Regional Information (3.2.R and Module 1)

1. What this module does

You list the manufacturing and testing sites with their role, country, FEI or DUNS number and EU manufacturing authorisation or GMP certificate, the CEPs and master files you reference, and the regional items (executed batch records, method validation package, comparability protocols, process validation scheme, device).

The tool calculates the US expected introduction concentration (EIC) to see whether a categorical exclusion under 21 CFR 25.31 applies, and the EU predicted environmental concentration in surface water (PECsw) to see whether an ERA Phase II is needed. It checks that an EEA site releases batches, that every site has the identifiers each region needs, and that a letter of access exists for each master file.

What you get

• US: 3.2.R regional information, establishment list for Form 356h, and the 1.12.14 environmental analysis (categorical exclusion claim or EA).
• EU: 3.2.R regional information, manufacturers for the application form, QP declaration basis and the 1.6 environmental risk assessment.

2. Before you start

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

• Each site's name and address, country, role, FEI or DUNS, MIA or GMP certificate and last inspection or audit.
• CEPs, DMFs and ASMFs referenced, with letters of access.
• Maximum daily dose, expected annual production in year five and log Kow of the active substance.
• Executed batch records, method validation package and any comparability protocols (US); process validation scheme, device status and QP declaration basis (EU).

3. Step by step with the example

Open the tool at app.cmcfy.com/app/regional-information.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. Choose the regions and the application

   Pick US, EU or both, the application type (NDA, ANDA, BLA or MAA) and the product type. Fields for a region you did not choose are hidden.

   

2. List the sites and master files

   One row per site with its role (drug substance, drug product, packaging, testing, batch release). Put names that contain commas in quotes. List each CEP, DMF or ASMF with the holder and whether you have a letter of access.

3. Read the environmental result

   The headline sums it up: "4 sites · US: categorical exclusion 25.31(b) · EU: ERA Phase II needed". The note gives the EIC against the 1 ppb limit and the PECsw against the 0.01 µg/L action limit.

   

4. Resolve alerts and download

   Missing FEI numbers, a missing EEA batch release site, master files without a letter of access, an EIC at or above 1 ppb and a log Kow above 4.5 are flagged. Then preview and download each document.

   

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 · Application

2 · Manufacturers and establishments

One row per site and activity. US: give the FEI or DUNS number. EU: give the manufacturing authorisation or GMP certificate. Role: drug substance, drug product, testing, packaging or batch release.

3 · US regional information (3.2.R) and environmental assessment shown when it applies

4 · EU regional information (3.2.R) and Module 1 shown when it applies

5. Checks and alerts

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

• US: FEI or DUNS for every site; EIC = annual production / (1.214 × 10¹¹ L/day × 365) against 1 ppb for 25.31(b); 25.31(a) and (c) where they apply; extraordinary circumstances.
• EU: an EEA site for batch release; MIA or GMP certificate for each site; PECsw = dose × Fpen / (200 L × 10) against 0.01 µg/L; PBT screening when log Kow is above 4.5; device opinion for an integral device.
• Letters of access for each CEP, DMF or ASMF referenced.

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: Environmental statement. 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 21 CFR 25 and the FDA guidance on environmental assessment of human drug and biologics applications (1998); the 3.2.R content follows the FDA M4Q guidance. EU follows the EMA guideline on the environmental risk assessment of medicinal products (EMEA/CHMP/SWP/4447/00 Rev. 1) and the notice to applicants for Module 1 and the application form.

8. Working with other modules

• Sites and master files also appear in the DMF & ASMF module and in 3.2.S.2.1 and 3.2.P.3.1.
• Assemble the sections in the QOS Composer & Dossier Assembler.

9. Common pitfalls

• Claiming a categorical exclusion without checking the fifth-year production estimate.
• Listing a non-EEA site as the batch release site.
• Forgetting the letter of access for a DMF or ASMF.

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 the production estimate

   Set Maximum expected annual production to 50000.

   Expected resultThe headline says the US needs an environmental assessment.

2. Enter a lipophilic substance

   Set log Kow of the active substance to 5.

   Expected resultThe note asks for a PBT screening.