Understand the role of the Safety Concern Threshold in E&L assessment, how it relates to mutagenic and non-mutagenic safety concerns, and how it serves as a safety starting point for AET.
The Safety Concern Threshold (SCT) is a safety-based exposure concept used in the draft ICH Q3E framework to help determine whether an E&L exposure is low enough to present negligible safety concern within the assumptions of the applicable threshold approach.
SCT is a safety concept, not an analytical concentration
The SCT is expressed as a patient-exposure threshold. It is different from the Analytical Evaluation Threshold (AET), which translates the safety objective into a study-specific analytical reporting context.
Multiple toxicological considerations can be relevant
The applicable safety starting point depends on the compound classification and exposure context. Mutagenicity, non-mutagenic toxicity, local toxicity and existing compound-specific limits can all affect which reference is appropriate.
High-concern leachables
High-concern compounds may not be suitable for evaluation using a generic SCT approach. In those cases, a compound-specific safety limit or a dedicated toxicological assessment may be required.
Relationship to AET
Once the appropriate safety starting point has been established, the AET translates that patient-safety objective into an analytical threshold appropriate for the product and study design.
Frequently asked questions
Is SCT the same as AET?
No. SCT is a safety-based exposure concept; AET is an analytical threshold derived for a specific study context.
Does the same SCT apply to every leachable?
No. Compound classification and compound-specific safety information can require a different limit.
What happens for high-concern leachables?
They may require a compound-specific safety limit or dedicated toxicological assessment.
Can local toxicity affect the safety threshold?
Yes, where local toxicity is relevant to the route and exposure scenario.
How does SCT support analytical study design?
It provides the safety starting point that can be translated into an appropriate analytical reporting threshold.
