Classification of highly potent active ingredients: Correctly categorizing OEB and OEL levels

Why the danger is not immediately apparent

Traditional, purely aseptic approaches are insufficient for HPAPIs because even low concentrations can pose significant health risks to operating personnel. Inadequately defined exposure limits lead to planning errors: Overly generous assumptions drive up costs, while overly strict assumptions compromise safety. Particularly critical are scenarios where the risk level varies depending on the dosage form – such as non-critical liquid formulations that form highly active dusts after freeze-drying. Without a clear classification, containment, airflow, filtration, and cleaning strategies cannot be designed with precision.

How market forces and regulations are tightening requirements

With personalized medicine, smaller batches, and a growing proportion of highly potent substances, product variability is increasing. Reliable OEL data is often lacking in early development phases. Companies therefore need robust classification concepts that mitigate development uncertainties while still being regulatorily sound. Complexity is increasing because both liquid and lyophilization routes are increasingly being run on a single line – including different exposure scenarios.

OEL and OEB as decision-making tools for planning and engineering

Two key parameters are central:

• OEL (Occupational Exposure Limit): A quantified limit value (e.g., µg/m³ or cumulative mass per shift) that specifies the maximum level of exposure to which employees may be exposed without an expected adverse health effect.
   
• OEB (Occupational Exposure Band): A band-based classification system (typically 1–5 or 1–6) that classifies the toxicity of the pure substance and derives requirements for technology and processes. Here, “5” or “6” denotes the highest toxicity.

In the absence of OEL data, OEB serves as a practical, internal company classification. OEB also promotes clarity within the project team: A value such as “OEB 4” can be communicated more quickly than a µg/m³ range. Technical specifications – such as isolator level, pressure cascades, filter design, wash-down, and bio-decontamination – are derived from this and, if necessary, differentiated on a substance-specific basis for liquid versus lyophilized materials.

The benefits of clear classification

• Planning certainty: Clearly defined OEL/OEB levels prevent over- or under-design.
   
• Targeted operator protection: Pressure zone concepts and containment strategies are scaled appropriately to the hazard level.
   
• Regulatory robustness: Traceable derivation of technical measures, consistent documentation, and validability.
   
• Portfolio flexibility: OEB-based range planning enables CDMOs to handle a broad spectrum of active ingredients.
   
• Process stability: Differentiated consideration of liquid vs. lyophilized materials reduces risks associated with aerosols and dust.

Conclusion: Active ingredient classification as the foundation of every HPAPI project

A reliable OEL/OEB classification forms the foundation of every HPAPI facility. It translates active ingredient properties into concrete, measurable requirements for technology, processes, and infrastructure – and enables both safety and cost-effectiveness to be achieved simultaneously.

Optima establishes the active ingredient classification early in the project: During the consulting phase, OEL/OEB, dosage forms, and application scenarios are identified. From these, containment levels, pressure cascades, and filtration and cleaning strategies are derived and verified through simulations (airflow, bio-decontamination, wash-down). This results in a holistically coordinated, qualifiable facility concept.