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Introduction
This document provides a summary of the updates to the codes, defined lists, matrixes, and technical validation criteria that transition eCTD AU Module-1 v3.1 to eCTD AU Module-1 v3.2.
This document applies to all regulatory activities submitted in electronic Common Technical Document (eCTD) format.
To allow for planning and software updates we have incorporated a transition period for the uptake of the AU Module 1 Version 3.2 specification.
- The AU Module 1 Version 3.2 specification will be effective starting April 2025.
- The AU Module 1 Version 3.1 specification will be accepted until October 2025.
Between April and October 2025, the TGA will accept both the Version 3.1 and Version 3.2 AU Module 1 specifications.
The purpose of this update is to:
- Ensure alignment with current business processes and incorporate flexibility to adapt to future needs through revision of the defined lists and matrixes.
- Support clear and consistent requirements through revision of the Australian eCTD validation criteria.
- Provide efficient document locations within eCTD Applications through amendment of Module 1 heading elements.
For further information on any of the updates please contact eSubmissions@health.gov.au.
Summary of updates in Version 3.2
The following supporting technical documents have been created:
| File type | File description | File name | File checksum value |
|---|---|---|---|
| Schema | Australian regional backbone | au-regional.xsd | efec6508c4ee0bfcf66326946852a535 |
| Stylesheet | Australian regional backbone | au-regional.xsl | 4e77e32b608c270d3c802da7649572ea |
| Stylesheet | Codes / defined list | codes.xsl | a2a94549a6e9ec159b71a76b274b4311 |
| Stylesheet | Sequence matrix | sequence-matrix.xsl | e5d25d72309b0e514f4e8e4a0080a0bd |
| Stylesheet | Document matrix | document.matrix.xsl | 948affd204cd0626e527c136163ca194 |
| Codes / defined list | Regulatory activity lead | reg-activity-lead.xml | 3b9b98f945c450acae51a83772f8ff8f |
| Codes / defined list | Sequence type | sequence-type.xml | 65cd30fe59c1bb5f920257eb45548c3a |
| Codes / defined list | Sequence description | sequence-description.xml | 72a10fe55bb57f0f85c2e7e0c20736e4 |
| Codes / defined list | Module 1 header | module-header.xml | 4e7664863fac90deeb6725a52eeaf273 |
| Codes / defined list | Sequence matrix | sequence-matrix.xml | 07c495fa86ecaf6403b060a3d54ede66 |
| Codes / defined list | Document matrix | document-matrix.xml | b653594ad8d58b3184cccc805fdaed0e |
| Spreadsheet | eCTD Validation Criteria v3.2 |
Australian eCTD validation criteria v3.2
[Excel, 25.21 KB]
| N/A |
AU Module 1 Specification updates
Module 1 Code-list Updates
New and updated version 3.2 regulatory activity leads, sequence types, sequence descriptions, and module 1 headers are highlighted in grey below.
