This presentation provides an update on the progress of eCTD in Australia.

1. eCTD in Australia and Experience in the Pilot Programme
Update on the latest Australian eCTD specification
Dr John Donohoe
Medicines Authorisation Branch
Market Authorisation Division, TGA
ARCS Scientific Congress 2015
6 May 2015

2. Implementing eCTD
Overview
• Late 2014 the TGA commenced a pilot of eCTD format submissions using Version 0.9 of the Australian
eCTD Module 1 and Regional Specification to validate, review and process electronic applications.
• April 2015 TGA published the final version of the Australian eCTD specifications: Australian eCTD
specification: Module 1 and regional information, Version 3.0.
• Regulatory submission publishing software packages can now incorporate AU eCTD specifications.
• Key dates
 Submissions in version 3.0 will be valid from 1 June 2015 onwards
 Submissions in version 0.9 will not be valid after 31 December 2015
 From 1 January 2016 you must use version 3.0 for your eCTD submissions
eCTD in Australia and Experience in the Pilot Programme 1

3. What happens to your submission when it arrives at TGA? (I)
1. TGA Records Management team checks if your eCTD submission meets the validation criteria
• It meets the validation criteria
− The submission goes to the relevant TGA business unit who will schedule and manage the registration
process
− Reduces administration effort
− Improves the quality of the dossier
− Checks completeness of the submission
• It does not meet the validation criteria
− TGA Records Management team checks why the submission has failed validation. Depending on the type
of errors and warnings, we either progress the submission to the relevant business unit or send it back to
you to address the validation issues
• We recommend you validate your submission with validation software prior to sending it to the TGA.
(See www.tga.gov.au for software suggestions)
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4. What happens to your submission when it arrives at TGA? (II)
2. An evaluator navigates your electronic dossier using hyperlinks and bookmarks within the docuBridge®
review tool:
• It is therefore vitally important that you manage the granularity of the application and maintain your
hyperlinks and bookmarks
Advantages for Sponsor and the TGA:
• More searchable than paper
• Eliminates storage and distribution of paper
• Provides lifecycle management
• Locating, navigating and evaluating submissions is easier
• Provides a collaborative environment for evaluators
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5. Reviewing an electronic dossier – Realities (I)
Tips to avoid common problems (PDFs)
Following these tips makes it easier for evaluators… and therefore you!
• Optimise your PDF documents
– Too many small documents?
• Combine one and two page documents into a single document in an eCTD section
• Provide a linked TOC (table of contents) with bookmarks
– Ensure changes in files are always apparent
– Make your PDF documents ‘text searchable’
– Generate your PDF documents from electronic source documents
– Scanned documents will limit the ability to text search because it copies the document as a graphic
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6. Reviewing an electronic dossier – Realities (II)
Tips to avoid common problems (leaf titles)
Following these tips makes it easier for evaluators… and therefore you!
• Better leaf titles
– Avoid excessively long leaf titles
– Ensure leaf titles are unique
– Make your leaf title concise, meaningful and related to the file content
• If your leaf title reflects the document’s content someone unfamiliar with the submission should be
able to understand the document content.
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7. Reviewing an electronic dossier – Realities (III)
Tips to avoid common problems (operator attributes)
Following these tips makes it easier for evaluators… and therefore you!
• Use the correct eCTD operator attributes.
Example:
– Failure to apply the ‘Replace’ operator will result in multiple versions of the same document.
– This causes confusion for the evaluator:
• Is there only one current version?
• Why there are multiple current versions?
• Will the leaf title tell me anything?
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8. eSubmission Identifier
You will need an eSubmission Identifier
The eSubmission Identifier is fundamental for the lifecycle management of your product
• The eSubmission Identifier is unique for a sponsor / active ingredient
– Six digits plus a letter e.g. e123456 or n765432
 ‘n’ for NeeS
 ‘e’ for eCTD
• Remains valid throughout entire lifecycle of product
• To obtain one, send an email to esubmissions@tga.gov.au with:
– Applicant’s name
– Name of medicine or subject of Master File
– Description of the Application (application type, dosage form) if a medicine
– Name and address of manufacturing site if a Master File.
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9. Module 1.0.2: Lifecycle management tracking
table
Sequence Sequence Type Sequence Description
Related
Sequence
0000 Baseline Reformat 0000
0001 C-Extension of Indication of COPD Initial 0001
0002 Supplementary information
Response to Request for
Information
0001
0003
H-Minor Variation, Not Resulting in a New
Register Entry
Initial 0003
0004 F-Major Variation—New Strength Initial 0004
• All sequences must contain an updated table:
– Omission will cause a validation error (for an eCTD submission)
– Its use is recommended for NeeS
• Use Defined lists for Sequence type and Sequence description
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10. Hyperlinks and bookmarks (I)
Be consistent using hyperlinks and bookmarks
Following these tips makes it easier for evaluators… and therefore you!
