This website uses cookies to store information on your computer. Some of these cookies are used for visitor analysis, others are essential to making our site function properly and improve the user experience. By using this site, you consent to the placement of these cookies. Click Accept to consent and dismiss this message or Deny to leave this website. Read our Privacy Statement for more.
Print Page   |   Contact Us   |   Sign In   |   Register
Impact Statement - No deal senario
Share |

Impact Statement

Lessons from the Sartan incidents



In the summer of 2018, a U.S. drug manufacturer told the FDA it had discovered the impurity N-nitrosodimethylamine (NDMA) in a valsartan active pharmaceutical ingredient made by its Chinese API supplier. Subsequently the FDA found NDMA and a similar chemical, NDEA, had contaminated certain valsartan APIs for years. The agency said the two contaminants, (both probable carcinogens), can form through specific and commonly used manufacturing processes.


FDA took action to identify the root causes of these nitrosamine impurities and to prevent a recurrence of this episode in the future. This continues to be an exhaustive effort led by a multidisciplinary team of chemists, toxicologists, physicians, pharmacists, communication specialists, investigators and analytical laboratory staff from across the FDA and in collaboration with global regulators.


Whilst regulators are still investigating the root causes of the impurities, FDA has determined that the impurities may be generated when specific chemicals and reaction conditions are present in the manufacturing process of the drug’s API, and may also result from the reuse of materials, such as solvents.


It’s unlikely that the subtle problems causing these impurities could have been found on a routine current good manufacturing practice (CGMP) inspection. Nonetheless, FDA inspections did reveal systemic problems of supervision that could have created the conditions for quality issues to arise. Investigations into the API process identified that a change made to the manufacturing process likely led to this impurity, and that the impurity went undetected by global regulators, including the FDA, for a period of time. Before FDA undertook this analysis, neither regulators nor industry fully understood how NDMA or NDEA could form during this particular manufacturing process. 


Impacts so far

·         Multiple product recalls across major markets. Import restrictions imposed in USA and CEP status altered in EU

·         FDA’s subsequent temporary risk based adjustment to the allowed level of these impurities in order to avoid the higher risk to patient of  product shortages

·         Need to answer the critical question of, why weren’t these impurities detected earlier? Plus whether the FDA could have prevented this from occurring if it had done something differently during surveillance inspections in the preceding years.

·         New methodology developed by FDA to quantify low levels of these impurities

·         A number of lawsuits in the USA against firms involved claiming injury from the adulterated drugs have been filed and many more are expected


Prepared by Malcolm Holmes.


Impact Papers

Item Name Posted By Date Posted
Lessons from the Sartan incidents PDF (166.59 KB) Administration 14/05/2019
Membership Software Powered by YourMembership  ::  Legal