What are Nitrosamines?
Nitrosamines are a group of highly potent mutagenic and carcinogenic compounds. These DNA-reactive impurities are closely regulated in pharmaceuticals under ICH M7 guidelines due to their high mutagenic and carcinogenic potential. They belong to the “cohort of concern” (COC) category, which includes compounds such as NDMA (N-nitrosodimethylamine), NDEA (N-nitrosodiethylamine), and N-nitrosoethylpropylamine, among others.
Nitrosamines can form through the nitrosation of the active pharmaceutical ingredient (API) or excipients, which poses significant risks to drug safety. These impurities may remain stable or increase over time, influenced by factors such as temperature, moisture, and storage conditions. Given the variability in nitrosamine formation, robust, stringent monitoring and control are essential to ensure the safety and quality of pharmaceutical products.
Ensure Safety and Compliance with Advanced Nitrosamine Testing
Partner with Emery Pharma to safeguard your pharmaceutical products from harmful nitrosamine impurities. We provide comprehensive analytical testing and quantitation services that meet regulatory standards, ensuring your products comply with US FDA, EMA, and Health Canada guidelines.
Why Choose Emery Pharma for Nitrosamine Risk Analysis in Your Biopharma, Drug Substance, or Drug Product Testing?
Analyzing nitrosamines can be extremely challenging, requiring the detection of ultra-low levels—often in trace, nanogram quantities—within complex drug matrices. Precision in method development is critical, followed by rigorous validation to meet GMP requirements.
Emery Pharma brings a distinguished history in nitrosamine testing, including our pioneering work in root cause analysis for the ranitidine molecule. With our extensive experience, as evidenced by our industry reputation and online presence, we are well-equipped to address these complexities.
Our advanced instrumentation includes state-of-the-art liquid chromatography-mass spectrometry (LC-MS/MS), gas chromatography-mass spectrometry (GC-MS), and high-resolution Orbitrap mass spectrometry (HR-MS), enabling us to detect, differentiate, and quantify nitrosamines with precision. In addition, we also employ a comprehensive toxicological and analytical risk assessment framework to evaluate drug substances and drug products.
Additionally, Emery Pharma will assist with risk analysis for both chemistry and toxicology, supporting you in developing acceptable intake limits and perform limit calculations. We provide method validation for stability testing and continuous monitoring of nitrosamines over time. Our team can evaluate nitrate and nitrite levels in excipients, drug substances, or final products and offer advanced screening methods to assess nitrosamine-related risks.
Regulatory Strategy and Testing Requirements per European Medicines Agency and US FDA
The regulatory strategy can be broken down into three critical steps:
- Evaluation of Nitrosamine Presence in API Manufacturing: All synthetic procedures used to manufacture the API must be carefully assessed to ensure that no materials capable of forming nitrosamines are involved in the process.
- Assessment of API and Component Nitrosatability: It is essential to evaluate the potential nitrosatability of the API, excipients, and other components. This requires the development and validation of a robust analytical method to accurately assess this risk.
- Implementation of Quality Controls to Mitigate Nitrosamine Formation: Effective quality control measures should be put in place to minimize nitrosamine formation. Special attention must be given to highly volatile nitrosamines, such as NDMA or NDEA, as well as the potential nitrosation of APIs, excipients, or other components.
These guidelines emphasize the importance of thorough risk management and continuous monitoring to ensure drug products meet safety standards and remain compliant with regulatory expectations.
Tailored Testing Solutions
Whether you need routine screening or advanced impurity characterization, our customized partnership models support your unique needs. From fee-for-service to collaborative testing programs, Emery Pharma is ready to scale with your operations.
Commitment to Patient Safety
By partnering with Emery Pharma, you can confidently deliver safe, compliant products to market while prioritizing patient safety and regulatory compliance every step of the way.