Improving access to evidence based listed complementary medicines - PowerPoint PPT Presentation

Complementary Medicines Regulatory Obligations Seminar Improving access to evidence based listed complementary medicines Lyndall Soper Assistant Secretary, Complementary and OTC Medicines Branch Medicines Regulation Division, TGA Complementary Medicines: Regulatory Obligations Seminar

Recommendation 39 3 assessment pathways for complementary medicines Panel recommendation: 3 options by which sponsors may seek ARTG entry for complementary medicines: Option 1: Listing in the ARTG following self-declaration by the sponsor regarding safety, quality and efficacy ( current listing pathway ) Option 2: Listing in the ARTG following self-assessment of the safety and quality but a TGA assessment for efficacy ( new pathway ) Option 3: Registration in the ARTG following full TGA assessment of safety, quality and efficacy ( current registered pathway ) Complementary Medicines: Regulatory Obligation Seminar 1

Recommendation 39 Three assessment pathways for complementary medicines Government Response The Commonwealth accepts the recommendation; noting that legislative amendments are required to implement Option Two. Implementing this recommendation would increase transparency for consumers, provide additional flexibility for sponsors and support innovation. Complementary Medicines: Regulatory Obligation Seminar 2

New Pathway: Key Features • A new assessment pathway sitting between the existing listed medicine (low risk) and registered medicine (high risk) pathways • Maintains low risk status based on their ingredients, the way they are presented and the potential harm associated with their use • Can use ‘intermediate claims’ which are not included on the permitted indications list:  Low level indication: ‘May help relieve muscle aches and pains’  Intermediate level indication: ‘May help relieve arthritis’ Complementary Medicines: Regulatory Obligation Seminar 3

New Pathway: Key Features cont. • Still required to comply with GMP requirements • TGA evaluates the evidence for efficacy before it is listed • Option to include a claimer on all promotional material stating it has been independently assessed. – ‘The efficacy of the product has been independently assessed for the approved indication’ – ‘Evidence has been reviewed by the TGA’ Complementary Medicines: Regulatory Obligation Seminar 4

Proposed Complementary Medicines Framework Listed Medicines New Pathway Registered Medicines Permitted ingredients Permitted ingredients Not limited to selecting from permitted ingredients list Good Manufacturing Practice Good Manufacturing Practice Good Manufacturing Practice Low level permitted indications At least one ‘intermediate May have higher level only indication’ indications No pre-market assessment Pre-market assessment of Full pre-market assessment evidence for efficacy Ability to claim that efficacy has been assessed Complementary Medicines: Regulatory Obligation Seminar 5

Indications to accepted through the new pathway Listed medicines New pathway Registered medicines Low level indications Intermediate level indications High level indications may refer to: may refer to: may refer to the; • health enhancement • a health benefit for a serious disease • prevention • health maintenance (i.e. restricted representations) • alleviation, • prevention/alleviation of dietary • prevention, alleviation or management • cure or of a non-serious disease or condition deficiency • management • a health benefit for a non- ( of a higher risk to consumers than low serious disease or condition level indications ) of a serious form of a ( symptomatic relief) disease, ailment, defect or injury (restricted reps) Eg: maintain/support healthy bones Eg: prevention of osteoporosis Must not refer to a prohibited representation 6

Proposed approaches to establishing efficacy 1. Sponsors all medicines must meet minimum evidence requirements 2. Existing approaches to establish efficacy for listed and registered complementary medicines will be retained 3. For the new pathway: • The evidence requirements can be met in two ways ( Method 1 or Method 2 ) • Sponsor will self-assess the safety and quality (permitted ingredients, compliance with quality standards and GMP) Complementary Medicines: Regulatory Obligation Seminar 7

