How to prepare Module 4 literature references

How should Module 4 literature references be prepared?

Reconcile the nonclinical claims and citations with identifiable source documents at the appropriate literature location. Check the actual methods, results, versions and limitations, not only the citation format. Explain the relevance of published evidence used in place of applicant studies and preserve gaps when a necessary source is unavailable.

Before you begin

Literature supporting the nonclinical dossier. A publication is not automatically a replacement for applicant-generated evidence or a right of reference.

What you will prepare: A citation-to-source record with correct identities, usable documents and a transparent account of limitations.

Start from the claims and citations actually used

Module 4 has a literature-reference location at 4.3. Assemble the references cited in the nonclinical narrative and evidence package, then reconcile them with the documents intended for the submission. The useful working unit is the source and its role, not a count of papers collected from a search.

For each reference, record its bibliographic identity, persistent identifier when available, cited claim, citing document/section, available full text, correction or retraction status and proposed destination. Distinguish a primary experiment from a review discussing that experiment. If the argument rests on the original study, obtain and assess the original rather than treating a review's sentence as the complete evidence.

Check what the paper can actually support

Read the methods and results around the cited passage. Identify the tested substance, test system, exposure conditions, measured endpoint and relevant limitations. FDA M4S discusses justification when published evidence is used instead of applicant studies; citation alone does not make the substitution adequate.

As an editorial exercise, write one sentence for the proposed claim and another for the result the paper actually reports. Compare them for changes in product, species, dose, duration or outcome. If the proposed claim goes further, narrow it or ask the scientific owner for the missing supporting evidence. Keep a literature limitation visible in the nonclinical assessment; do not hide it in an inaccessible bibliography note.

Prepare source documents that remain identifiable

Obtain a lawful usable copy of each source needed for the actual dossier and check the publication identity against the citation. Inspect page completeness, figures, supplementary material relevant to the claim and any correction linked by the publisher. An abstract-only record should be labeled as such, not presented as a full report.

If a source is unavailable, assign an owner and document the gap. Do not invent page numbers, data or a missing full-text file. Where translation is needed, follow the organization's controlled translation and review process and preserve the relationship to the original. This guide does not claim that a publisher subscription grants every form of redistribution right.

Resolve duplicates by source identity, not filename. A corrected article and an earlier version may require a relationship record; two filenames for the same unchanged article generally should not become two independent pieces of evidence.

Follow a citation discrepancy to the affected claim

Fictional example: the nonclinical overview cites a review article as support for absence of a developmental effect. The primary experiment discussed in the review used a different compound, and the dossier has neither the original paper nor an explanation of its relevance.

The reviewer should identify the mismatch, obtain the primary source if it is needed, and ask the nonclinical lead to assess the relevance. The outcome may be a qualified analogy, another source or removal of the unsupported assertion. A correctly formatted citation does not resolve a scientific mismatch.

Before handoff, open the actual source files from the draft package and follow representative citations in both directions. Confirm that amended reports and summaries still point to the intended references. That last check verifies retrievability and consistency; it is separate from the scientific assessment of the evidence.

Audit the path from a scientific claim to the source file

Use a claim-to-source register as an editorial review aid. It is more useful than a bibliography checklist because it tests what each reference contributes.

When several sources support a sentence, record what each contributes. A primary experiment may establish an observation while a review supplies background context; they are not two independent replications of the same result.

Correction exercise: a paper's corrected table changes a value quoted in the nonclinical overview. Obtain the correction, identify the affected claim and have the scientific owner assess its significance. Update the source relationship and the actual affected text. Replacing a PDF without reviewing the argument leaves the dossier inconsistent.

Run the register against the nonclinical overview and the summary plan. Check the files in the assembled package as well as the writing repository: a verified reference is useful only if the intended source and any necessary qualification remain retrievable by the reviewer.

Frequently asked questions

Sources and revisions

Requirements, source recommendations and editorial preparation advice have different roles. Review the scope and revision of the source you use.

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