Health risk assessment of impurities in a nasal spray device

Client

A pharmaceuticals manufacturer.

Background

A partially characterised impurity (refined to one of two isomers) was identified in a nasal drug product after storage under exaggerated conditions.

Project goals

Bibra was asked to evaluate the toxicological risks posed to patients by one or other (or both) of the potential impurity isomers following acute inhalation exposure.

Approach

Different approaches were employed to conclude on the safety of the impurity isomers, including literature searches for substance-specific toxicological data, and visual and structure-activity relationship (SAR)-based comparisons with the active pharmaceutical ingredient (API). Where necessary, a threshold of toxicological concern (TTC)-based analysis was performed. The evaluation was conducted in the context of relevant Expert Group guidance on the assessment of pharmaceutical impurities.

Project outcome

Considering the structures of the isomers, it was considered that neither one would exhibit a markedly different toxicological profile to that of the other, or of the API. This information, together with the low levels of impurity detected and a TTC-based analysis, led bibra to conclude that neither isomer (if present) is likely to pose a significant threat to human health, over and above any posed by the API itself.

Bibra project team

Beth O’Connell
Pete Watts

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