This presentation will describe how the TGA undertakes the screening process and will discuss the mandatory requirements for applications, including specific examples of problems commonly encountered.

1. Overcoming the stress of non-prescription medicine
application screening
Over-the-counter (OTC) medicines
Dr Sven Johanson
Senior Evaluator
OTC Medicines Evaluation Section, Complementary & OTC Medicines Branch, TGA
ARCS Annual Conference
21 August 2018

2. Overview
• Why do we screen applications?
• Legislative requirements for passing screening
• Information and formatting requirements
• Mandatory requirements for an effective over-the-counter medicines
application
• Outcomes of screening and screening questions
• Examples of deficiencies resulting in not-effective (‘refused’)
applications
• Change applications and cover letters

3. Application screening (‘preliminary assessment’)
Why do we screen applications?
• To ensure that they are ready for evaluation
Screened to ensure that they are:
‒ At the correct application level
‒ Accompanied by correct / complete data set
‒ Correctly formatted (CTD format)
• Legislative requirement (s.23B(1) of the Therapeutic Goods Act)

4. Legislative requirements for passing screening
Section 23B of the Therapeutic Goods Act sets out requirements for
passing ‘preliminary assessment’ (screening).
• These include:
‒ must be on correct application form
‒ must be accompanied by specific information in a specific format
‒ For ‘restricted medicines’, must include product information in the
approved form
‒ Application fee must be paid

5. Information and formatting requirements
• Applications must be consistent with the following documents:
‒ Common Technical Document Module 1: OTC medicines
‒ Mandatory requirements for an effective over-the-counter
medicines application
‒ General dossier requirements
‒ Relevant guidelines applicable to OTC medicines, as cited in the
above documents
• For ‘restricted medicines’, must include product information in the
approved form

6. Australian regulatory guidelines for OTC medicines (ARGOM) landing page
Has links to the documents specifying dossier requirements

7. Mandatory requirements for an effective over-the-counter
medicines application
Comprises:
• Mandatory requirements
• Appendix A - Specific technical data requirements
‒ Details the mandatory requirements with respect to the different
application levels / properties
‒ Set out in CTD format

8. Mandatory requirements for an effective over-the-counter medicines application

9. Mandatory requirements for an effective over-the-counter medicines application
Appendix A - Module 5
• 3 separate tables covering:
– General application requirements
– N4 application requirements
– N5 and C4 application requirements

10. Mandatory requirements for an effective over-the-counter medicines application

11. Outcomes of screening
 Passes Advised of acceptance for evaluation
 Refused Notice given that has not passed preliminary assessment
? Screening
questions
Sponsor requested to address minor deficiencies
(within 5 working days)

12. Screening questions
• Opportunity to make minor corrections
– 5 working days permitted for response
• Examples of typical screening questions / issues:
– Request for letter of authorisation from another sponsor to access data on file
– Request for confirmation that stability data were generated using test methods
as described and validated in sub-module 3.2.P.5
– Request for any other documentation accidently omitted
– Clarification of the nature / scope of the application
– General administrative / housekeeping issues (e.g. GMP clearance expiry)

13. Examples of deficiencies resulting in refused applications
Bioequivalence / therapeutic equivalence data
 Absence of data demonstrating bioequivalence with the ‘originator’ product (when
required)
 Inadequate justification for not providing a bioequivalence study report
– Justifications need to address all points as specified in both:
 Guidance 15: Biopharmaceutical studies
 Appendix III of the European Union (EU) Guideline on the investigation of
bioequivalence
 Use of a foreign reference product in therapeutic equivalence or BE studies, rather than
the Australian ‘originator’ product
‒ For use of a foreign reference product in BE study, you must demonstrate that it is
identical to the Australian reference (Guidance 15: Biopharmaceutical studies).

14. Examples of deficiencies resulting in refused applications (cont)
Non-generics submitted as generics
 Proposed ’generic’ is not eligible for consideration because the originator
medicine has not been fully evaluated. Application should be submitted at N5
level with appropriate data
– ARGOM requires ‘originator’ medicine to have been approved for marketing in
Australia on the basis of a full dossier
 Proposed generic is actually novel quantitative combination of active
ingredients. Application should be submitted at the N5 level with appropriate
data

15. Examples of deficiencies resulting in refused applications (cont)
 Absence of other clinical / efficacy data – e.g. for antiseptic products or in
relation to ‘fast’ claim in product name
Literature based submissions (LBS)
 Searches not conducted and/or data not presented in accordance with LBS
requirements; or does not cover all relevant aspects of efficacy or safety
– Must be in accordance with TGA guidance Literature based submissions
– Requires Module 2

16. Examples of deficiencies resulting in refused applications (cont)
Umbrella branding extensions
 Umbrella branding assessment is incomplete or missing
– Refer to Application route for umbrella branded medicines to determine if
assessment is required
– If required, assessment must address each of the points identified in the
ARGOM Appendix 3 guideline 2.2 ‘Umbrella’/family brand names:
 association, differentiation, safety, efficacy, other information
– Requirement for assessment is specified in Common Technical Document
Module 1: OTC Medicines under sub-module 1.5.8

17. Examples of deficiencies resulting in refused applications (cont)
Module 3 deficiencies
 Antimicrobial preservative efficacy testing (PET) data not provided
– Required for multi-dose liquids and aqueous semi-solid medicines
 Antimicrobial preservative content testing not included in stability studies
 Stability data not consistent with other requirements – eg. absence of data under
accelerated storage conditions
 Absence of analytical method validation data

18. Change applications
• Screened to ensure correct application level, data, and format.
• Also screened to ensure:
– Appropriate change types selected in the application form
– Appropriate changes made to the product details in the application form
• Changes outside the scope of the chosen application level will not be accepted

19. Cover letters
Need to be consistent with the guidance Preparing an OTC application cover letter.
They should:
• Outline the nature and scope of the application
• Provide a brief rationale for the application level
• Note any justifications being provided for non-compliance with guidelines
• Include request for PBS equivalence statement, if applicable
• Provide relevant background information
– eg. outline any relevant relationships with existing medicines or related
applications
• Information regarding fees (reduction/waiver requests)

20. Cover letter – change applications
• Consider including a table as follows:
• If relevant, include in your cover letter, reference to:
– previous same/similar approvals
– related concurrent, ongoing or soon to be submitted applications
Change
code
Application
level
Current details Proposed details Reasons for
change/comments