Regulator Activity Lead updates
Table 1: New Regulatory Activity Leads
| Code | Regulatory Activity Lead | Rationale |
|---|---|---|
| reg-act-lead-8 | Prescription meds-vaccine | Allows for collection of vaccine data |
Table 2: Removed Regulatory Activity Leads
| Code | Regulatory Activity Lead | Rationale |
|---|---|---|
| reg-act-lead-5 | Pharmacovigilance | Sequences previously using this lead will instead be defined using sequence type and description |
Sequence Type updates
Table 3: New Sequence Types
| Code | New Sequence Type v3.2 | Rationale |
|---|---|---|
| seq-type-63 | Minor Variation (Cat 3) | Required to distinguish between Category 1 and Category 3 minor variation applications |
| seq-type-64 | Minor Editorial Change (MEC) | Required to accommodate potential work sharing functionality |
| seq-type-65 | Generic extension of indications | Required to accommodate potential work sharing functionality |
| seq-type-66 | Pre-Advice | Pre-submission information (pre-submission meeting or early scientific advice) |
| seq-type-67 | Designation / Determination | Designations and determinations |
| seq-type-68 | S14/14A | S14/14A exemptions |
| seq-type-69 | Post-requirement or Administrative | On-going reporting requirements (annual reports for biologicals for example) that are not vigilance requirements |
| seq-type-70 | RCM – New – 1 | Registered complementary medicines |
| seq-type-71 | RCM – New – 2 | Registered complementary medicines |
| seq-type-72 | RCM – New – 3 | Registered complementary medicines |
| seq-type-73 | RCM – New – 4 | Registered complementary medicines |
| seq-type-74 | RCM – New – 5 | Registered complementary medicines |
| seq-type-75 | RCM – Change – 1 | Registered complementary medicines |
| seq-type-76 | RCM – Change – 2 | Registered complementary medicines |
| seq-type-77 | RCM – Change – 3 | Registered complementary medicines |
| seq-type-78 | RCM – Change – 4 | Registered complementary medicines |
| seq-type-79 | Transition to full registration | Transition from provisional to full registration. |
Table 4: Updated Sequence Types
| Code | Sequence Type v3.1 | Sequence Type v3.2 | Rationale |
|---|---|---|---|
| seq-type-1 | A – NCE New Chemical Entity | New Entity | Removed application type to allow use by other therapeutic areas |
| seq-type-3 | A – NCE Similar Biological Medicinal Product | Similar Biological Medicinal Product | Removed application type to allow use by other therapeutic areas |
| seq-type-4 | B – New Combination | New Combination | Removed application type to allow use by other therapeutic areas |
| seq-type-5 | C – Extension of Indication | Extension of Indication | Removed application type to allow use by other therapeutic areas |
| seq-type-6 | D – New Generic Medicine | New Generic Medicine | Removed application type to allow use by other therapeutic areas |
| seq-type-7 | E – Additional Tradename | Additional Tradename | Removed application type to allow use by other therapeutic areas |
| seq-type-17 | J – PI Change requiring evaluation | PI Change requiring evaluation | Removed application type to allow use by other therapeutic areas |
| seq-type-8 | F – Major Variation - New Strength | Major Variation | Reduction in major variation sequence types to simplify process |
| seq-type-13 | G – Minor Variation (Cat 1), New Register Entry - Change of Formulation | Minor Variation (Cat 1) | Required to accommodate potential work sharing functionality |
| seq-type-53 | 9D(1) - Correction of Register Entry | Correction of Register Entry | Broadened to allow use by other therapeutic areas |
| seq-type-54 | 9D(2) – Safety Related Request/Variation | Safety Related Request/Variation | Broadened to allow use by other therapeutic areas |
| seq-type-55 | 9D(3) – Change to PI (not J) | Self Assessable Request/Variation | Broadened to allow use by other therapeutic areas |
| seq-type-20 | OTC – N1 | OTC – New – 1 | More descriptive sequence type title |
| seq-type-21 | OTC – N2 | OTC – New – 2 | More descriptive sequence type title |
| seq-type-22 | OTC – N3 | OTC – New – 3 | More descriptive sequence type title |
| seq-type-23 | OTC – N4 | OTC – New – 4 | More descriptive sequence type title |
| seq-type-24 | OTC – N5 | OTC – New – 5 | More descriptive sequence type title |
| seq-type-25 | OTC - C1 | OTC – Change – 1 | More descriptive sequence type title |
| seq-type-26 | OTC - C2 | OTC – Change – 2 | More descriptive sequence type title |
| seq-type-27 | OTC - C3 | OTC – Change – 3 | More descriptive sequence type title |
| seq-type-28 | OTC - C4 | OTC – Change – 4 | More descriptive sequence type title |
| seq-type-44 | Pharmacovigilance | Vigilance | Encompasses all additional vigilance activities that are non-pharmaceutical (bloods and biologicals) |
Table 5: Removed Sequence Types
| Code | Removed Sequence Type | Rationale |
