The presentation was given by the TGA at the 2014 ARCS Scientific Congress, and covers the requirements, format and problems encountered with OTC dossiers

1. General dossier requirements for OTC medicines
Kevin Eager
OTC Medicines Evaluation, Market Authorisation Group,
Office of Medicines Authorisation, TGA
ARCS Scientific Congress 2014
11 September 2014

2. 1
Overview
• Requirements for an OTC dossier
– general dossier requirements
– format of an electronic dossier
• Problems encountered with OTC dossiers
General dossier requirements for OTC medicines

3. General dossier requirements
General dossier requirements for OTC medicines 2

4. General dossier requirements
General requirements
• Language
– English
• Common Technical Document format - CTD
• Electronic
General dossier requirements for OTC medicines 3

5. General dossier requirements
CTD format
• CTD format:
– required for OTC dossiers since September 2013
• CTD format prescribes:
– the organisation of the dossier across 5 modules
– the order in which documents must appear so they are grouped logically and can be easily located
General dossier requirements for OTC medicines 4

6. General dossier requirements
CTD format
• Under the CTD format:
– each application is a collection of documents broken into one or more of 5 modules
– actual content of a dossier is dependent on the application level
– format of Modules 2, 3, 4, and 5 is described in the CTD guidelines
– format of Module 1 (for OTC applications) is to be described in an OTC CTD Module 1
General dossier requirements for OTC medicines 5

7. General dossier requirements
CTD format
Module Descriptor
Table of contents
1.0.1 Cover letter (letter of application)
1.0.3 Response to request for information
(including screening questions)
1.2.3 Patent certification
1.3.1
1.3.1.1
1.3.1.2
1.3.1.3
Product Information and package insert
Product information – clean
Product information – annotated
Package insert
1.3.2
1.3.2.1
1.3.2.2
Consumer medicine information
Consumer medicine information – clean
Consumer medicine information -
annotated
1.3.3 Label mock-ups and specimens
1.4
1.4.1
1.4.2
1.4.3
Information about the experts
Quality
Nonclinical
Clinical
6
• Modular structure aligned with Prescription Medicines
eCTD structure
• Changes from current OTC module 1 structure
– table of contents was 1.1
– no application form – was 1.2.1
– label mock-ups at 1.3.3 – was 1.3.4
General dossier requirements for OTC medicines

8. General dossier requirements
CTD format
Module Descriptor
1.5 Specific requirements for different types of
applications
1.5.1 Literature-based submission documents
1.5.5 Co-marketed medicine declarations (letters of
authorisation)
1.5.7 OTC medicine assurances
1.5.8 Analytical validation summary
1.6
1.6.1
1.6.2
1.6.3
1.6.4
Master files and certificates of suitability
Relevant external sources
Applicant’s declaration
Letters of access
Certificates of suitability
1.9
1.9.1
1.9.2
Summary of biopharmaceutic studies
Summary of bioavailability or bioequivalence
study
Justification for not providing biopharmaceutic
studies
1.11
1.11.1
1.11.2
1.11.3
1.11.4
Foreign regulatory information
Foreign regulatory status
Foreign product information
Data similarities and differences
Foreign evaluation reports
7
• Changes from current OTC module 1 structure
– removal of quality related aspects of N1 & N2
applications
 now in Module 3 (if required)
– inclusion of OTC specific
 1.5.7 - assurances
 1.5.8 - validation summary
– removal of 1.7 - GMP
General dossier requirements for OTC medicines

9. Format of an electronic dossier
General dossier requirements for OTC medicines 8

10. Format of an electronic dossier
Ideal format:
• Electronic Common Technical Document – eCTD
• Not a requirement
Can also use:
• Non-eCTD electronic Submission – NeeS
• Not a requirement
Minimum requirement
• Compliance with TGA guideline – Guidelines on electronic OTC dossiers
General dossier requirements for OTC medicines 9

11. Format of an electronic dossier
Key aspects of compiling a workable dossier
1. Organising the dossier using folders
2. Having a comprehensive table of contents
3. Using meaningful file names
4. Text searchable
5. Appropriate use of bookmarks
6. Security
7. Uploading the dossier
General dossier requirements for OTC medicines 10

12. Format of an electronic dossier
1. Organising the dossier using folders
Documents must be organised within folders that correspond to the CTD modules appropriate to the
application.
Example 1
C2 application
to change
labelling
General dossier requirements for OTC medicines 11

13. Format of an electronic dossier
Example 2
N3 application
General dossier requirements for OTC medicines 12

14. Format of an electronic dossier
2. Table of contents
– Located in the top level folder
– Will have hyperlinks that navigate
to the individual documents in the dossier
General dossier requirements for OTC medicines 13

15. Format of an electronic dossier
3. File names
• Follow ICH conventions
– not prescriptive
• Should be meaningful and indicative of the
position of the document within the CTD
structure
General dossier requirements for OTC medicines 14

16. Format of an electronic dossier
Key aspects of compiling a workable dossier ….. continued
4. Text searchable content
– with limited exceptions, the documents should be text searchable
– expect PDF documents to have been generated from electronic source documents
5. Bookmarks and hypertext links
– appropriate use can greatly enhance navigation through a dossier
General dossier requirements for OTC medicines 15

17. Format of an electronic dossier
Key aspects of compiling a workable dossier ….. continued
6. Security on files
– Dossier must not contain security settings
7. Uploading the dossier through eBS
– preference is for the entire dossier to be ‘zipped’
– maximum individual file size for upload – 100MB
General dossier requirements for OTC medicines 16

18. Problems encountered with OTC dossiers
General dossier requirements for OTC medicines 17

19. Problems encountered with OTC dossiers
Main impediments to a workable dossier
1. File naming - not meaningful
2. Not separating the dossier into the modular CTD structure
3. Lack of bookmarking
General dossier requirements for OTC medicines 18

20. Problems encountered with OTC dossiers
File naming - not meaningful
N1 application
• naming of files is not particularly helpful
• some reference to CTD structure
General dossier requirements for OTC medicines 19

21. Problems encountered with OTC dossiers
General dossier requirements for OTC medicines 20

22. Problems encountered with OTC dossiers
Not separating the dossier into the modular CTD structure
N4 application
– a single pdf
– ~200 pages
– comprised of Modules 1, 2, 3 & 5
General dossier requirements for OTC medicines 21

23. Problems encountered with OTC dossiers
On the positive side:
– the pdf was well bookmarked
General dossier requirements for OTC medicines 22

24. Problems encountered with OTC dossiers
23
Lack of bookmarking can hinder the evaluation process
C1 application
• a single document: >70 pages
• not broken into the CTD modules
 included M1 & M3
• not appropriately named
• not text searchable
• no bookmarking at all
General dossier requirements for OTC medicines

25. Problems encountered with OTC dossiers
24
Bookmarking: use where it helps with navigation
C1 application
• a simple change application
• broken into the CTD modules
• clearly named
• text searchable
• no bookmarking – not required in this instance
General dossier requirements for OTC medicines

26. Summary
General dossier requirements for OTC medicines 25

27. Summary
1. Provide dossiers in eCTD or NeeS format where possible
– not a requirement
2. Dossiers to comply with the Guidelines on electronic OTC dossiers
3. To have workable dossiers for all applications
– modular CTD structure
– naming of documents
– bookmarks
– text searchable
General dossier requirements for OTC medicines 26

28. Thank you
General dossier requirements for OTC medicines 27