Biologics Characterisation & Specification

1. What this module does

The module writes 3.2.S.3.1, 3.2.S.3.2, the specification and its justification (3.2.S.4.1 and 4.5, or 3.2.P.5.1 and 5.6) and 3.2.S.5.

It checks your characterisation against the ICH Q6B list (primary structure, post-translational modifications, glycans, higher-order structure, variants, biological activity), converts host cell protein and DNA to amounts per dose, and calculates the endotoxin limit from the dose and route (K/M).

What you get

• Word or PDF files for characterisation, impurities, specification, justification and reference standards.
• A summary file for the QOS Composer & Dossier Assembler.

2. Before you start

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

• Maximum dose, route, shortest infusion time and protein concentration.
• Characterisation results by attribute and method, with the lots tested.
• Host cell protein (ng/mg), residual DNA (pg/mg) and leached Protein A (ng/mg), with the HCP assay and its coverage; other process-related and product-related impurities.
• Tests, methods and acceptance criteria, and the lots (toxicology, clinical, PPQ) that support them.
• Primary and working reference standards and the protocol for new ones.

3. Step by step with the example

Open the tool at app.cmcfy.com/app/biologics-characterisation.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. Enter product and dose

   Choose drug substance or drug product specification, the route, the maximum dose (1500 mg in the example), the shortest infusion time and the concentration. These drive the per-dose calculations.

   

2. Enter characterisation and impurities

   One row per attribute studied. Enter HCP, DNA and Protein A as the highest level across lots.

3. Read the result

   The headline reports missing Q6B attributes, and the note gives the endotoxin limit from the dose (0.23 EU/mg with K = 5 EU/kg and M = 21.43 mg/kg/h) and residual DNA per dose (0.75 ng). The facts show HCP per dose (6.75 µg).

   

4. Check the specification against Q6B and the lots

   The tables show which expected tests are in the specification and whether every supporting lot meets the proposed criteria.

   

5. Resolve alerts

   In the example a minor alert notes that the glycan profile is not in the drug product specification; add it or justify why it is controlled elsewhere.

   

6. Preview and download

   Preview each section, read the review 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 and dose

2 · Characterisation (3.2.S.3.1)

One row per attribute studied. The tool checks the ICH Q6B list: primary structure, PTMs, glycans, higher-order structure, variants and biological activity.

3 · Impurities (3.2.S.3.2)

4 · Specification (3.2.S.4.1 or 3.2.P.5.1)

5 · Reference standards (3.2.S.5)

5. Checks and alerts

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

• Every ICH Q6B attribute group is characterised, each with a result, and the lots used are named.
• HCP reported (flagged above about 100 ng/mg), with the assay and coverage; residual DNA reported (flagged above 10 ng per dose); product-related impurities and aggregates addressed.
• Each test has a criterion and a method; the endotoxin criterion is not above the limit from the dose (critical) and is in EU/mg or EU/mL.
• Supporting lots meet the proposed potency and monomer criteria; at least three lots, including clinical or toxicology lots; a justification is given.
• Primary and working reference standards and a protocol for new standards; criteria that apply at shelf life.

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: Characterisation summary; Impurities; Justification of specification. 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 mode cites USP methods (for example USP <85> bacterial endotoxins, <787>/<788> particulate matter). EU mode expects Ph. Eur. methods (2.6.14, 2.9.19) and flags methods that cite USP/NF only; choose both regions to cite both. ICH Q6B applies in both.

8. Working with other modules

• Clearance of HCP, DNA and Protein A is shown in the Biologics Process Writer.
• Stability-indicating attributes and limits go to the Biologics Stability Studio module.
• For small molecules use the Specification Builder instead.

9. Common pitfalls

• Entering HCP in ng per dose instead of ng/mg: the per-dose calculation does that for you.
• Forgetting the infusion time for IV products, which changes the endotoxin limit.
• Setting criteria tighter than a clinical lot already released, or looser than lots support without justification.
• No working standard or no protocol for replacing standards.

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. Double the dose

   Change Maximum dose (mg) from 1500 to 3000.

   Expected resultThe endotoxin limit from the dose in the headline note becomes 0.12 EU/mg.

2. Enter a high host cell protein level

   Change Host cell protein in drug substance to 150.

   Expected resultA major alert says HCP is 150 ng/mg, above the level usually seen for a purified product.