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Valsartan drug product impurity analysis for NDMA according to the FDA headspace gas chromatography-mass spectrometry (GC/MS) method and determination of NDEA contamination
N-nitrosodimethylamine (NDMA) is an impurity found in valsartan APIs and products and was the driver for a product recall by the FDA in July 2018. Since then the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) have reported the presence of a second impurity, N-nitrosodiethylamine (NDEA), also found to be present in valsartan products. Both NDMA and NDEA are classified as a probable human carcinogens.
The presence of NDMA in finished pharmaceutical products is thought to be the result of the manufacturing process of the drug substance and the FDA Office of Testing and Research have developed a headspace gas chromatography-mass spectrometry (GC/MS-HS) method to detect and quantify the presence of NDMA in drug substance samples of valsartan at levels of ≥ 0.3 ppm. The presence of these impurities drive the need for robust analysis to detect and quantify these substances in valsartan products.
Intertek has established the FDA GC/MS-HS method within our GMP laboratory services to assist clients in performing the required method validations where the data can be used to support regulatory submissions or quality assessment of the API or drug product. We can also support the determination of NDEA in APIs or in drug products.
With scientists who are adept at method development and validation of suitable analytical procedures, we regularly help clients overcome the challenges of low detection levels, difficult matrices and identification of unknowns in the course of pharmaceutical impurities analysis. Additionally, we offer highly sensitive and specific method development and validation expertise to assess other carcinogenic or genotoxic impurities in drug products.
In addition to experienced pharmaceutical impurity analysis, we can support with toxicological risk assessments. Our experienced consultants conduct risk assessments to address the impact associated with exposure to residual solvents, process impurities, extractables & leachables, elemental impurities (ICH Q3D) and other substances that may find their way into a given pharmaceutical product.