eCTD Module 1 Requirements: Prepare the Regional Package

Module 1 preparation often starts with an old application folder. That folder can help identify previous work, but it cannot decide what belongs in the next transaction. The product may have changed, the activity may be different, and the regional implementation may have been revised.

This guide helps regulatory operations teams establish the applicable work, assign the supporting evidence, and decide whether a regional package is ready for publishing review. It covers FDA, EU and Health Canada source selection. It does not provide one universal list of documents required in every application.

For a section-by-section destination, use the separate Module 1 structure reference. For the relationship between regional material and the technical modules, see the ICH M4 guide. The practical deliverable here is an applicability and evidence record, with a complete fictional example below.

Establish the application context before collecting forms

Record five facts at the top of the content plan:

1. Receiving authority and route: identify the recipient and procedure, not simply “Europe” or “global.”
2. Product and application type: distinguish an investigational application from a marketing application and identify material product-specific conditions.
3. Current activity: an original application, amendment, supplement, response or annual report is not the same content request.
4. Electronic implementation and history: record the format and whether the application already has a submission history.
5. Source set: identify the content guidance, technical specification, forms and validation criteria used for this transaction.

If a material input is missing, leave the affected decision unresolved. “The publisher will choose” is insufficient when the missing fact changes which procedure or content applies. The regulatory lead supplies the context; the publishing lead confirms its technical implementation.

For example, a request labeled only “NDA patent document” does not tell the preparer whether the patent information is being submitted before or after approval. A folder containing last year's form does not resolve that distinction. The requirement owner must establish the application state before selecting the document.

Use a source set, not a single generic checklist

The following source map was checked on October 6, 2026. It identifies the starting documents and their limits; it is not a substitute for product- and procedure-specific content requirements.

A table of contents identifies where a type of information belongs. It does not establish that every application needs that information. Likewise, a validation rule can test a package property without answering the scientific or legal applicability question behind the document.

Retain a source's document revision and relevant passage alongside its URL. A working link can later serve a different revision. At release, compare the selected source set with the authority's current notice and resolve any change before assuming the earlier content plan remains valid.

Prepare FDA Module 1 around the actual activity

Select the form and its instructions together

FDA's current forms page provides Form 1571 for investigational new drug applications and Form 356h for marketing applications within its stated scope. Start from that official page and retain the form version and instructions selected for your activity. Do not copy a form from an unrelated product merely because its fields are familiar.

Review application identifiers, applicant information, submission type and signatures against the content plan. FDA's electronic-signature information specifically discusses signatures on forms and the importance of application number and submission type. The signature check and the metadata comparison should each have an owner.

Patent-information boundary: FDA's patent and exclusivity FAQ, question 16 distinguishes Form 3542a for patent information submitted with an original NDA, amendment or supplement before approval from Form 3542 for the described postapproval patent information. This is not a rule to include the same form in every NDA-related package. Patent information, patent certification and exclusivity are separate questions for the responsible regulatory or legal reviewer.

Separate applicability from placement

The FDA TOC places financial certification/disclosure under 1.3.4 and patent/exclusivity material under 1.3.5. Environmental analysis is under 1.12.14, promotional material under 1.15, risk management under 1.16, and postmarketing studies under 1.17. REMS sits within 1.16.2. These corrected locations do not imply that every transaction requires each category. See the linked FDA TOCs above and the detailed structure reference.

For each potentially relevant item, the requirement owner should answer: why is it applicable to this activity, what approved material addresses it, and which exact subheading is appropriate? When the answer is “not applicable,” retain the rationale rather than silently dropping the item from a generic checklist.

Do not equate a risk-management heading with an automatic requirement for a REMS. Similarly, the existence of an environmental-analysis heading does not select an assessment or an exclusion claim for the product. Those determinations need their own applicable sources and review.

Confirm the electronic version independently

FDA supports v4.0 for eligible new applications and states that forward compatibility is not yet available. An existing 3.2.2 application's next transaction cannot be treated as a v4.0 conversion merely because a supplier now offers v4.0. The FDA notice is the starting gate.

Also keep the TOC revision separate from the eCTD version. The v4.0 TOC has its own revision number and contains some differences from the 3.2.2 TOC. A spreadsheet headed only “latest Module 1” loses information the publisher needs.

Prepare EU Module 1 for the selected procedure

For EU 3.2.2 work, the current M1 Implementation Guide 3.1.1 defines the regional structure and metadata. The related technical guidance distinguishes procedure types and treats application forms, product information, cover letters and tracking information in their own sections. Record the procedure and receiving route before adapting an existing dossier.

The content review should separately address the application form, regional product information, expert information, environmental material, and pharmacovigilance material where applicable. These are review topics, not a declaration that the same documents are universally mandatory. A US label, an EU product-information document and a Canadian product monograph should not be treated as interchangeable approved artifacts.

Do not label environmental review as exclusively American or pharmacovigilance content as irrelevant to FDA Module 1. Those broad comparisons obscure the different regional categories and applicability conditions. Compare the actual required output for the chosen procedure instead.

