Nitrosamine Impurities in Pharma: Advanced Detection and Regulatory Strategy
Nitrosamine impurities have become one of the most pressing safety concerns in the pharmaceutical industry. Since their detection in common medications like ranitidine, valsartan, and metformin, regulatory authorities worldwide, including the US FDA, EMA, and CDSCO, have mandated rigorous testing, risk assessments, and controls. For pharmaceutical manufacturers, mitigating the risk of nitrosamines is no longer optional; it is a regulatory and ethical imperative.
At Pharmaffiliates, we support companies with nitrosamine impurity detection, NDSRI synthesis, method development, and regulatory-ready documentation to ensure safe, compliant, and globally accepted formulations.
What Are Nitrosamines and Why Do They Matter?
Nitrosamines are a class of compounds classified as probable human carcinogens. They can form unintentionally during the manufacture or storage of drug substances and finished products, especially in the presence of certain amines and nitrite sources.
Sources include:
- API degradation
- Manufacturing process contaminants
- Reactions between excipients and solvents
- Recycled solvents or reagents
- Inadequate process controls
Particularly concerning are NDSRIs (Nitrosamine Drug Substance-Related Impurities), which are structurally related to the active pharmaceutical ingredient and may form under specific conditions.
Pharmaffiliates’ Role in Nitrosamine Detection and Control
Pharmaffiliates provides advanced analytical and synthesis services to support global pharmaceutical companies in meeting nitrosamine compliance requirements.
Our Services Include:
- Analytical Detection Using advanced techniques like LC-MS/MS, GC-MS, and high-sensitivity NMR, we detect trace levels of nitrosamines in APIs and drug products down to parts per billion (ppb).
- Custom Synthesis of Nitrosamines We synthesize both standard and complex nitrosamine impurities and NDSRIs that are not commercially available, tailored for method validation, toxicology studies, or regulatory filings.
- Method Development & Validation ICH M7-compliant methods, supported with validation reports, chromatograms, and CoA/MSDS documentation.
- ISO 17025-Accredited Testing All analysis is conducted in accredited laboratories, ensuring defensible data for DMF, ANDA, or CTD submissions.
Global Regulatory Landscape for Nitrosamines
Regulators have issued specific guidelines for nitrosamine control:
|
Regulatory Body |
Requirement |
|
USFDA |
Risk assessment, confirmatory testing, and mitigation strategy for all products |
|
EMA |
Stepwise risk-based evaluation for all human medicines |
|
CDSCO (India) |
Guidance aligning with USFDA/EMA for risk evaluation and testing |
|
ICH M7 |
Framework for impurity classification and control in marketing applications |
Pharmaffiliates assists clients in compiling submission-grade documentation that supports nitrosamine risk assessments and analytical controls.
Use Case: NDSRI Synthesis for ANDA Submission
A European generic manufacturer required three complex NDSRIs to be synthesized for submission to the USFDA. Pharmaffiliates:
- Delivered each impurity at >98% purity
- Supplied a complete analytical data package (NMR, HPLC, CoA, MS)
- Supported method validation and documentation for the client’s ANDA filing
Why Choose Pharmaffiliates for Nitrosamine Services?
- Presence in 90+ countries
- ISO 17025-accredited labs
- Global clientele, including CROs, CDMOs, and generic manufacturers
- Custom synthesis capabilities for difficult-to-source impurities
- Regulatory-aligned documentation to support global filings
Conclusion:
With increasing global scrutiny on nitrosamine impurities, pharmaceutical companies must act proactively to mitigate risk. Pharmaffiliates offers the tools, talent, and technology to ensure your products meet safety standards while accelerating regulatory timelines.
Talk to our nitrosamine and impurity profiling team today to safeguard your formulations and filings.
FAQs
Q1. What are nitrosamines and why are they dangerous?Nitrosamines are chemical substances considered likely to cause cancer in humans. Their presence in drugs, even at trace levels, has raised global health concerns.
Q2. What are NDSRIs? Nitrosamine drug substance-related impurities are nitrosamines that share a structural relationship with the active drug molecule. They often require custom synthesis and toxicological assessment.
Q3. Can Pharmaffiliates synthesize NDSRIs? Yes. We offer custom synthesis of NDSRIs, degradation products, and other nitrosamines, along with full characterization and documentation.
Q4. Are your testing methods validated? Yes. All analytical methods follow ICH M7 and are validated for sensitivity, specificity, and reproducibility.
Q5. How does Pharmaffiliates help with regulatory submissions? We provide complete data packages, including method validation reports, CoAs, MSDS, and impurity profiles, suitable for DMF, ANDA, and CTD submissions.
