FDA Identifies ARBs Without Impurities
For the first time since the US Food and Drug Administration (FDA) discovered a nitrosamine impurity in angiotensin II receptor blockers (ARBs) last summer, the agency has now identified 40 ARBs and counting that do not contain a nitrosamine impurity.“Our goal is for this information to help health care providers as they consider acceptable treatment options for their patients,” outgoing FDA Commissioner Scott Gottlieb and CDER Director Janet Woodcock said in a joint statement. “Our assessment takes into consideration testing for impurities conducted by the FDA’s laboratories, an evaluation of the manufacturing process used by multiple manufacturers of the active pharmaceutical ingredient (API) found in ARB medicines, as well as other information available to the agency from manufacturers and international regulators.”
The creation of the list follows FDA’s identification of several impurities in ARBs, including N-Nitrosodimethylamine (NDMA) and N-Nitrosodiethylamine (NDEA) impurities, which prompted recalls of ARB drugs containing APIs manufactured by Hetero, Mylan Pharmaceuticals and Zhejiang Huahai Pharmaceuticals.
“Removing the affected medications from the market has led to shortages, and since then we’ve been working to mitigate and prevent shortages as often as possible. Currently, valsartan products are in shortage, and we know that other types of products have the potential to fall into shortage soon,” Woodcock and Gottlieb said.
And to ensure patient access to the blood pressure medicine losartan, most recently FDA said it will not object to certain manufacturers temporarily distributing losartan with another impurity above the interim acceptable intake limit until that impurity can be eliminated.
The agency also recently sent manufacturers a letter to inform them “about factors that can contribute to the formation of nitrosamine impurities during manufacturing (which we understand may be generated when specific chemicals and reaction conditions are present in the manufacturing process of the drug’s API) and to reiterate steps they should take to ensure these impurities are not present in any ARB in the future.”
FDA's Assessment of Currently Marketed ARB drug products