• Their use should be well thought out:
– be used throughout a submission
– be used in all tables, figures, publications, and appendices from the table of contents
– be indicated typographically with blue text or a blue box around the text
– This will aid the evaluator to efficiently navigate to annotations, related sections, publications, appendices,
tables, and figures not located on the same page.
• Overuse can lengthen the evaluation process because it can create confusion for evaluators.
• Underuse can lengthen the evaluation process because the evaluator will need to search and find the
relevant information or may find the wrong information.
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11. Hyperlinks and bookmarks (II)
External Links
Following these tips makes it easier for evaluators… and therefore you!
• Links to external destinations (not web or email) will result in a validation error
• Links to web or email destinations are retrieved for information at validation
– Some links to a web page "www.*****" (such as sponsors own websites) or e-mail addresses "*****@****"
are acceptable for some labelling documents and literature references
• External links to information pertinent to the evaluation process need to be submitted
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12. Hyperlinks and bookmarks (III)
Following these tips makes it easier for evaluators… and therefore you!
• TGA does not routinely require the submission of individual patient data
• We do require complete study reports
– The ICH guideline on the Structure and Content of Clinical Study Reports describes several appendices
that “where permitted by the regulatory authority, some of the following appendices need not be submitted
with the report but need to be provided only on request.”
• Appendices 16.1 – 16.3 should routinely be submitted
– 16.1 Study information
– 16.2 Patient data listings
– 16.3 Case report forms
– 16.4 Individual patient data listings.
• If dossiers have been previously submitted to other agencies and appendices have been added or deleted to
the TGA version, sponsors must ensure that hyperlinks in the dossier to these appendices have also been
added or deleted.
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13. Hyperlinks and bookmarks (IV)
Following these tips makes it easier for evaluators… and therefore you!
Considerations
• Does the bookmark name indicate the bookmark’s destination/content?
• Is the bookmark too long?
• Are bookmarks provided for the TOC items?
• Does the bookmark match the description/title showing on the TOC?
• Will someone who is unfamiliar with the application know what content they’ll see before they click on the
bookmark?
• Are bookmarks set to Inherit Zoom?
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14. Key technical highlights v3.0
• Baseline sequence
• Change of sponsor
• Pre-Advisory Committee Response
• Regulatory Activity is Rejected or Withdrawn
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15. Baseline sequence
Sequence type = Baseline
Sequence description = Reformat
• Is a resubmission of currently valid documents already provided in another format
• Always a separate sequence
• Never includes new regulatory activities
• Sponsor must verify:
– formatting is the only change to the previous dossier(s)
– no amendments to content
– all the information was in the previous version(s) of the dossier
– any omissions do not cause the content to be misleading.
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16. Change of sponsor – what to do (I)
Sponsor F
e000111
Sponsor P
e000222
Sponsor Y
e000333
Activity/Task
Product A; Product B;
Product C; Product D
0001 Application for Products A, B, C and D from Sponsor F
0002 A regulatory activity or notification
Product A; Product B Product C; Product D
0003
Sponsor P submits first sequence as 0003 referencing
the transfer from e000111 and submitting a regulatory
activity.
0003 0004 Sponsors F and P undertake business as usual
Product C Product D
0005 Sponsor Y submits first sequence as 0005 referencing
e000222
0004 0005 0006 Sponsors F, P and Y undertake business as usual
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17. Change of sponsor – what to do (II)
Sequence type: Change of Sponsor
Sequence description: Initial
• Module 1.2.4 Change of sponsor
– a copy of the form Notification: Transfer of Sponsorship following transfer/assignment of business or
interest in therapeutic goods
– a letter from the original sponsor confirming access to all previously submitted data OR the original
sponsor and the new sponsor must complete the Co-marketed medicines declarations (Module 1.5.5).
