Nitrosamines: New Regulatory Updates And What They Mean For Industry

Nitrosamines have become a central focus for global regulators due to their potential carcinogenicity and their unexpected presence in pharmaceuticals and food products. In 2025, both the US FDA and the European Union have introduced significant new requirements to control and limit nitrosamine impurities, impacting drug makers, food manufacturers, and ultimately, consumer safety.

What Are Nitrosamines and Why Are They a Concern?

Nitrosamines are chemical compounds that can form during manufacturing processes, storage, or even from certain ingredients. Some nitrosamines are classified as probable human carcinogens, meaning long-term exposure—even at low levels—could increase cancer risk. Their detection in widely-used drugs and foods has prompted recalls and stricter oversight worldwide.

Latest Regulatory Updates

United States: FDA’s New Acceptable Intake Limits

• August 1, 2025 Deadline: The FDA now requires all drug products on the US market to comply with newly published Acceptable Intake (AI) limits for specific nitrosamine impurities, including N-nitrosamine drug substance-related impurities (NDSRIs).
• Product-Specific Limits: The FDA has set interim AI limits for individual drugs. For example, N-nitroso-nortriptyline in nortriptyline capsules is limited to 600 ng/day, while N-nitroso-ciprofloxacin in ciprofloxacin tablets is capped at 12,000 ng/day.
• Risk Assessment and Confirmatory Testing: Manufacturers must conduct risk assessments, perform sensitive confirmatory testing, and, if nitrosamines are detected, identify and control the root cause.
• Reporting and Compliance: Any changes to manufacturing or specifications must be reported to the FDA. Products not in compliance by the deadline risk regulatory action.

Europe: Stricter Food Additive Controls

• Reduced Nitrite/Nitrate Limits: Effective October 9, 2025, the EU will lower the maximum permissible levels of nitrites and nitrates in processed meat products to reduce nitrosamine formation.
  • General meat products: 80 mg/kg (down from 150 mg/kg)
  • Sterilised meat products: 55 mg/kg (down from 100 mg/kg)
  • Residual nitrite/nitrate limits introduced for various categories
• Industry Impact: Food businesses must reformulate products, monitor residual levels, and ensure compliance to maintain EU market access.

Why These Changes Matter

• Consumer Safety: Reducing nitrosamine exposure lowers cancer risk and protects public health.
• Regulatory Scrutiny: Non-compliance can lead to recalls, loss of market access, and reputational damage.
• Industry Responsibility: Manufacturers must proactively assess risk, update processes, and document compliance.

Key Steps for Industry

1. Conduct Comprehensive Risk Assessments: Evaluate all raw materials, manufacturing processes, and finished products for nitrosamine risk.
2. Implement Sensitive Testing: Use validated analytical methods to detect even trace levels of nitrosamines.
3. Mitigate and Control: Adjust processes, change suppliers, or reformulate products as needed to stay within regulatory limits.
4. Document and Report: Maintain thorough records and report changes or findings to regulators in line with updated guidance.
5. Monitor Regulatory Updates: Stay informed of evolving standards in all markets where products are sold.

Conclusion

The regulatory landscape for nitrosamines is rapidly evolving, with new deadlines and lower limits now in force. Proactive compliance is essential—not just to satisfy regulators, but to safeguard consumers and preserve trust in pharmaceutical and food brands. As science advances, expect further refinements and ongoing vigilance in the fight against nitrosamine contamination.