|---|---|---|
| seq-type-2 | A – NCE New Salt or Ester of Existing Active Ingredient | Captured under “New Entity” |
| seq-type-9 | F – Major Variation - New Dosage Form | Captured under “Major Variation” |
| seq-type-10 | F – Major Variation - New Route of Administration | Captured under “Major Variation” |
| seq-type-11 | F – Major Variation - Change in Patient Group | Captured under “Major Variation” |
| seq-type-12 | F – Major Variation - Change of Dosage | Captured under “Major Variation” |
| seq-type-14 | G – Minor Variation, New Register Entry - New Container Type | Captured under “Minor Variation” |
| seq-type-16 | H – Minor Variation, Not Resulting in a New Register Entry | Captured under “Minor Variation” |
| seq-type-58 | Provisional registration – TGA initiated variation | |
| seq-type-60 | CN | Captured under “General Notifications” |
| seq-type-47 | Periodic Safety Update Report | Captured as sequence descriptions |
| seq-type-48 | Risk Management Plan | Captured as sequence descriptions |
| seq-type-56 | Change of Sponsor | Now tracked via XML envelope |
| seq-type-62 | Duplicate |
Sequence Description updates
Table 6: New Sequence Descriptions
| Code | New Sequence Description v3.2 | Rationale |
|---|---|---|
| seq-desc-27 | Partial withdrawal | Withdraw part of an active submission/sequence or cancel some ARTG records |
| seq-desc-28 | Annual Report | Annual TGA reporting requirements |
| seq-desc-29 | CPD (Certified product details) | Certified product details |
| seq-desc-30 | Administrative update | Administrative updates (meeting minutes) or corrections to forms |
| seq-desc-31 | Early scientific advice | Advice on quality aspects prior to eCTD Application submission |
| seq-desc-32 | International work-sharing information | ACCESS Consortium and Project Orbis |
| seq-desc-33 | Final | Close a submission (for example, approved copies of PIs, CMIs, and labels) |
| seq-desc-34 | Errors of fact or omissions | Response to Round 2 reports |
Table 7: Updated Sequence Descriptions
| Code | Sequence Description v3.1 | New Description v3.2 | Rationale |
|---|---|---|---|
| seq-desc-19 | RMP Version {number:I} – {date:d} | RMP | Removed version and date requirement |
| seq-desc-26 | Provisional approval – rolling data submission – {date: d} | Rolling data submission | Removed date requirement |
| seq-desc-5 | Response to Request for Information – {date:d} | Response to Request | Removed date requirement |
| seq-desc-22 | Comments on evaluation reports – {date:d} | Comments on evaluation reports | Removed date requirement |
Table 8: Removed Sequence Descriptions
| Code | Removed Sequence Description | Rationale |
|---|---|---|
| seq-desc-4 | Minutes of Meeting {date:d} | Captured under ‘Administrative update’ |
| seq-desc-14 | Risk Communication Document | Captured under ‘Administrative update’ |
| seq-desc-12 | Patent Certification | Certification in relation to patents or Notification to the Secretary that a certification under subsection 26B(1) of the Therapeutic Goods Act 1989 is not required |
Module 1 header updates
Table 9: Updated headers
| Current header | New header | Rationale |
|---|---|---|
| m1.3.1.4 Package insert | m1.3.1.3 Package insert—clean | Changed to distinguish between clean, annotated and approved package inserts |
| m1.8.2 Risk management plan | m1.8.2 Risk management plan—clean | Changed to distinguish between clean, annotated and approved RMPs. |
Table 10: New headers
| New header | Rationale |
|---|---|
| m1.3.1.5 Package insert—annotated | Sections have been divided to clearly distinguish the clean, annotated and newly added approved sections |
| m1.3.1.6 Package insert—approved | Sections have been divided to clearly distinguish the clean, annotated and newly added approved sections |
| m1.8.3 Risk management plan—annotated | Sections have been divided to clearly distinguish the clean, annotated and newly added approved sections |
| m1.8.4 Risk management plan—approved | Sections have been divided to clearly distinguish the clean, annotated and newly added approved sections |
| m1.8.5 Australian Specific Annex—clean | Australian specific versions of the EU RMP. |
| m1.8.6 Australian Specific Annex—annotated | Australian specific versions of the EU RMP. |
| m1.8.7 Australian Specific Annex—approved | Australian specific versions of the EU RMP. |
| m1.8.8 Other RMP materials | RMP materials not captured under other parts of the module |
| M6.1 Medical Device | Medical device information, including companion diagnostics and drug delivery apparatus. |
We have added M6.1 to the AU Module-1 folder structure to accommodate information relating to any medical device, apparatus or diagnostic aid associated with a combination application. The term “Medical Device” is not intended to be limiting in scope.
