This is a ready-to-use summary form. Replace every <<FILL: ...>> placeholder, confirm the current route-specific PDE for each element against the current ICH Q3D text, and route through your normal technical and QA review. A filled specimen follows.
1. Product and scope
| Field | Entry |
|---|---|
| Product / drug substance | <<FILL>> |
| Route of administration | <<FILL: oral / parenteral / inhalation, since PDEs differ by route>> |
| Maximum daily dose | <<FILL>> |
| Assessment date and author | <<FILL>> |
| Approach used | <<FILL: component approach (sum contributions) or drug-product approach (test finished product directly)>> |
2. Element classification (per ICH Q3D)
| Class | Elements | Assessment trigger |
|---|---|---|
| Class 1 | Arsenic, cadmium, mercury, lead | Assess in every case |
| Class 2A | Cobalt, nickel, vanadium | Assess in every case (likely to occur) |
| Class 2B | Silver, gold, palladium, platinum, and related precious/platinum-group metals | Assess only if deliberately introduced |
| Class 3 | Barium, chromium, copper, lithium, molybdenum, antimony, tin, and others of lower oral toxicity | Assess based on route of administration |
3. Component-approach summation (repeat this table per element assessed)
| Element assessed | <<FILL>> | Route-specific PDE | <<FILL: microgram/day>> |
|---|---|---|---|
| Source | Estimated contribution (microgram/day) | Basis for the estimate | |
| --- | --- | --- | |
| Drug substance | <<FILL>> | <<FILL: synthesis route data, supplier CoA, or ICP-MS data>> | |
| Excipient(s) | <<FILL>> | <<FILL>> | |
| Water | <<FILL>> | <<FILL>> | |
| Manufacturing equipment (leachable) | <<FILL>> | <<FILL>> | |
| Container closure (leachable) | <<FILL>> | <<FILL>> | |
| Sum | <<FILL>> | ||
| Sum vs. PDE, with margin | <<FILL: e.g. "13 of 30 microgram/day, 57% margin">> |
4. Control strategy decision
| Field | Entry |
|---|---|
| Does the sum sit below the PDE with adequate margin, using real data under change control? | <<FILL: Y/N>> |
| If Yes | Documented control strategy (no routine release testing) is justified for this element |
| If No, or margin is thin | Routine testing required, or a specific high-contributing source must be reduced/controlled |
| Analytical method (if routine testing applies) | <<FILL: ICP-MS or ICP-OES method ID, validated per the general chapter framework>> |
5. Approval
| Field | Entry |
|---|---|
| Analytical / QA preparer | <<FILL: name, date>> |
| QA approval | <<FILL: name, date>> |
| Next scheduled review or re-trigger condition | <<FILL: e.g. supplier change, route change, periodic review date>> |
Filled specimen
Scope. Example Injectable 10 mg/mL, parenteral route, maximum daily dose 5 mL. Assessed 10 August 2026 by S. Beaumont (Analytical). Component approach used.
Element assessed: nickel (Class 2A). Parenteral PDE: 20 microgram/day.
| Source | Estimated contribution (microgram/day) | Basis |
|---|---|---|
| Drug substance | 3 | Synthesis uses a nickel catalyst; ICP-MS data on three registered-range batches |
| Excipient(s) | 1 | Supplier CoA, sum of two excipients |
| Water for injection | <1 | WFI system routine monitoring data |
| Manufacturing equipment | 2 | Stainless-steel contact surface leachable study |
| Container closure | 1 | Vial and stopper extractables study |
| Sum | ~7 | |
| Sum vs. PDE, with margin | 7 of 20 microgram/day, 65% margin |
Control strategy decision. Sum sits well below the PDE with adequate margin, and all inputs are under change control (approved supplier, qualified equipment train, registered synthesis route). Documented control strategy adopted; no routine ICP-MS release testing required for nickel on this product. Re-triggered if the nickel catalyst step changes, the excipient supplier changes, or the container-closure system changes.
Approval. Prepared by S. Beaumont, 10 August 2026. Approved by QA, R. Nakamura, 18 August 2026. Next scheduled review: 24-month periodic review cycle or any triggering change, whichever comes first.
Common inspection findings this form prevents
- A Q3D risk assessment full of assertions (“nickel is not expected to be present”) with no ICP-MS or supplier data behind the number.
- Applying an oral PDE to a parenteral or inhalation product, or vice versa, because the route-specific table was not consulted.
- A “documented control strategy” conclusion where one or more input sources are not actually under change control, so the assessment’s basis can silently go stale.
- Missing container-closure or equipment leachable contributions entirely, assessing only the drug substance and excipients.
How to adapt this form
- Confirm the current route-specific PDE for every element assessed against the current ICH Q3D text before use.
- Repeat Section 3 for every element that meets the assessment trigger in Section 2; do not limit the assessment to Class 1 elements alone.
- If using the drug-product approach instead of the component approach, replace Section 3 with the finished-product ICP-MS/ICP-OES result directly compared to the PDE, and note why the component approach was not used.