A human health risk assessment of detected extractables

Client

A specialty pharmaceutical company.

Background

The client produces a foam-based drug product that patients can self-administer from an aerosol cannister. According to the manufacturer of the container-closure-system (CCS), several compounds (including some unknown constituents) were identified as extractables from two components of the cannister that directly contact the drug product.

Project goals

The client asked bibra to evaluate, in line with ICH guidance, the potential health risks that may be posed to adult patients who could be exposed to these extractables through use of the drug product.

Approach and outcome

Based on the reported concentrations from extractables studies, the worst-case estimates of exposure to each of the extractables were calculated. Where possible, comprehensive literature searches were undertaken using bibra’s in-house database (TRACE) as well as certain external databases to identify key toxicity and Absorption, Distribution, Metabolism and Excretion (ADME) data on each of the chemical compounds. Individual extractable monographs were then generated which summarised the available hazard data and characterised the potential health risks posed to patients.

All chemically-identified extractables were demonstrated to be non-mutagenic and were therefore assessed as threshold toxins. The systemic health risk assessments of these compounds were then carried out by comparing the worst-case estimates of exposure with lifetime parenteral Permitted Daily Exposure (PDE) values, derived following ICH guidance. This allowed Margin of Safety (MoS) values to be estimated, all of which were reassuring. In the absence of further chemical information, the unknown extractables were assessed by adopting worst-case assumptions and treated as potential mutagens. By applying the Threshold of Toxicological Concern (TTC) approach, it was demonstrated that the cancer and non-cancer risks posed to these unknowns were within tolerable limits.

The result

The local toxicity potential of the extractables was also considered. Based on the amounts detected, it was deemed that the concentration of extractables in the product would not be expected to pose any risk of local irritation.

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!