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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

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 Non-prescription medicine application screening – OTC medicines 1

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)

Non-prescription medicine application screening – OTC medicines 2

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


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 Non-prescription medicine application screening – OTC medicines

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

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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

Non-pr escription medicine application screening – OTC medicines

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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

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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)


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) Non-prescription medicine application screening – OTC medicines 11

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). 12

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


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

L iter ature 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


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

Non-prescri ption medicine application screening – OTC medicines 15

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


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


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)


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


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