Don’t be Caught Off Guard by Ever-Changing Nitrosamine Regulatory Landscapes

[JonBardsley]

This month the European Medicines Agency (EMA) issued further revisions to the ever-changing guidance for drug producers when it comes to nitrosamine testing. In 2018 the Federal Drug Administration (FDA) showed the presence of n-nitroso dimethylamine (NDMA) at unacceptable levels in angiotensin receptor blockers (ARBs), and since then further nitrosamine compounds were found in other drug products such as metformin. This topic has had marketing authorization holders (MAHs) around the globe scrambling to better understand the impact on their products, implement risk assessments, and devising analytical strategies.

Further background on nitrosamine testing strategies can be found here within a handy toolkit.

The recent announcement by the EMA has three highlights;

1. Introduction of NDPA as a new nitrosamine of interest
2. Practical options for deciding on limits when multiple nitrosamines are present
3. Multi-step review of the manufacturing process

But what does this mean to my analytical methods and testing strategies?

Advanced LC-MS solutions with increased sensitivity and separation efficiency for nitrosamine detection

It is now more important than ever to stay ahead of the changes. Implementing proven instruments and solutions with increased sensitivity and separation efficiency to detect a wide range of nitrosamine impurities, including the new impurity NDPA, to help future-proof your methods. This ensures your routine monitoring can accurately and reliably meet worldwide regulatory requirements. 

Application benefits:

• Detection and quantification of 11 nitrosamines in a single liquid chromatography, high-resolution accurate-mass mass spectrometry (LC-HRAM-MS) method
• Quantitation of nitrosamine impurities in metformin drug products below the daily acceptable intake level, that meets U.S. FDA regulatory guidelines
• Compliant data acquisition, processing and auditing built for a U.S. FDA 21 CFR part 11 compliant environment

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Advanced Ion Chromatography solutions to accurately and quickly monitor nitrosamine precursors

Proactively monitoring drug products and ingredients can help you understand the risk level and impact when the presence of nitrosamine precursors is suspected to be present. Predictions can be made through understanding the chemical properties of each stage of the production process, but we also need to be aware of potential contaminated ingredients.

Selecting the right technologies to enable the analysis and monitoring of nitrosamine precursors — such as nitrite — ensures you know exactly what is in the raw ingredients. This helps to understand the risk of nitrosamine formation in the manufacturing process and product storage.

Application benefits:

• Cost-effective determination of nitrite in pharmaceuticals by coupling IC with UV absorbance detection
• The method is accurate and precise due to the high reproducibility of the reagent-Free ion chromatography system
• This method is applicable to the determination of nitrite throughout the manufacturing process of a drug product to assess the likelihood of nitrosamine formation

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