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Electronic submissions New specifications experiences and challenges Emma Richards Assistant Director Business Systems Review and Reporting Section Prescription Medicines Authorisation Branch, TGA ARCS Conference 2018 21 August 2018

Electronic submissions New specifications experiences and challenges Emma Richards Assistant Director Business Systems Review and Reporting Section Prescription Medicines Authorisation Branch, TGA ARCS Conference 2018 21 August 2018

Presentation Overview • The road to now – Key Milestones • Focus on the eCTD XML envelope – Why it is important – What has changed as part of the specification update • Validation criteria – Common errors and how to overcome these • The road to the future 2

Key Milestones The road to now 2004 2011 2015 Transitioned Implemented Implemented eCTD to CTD NeeS 3

Implementation The road to now - specifications and validation criteria Late 2014 April 2015 January 2018 • eCTD pilot • Version 3.0 • NeeS envelope Regional • NeeS validation • Version 3.1 Specifications & Regional • Version 0.9 Validation criteria Specifications & Regional Validation criteria Specifications & Validation criteria 4

Current Status Some numbers • Currently over 4000 dossiers (e-IDs) within our system • In 2017 alone: – ~1200 new dossiers – ~4000 submissions – ~7000 sequences *2018 data until 30 April 2018 5

Prescription medicine applications eCTD Uptake by Application Type % eCTD 2017 % eCTD 2018 100% 100% 80% 80% 60% 60% 40% 40% 20% 20% 0% 0% Combination Generic EOI Major Variation involving data Minor Variations 9D Changes Trade name PSUR / RMP Master Files New Entity / Change to PI *2018 data until 30 April 2018 6

Why consider eCTD - Benefits SPONSORS REGULATOR Access to expedited Enhanced validation pathways Internationally Internationally standardised format standardised format Lifecycle management Lifecycle management 7

Updates January/July 2018 – introducing version 3.1 Updated specifications and validation criteria • Last update 2015 • MMDR • Greater knowledge / understanding • Automation • File downloads – react fast! 8

Requirements - eCTD • eCTD Version 3.1 File downloads • Checksums • Australian eCTD regional specification and validation criteria version 3.1 excel spreadsheets 9

Requirements - NeeS • NeeS Version 2.0 File downloads and checksum • NeeS envelope form • Relevant eCTD Version 3.1 file downloads • Australian eCTD regional specification and validation criteria version 3.1 excel spreadsheets

Focus on the eCTD XML Envelope 11

Version 3.1 XML Elements XML Element Description Constraint Occurrence Defined List esub-id e-Identifier Mandatory Single client-id eBS Client ID Mandatory Single Australian AAN Mandatory Multiple Approved Name(s) product-name Trade Name(s) Mandatory Multiple ARTG artg-number Optional Multiple Number(s) Key points: • The XML envelope is the key part of the eCTD specification • Provide a separate element for each entry when submitting multiple values 12

Version 3.1 XML Elements XML Element Description Constraint Occurrence Defined List Submission or submission- Mandatory Multiple Application number Number(s) sequence- Sequence Mandatory Single number Number related- Related sequence- Sequence Mandatory Single number Number Key points: • Include the full submission number/application number • Sequence numbers must be in chronological order 13

Version 3.1 XML Elements XML Element Description Constraint Occurrence Defined List Regulatory reg-activity-lead Mandatory Single Yes Activity Lead Defined List • File downloads maintained by the TGA • Contain a standard set of codes for the corresponding envelope element 14

Version 3.1 XML Elements XML Element Description Constraint Occurrence Defined List sequence- Sequence Mandatory Single Yes description Description sequence-type Sequence Type Mandatory Multiple* Yes email Contact Email Mandatory Multiple 15

Version 3.1 XML Elements XML Element Description Constraint Occurrence Defined List submission- Submissions Mandatory Single Yes mode mode Work Grouping Work Sharing Change 2 Change 1 Change Change 1 3 Product A Product B Product C Product A Multiple changes for one product One change for multiple products 16

Changing Envelope Data • To remove a trade name / ARTG number: – Sequence Type – Undefined Regulatory Activity (seq-type-52) – Sequence Description – Uncategorised {tradename removal} (seq-desc-24) – In the cover letter indicate which trade name/s and/or ARTG number/s are being maintained or removed • DO use the operation Delete to remove the ARTG number 17

Withdrawals • Use the withdrawal function to…. ‒ Withdraw an entire product lifecycle history (eID)  Sequence type – Product Withdrawal (seq-type-57)  Sequence description – Withdrawal (seq-desc-23) ‒ Withdraw a regulatory activity (submission)  Sequence type – Initial sequence type i.e. C – Extension of Indication  Sequence description – Withdrawal (seq-desc-23) • DO NOT use withdrawal to remove a trade name or ARTG number (to change envelope data) 18

Provisional Registrations • Initial application – Sequence type (type of application i.e. NCE) – Sequence description - Initial (seq-desc-2) – S31 responses as per normal process • Extension of provisional registration – Sequence type - Extension of provisional registration (seq-type-61) – Sequence description - Initial (seq-desc-2) • Provision of additional clinical data – Sequence type - Supplementary information (seq-type-45) – Sequence description - Provisional approval – rolling data submission – {date: d} (seq-desc-26) 19

Validating sequences • Recommend validation prior to submitting to TGA • Validation errors result in delay Review • Good document management practices are important!! – Currently too many instances of poor document management practices are being seen Validate Publish TIPS:  DO ensure that all documents within the sequence are closed prior to finalisation and validation  DO ensure that the dossier is structured with the e-ID as the root folder when compressed  DO NOT make changes to previous sequences 20

Importance of validation • TGA data demonstrates that the administrative burden of submission acceptance for eCTD is greatly reduced when compared to NeeS • A well-structured eCTD dossier can streamline the administrative processing and evaluation May 2018 Pass Fail Total eCTD 482 10 492 NeeS 284 107 391 21

NeeS Validation Error In general: • Wide range of validation errors occur for NeeS • Multiple reasons and fixes for these errors • Difficult to manually meet all validation requirements Top cause of validation errors in NeeS is: Criterion 1.6 - Expected hyperlinks are present and functioning in Module TOC files • Hyperlink errors may be attributed to the link properties in the PDF files. This can be resolved by changing the type of action within the Link Properties menu. 22

eCTD Validation Errors Criterion 4.2.10 – Envelope: submission-number • If there is content in M5.3.6 or M1.8 you MUST include ‘PV’ • Example – Criterion 2.3 – Unreferenced files are not allowed • This is often caused by the inclusion of ‘thumbs.db’ files • Can be resolved by ‘un-hiding’ hidden/system files and locating and then deleting Criterion 4.2.9 - Envelope: Sequence type vs. Sequence Description • Make sure the pairing is appropriate by checking eCTD Sequence Matrix File Download Criterion 4.1.8 – Modified file existence • Be careful when making last minute changes 23

The road to the Future AU Regional specification update Update guidance New guidance Dossier Portal Greater collaboration with software vendors SME assist Working groups Transition to eCTD Greater collaboration with industry eCTD version 4.0 Internal dossier management system updates Greater collaboration with CORs Further automation of the dossier receipt system 24

Electronic Submissions and Data Review Webpage New Electronic submission hub https://www.tga.gov.au/electronic-submissions-and-data-review. 25

How to contact us • Submission of dossier via eSubmissions@health.gov.au • General dossier questions via eSubmissions@health.gov.au • Questions and feedback on specifications or electronic submission reform activities via edr@health.gov.au 26