Elemental Impurities Risk Assessment Checklist (ICH Q3D)

Risk Assessment Scope and Sources

Identify all potential contributors of elemental impurities.

• Are all four potential sources of elemental impurities evaluated: drug substance, excipients, water, and manufacturing equipment and container closure? *
• Is the assessment completed for each product and route of administration (oral, parenteral, inhalation)? *
• Are intentionally added catalysts and reagents (Class 1 and Class 2A/2B elements) specifically addressed? *
• Is supplier data or elemental analysis obtained for each excipient contribution?

PDE Limits and Calculation

• Are permitted daily exposure (PDE) limits applied for each element based on route of administration? *
• Is the maximum daily dose used to convert PDE limits into concentration limits using an appropriate option (1, 2a, 2b, or 3)? *
• Are contributions summed across components to confirm the total does not exceed the PDE? *
• Select the concentration-limit option used in the assessment.

Analytical Method and Verification

• Is the analytical method (e.g., ICP-OES or ICP-MS) validated per USP <233> for target elements? *
• Are spike recovery, precision, and specificity demonstrated at the target J-value (30% of PDE)? *
• Is periodic verification testing performed to confirm the risk-based control conclusion? *

Control Strategy and Lifecycle

• Is a control strategy documented where any element exceeds 30% of the PDE (control threshold)? *
• Is the elemental impurity assessment reviewed under change control for new suppliers, equipment, or process changes? *
• Is the risk assessment approved by the quality unit and retained? *