Container Closure & E&L

1. What this module does

The module writes 3.2.P.7 (container closure system) and 3.2.P.2.4 (its suitability) for a drug product, or 3.2.S.6 for a drug substance.

It sets the degree of concern from the dosage form (FDA 1999 container closure guidance), calculates the safety concern threshold (SCT) and the analytical evaluation threshold (AET) from the units used per day, and checks each component for the compendial tests its material needs.

What you get

• Word or PDF files for 3.2.P.7 and 3.2.P.2.4 (or 3.2.S.6).
• A summary file for the QOS Composer & Dossier Assembler, which checks light and moisture protection against the storage statement.

2. Before you start

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

• Every component: material, whether it contacts the product, compendial tests, supplier and DMF, and drawing or specification reference.
• Photostability (ICH Q1B) outcome and moisture sensitivity, with water vapour transmission data if moisture sensitive.
• Extractables and leachables results with estimated daily exposure and any toxicological limit.
• Container closure integrity data for sterile products.

3. Step by step with the example

Open the tool at app.cmcfy.com/app/container-closure-studio.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 section and route

   Choose drug product or drug substance, the dosage form and route, and Units used per day. The headline gives the degree of concern (low for an oral solid) and the result panel shows SCT 1.5 µg/day and AET 0.75 µg per unit for 2 units a day.

   

2. Enter the components

   One row per component. Mark direct product contact, and give the compendial tests (USP <661.1> for plastics, <660> for glass, <381> for elastomers; Ph. Eur. 3.1 and 3.2 in EU mode).

   

3. Enter protection data

   Say whether the product is light or moisture sensitive and whether the pack protects it. Give WVTR data for a moisture-sensitive product.

4. Enter E&L and integrity

   Enter extractables and leachables with exposures; the tool compares them with the SCT and any toxicological limit. For sterile products, enter container closure integrity methods and results.

5. Resolve alerts

   In the example, two plastic components in product contact do not cite USP <661.1>. Add the test to the component row to clear each alert.

   

6. Preview and download

   Preview 3.2.P.7 and 3.2.P.2.4, 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 route

2 · Components

3 · Protection

4 · Extractables, leachables and integrity

5. Checks and alerts

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

• Components have materials; plastics in contact cite USP <661.1> (Ph. Eur. 3.1); glass cites USP <660> and Type I where needed; elastomers cite USP <381>; a packaging-system test to USP <661.2> is present.
• Supplier or DMF and a drawing or specification for each component.
• Photostability tested; a light-sensitive product needs a light-protective pack; a moisture-sensitive product needs WVTR data; stability in the proposed pack is cited.
• Leachables data for products with a higher degree of concern; extractables data; a food-contact statement for plastics in oral solids.
• Leachables against the toxicological limit (critical above) and against the SCT without an assessment (major).
• Sterile products: container closure integrity data; probabilistic methods are flagged in favour of deterministic ones (USP <1207>).

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 container closure system; Suitability (protection, compatibility, safety, performance). 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 uses the FDA 1999 container closure guidance, USP <661.1>, <661.2>, <660>, <381>, <671> and 21 CFR 174–186 for food contact. EU mode uses Ph. Eur. 3.1 and 3.2, the EMA guideline on plastic immediate packaging materials, and Regulation (EU) 10/2011 for food contact.

8. Working with other modules

• Photostability and storage conditions come from the Stability Studio or Biologics Stability Studio.
• Nitrocellulose in blister lidding is a nitrosamine risk factor in the Impurity & Risk Studio.
• The QOS Composer & Dossier Assembler checks that a light-sensitive product says "protect from light" on the storage statement.

9. Common pitfalls

• Listing the material but no compendial test.
• Marking a component as "no contact" when it is a liner or seal that touches the product.
• Using units per day for a different dose than the maximum daily dose.
• Relying on dye ingress (probabilistic) alone for container closure integrity of a sterile product.

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. Make the product light sensitive in a clear pack

   Set Photostability (ICH Q1B) to "Light sensitive" and untick The container protects from light.

   Expected resultA major alert says the product is light sensitive but the container does not protect from light.

2. Switch to an injection

   Set Dosage form and route to "Parenteral (injection)".

   Expected resultA major alert says there are no container closure integrity data for a sterile product.