Biologics Process Writer

1. What this module does

The module writes 3.2.S.2.1 to 3.2.S.2.6 for a recombinant protein or monoclonal antibody, from the cell bank to the purified drug substance.

It checks the cell substrate and cell bank testing against ICH Q5B and Q5D, the critical steps and their controls, hold times and resin lifetimes, clearance of process-related impurities, PPQ status and the comparability of process versions (ICH Q5E).

What you get

• Word or PDF files for 3.2.S.2.1 to 3.2.S.2.6, with the upstream and downstream flow diagram.
• 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.

• Manufacturers with address, responsibility and FEI or EU GMP certificate number; production bioreactor scale.
• Host cell line and source, expression construct, evidence of clonality.
• Cell banks (MCB, WCB, end-of-production cells) with lot, population doublings, storage and tests; the limit of in vitro cell age.
• Raw materials with origin and controls, especially anything of animal or human origin.
• Process steps with parameters and in-process controls, hold times, resin and membrane lifetimes, reprocessing.
• PPQ batches, impurity clearance data, and the process versions used for toxicology, clinical and commercial supply with the comparability outcome.

3. Step by step with the example

Open the tool at app.cmcfy.com/app/biologics-process.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 sites

   Enter the drug substance, region, bioreactor scale and manufacturers. The example is CMB-201, a humanised IgG1 made at 2000 L.

   

2. Describe the cell substrate and banks

   Enter the host cell line, construct and clonality evidence, then the cell banks. Give each bank its tests, and the limit of in vitro cell age with the end-of-production cell age that supports it.

3. Enter the process

   One row per step from vial thaw to final filtration. Mark the critical steps. The headline counts 4 upstream and 7 downstream steps, 7 of them critical, and the flow diagram is drawn from the table.

   

4. Add hold times, resin lifetimes and validation

   Enter maximum hold times and how they were validated, resin lifetimes, PPQ batches, impurity clearance and process versions.

5. Resolve alerts

   The example has three minor alerts: a test lab without an FEI number, a 7-day hold of the virus-filtered pool without supporting data, and a resin lifetime of 150 cycles that is not supported.

   

6. Preview and download

   Preview each 3.2.S.2 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 sites

2 · Cell substrate and cell banks (3.2.S.2.3)

3 · Upstream and downstream process (3.2.S.2.2, 3.2.S.2.4)

Mark the steps that are critical. Give parameters with ranges and the in-process controls with action or acceptance limits.

4 · Process validation and development (3.2.S.2.5, 3.2.S.2.6)

5. Checks and alerts

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

• Manufacturers with address, responsibility and the regional identifier.
• Host cell line, construct and clonality described; MCB, WCB and end-of-production cell testing present; rodent lines tested for retroviruses; genetic stability at the limit of in vitro cell age; the end-of-production cell age covers the WCB age plus the proposed limit; a protocol for new WCBs; storage in separate locations.
• Raw materials of animal origin need a TSE certificate; human-origin materials are flagged; every raw material has a quality standard.
• A production culture step; unprocessed bulk tested for mycoplasma and adventitious viruses; bioburden and endotoxin in-process controls; a dedicated viral inactivation or virus filtration step.
• Critical steps marked, with parameters (numerical ranges) or controls, and equipment or scale.
• Hold times and resin lifetimes given and supported by data.
• Process validation addressed with PPQ batches; clearance of host cell protein, DNA and leached Protein A shown; each process version assessed for comparability.

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: Description of the manufacturing process; Cell substrate and cell banks; Process validation; Manufacturing process development and comparability. 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 asks for FEI numbers and cites FDA guidance for BLAs. EU mode asks for EU GMP certificate or MIA numbers, notes active substance manufactured outside the EEA, and cites the EMA guideline on process validation for biotechnology-derived active substances. ICH Q5A to Q5E and Q11 apply in both.

8. Working with other modules

• Viral clearance and adventitious agent testing are written in full in the Viral Safety Studio module.
• Impurity levels per dose and the specification are in Biologics Characterisation & Specification.
• Facility and equipment segregation go in the Facilities & Equipment Writer module.

9. Common pitfalls

• Listing cell bank tests in one long cell without the key ones (sterility, mycoplasma, adventitious viruses, retroviruses, identity).
• Hold times without the study that supports them.
• Comparing process versions without saying what was compared and the outcome.
• Forgetting the contract test labs in the manufacturers table.

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. See the EU site requirements

   Set Submission region to EU.

   Expected resultA minor alert says a site has no EU GMP certificate or MIA number.

2. Remove the clonality evidence

   Clear Evidence of clonality.

   Expected resultA major alert says there is no evidence that the production cell line is clonal.