Focus on nitrosamines: containment and filter solutions for maximum pharmaceutical safety

Nitrosamines have been a key quality and safety issue in the pharmaceutical industry for several years. The discovery of nitrosamine-containing impurities in active ingredients and medicines has led to stricter regulatory requirements worldwide. Pharmaceutical manufacturers must now prove that they are aware of, control and minimize nitrosamine risks throughout the entire manufacturing process. An important component of this is containment and air filtration systems that create stable, clean and reproducible process conditions. This is because the formation and unintentional introduction of nitrosamine-forming substances can only be effectively prevented with cleanly controlled processes.

Nitrosamines: a challenge for the entire value chain

Nitrosamines are formed when amines react with nitrosating reagents such as nitrite – and can occur as by-products or degradation products in pharmaceutical production processes. Typical causes are chemical reactions, raw material impurities, cleaning residues or cross-contamination between process steps.

For the industry, this means: risk assessments, optimized synthesis routes, precise raw material control, analytical monitoring – and a controlled production environment that prevents accidental contact of potential precursors.

The role of containment systems

Containment technologies such as RABS systems ensure that materials and air flows are controlled, processes are sealed off and cross-contamination is prevented. Unlike classic containment scenarios, the focus with nitrosamines is not on protecting operating personnel from highly potent substances, but on product safety and process integrity.

Suitable containment systems make a decisive contribution here:

• Controlled material and product flows
• Clearly defined production and cleaning zones
• Safe CIP/WIP processes without nitrite or amine-containing residues
• Reproducible ambient conditions (particles, temperature, humidity)
• Verification in accordance with GMP, EMA and FDA standards

This not only prevents the unwanted formation of nitrosamines, but also reduces the risk of nitrosamine precursors accidentally entering critical process steps.

HET filter technology: Safety through two-stage HEPA filtration

In addition to closed containment solutions, the HET exhaust air and recirculating air filter systems also make a significant contribution to nitrosamine control. The combination of innovative extraction and filtration concepts and double HEPA redundancy ensures:

• Safe discharge of potentially contaminated process air
• Reliable filtration up to OEB-6 protection level
• Validation and GMP-compliant documentation
• Technical cleanliness thanks to hygienic design and stainless steel components
• Maximum operational reliability thanks to pressure monitoring and filter integrity tests

This creates a stable, clean process space in which microchemical side reactions and contamination are minimized.

Clean processes, safe products – and trust in the supply chain

Nitrosamine risk analysis and process control are not one-off projects, but an essential part of modern pharmaceutical quality. With efficient containment solutions, robust filter systems and validated airflow concepts, HET Filter supports the pharmaceutical industry in meeting regulatory requirements and ensuring maximum product safety.