ICH Q11 - Development and Manufacture of Drug Substances

What it says

A systematic approach to drug substance development should identify critical quality attributes, evaluate the impact of raw materials and process parameters, and establish an appropriate control strategy, applying the same Quality by Design principles described in ICH Q8(R2) specifically to drug substance rather than drug product development.

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

What it means in practice

• This guideline extends the Quality by Design framework from ICH Q8(R2), originally focused on drug product, specifically to drug substance development and manufacturing.
• A control strategy developed under this guideline can combine controls at multiple points, raw material specifications, in-process controls and final drug substance testing, rather than relying on final testing alone to assure quality.
• Understanding which raw material attributes and process parameters genuinely affect drug substance quality, established through documented development studies, is what allows a risk-based control strategy to be defensibly designed.

What inspectors look for

• Whether the drug substance control strategy is genuinely supported by development data demonstrating which parameters and raw material attributes actually affect quality.
• Whether critical process parameters identified during development are consistently controlled and monitored during commercial manufacturing.
• Whether changes to the manufacturing process are assessed against the development-stage understanding of what parameters are actually critical.

Related regulations