The EU technical guidance's scope also matters: its exceptions include specified premarketing activities such as clinical-trial applications and paediatric investigation plans. A team preparing one of those activities must follow the relevant route rather than importing the marketing-application eCTD instructions wholesale. See section 2.1.5 of the Harmonised Technical Guidance.

For regional adaptation, reuse approved underlying facts through a controlled source record. Then review the destination document's wording, language, local identifiers and procedural context. Reuse can reduce re-entry without turning a previously approved regional document into an automatically suitable new one.

Resolve Canadian activity requirements from the current filing route

Health Canada's pre-application and filing guidance points applicants to the appropriate electronic-filing guidance and describes the Regulatory Enrolment Process and submission gateway context. Its filing index separates eCTD from non-eCTD preparation and provides current notices.

For document placement, use the public Canadian Module 1 organization table, updated April 2, 2024. It states that its placement instructions take precedence over other publications. For example, a copy of Health Canada's request belongs under 1.0.3, while the summary response belongs under 1.0.4; supporting data belong in their appropriate module. A response packet therefore needs more than one undifferentiated correspondence file. The table also distinguishes the non-eCTD table of contents from eCTD transactions, for which it says not to provide that document.

The index still links the Canadian Module 1 backbone guidance and schema 2.2 for technical implementation. Its historical statements about which activities were accepted in 2012 should not determine today's filing eligibility.

The fuller preparation guidance is listed as available on request. If your team does not hold the applicable current document, record that source gap and obtain it through the listed route before finalizing affected requirements. This guide does not fill that gap with an invented Canadian section map or a universal bilingual-document checklist.

Use the Canadian source set to establish the required forms, product information, languages, identifiers and transaction details for the activity. Then compare those facts with the proposed package. A US application number, form or section label is not a substitute for the Canadian equivalent merely because the scientific program is shared.

Build the applicability and evidence record

Use one row per consequential item. The following is a proposed internal working record, not an agency-prescribed form.

Do not use “document received” as a synonym for “requirement satisfied.” The document may be a draft, may concern a different activity, or may still contain an unresolved discrepancy. Keep content approval separate from the fact that a file has reached the publisher.

Likewise, avoid defaulting every empty row to “not applicable.” Missing evidence and an approved exclusion are different states. The unresolved state gives the team a visible decision to close before release.

Worked example: one regional package with two unresolved decisions

Fictional context: Larch Therapeutics is preparing an original NDA for a new application. Its regulatory lead has already confirmed an eligible FDA v4.0 route. For this exercise only, the lead has determined that patent information must be included before approval. The package contains an approved cover letter, a candidate application form, and a patent-information draft. This small packet illustrates review decisions; it is not a complete NDA checklist.

Supplied records

Review decisions

L-03: The supplied facts support the narrow consistency check against C-01. Retain its approval record and confirm that the publisher receives that exact revision. This does not by itself establish that all cover-letter content is sufficient.

F-02: Hold the form for correction and signature review. Its contact conflicts with the approved context. The owner should verify the intended contact, prepare the corrected revision, and retain the reviewed form. Do not fix only the XML while leaving the form inconsistent.

P-01: Return the form-selection decision to the requirement owner. Under the exercise's preapproval facts, the FDA FAQ points to 3542a rather than the postapproval 3542. Legal review must still establish the correct substantive information. Merely renaming the file does not change the form or resolve that review.

Package disposition: Not ready for the team's release approval. Assign the form correction to regulatory operations and the patent-document review to the designated regulatory/legal owner. Retain the two findings and require reviewed replacement artifacts before closing them. This is an internal preparation decision, not a predicted FDA rejection.

Change one fact and reassess

For a separate intake case, supply only a file labeled “NDA patent information,” with no application status, activity description or applicability determination. None of the original-NDA or preapproval facts from the first packet carries into this case. The patent-form decision is unresolved; request those facts rather than infer them from the filename. If the owner then confirms the relevant postapproval patent-information activity, reassess the form using that different context.

Now change the destination to an EU clinical-trial application. The FDA forms and this NDA route no longer answer the task. The team must establish the separate applicable route and source set. The scientific product's identity staying the same does not preserve the administrative decision.

These boundary cases make the record useful: it exposes exactly which input changed the answer.

Review content, technical output and delivery separately

Before publishing, reconcile the context record with the approved forms, cover letter, document identities and metadata. Resolve material contradictions with the source owners; do not choose whichever value is easiest to enter.

After publishing, inspect the actual candidate output and its applicable technical report. The eCTD validation guide explains that review boundary. A passed technical check does not establish that an unreviewed legal or scientific determination is correct.

For delivery, use the correct authority workflow and retain actual receipt evidence. The FDA submission gateway guide covers the US operational path. A package being prepared, transmitted and received represents different evidence; a planning dashboard should preserve those distinctions.

Carry open administrative findings into the submission readiness checklist. If an authority response generates follow-up work, use the response-management evaluation to define the source question, accountable owner and accepted completion evidence.

For an eligible FDA v4.0 preparation workflow, discuss the package with Assyro, bringing the context record and approved sample material. Assyro's current scope does not include 3.2.2 publishing, and EMA support remains on the roadmap. The useful demonstration is whether the supported workflow preserves the decisions and evidence your team has already established.