Nitrosamine Prevention in API Manufacturing and Formulations of Pharmaceutical

ー Continuous Monitoring Trace-level NOx, NO₂, NO Gas Concentration ー

HORIBA's highly accurate trace gas analyzers can continuously monitor N compounds (NOx, NO2, NO) to help clarify the cause of nitrosamine formation during the process of API* and formulation of pharmaceutical manufacturing.

Recently, nitrosamines, which are likely carcinogenic to humans, have been detected globally in the pharmaceuticals such as Sartan class of drugs. The European Medicines Agency (EMA) and the United States Food and Drug Administration (FDA) recommend efforts to prevent the formulation of nitrosamines. Additionally, Japanese Ministry of Health, Labour and Welfare (MHLW) has notified pharmaceutical manufacturers and distributors to conduct self-inspections to assess the risk of nitrosamine contamination. The mechanism of nitrosamine formation is still under research, but one hypothesis suggests atmospheric N compounds could cause nitrosamine formation when ambient air is heated and used for drying formulation during the granulation process.

*API: Active Pharmaceutical Ingredient

Do you face any challenges for monitoring NOx during the manufacturing process of API and formulations?

Require to measure the impurity concentration in ppb level
Need to measure continuously
Require to measure multiple locations efficiently

Solution from HORIBA

Advantages of APNA-380

Continuous monitoring of NOx, NO₂, NO in ppb level
- Chemiluminescence method offers excellent sensitivity, long-term stability, and low zero drift
- Wide measurement range allows for the measurement of different gas concentrations

Measurement of multiple points with a single unit
- Multipoint switching system allows periodic measurement of each sampling point by switching sampling lines and sampling from multiple measurement points.

Reduction of environmental impact and cleaner exhaust gas
- Utilization of UV lamp for internal ozone generator
- The applied UV lamp ozone generator minimizes NOx exhaust to near-zero level, resulting in a cleaner exhaust compared to the dielectric barrier discharge generation method.

Remote operation function equipped as standard
- Can be remotely accessed from PC, tablet or smartphone　
- Measurement confirmation and operation can be performed remotely without visiting the installation site.