eSubmissions in Australia Part 1 Dr John Donohoe Director, - PowerPoint PPT Presentation

eSubmissions in Australia Part 1 Dr John Donohoe Director, Knowledge Management Office of Medicines Authorisation Market Authorisation Group eCTD Workshop – Melbourne 16 December 2014

The Road to eCTD • Transition to CTD – 2004 • Implementation of NeeS – 2011 • Implementation of eCTD capability – 2014 – Revised AU Module 1 Past Activities 1 eSubmissions in Australia

eCTD at TGA • Integration of business processes – Records management, application management , evaluators – Total Lifecycle Management of products • Capacity and capability building – Support, training for internal and external staff – Updating guidance, processes, services Update on progress with the Pilot phase 2 eSubmissions in Australia

The Road to eCTD Past Activities – revised AU Module 1 • Alignment with EU – revised structure • Separate lifecycle tracking table • Moved to application form - human embryos/embryonic stem cells - GMP information - individual patient data • Used global terminology where possible e.g. changed “Overseas” to “Foreign” • Flexibility for non-prescription medicines 3 eSubmissions in Australia

The Road to eCTD • Expanded internal training programme • Lessons from pilot submissions • Alignment of existing business process • Review of consultation process • Updates to specifications and system configuration • February 2015 – Assessment of experience with, and readiness for, eCTD Current Activities and Next Steps 4 eSubmissions in Australia

The Road to eCTD Some numbers… • 1231 NeeS Submissions as of June 2014 • 1856 Approvals in 2013 for Prescription Category 1 and Category 3 Applications* • 2808 Approvals in 2013 for Over the Counter Applications* • Developing capacity to evaluate electronically • 7 eCTD submissions received in eCTD pilot * Numbers taken from the TGA Half-yearly performance reports, July to December 2013, Published May 2014 5 eSubmissions in Australia

The Road to eCTD The eCTD Pilot Phase • Working with applicants to identify suitable eCTD submissions for the pilot phase • Developing various aspects of system • Looking for a range of application types: – new chemical entity – major variations to a prescription medicine (both with and without baseline) – generic medicine – submissions prepared with different publishing tools – prescription / non-prescription medicines – master files • Please contact esubmissions@tga.gov.au if you wish to discuss being involved with the pilot phase 6 eSubmissions in Australia

The eCTD Pilot Current Business Protocol for Submitting an eCTD • Participation in pilot phase • Obtaining the eSubmission Identifier – submit written request to eSubmissions@tga.gov.au • The Cover Letter – Paper copy should be submitted until Portal is implemented • Validation Reports – Electronic copy should be submitted in e.g. “0000-validation-report” folder • Expected Structure of Submitted Media – Submit in folder named after eSubmission Identifier. – Preference is that entire application should not span multiple devices • Media Formats – flexible • Feedback on Validation of Application – TGA will inform applicants if problems are experienced during the upload of an eCTD sequence. – Confirmation of delivery is through the courier company 7 eSubmissions in Australia

eCTD Document Matrix Category 1 / Category 2 TGA eCTD Document -PI Change requiring evaluation M atrix C-Extension of indication D-New generic medicin B-New Combination A-NCE F-M ajor variation Change in patient group (not New salt or ester of existing New route of administration similar biological medicinal New chemical entity New dosage form Change of dosage active ingredient New strength decrease) product J Section Section Title 1.0 Correspondence 1.0.1 Cover letter E E E E E E E E E E E E 1.0.2 Lifecycle management tracking table E E E E E E E E E E E E 1.0.3 Response to request for information NE NE NE NE NE NE NE NE NE NE NE NE 1.2 Administrative Information 1.2.1 Application form E E E E E E E E E E E E 1.2.2 Pre-submission details E E E E E E E E E E E P 1.2.3 Patent certification P P P P P P P P P P P NE 1.2.4 Change of sponsor NE NE NE NE NE NE NE NE NE NE NE NE 1.3 Medicine information and labelling 1.3.1 Product information and package insert 1.3.1.1 Product information - clean E E E E E E E E E E E E 1.3.1.2 Product information - annotated P P E P E E E E E E E E 1.3.1.3 Package insert P P P P P P P P P P P P 1.3.2 Consumer medicines information 1.3.2.1 Consumer medicines information - clean E E E E E E E E E E E P 1.3.2.2 Consumer medicines information - annotated P P E P E E E E E E E P 1.3.3 Label mock-ups and specimens E E E E NE E E E E P P NE 1.4 Information about the experts 1.4.1 Quality E E E E P E P P P P P P 1.4.2 Nonclinical E E E E P P P P P P P P 1.4.3 Clinical E E E E P W P P P P P P 1.5 S pecific requirements for different types of applications 1.5.1 Literature-based submission documents P P P P P P P P P P P P 1.5.2 Orphan drug designation P P P P P P P P P P P NE 1.5.3 Genetically modified organisms consents P P P P P P P P P P P NE 8 eSubmissions in Australia

Building Regulatory Activities and Submission Numbering Regulatory Activity The entire group of sequences supporting a specific regulatory activity Identified/established by the submission type e.g., an original application and all its amendments leading to approval Sequence-number Must be unique within the application Incremented for each new submission to an application eSubmissions in Australia 9

eCTD: General Information & Advice • Once an eCTD always an eCTD means don’t send non-eCTD or paper to an eCTD application • Don’t send files outside the eCTD sequence folder • Don’t send files that are not referenced in the correct, appropriate eCTD backbone (index.xml, au-regional.xml) • Develop checklists to ensure the submission is complete 10 eSubmissions in Australia

Always Check Your Submission • Quality check (QC) your submission prior to submitting it • Use checklists and establish a good, efficient QC process • Ensure the media contains the submission • Ensure no files are truncated • Check submission using a validation tool eSubmissions in Australia 11

eCTD Validation • Use an eCTD Validator to identify technical problems with your submission BEFORE sending it to TGA • Do not ignore errors • High error content will result in the rejection of your submission – lost time and $ • Current eCTD Validation Specifications are available on the TGA eCTD webpages 12 eSubmissions in Australia

Rejections Submissions that are technically deficient or otherwise cannot be processed: • Cannot determine the correct application number/type • High level of validation errors • Duplicate eCTD sequence numbers • Non-allowed file types eg .exe eSubmissions in Australia 13

Font embedding • The intent is to ensure evaluator can access all the information in your submission • Use the “standard fonts” and there is no need to embed, these fonts are always available on the evaluator’s PCs • If you use “non-standard fonts” you should fully embed the font. 14 eSubmissions in Australia

PDF Errors • Create text-based PDFs from source documents • Avoid scanning documents or embedding scanned documents • Use validated OCR if you must scan a document – Use only standard fonts – Fully embed all non-standard fonts if used • Initial View Settings – Set the Navigation Tab to open to “Bookmarks Panel and Page.” If there are no bookmarks, set the Navigation Tab to “Page Only.” Page Layout and Magnification should be set to “Default.” 15 eSubmissions in Australia

PDF Errors • Navigation – Provide bookmarks and a hyperlinked TOC – Use hypertext links throughout the body of the document to link to: § supporting annotations § related sections § references § appendices § tables, or § figures that are not located on the same page as the narrative text. 16 eSubmissions in Australia

Improving PDF Documents • Include page numbers • Include document date • Avoid use of scanned documents: – Limits ability to text search – Can copy only as a ‘graphic’ • Hypertext links: Within a document and between documents in an application – May be challenge to create, QC and maintain, but – Very useful to the evaluator e.g., Links to Pharm/Tox studies for qualification of impurities in Module 4 17 eSubmissions in Australia