• Module 1.3.1.1 Product information – clean
• Module 1.3.1.2 Product information – annotated
• Module 1.3.1.3 Package insert
• Module 1.3.2.1:Consumer medicines information – clean
• Module 1.3.2.1:Consumer medicines information – annotated
• Module 1.3.3 Label mock-ups and specimens
• Module 1.6.3 Letters of access (from DMF, PMF and CEP holders)
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18. Cross referencing
• <m1-4-3-clinical>
<leaf ID="N3774598bcdd74d5891d954542c552eee" operation="new" xlink:href=
"../../../../e000111/0000/m1/au/104-expert/1043-clinical/dr-a-jones.pdf" checksum=
"b6ba67a7740d12bcb938f2850baa584e" checksum-type="MD5">
<title>Expert Dr. A. Jones</title>
</leaf>
<leaf ID="N3ad8bf59e3fd4cb5bbd4f82b31350887" operation="new" xlink:href=
"104-expert/1043-clinical/dr-b-schmidt.pdf" checksum="bf30251122458c7c5c17dc3ed0002c1e"
checksum-type="MD5">
<title>Expert Dr. B. Schmidt</title>
</leaf>
<leaf ID="Ne0eeb59ae2f74ba5832965154db4cc13" operation="new" xlink:href=
"104-expert/1043-clinical/dr-c-smith.pdf" checksum="f1e209870c05f15eef24f4b2e1e74a0f" checksum-type="MD5">
<title>Expert Dr. C. Smith</title>
</leaf>
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19. Pre-Advisory Committee response (I)
A3 Pre-ACPM covering letter eCTD
A3a Sponsor’s comment on evaluations (remaining
issues).
Module 1.0.3 Response to request for information
A3b International regulatory history Module 1.11.1 Foreign regulatory status
A3c Adverse reactions update Module 1.0.3 Response to request for information
A3d Sponsor’s comments on PI Module 1.0.3 Response to request for information
A3e Sponsor’s comments on foreign PI Module 1.0.3 Response to request for information
A3f PSUR Module 5.3.6 Reports of Post-Marketing Experience
A3g, A3h etc Other documents Module 1.0.3 Response to request for information
C1 PI (annotated and non-annotated) Module 1.3.1.1 Product information - clean
Module 1.3.1.2 Product information – annotated
C1a CMI (annotated and non-annotated) Module 1.3.2.1 Consumer medicines information – clean
Module 1.3.2.2 Consumer medicines information - annotated
C2 European SmPC (including UK or Swiss) Module 1.11.2 Foreign product information
C2a US Prescribing Information Module 1.11.2 Foreign product information
C2b Canadian Monograph Module 1.11.2 Foreign product information
C2c New Zealand Product Information Module 1.11.2 Foreign product information
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20. Pre-Advisory Committee response (II)
Sequence type: A - NCE New Chemical Entity
Sequence description: Pre-Advisory Committee response
Sequence elements:
Module 1.0.1 Cover letter
Module 1.0.2 Lifecycle management tracking table
Module 1.0.3 Response to request for information
Module 1.3.1 Product information
Module 1.3.2 Consumer medicines information
Module 1.11.1 Foreign regulatory status
Module 1.11.2 Foreign product information
Module 5.3.6 Reports of Post-Marketing Experience
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21. Submission is rejected or withdrawn (I)
• If a complete submission is withdrawn or rejected,
– You should submit a consolidation sequence to remove the scientific and regulatory content from the
current view.
Example:
Sequence type = A - NCE New Chemical Entity
Sequence description = Withdrawal
• Not all of the content submitted in the rejected or withdrawn submission should be removed :
– Certain administrative, scientific or regulatory information may be used in future submissions (e.g. a
clinical study report for a rejected new indication will still contribute data about clinical safety in future
submissions)
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22. Submission is rejected or withdrawn (II)
• Module 1
– The original cover letter, lifecycle management tracking table and application form should not be removed
from the current view.
– All other documents should be removed.
– Particular care should be taken to remove from the current view the versions of any labelling documents
associated with the rejected or withdrawn regulatory activity.
• Module 2
– All summary documents should be removed from the current view.
• Module 3
– All content files associated with the rejected or withdrawn regulatory activity should be removed from the
current view so that only the previously approved/submitted content remains in the current view.
• Modules 4 and 5
– Content should not be removed from the current view unless the TGA specifically requests you to do so.
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23. Submission is rejected or withdrawn (III)
• Removal of documents associated with a rejected or withdrawn regulatory activity may be achieved in the
following manner:
– Any leafs (associated only with the rejected or withdrawn regulatory activity) where content was submitted
for the first time in this section, should be updated with a “delete” operation leaf.
– Any leafs (associated only with the rejected or withdrawn regulatory activity) where content was submitted
for a second or subsequent time in this section, should be updated with a “replace” operation leaf that
points the content back to the version of the leaf used prior to the submission of the rejected or withdrawn
regulatory activity.
– Any leafs (associated with the rejected or withdrawn regulatory activity) but with content also shared with
other approved regulatory activities should be updated with a “replace” operation leaf that points to a new
content file that contains only the approved content.
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24. Questions?
Please email any questions to
esubmissions@tga.gov.au
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