Non-clinical overview

Client

An independent pharmaceutical company.

Background

Following the reformulation of an emollient, an increased level of an impurity was detected compared with the previous formulation. Based on this, the client proposed a new shelf-life specification limit for the impurity. 

Project goals

Bibra was asked to produce a non-clinical overview focusing on the new shelf-life specification limit proposed for the impurity.

Approach and outcome

Based on the usual dose of the product in adults, impurity exposure estimates were calculated for the relevant patient subgroups (adults and children). Literature searches were conducted, and data on the Absorption, Distribution, Metabolism and Excretion (ADME), acute toxicity, repeated-dose toxicity, and genotoxicity of the impurity were identified and summarised. Data on a variety of other toxicological endpoints were unavailable. 

An assessment using the Threshold of Toxicological Concern (TTC) concept was conducted, as the identified toxicity data were deemed unsuitable. Toxtree identified the substance as a Cramer Class III compound and Quantitative Structure-Activity Relationship (QSAR) models supported the experimental data showing that this impurity lacked mutagenic potential. Comparison of the impurity exposures with the appropriate dermal TTC benchmark values, converted from their oral equivalents, resulted in reassuring Margin of Safety (MoS) values for adults and children.

Local toxicity was also considered, and it was deemed that at the applied concentration, the impurity is highly unlikely to induce skin irritation. Based on a comparison of the applied concentration with the relevant Dermal Sensitisation Threshold (DST), it was considered highly unlikely that the impurity would pose a significant risk of skin sensitisation.

The result

In conclusion, the non-clinical overview supported the qualification of the impurity at the new shelf-life specification limit proposed by the client.

Why bibra?

• An extensive in-house database TRACE enables comprehensive literature searching 
• All of our senior team are UK and European Toxicologists 
• Bibra has been providing expert, industry-leading toxicology consulting for the pharmaceutical industry for decades, and we have established ourselves as authorities in this area 

Learn more about our work in pharmaceutical toxicology

Our team has many years of experience in preparing toxicological assessments required in the pharmaceutical sector. We regularly provide our clients with assessments of novel or unexpected impurities, excipients and other intentionally-added substances, and extractables and leachables. Get in touch if we can help you!