Peptide & Oligonucleotide Impurities

1. What this module does

You choose the modality and whether the product is a new drug or a generic referring to an rDNA-origin listed drug, then enter each impurity with its level and, for a generic, its level in the RLD.

The tool checks the identification and qualification thresholds, impurities above the RLD, new impurities above 0.5%, and new impurities between 0.1% and 0.5% that need an immunogenicity assessment.

What you get

• A Word or PDF section: 3.2.S.3.2 Impurities (synthetic peptide or oligonucleotide).

2. Before you start

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

• Impurity levels from LC-MS with their identity and type.
• RLD impurity levels (for a generic).
• Counter-ion, residual TFA, residual solvents and aggregation results.

3. Step by step with the example

Open the tool at app.cmcfy.com/app/peptide-oligonucleotide.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 substance

   Choose the modality and the application type, and confirm the sequence and higher-order structure work.

   

2. Enter the impurities

   One row per impurity. Leave the RLD level empty for an impurity not found in the RLD (a new impurity).

3. Read the result

   The headline gives the outcome: "6 impurities · profile acceptable".

   

4. Resolve alerts and download

   A new impurity above 0.5% is critical. Impurities above the RLD, unidentified impurities above the threshold and missing immunogenicity assessments 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 · Drug substance

2 · Impurities

Levels in % (area). For a generic, give the highest level in the RLD lots tested; leave empty for an impurity not found in the RLD.

3 · Other impurities

5. Checks and alerts

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

• Reporting, identification and qualification thresholds.
• ANDA: each impurity at or below the RLD; new impurities ≤ 0.5%.
• Immunogenicity assessment, aggregation and higher-order structure.

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: Impurity discussion. 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 generics follow the FDA ANDA synthetic peptide guidance (2021). EU follows Ph. Eur. 2034 and the EMA synthetic peptide and oligonucleotide guidelines.

8. Working with other modules

• Mutagenic and nitrosamine impurities are assessed in the Impurity & Risk Studio and the Nitrosamine Risk Assessment.

9. Common pitfalls

• Applying ICH Q3A thresholds to a peptide.
• A new impurity with no immunogenicity assessment.

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 a new impurity

   Change [+Gly] liraglutide from 0.12% to 0.62%.

   Expected resultThe headline shows one new impurity above 0.5%.