Changes to the Sequence Matrix
The Sequence Matrix has been amended to incorporate new sequence type and description combinations. Please refer to the Sequence Matrix for further details on updated items.
Changes to the Document Matrix
The Document Matrix has been amended to incorporate new sequence type document requirements. In addition, existing sequence types have been amended to more accurately reflect CTD document requirements. Please refer to the Document Matrix for a full overview.
eCTD validation criteria
Table 11: eCTD validation criteria description updates
| Criterion | Change Type | Change Description |
|---|---|---|
| 2.4 – File types (file extensions) check | Updated description | “All referenced files must have exactly one file extension and the extension must match one of the accepted file types. The use of other file types must be approved by the TGA prior to submission.” |
| 2.9 – Sequence folder requirements should be followed | Updated description | “Checks the sequence folder name. The rule will report a finding if the sequence seems to be the initial sequence for the eCTD application but its name is not 0000. NeeS applications progressed to new eCTD applications without a baseline sequence will always return an error due the initial sequence commencing at 0001.” |
| 2.10 – File warnings.xml must exist if sequence has priority validation warnings | New criterion | [Error] “The warnings.xml file must be present in the sequence root folder if the sequence has one or more priority validation warnings. See guidance for list of priority warnings.” |
| 2.11 – File warnings.xml should justify all priority validation warnings | New criterion | [Warning] “The warnings.xml file should include justification for each unique priority warning encountered. See guidance for list of priority warnings.” |
| 3.7 – Leaf operation attribute | Updated description | “With this criterion the following checks are performed: All leaves with an operation attribute value of new, replace or append must have a value for the cross reference (xlink:href). All leaves with an operation attribute value of delete must have no value for the cross reference (xlink:href). All leaves with an operation attribute value of replace, delete or append must have a value for modified-file. Only new operations are being used in the initial sequence of the eCTD application.” |
| 4.1.23 – Foreign regulatory status operation | Updated severity | Severity downgraded from ‘Error’ to ‘Warning’. |
| 5.3 – Content Blocks are not accepted | Updated title and description | “Use of content-block is not recommended Although content block is defined in the DTD, the specification does not refer to it; it is recommended that you do not use it.” |
| 5.5 – Study Identifier category must not be empty | Removed | |
| 6.11 – Hyperlinks with web or email destinations | Removed |
Please refer the eCTD Validation Criteria for further details on updated items.
-
Australian eCTD validation criteria v3.2 [Excel, 25.21 KB]
Expansion of allowable file type
Noting increased collaboration with CORs, and movement into a more fluid data environment where unstructured data requests may not suit .pdf and .xml format, we are expanding the allowable file types to include .txt and .doc formats. Guidance on where new file types may be utilised will be published once finalised.
Justification of validation warnings
All validation warnings must be justified when submitting a sequence. However, we no longer require explanation of the findings within the sequence cover letter. We are implementing an alternative method of justifying validation warnings which will utilise an xml file packaged within sequences, forgoing the need to amend the sequence cover letter post publication of the sequence. Guidance on how to utilise this function will be published once tested and finalised.
