Biologics Comparability (ICH Q5E)

1. What this module does

You describe the change and the risk assessment, and enter each attribute with its method, criticality, criterion and the pre- and post-change results. The criterion can be a tolerance interval, mean ± 3 SD, the pre-change min–max, a fixed limit or a qualitative comparison.

The tool builds each range, finds the post-change results outside it, charts the attribute you choose and writes the report. A difference in a high-criticality attribute must be recorded with its impact assessment.

What you get

• A Word or PDF report: Comparability report (ICH Q5E), for 3.2.S.2.6 or 3.2.R.

2. Before you start

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

• The change description and risk assessment.
• Pre-change and post-change results for each attribute, with the criteria in the comparability protocol.
• The stability comparison and any structure–function data.

3. Step by step with the example

Open the tool at app.cmcfy.com/app/biologics-comparability.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 change

   Enter the change, the risk assessment, the batches and the tolerance interval coverage and confidence (99% and 95% by default).

   

2. Enter the attributes

   One row per attribute. Criterion: TI, 3SD, minmax, a fixed limit (for example ≤ 100) or qual. Results separated by ";".

3. Read the result

   The headline says whether the batches are comparable: "1 attribute outside the pre-change range". The chart shows the pre- and post-change results against the range.

   

4. Resolve alerts and download

   A difference in a high-criticality attribute is critical. Missing post-change results, too few pre-change results, no potency comparison, and missing risk, stability or impact assessments 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 · Change

2 · Attributes

One row per attribute. Criterion: TI (tolerance interval), 3SD, minmax, a fixed limit such as ≤ 2.0, or qual. Criticality: high, medium or low. Results separated by ";".

3 · Stability and conclusion

5. Checks and alerts

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

• Each post-change result against its range; high-criticality differences are critical.
• Number of pre- and post-change results; potency included.
• Risk assessment, stability comparison, impact assessment and further studies.

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: Discussion 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

Both regions follow ICH Q5E. The EU guideline on comparability after a manufacturing change (EMEA/CHMP/BMWP/101695/2006) and the FDA guidance on comparability protocols (2022) apply.

8. Working with other modules

• Classify the change in Post-approval Change Classifier and assess it in Change Control.
• Characterisation methods are in the Biologics Characterisation & Specification module.

9. Common pitfalls

• Setting the range after seeing the post-change data.
• Using a tolerance interval from three batches, which is too wide to detect a difference.

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. Introduce a potency shift

   Change the post-change potency results from 101;99;103 to 101;99;125.

   Expected resultThe headline shows two attributes outside the pre-change range.