ICH Q5B - Analysis of the Expression Construct in Cells Used for Production

What it says

The expression construct, the genetic material introduced into a host cell to direct production of a recombinant protein, must be analyzed and characterized to confirm its structure, sequence and stability within the production cell line, providing assurance that the cell substrate will consistently express the intended product.

Paraphrased for plain-language clarity. Always verify against the current published regulation text.

What it means in practice

• Expression construct characterization under this guideline sits upstream of, and provides foundational assurance for, the broader cell substrate characterization described in ICH Q5D, since the construct is what actually directs what the cell produces.
• Genetic stability of the expression construct over extended cell culture, sometimes across many generations during manufacturing scale-up, is a central concern, since a construct that drifts can change product quality attributes without an obvious external signal.
• Characterization data generated under this guideline typically becomes part of the supporting package for comparability assessments whenever the cell substrate or expression system is modified.

What inspectors look for

• Whether expression construct characterization data demonstrates the construct's structure and sequence match what was intended and originally qualified.
• Whether genetic stability of the construct has been evaluated across the full range of generations or population doublings actually used in commercial-scale manufacturing.
• Whether any modification to the expression construct or host cell system triggered an appropriate comparability assessment.

Related regulations