Biosimilar Analytical Similarity

1. What this module does

You enter each attribute with its method, criticality, and the results of the reference and biosimilar lots (or the outcome of a profile comparison). The tool builds the quality range (reference mean ± k SD), counts the biosimilar lots inside it, shows the mean shift and the reference min–max, and groups attributes by category.

It checks the number of lots, that primary structure is identical, that higher-order structure and biological activity are covered, and that US and EU reference lots are bridged when both regions are chosen.

What you get

• A Word or PDF report: Comparative analytical assessment, with a chart of the attribute you choose.

2. Before you start

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

• Results of at least 10 reference product lots and 6 to 10 biosimilar lots.
• Profile comparisons for structure.
• Structure–function data for any difference and the comparative stability results.

3. Step by step with the example

Open the tool at app.cmcfy.com/app/biosimilar-similarity.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 products

   Enter the proposed biosimilar and the reference product, the k multiplier (3 by default) and the share of lots required in range (90% by default).

   

2. Enter the attributes

   One row per attribute. Results per lot separated by ";". For profiles, write identical or comparable.

3. Read the result

   The headline gives the outcome: "Analytically similar on all 10 attributes". The table shows the quality range, the lots in range and the mean shift.

   

4. Resolve alerts and download

   An attribute below the target share is flagged (critical for high criticality). Few lots, missing structure or function categories, a mean shift above 2 SD and missing bridging 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 · Products

2 · Attributes

One row per attribute. Tier or criticality: high, moderate or low. Results per lot separated by ";". For profiles (peptide map, CD) write the comparison outcome instead.

3 · Residual uncertainty

5. Checks and alerts

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

• Share of biosimilar lots inside the quality range against the target.
• Mean shift in SD units.
• Lots: at least 10 reference and 6 biosimilar.
• Identical amino acid sequence; higher-order structure and biological activity compared; three-way bridge for US and EU.

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

US follows the FDA comparative analytical assessment guidance (2019 draft) and Scientific Considerations (2015). EU follows EMA/CHMP/BWP/247713/2012 and the reflection paper on statistical methodology (EMA/CHMP/138502/2017).

8. Working with other modules

• Characterisation methods are in the Biologics Characterisation & Specification module.

9. Common pitfalls

• Too few reference lots, which gives a narrow, unreliable quality range.
• Ignoring a mean shift because every lot is inside the range.

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 afucosylation

   Change the biosimilar afucosylation results to 10.8;11.4;10.9;11.2;10.6;11.0;11.3;10.7.

   Expected resultThe headline shows one attribute outside the quality range.