Proposed Categories of Evidence Category A Category B Category C Category D Traditional Reference text Non-systematic, Observational studies e.g. Double blind randomised generalised reviews - cohort and case control controlled trials (including including databases studies cross-over trials) Herbal Monograph Publicised international Comparative studies Systematic reviews Regulatory Authority (non-control) Articles Herbal Pharmacopoeia Evidence based reference text - scientific Materia Medica Scientific Monographs Publicised International Pharmacopoeias Regulatory Authority Articles – Traditional only Complementary Medicines: Regulatory Obligation Seminar 8

Proposed minimum literature requirements Listed medicines New Pathway Registered medicines Indication Traditional Low Level Scientific Intermediate Level Indications Non-prohibited Indications Minimum of two Minimum of two Primary indication Primary indication independent sources from independent sources from Evidence Minimum of one from Category D Minimum of one from Category A Category B Category Category D OR OR PLUS (where required) Required Minimum of 2 independent evidence A minimum of one from A minimum of one from sources from Category B, AND a Category B Category C minimum of one from Category C Secondary indications Secondary indications Evidence Minimum 1 from Category Minimum of 1 from One from Category D One from Category D Category A to support specific Category B to support OR OR therapeutic claims (where specific therapeutic claims Supplementary relevant) (where relevant) Minimum of 2 independent Minimum of 2 independent evidence sources from Category B, AND a sources from Category B, minimum of one from Category C AND a minimum of one from Category C Complementary Medicines: Regulatory Obligation Seminar 9

Options for submission of efficacy evidence Method 1: • Clinical Trial data on the finished product that supports the specific indication – Potential 3 years data protection . Method 2 : • A data package containing: – evidence for efficacy of all ingredients; AND – evidence for efficacy of the product formulation; (e.g. bioavailability data and/or dissolution testing) AND – justification of the combination of ingredients. 10

Proposed evidence dossier requirements for New Pathway Data Type Method 1 Method 2 Primary A minimum of one randomised controlled A minimum of one randomised controlled indication clinical trial (including cross-over trial) or clinical trial (including cross-over trial) or systematic review on the product. systematic review on each active ingredient. Body of Full literature search report on the Full literature search report on all active scientific product or formulation. ingredients and formulation. information Non-clinical data N/A Dissolution data and bioequivalence data on the product . Formulation N/A Justification of the use of the particular combination of ingredients, including potential interactions. Quality Evidence of GMP. Evidence of GMP. Complementary Medicines: Regulatory Obligation Seminar 11

Examples of products and evidence packages suitable for the New Pathway Product Type Example of products Method 1 A sponsor proposes to list a product consisting of 1000 IU of Vitamin D (cholecalciferol 25 micrograms) and 1200 mg calcium indicated for reducing the Standard product risk of fractures associated with osteoporosis. The sponsor has evidence from (e.g. multiple active ingredients) multiple clinical trials and a systematic review of the literature indicating that daily supplementation with the product reduces the risk of fractures associated with osteoporosis. Method 2 A product contains 450 micrograms of folic acid. The sponsor wishes to use the Single ingredient active restricted representation ‘prevents neural tube defects when used during the first (immediate release only) with trimester of pregnancy’. The sponsor can provide dissolution studies indicating established bioavailability that the product results in appropriate release of the active, and full literature search supporting the indication. 12

Initial outcomes of public consultation New Pathway • Broad support for the introduction of the new pathway Efficacy evidence • General support for the proposed evidence hierarchy • Significant concerns around excluding traditional medicines from the new pathway • Some industry stakeholders feel there is too much emphasis on the finished product Complementary Medicines: Regulatory Obligation Seminar 13

Recommendation 45: Claimers for assessment of efficacy Panel Recommendation: Where a medicinal product is listed in the ARTG following an assessment by the TGA of an application under Option Two, the sponsor is able to indicate on all promotional materials and on the product label, that the efficacy of the product has been independently assessed for the approved indications . Government response: Accepts-in-principle Recommendation 45, noting that the design and use of the promotional statements will require careful consideration by the TGA and further consultation with stakeholders. Complementary Medicines: Regulatory Obligation Seminar 14