Derivation of PDEs for metallic and non-metallic elemental impurities in pharmaceutical products


An analytical lab working on the behalf of a drug manufacturer.


Metallic and non-metallic elements may be unintentionally present in pharmaceutical products as a result of their leaching from processing equipment, pharmaceutical packaging or drug delivery systems, or from their presence as impurities in drug constituents (actives, excipients or solvents). Many (but not all) of these elements have permitted daily exposures (PDEs) defined by organisations such as ICH (the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use).

Project goals

Bibra was asked to derive PDEs, defining tolerable daily intakes for long-term parenteral exposure, for two elemental impurities which do not currently have ICH PDEs available. This allows risks for exposed patients to be assessed, should these elements be detected as pharmaceutical impurities in future.


Bibra conducted a wide-ranging search for toxicological endpoint data relating to the two elements, as well as related salts and other compounds. Sources included our in-house toxicity database TRACE. All potentially relevant data were subsequently collected and assessed with a focus on repeated-dose injection data and expert group reviews. Existing health criteria values (HCVs) derived from expert groups for both impurities were also highlighted.

Project outcome

Bibra toxicologists were able to provide a detailed assessment of relevant toxicological endpoints and to derive parenteral PDEs for both elements.

Bibra project team

Beth O’Connell
James Hopkins


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