Ultra-Potent pharmaceuticals: Verifying containment


1. SafeBridge Regulatory & Life Sciences Group, Bury St. Edmunds, Suffolk, United Kingdom
2. SafeBridge Regulatory & Life Sciences Group, New York, USA
3. Cheshire, United Kingdom


The pharmaceutical sector, uniquely carries out extensive testing of their products on human subjects. This testing provides data that allows toxicologists to develop safe limits for occupational exposure. However, ultra-high potent pharmaceuticals, with exposure limits below 10 ng/m3 provide challenges by pushing the containment technology and the verification of this technology to the limits of what is achievable.

Over the past twenty or so years, it has been a recurring theme within the pharmaceutical industry that active pharmaceutical ingredients (APIs) are becoming more and more potent and toxic. The potency of these APIs is generally indicated by the occupational exposure limit (OEL) which is defined as the airborne concentration of a chemical substance that a worker can be safely exposed to for a 40-hour work week, over a working lifetime. The methodology used in deriving these values for APIs was initially published in 1988 by Sargent and Kirk (1), and has been repeatedly refined over the years, but the basic premise remains the same:


  • Find the adverse effect that the API has in human or animal studies.
  • Define the lowest dose of the API that causes the effect or the highest dose that does not cause the effect (point of departure, or POD).
  • Apply adjustment factors, accounting for variability of effects and other uncertainties, to lower the POD to an effect that is believed to be safe for workers repeatedly exposed to the API.
  • Divide by the amount of air i ...
  • ...