Overcoming the stress of non-prescription medicine application - - PowerPoint PPT Presentation

Overcoming the stress of non-prescription medicine application screening

Complementary medicines

Dr Natasha Kelly Scientific Evaluator Complementary Medicines Evaluation Section, Complementary & OTC Medicines Branch, TGA ARCS Annual Conference 21 August 2018

Overview

• Screening process of complementary medicines evaluated by

Complementary Medicines Evaluation Section (CMES)

– Applications screened – Workflow and key changes

• Discuss the new mandatory requirements

– Registered complementary medicines (RCM) – Assessed listed L(A) medicines

• Common pitfalls and how to overcome them

Submit effective applications

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Applications screened by CMES

Application type Section of Act Evaluation Screened Timeframe Regulation Applications for new complementary medicine products RCM Section 23 Quality, Safety & Efficacy Yes 40 wd

• Reg. 16GH

L(A) medicine Section 23 Efficacy Yes 40 wd

• Reg. 16GH

Other applications RCM Change/ Variations Section 23/ Section 9D Quality, Safety & Efficacy Yes 40 wd

• Reg. 16GH/
• Reg. 16GG

Substances for LM Subsection 26BE Quality & Safety Yes 40 wd

• Reg. 16GI

wd – working days

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General workflow for screening applications

Application received and application fees paid

Date = 40 working day start

Application screened by CMES Application has minor deficiencies Opportunity to remedy minor deficiencies

Deficiencies unresolved

Application has critical issues/ unresolved deficiencies Notice of refusal sent

Deficiencies resolved

Application acceptable Notice of acceptance sent Payment of evaluation fees

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Key changes

Current Screening Process Previous Screening Process Application fee

Paid upon submission One fee

Evaluation fee

Payable after passing preliminary assessment

Timeframes

Yes - 40 working days No timeframe

Information on data requirements

Guidance in ARGCM L(A) evidence guidelines Section 23 Legislative instruments Guidance in ARGCM

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Requirements for effective applications

• Legislative requirements of section 23 of the Act
• Mandatory requirements for effective:

– RCM applications – L(A) applications

• General dossier and CTD module format
• Further information:

– ARGCM for application process – Assessed listed medicines evidence guidelines – Australian and adopted international guidelines

• Quality, Safety & Efficacy

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Mandatory requirements for effective applications

• Separate documents for RCM and

L(A) medicines

• Content structure

– Mandatory requirements – Appendix A – specific mandatory requirements

• Application category
• CTD module

RCM - https://www.tga.gov.au/book-page/mandatory-requirements-1 L(A) - https://www.tga.gov.au/book-page/mandatory-requirements-0

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Mandatory requirements

• Organisation and format
• Content

– Technical data requirements

• Appendix A – specific mandatory requirements

– Australian and adopted international guidelines

• Justification of data gaps
• Administrative requirements

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Specific requirements for an effective RCM

Requirements for RCM 1 applications:

• CTD Module 1: registered complementary medicines including:

– a letter of authorisation from the sponsor of the fully evaluated originator medicine to access the medicine information in Module 1 under ‘letters of authorisation’ (1.5.5); and – assurance that all quality aspects of the proposed medicine are identical to the originator medicine, other than differences that are specifically permitted (as listed in the permitted differences guidance) in Module 1 under ‘Assurances’ (1.5.7)

• If the proposed product includes a new flavour, fragrance or colour (including printing inks), provide the proposed specifications and details of

the test methods for the new flavour/fragrance/colours(s) in Module 3 under ‘control of excipients’ (3.2.P.4). Application type (more than one type may apply) RCM Appln. level CTD Module Module 5 Requirement Applications that include comparative bioavailability/ bioequivalence reports RCM4, RCM5, C4-RCM 5.3.1 Provide bioavailability/bioequivalence study reports in accordance with requirements detailed in:

• Guidance 15: Biopharmaceutical Studies

Note:

• The Australian originator reference medicine used in the studies

must have been registered on the basis of a full dossier, which may include chemical, biological, pharmaceutical, pharmacological- toxicological and clinical data.

• The bioavailability/bioequivalence summary is placed in Module

1.9.1

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Specific requirements for L(A) medicines

Requirements for L(A)1 applications

• CTD Module 1: Administrative information for assessed listed medicines including:

– Co-marketed medicines declarations (letters of authorisation) (section 1.5.5). – Assessed listed medicine assurances (section 1.5.7). Requirements for L(A)2 applications

• CTD Module 1: Administrative information for assessed listed medicines including:

– For applications using the Comparable overseas regulator (COR) report based process, provide the assessment and other information as described in the document ‘Comparable overseas regulators (CORs) for complementary medicines – guidance for use of COR reports in Module 1’ (section 1.11). – For generic based applications, provide Summary of bioavailability or bioequivalence study (section 1.9.1) or Justification for not providing biopharmaceutic studies (section 1.9.2).

• Module 2 (only for generic based applications)
• Module 5 (only for applications providing biopharmaceutic data).

Requirements for L(A)3 applications

• CTD Module 1: Administrative information for assessed listed medicines
• Module 2
• Module 5

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Common pitfalls

• Shared queries and deficiencies with OTC

– E.g. accidently omitted documents, literature searches

• Gross deficiency or insufficiency

– E.g. entire module or important component of module

• Lack of justification for gaps in data
• Format of reports

– Summary / unpublished manuscripts instead of full study reports – Not in English

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Common pitfalls

• Inadequate safety and/or efficacy data

– E.g. for target population, duration of use, indications

• Bioequivalence and biowavers

– Inadequate justification – Biowaver not appropriate for the formulation (E.g. prolonged release) or active ingredients (E.g. ferrous salts plus folic acid)

• Guidance 15: Biopharmaceutic studies
• European Union Guideline on the investigation of bioequivalence
• Application category

– RCM 2 for evaluation of a complementary medicine based on comparable

• verseas regulator (COR) reports

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Substance application categories (subsection 26BE)

Category TGA evaluation Quality data Safety data Timeframe

IN1 Abridged evaluation of quality and safety. COR evaluation report COR evaluation report 70 wd IN2 Abridged evaluation of safety. Full independent evaluation of quality. Full quality data set COR evaluation report 120 wd IN3 Full independent evaluation of safety. Abridged evaluation of quality. COR evaluation report;

• r compliance with a

monograph from a default standard Full safety data set 150 wd IN4 Full independent evaluation of safety and quality. Full quality data set Full safety data set 180 wd

COR – comparable overseas regulator; wd – working days

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More common pitfalls

• Substance not eligible for use in

listed complementary medicines

– Schedule 14 of the Act – The Poisons Standard

• Data pertaining to combined

substances

• Unacceptable dossier format

– General dossier or CTD module format – Searchable

Designated Active Ingredients (Schedule 14)

Amino acid Microorganism Charcoal Mineral Choline salt Mucopolysaccharide Essential oil Lipid Non-human animal material Substance produced by bees Plant or herbal material (or synthetic) Sugar polysaccharide or carbohydrate Homoeopathic preparation Vitamin or pro-vitamin

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Benefits of the CTD format

• General dossier requirements applies to substance applications
• Use of the CTD format is encouraged

– Tracking of communication – Consistent format/ presentation – Ease of navigation

Facilitate smooth and efficient evaluations

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How we can help

• Email – complementary.medicines@health.gov.au
• Pre-submission meetings
• Regulatory affairs consults
• SME Assist hub

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