Health risk assessment of an impurity in an intravenous drug product


A bio-pharmaceutical company.


A pharmaceutical company has identified an impurity in an intravenous drug intended for intravenous administration.

Project Goals

Bibra was asked to evaluate the toxicological risks posed to patients by the presence of this impurity, at the estimated ‘worst-case’ maximum dose, and to calculate a margin of safety  for the proposed use.


Toxicity data searches using the bibra TRACE database, PubMed, TOXNET and RTECS were performed using the specific impurity CAS RN, including synonyms, with additional searches on closely-related substances. The substance is a large molecule found in various natural food products and the literature identified was rapidly filtered  so that only those papers investigating adverse effects were considered in detail. Based on the impurity’s chemical structure and various in vivo studies, the substance was concluded not to be genotoxic and the risk assessment therefore focussed on threshold toxicity .

Due to its presence in food, expert group evaluations  concerned exposure via an oral route and were therefore of limited relevance for this intravenous administration, particularly since the large molecular size suggested that absorption from the digestive tract would be low. Consideration of the literature available on administration by intravenous injection or infusion indicated an absence of overt adverse effects in healthy volunteers, patients or laboratory animals given a single or repeated doses, which provided reassurance regarding toxicity.

Project Outcome

A health risk assessment report, giving a very large margin of safety, was provided to the client  as the overall weight of evidence indicated there would be no significant toxicological risk from exposure to the impurity.

Project Team

Anne Edwards

James Hopkins



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