic aromatic hydrocarbons and 2-mercaptobenzothiazole) to be "special case" leachables in inhalation drug products, meaning that there are no recognized safety or analytical thresholds and these compounds must therefore be identified and quantitated at the lowest practical level.

Best practices for extractables and leachables in orally inhaled and nasal drug products: an overview of the PQRI recommendations.

The Product Quality Research Institute Leachables and Extractables Working Group includes pharmaceutical development scientists representing industry, government, and academia. The Working Group was created and constituted to address scientific and regulatory questions concerning the pharmaceutical development process for Orally Inhaled and Nasal Drug Products (OINDP) related to organic extractables and leachables. This effort has resulted in the creation of a detailed "Recommendation Document", which was submitted to the U.