Elemental Impurities Risk Assessment

1. What this module does

You enter the route, the daily dose, the components and the element data you have. The tool lists the elements that must be assessed (class 1, 2A, intentionally added and route-specific class 3).

It sums the contribution of each component, compares the intake with the PDE, and gives the Option 1 and Option 2a concentration limits.

What you get

• A Word or PDF report: Elemental impurities risk assessment (3.2.P.5.5).

2. Before you start

Have these ready. You can still start with the example data and replace it piece by piece.

• The maximum daily dose of the drug product and the amount of each component in it.
• Element data for each component (supplier, published or measured) or the finished product.
• Elements intentionally added (catalysts).

3. Step by step with the example

Open the tool at app.cmcfy.com/app/elemental-impurities.html. The example is loaded when the page opens, so every panel already has realistic data. Follow the steps to see how it works, then replace the example with your own data.

1. Describe the product

   Choose the route and approach, enter the daily dose and any intentionally added elements.

   

2. Enter components and data

   One row per component with its amount in the daily dose. One row per component and element with the level in µg/g.

3. Read the result

   The headline gives the outcome: "All 8 elements below 30% of the PDE".

   

4. Resolve alerts and download

   An element above the PDE is critical; above 30% without a control is major. Required elements without data are flagged. Then preview and download.

   

4. Field reference

Every input in the tool, panel by panel. Tables accept rows pasted straight from Excel, comma-separated text, or a loaded file; check the columns after loading a file. Fields marked “when it applies” appear only for the choices that need them.

1 · Product

2 · Components

Amount of each component in the maximum daily dose. For Option 3, list the drug product only.

3 · Element data

One row per component and element. Level in µg/g (ppm). "<0.5" counts at the LOQ.

4 · Other sources and control

5. Checks and alerts

Calculations and pass/fail outcomes always come from fixed rules, never from AI. The tool checks:

• Elements required for the route.
• Intake against the PDE and the control threshold.
• Sources: components, equipment, water and container closure.

How to resolve alerts

• Critical alerts block the download and must be fixed in the data. A failing result can instead be linked to an investigation: type the investigation reference and outcome and press Record.
• Major alerts block the download until you fix them or type a justification and press Accept justification.
• Minor alerts do not block anything. They are listed in the documents so the reviewer sees them.
• Some alerts have an Apply fix button that makes the change for you. Reopen undoes a justification.

Narratives

This module writes: Risk assessment and conclusion. Each narrative is written by fixed rules from your data. You can edit it in the box. Rewrite with AI (where your plan includes AI) rewrites it in regulatory style; every number in the text is checked against your data, and a number that does not match is flagged under the box and blocks the download until you correct it. Reset to rule-based text brings back the original.

6. Preview, gap review and download

1. Press Preview next to a section, or Preview and download all. The document opens in a preview window, exactly as the Word file will read.
2. The left side lists the review, run on your device: gaps in the data (missing values, open alerts), gaps in the report (missing content the guidance expects, placeholders such as [site] or TBD left in the text) and, if you load the approved protocol under Compare with the protocol, differences from the protocol (requirements, criteria, batches or time points it plans that the report does not show).
3. Click a finding to jump to the place in the preview. Fix it in the tool, then preview again.
4. Optional AI review: a second read for contradictions, claims without data and vague wording. The report text is sent to Claude only when you press it, and only where your plan includes AI. Check every AI finding; AI can be wrong.
5. Press Download Word (.docx) or Download PDF. With several documents open, All as Word (.zip) and All as PDF (.zip) download the set. The download buttons stay disabled while a blocking alert is open; the preview still works.

Documents this module produces

Use Save project to keep your work as a file on your computer, and Open project to continue later. Start blank clears every field; Load example brings the example back. Nothing is stored on CMCfy servers.

7. US and EU submissions

ICH Q3D(R2) applies in both regions. US: USP <232>/<233>. EU: Ph. Eur. 5.20 and 2.4.20.

8. Working with other modules

• Element results also appear in the Impurity & Risk Studio and the Specification Builder.

9. Common pitfalls

• Leaving out a class 2A element because it is not expected.
• Using the wrong PDE column for the route.

10. Practice exercises

Each exercise starts from the example (press Load example to reset). We run these on every update of this guide, so the result you see should match.

1. Raise palladium

   Change the palladium level in the drug substance from 4.2 to 800 µg/g.

   Expected resultThe headline shows one element above the control threshold.