There are various tools to identify risk, such as fishbone diagrams, process mapping, and process breakdowns. It serves as a prelude to the later steps of risk analysis and risk evaluation that ultimately lead to the appropriate control and management of risk. This first step in the risk assessment process also identifies possible consequences. All available data should be reviewed to address the question “What could go wrong?” Risk identification, which starts with qualitative hazard identification, is the process by which existing hazards are identified, initially without assigning magnitude. Risk identification, risk analysis, and risk evaluation. At the conclusion of the risk assessment, risk should be expressed in quantitative or qualitative terms, depending on the data available from the three steps of the risk assessment: 7 Part of the risk assessment process is to consider whether there are any possible pathways that might realistically give rise to formation of impurities. ![]() If the risks are not identified, analyzed, and evaluated properly, decisions about how to control risk cannot be made efficiently. The risk assessment steps may be considered the most important aspects of an overall QRM process. “Technical Fact Sheet-N-Nitroso-dimethylamine (NDMA).” 2014. During QRM, the following steps are carried out: This team acts as a unit to determine all possible or probable causes of the generation of impurities and to then identify the adequacy of current controls used to bring these impurities within the desired limit. To assess the risk of impurities, a company should form a cross-functional team with personnel from research and development, quality, manufacturing, regulatory, and other relevant departments. This approach requires a thorough knowledge of the product, its manufacturing process, the impurity, the product’s and the impurity’s chemical structures, situations ideal for the formation of the impurity, and the controls adopted. One of the best and more proactive strategies uses QRM as a tool to assess the risk for and control of impurities such as NDMA. Manufacturers adopt various strategies to ensure impurities are quantified and well within the desired limit. No matter how impurities are formed, the mechanism of their formation should be known and controlled. Generation of impurities like NDMA in drug products has raised questions about manufacturing process controls. ![]() NDMA, a known contaminant found in water and foods (meats, dairy products, and vegetables), is also found in drugs as an impurity. īased on analytical lab test results, NDMA may be classified as a carcinogenic substance for humans. “Questions and Answers: NDMA Impurities in Ranitidine (Commonly Known as Zantac).” 1 April 2020. ![]() “FDA Updates and Press Announcements on NDMA in Metformin.” 13 July 2020. “FDA Updates and Press Announcements on NDMA in Zantac (Ranitidine).” 16 April 2020. “Statement Alerting Patients and Health Care Professionals of NDMA Found in Samples of Ranitidine.” 13 September 2019. “Recalls of Angiotensin II Receptor Blockers (ARBs) Including Valsartan, Losartan and Irbesartan.” Updated 3 February 2020. In this article, all plausible pathways related to the formation of NDMA impurities in pharmaceutical products and a possible control strategy using quality risk management (QRM) as a tool are discussed. Recently, recalls of angiotensin receptor antagonists, particularly valsartan, and warning alerts about N-nitrosodimethylamine (NDMA) impurities in drug substances such as ranitidine and metformin have demonstrated the urgent need for manufacturers and regulators to control impurities throughout the product life cycle to ensure patient safety.
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