Work-sharing
Work sharing allows for a single sequence to be applied across multiple eCTD applications. The information provided within a work sharing transmission must relate to all eCTD applications and is utilised by other regulators to allow common documents to be applied across many eCTD applications. The TGA has considered the use of work-sharing in consultation with Industry stakeholders arriving at the conclusion that the practice has very limited utility due to our eCTD application assignment process. As a result, we do not accept work-sharing sequences.
Work-grouping
Work grouping allows multiple regulatory submissions relating to one eCTD application to be submitted as a single sequence. This format can be used when providing information for bundled minor variation submissions. We do not accept work-grouping sequence types for submissions outside the minor variation application pathway.
To prepare a work grouping sequence, the submission mode must be set to work-grouping within the XML envelope. To support good lifecycle management, we have introduced the sequence description ‘Partial Withdrawal’ {seq-desc-27} to support scenarios where part of a bundled minor variation sequence needs to be withdrawn.
Partial withdrawal of work-grouped minor variation submissions
Partial withdrawal of a bundled eCTD sequence consisting of multiple minor variation submissions is possible with Partial Withdrawal {seq-desc-27}.
Example
ABC Pharmaceuticals has submitted a bundled minor variation sequence consisting of a minor editorial change submission and a general extension of indications submission. After submitting the sequence, the sponsor decided not to progress with the generic extension of indications submission. They submit a partial withdrawal sequence to remove the information relating to it.
Example of an eCTD Application containing of a bundled minor variation partial withdrawal sequence
| Sequence | Sequence Type | Sequence Description | Related Sequence | Submission Number |
|---|---|---|---|---|
| 0000 | Baseline | Reformat | 0000 | PM |
| 0001 | Minor Variation (Cat 3) | Initial | 0001 | PM-2024-12345-1, PM-2024-67890-1 |
| 0002 | Supplementary Information | Partial Withdrawal | 0001 | PM-2024-67890-1 |
When providing the sequence, ensure:
- The sequence type is Supplementary Information {seq-type-45} and the sequence description is Partial Withdrawal {seq-desc-27}.
- Relate the sequence to the initial bundled submission sequence.
- Input the number for the submission that will be removed from evaluation as the submission number.
- Remove only the documents associated with the withdrawn minor variation by using the ‘delete’ operator and reference the leaf ID of the document.
- Remove all reference to the withdrawn variation by replacing the documents that reference the submission, excluding the cover letter.
- All removed documents are listed in the cover letter, and an assurance that no changes beyond removing references to the withdrawn variation have been made.
- All validation warnings are justified.
Example of using the delete operator to remove a document
<m1-3-1-1-pi-clean> <leaf ID="a655da252b9d34fcf22ed1fcf39b1c241" operation="delete" checksum=" b6ba67a7740d12bcb938f2850baa584e " checksum-type="md5" modified-file="../../../0044/m1/au/auregional.xml#af3c456d247f0a36e63d" xlink:type="simple"> <title>Expert Dr. C. Smith</title> </leaf>Example of using the replace operator to replace a document
<m1-3-1-2-pi-annotated> <leaf ID="aa4375bfbf4cc59173b26231705405568" operation="replace" checksum="0d68efc0fee4eb602bc03b485b17263f" checksum-type="md5" modified-file="../../../0044/m1/au/auregional.xml#ad3c456d22424a366646" xlink:href="103-med-info/1031-pi/10311-pi-clean/PI-Doc.pdf" xlink:type="simple"> <title>Expert Dr. D. Smith</title>Do not:
- Submit partial withdrawals as full withdrawals.
- Remove and re-add documents that are identical as this will affect the lifecycle.
- Provide any additional submissions or data for evaluation within this sequence (this will have to be submitted as a new sequence.)