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 1

Applications screened by CMES Application type Section of Act Evaluation Screened Timeframe Regulation Applications for new complementary medicine products RCM Section 23 Quality, Safety Yes 40 wd Reg. 16GH & Efficacy Efficacy Yes 40 wd Reg. 16GH Section 23 L(A) medicine Other applications RCM Change/ Section 23/ Quality, Safety Yes 40 wd Reg. 16GH/ Variations Section 9D & Efficacy Reg. 16GG Substances for LM Subsection 26BE Quality & Safety Yes 40 wd Reg. 16GI wd – working days 2

General workflow for screening applications Application received and application fees paid Date = 40 working day start Application screened by CMES Application has minor deficiencies Application has Deficiencies Deficiencies Application Opportunity to remedy minor critical issues/ resolved unresolved acceptable deficiencies unresolved deficiencies Notice of acceptance sent Notice of refusal sent 3 Payment of evaluation fees

Key changes Current Screening Process Previous Screening Process Paid upon submission One fee Application fee Payable after passing preliminary Evaluation fee assessment Yes - 40 working days No timeframe Timeframes Guidance in ARGCM Guidance in ARGCM Information on data requirements L(A) evidence guidelines Section 23 Legislative instruments 4

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 5

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

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 7

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 RCM Appln. CTD Module Module 5 Requirement type may apply) level Applications that include comparative RCM4, RCM5, 5.3.1 Provide bioavailability/bioequivalence study reports in accordance bioavailability/ bioequivalence reports C4-RCM 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 8 1.9.1

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 9

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 10

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 overseas regulator (COR) reports 11

Substance application categories (subsection 26BE) Category TGA evaluation Quality data Safety data Timeframe IN1 Abridged evaluation of quality COR evaluation report COR evaluation report 70 wd and safety. IN2 Abridged evaluation of safety. Full quality data set COR evaluation report 120 wd Full independent evaluation of quality. IN3 Full independent evaluation of COR evaluation report; Full safety data set 150 wd safety. or compliance with a monograph from a Abridged evaluation of quality. default standard IN4 Full independent evaluation of Full quality data set Full safety data set 180 wd safety and quality. COR – comparable overseas regulator; wd – working days 12

More common pitfalls • Substance not eligible for use in Designated Active Ingredients (Schedule 14) listed complementary medicines Amino acid Microorganism Charcoal Mineral – Schedule 14 of the Act Choline salt Mucopolysaccharide – The Poisons Standard Essential oil Lipid Non-human animal material Substance produced by bees • Data pertaining to combined Plant or herbal material (or Sugar polysaccharide or synthetic) carbohydrate substances Homoeopathic preparation Vitamin or pro-vitamin • Unacceptable dossier format – General dossier or CTD module format – Searchable 13

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 14

How we can help • Email – complementary.medicines@health.gov.au • Pre-submission meetings • Regulatory affairs consults • SME Assist hub 15