Nonclinical · Training guide
Nonclinical Overview & Summaries
Write the nonclinical overview (CTD 2.4), the toxicology tabulated summary (2.6.7) and the nonclinical section of the Investigator's Brochure from your study list, checked against ICH M3(R2) for the clinical stage you are supporting.
Open the tool at https://app.cmcfy.com/app/nonclinical-overview.html. This guide is also online at https://cmcfy.com/guides/nonclinical-overview.html
1. What this module does
You choose the modality and the clinical stage, give the longest planned dosing, the clinical dose and human exposure, and list the studies with their species, duration, NOAEL, exposure and GLP status.
The tool checks the repeat-dose duration in a rodent and a non-rodent, the safety pharmacology core battery and hERG, the genotoxicity battery, the timing of reproductive studies (which differs between the US and the EU), carcinogenicity, photosafety and juvenile studies. It works out the human equivalent dose, the maximum recommended starting dose and the exposure margins.
What you get
- A Word or PDF document for each: 2.4 Nonclinical overview, 2.6.7 Toxicology tabulated summary, and IB section 5.
2. Before you start
Have these ready. You can still start with the example data and replace it piece by piece.
- The study list with species, duration, NOAEL and GLP status.
- AUC at the NOAEL for the pivotal repeat-dose studies.
- The planned clinical dose, duration and population.
3. Step by step with the example
Open the tool at app.cmcfy.com/app/nonclinical-overview.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.
Describe the programme
Choose the modality and the stage the package supports, and tick whether women of childbearing potential or children are included.
Enter the studies
One row per study. Name the endpoint in the title (Ames, micronucleus, hERG, CNS, embryo-fetal development) so the coverage check finds it.
Read the result
The headline gives the outcome: "Nonclinical package supports phase 2".
Safety margins and ICH M3(R2) coverage. Resolve alerts and download
A repeat-dose study shorter than the clinical dosing, a missing core battery or Ames test, and a starting dose above the MRSD are critical. Non-GLP pivotal studies and exposure margins below 1 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 · Programme
| Field | What to enter |
|---|---|
| Product | Type it in. |
| Submission region | Choose one: US: FDA (NDA, ANDA, BLA, IND); EU: EMA and national agencies (MAA); Both US and EU. |
| Modality | Choose one: Small molecule; Biotechnology product (ICH S6). |
| Supports | Choose one: First-in-human (phase 1); Phase 2; Phase 3; Marketing application. |
| Longest planned clinical dosing (weeks) | Type a number. |
| Document number | Type it in. |
| Indication and population | Type it in. |
| Women of childbearing potential included | Tick the box if it applies. |
| Paediatric patients included | Tick the box if it applies. |
| Expected clinical use is chronic (6 months or more) | Tick the box if it applies. |
| Absorbs light at 290–700 nm (MEC above 1000 L/mol/cm) | Tick the box if it applies. |
2 · Clinical dose
| Field | What to enter |
|---|---|
| Highest planned clinical dose (mg/day) | Type a number. |
| Proposed starting dose (mg/day, first-in-human) when it applies | Type a number. |
| Human AUC at the highest dose (ng·h/mL, steady state) | Type a number. |
3 · Studies
One row per study. Type: repeat-dose, safety pharmacology, genotoxicity, reproductive, carcinogenicity, phototoxicity, juvenile, pharmacokinetics or local tolerance. Name the endpoint in the title (Ames, micronucleus, hERG, CNS, EFD, fertility). Use ";" inside the findings.
| Field | What to enter |
|---|---|
| Studies | Use ";" inside the findings column. Write "in vitro" as the species for in vitro assays. A table. Columns: Study ID | Type | Title | Species | Duration (weeks) | NOAEL (mg/kg/day) | AUC at NOAEL (ng·h/mL) | GLP (yes/no) | Key findings. Paste rows from Excel, type comma-separated rows, or press Load file (Excel, CSV, Word, PDF or a scan). |
5. Checks and alerts
Calculations and pass/fail outcomes always come from fixed rules, never from AI. The tool checks:
- Repeat-dose duration against ICH M3(R2) Tables 1 and 2.
- Safety pharmacology, genotoxicity and reproductive timing.
- HED, MRSD, exposure margins and GLP status.
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: Overview and conclusions. 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
- 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.
- 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).
- Click a finding to jump to the place in the preview. Fix it in the tool, then preview again.
- 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.
- 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
| Section | Document |
|---|---|
| 2.4 | Nonclinical overview |
| 2.6.7 | Toxicology tabulated summary |
| IB 5 | Investigator's Brochure nonclinical section |
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: embryo-fetal development can follow early trials with contraception, before phase 3; 9-month non-rodent study for long trials; starting dose by the FDA 2005 guidance. EU: EFD before women of childbearing potential are dosed; 6-month non-rodent accepted; EMA first-in-human guideline.
8. Working with other modules
- Each pivotal toxicology study report is written in the GLP Toxicology Study Report.
9. Common pitfalls
- A rodent study shorter than the planned clinical dosing.
- Calling a dose range-finding study pivotal without GLP.
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.
Plan a longer trial
Change the longest planned clinical dosing from 12 to 26 weeks.
Expected resultThe headline shows two critical gaps: both repeat-dose studies are too short.