An overview of the new regulatory pathway for listed medicines - - PowerPoint PPT Presentation
An overview of the new regulatory pathway for listed medicines Assessed listed medicines Ali Alaraji Director (A/g), Complementary Medicines Evaluation Section Complementary and OTC Medicines Branch Medicines Regulation Division, TGA ARCS
Ali Alaraji Director (A/g), Complementary Medicines Evaluation Section Complementary and OTC Medicines Branch Medicines Regulation Division, TGA ARCS 21 August 2018
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Three pathways for complementary medicines
Australian Register of Therapeutic Goods (ARTG) AUST L Listed medicines
No pre-market evaluation BUT
Assessed Listed medicines
AUST L(A)
BUT Pre-market evaluation for:
permitted) level indications
AUST R Registered medicines
Pre-market evaluation for:
Lower risk Higher risk
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Ingredients Must draw exclusively from the permitted ingredients list. Ingredients must not be included (or meet the criteria for inclusion) in a schedule to the Poisons Standard. Product & manufacturing quality Must comply with applicable standards and meet the PIC/S guide to GMP. Must not be of a type required to be sterile. Indications Product must contain at least one intermediate level indication which exceeds the permitted indications list but are not high level indications. Can also have other low level indications. Evidence Evidence of efficacy of the finished product submitted by the sponsor to support associated indications and claims. Pre-market assessment Pre-market assessment of efficacy evidence for all indications, and pre-market assessment
Presentation AUST L(A) number. Sponsors have the option to use a ‘claimer’ on product label and promotional material to indicate the product has been independently assessed. Post-market compliance Products may be selected for random or targeted review to confirm applicant certifications are correct. Efficacy evidence would not be routinely reassessed post-market
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Low level Intermediate level High level
A low level indication may refer to:
injury other than a serious form
Indications that are not appropriate for the list
indications. Intermediate level indications may refer to:
non-serious disease, ailment, defect or injury
form of a disease). Indications that refer to the prevention, alleviation or cure of a serious form of a disease, ailment or injury (i.e. restricted representations).
Lower risk Higher risk
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Low level Intermediate level High level
A low level indication must not:
alleviation, or cure of any form of a disease, ailment, defect or injury
indications list
An intermediate level indication must not:
alleviation or cure of a restricted representation (i.e. a serious form of disease)
representation A high level indication must not:
representation
Lower risk Higher risk
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Low level indications (AUST L) Intermediate level indications AUST L(A)
stamina
disseminate Lung Qi
to improve digestion
inflammation and pain
disease
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product (rather than active ingredients in isolation) and include a detailed evaluation of evidence to support all indications and claims
efficacy will be accepted for assessment through this pathway
TGA website
First twelve months 'implementation phase‘ to review and refine the evidence guidelines, administrative processes and timeframes
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L(A)1 L(A)2 L(A)3
Products identical to existing AUST L(A) other than permitted differences Generic of TGA fully evaluated AUST L(A) OR Comparable Overseas Regulator (COR) report for efficacy. Note: COR guidance currently under development Products not covered by L(A)1 or L(A)2 i.e. new product requiring de novo evaluation or a variation to an existing AUST L(A) 40 working days preliminary assessment 45 working days evaluation 60 working days evaluation 150 working days evaluation
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L(A)1 L(A)2 L(A)3
Access to reference medicine dossier Generics
pharmacokinetic study requirements
ingredient combinations, including potential interactions COR
report Method 1
Method 2A
data to support product efficacy Method 2B
pharmacokinetic studies to support product efficacy
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Method Suitable product type
1 All product types including traditional, herbal, probiotic and conventional medicines 2A Systemically acting isolated chemical substances 2B Products with a compliant biowaiver or that do not require biopharmaceutic studies or clinical efficacy studies
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Efficacy data Method 1 (all types) Method 2A (systemically acting isolated chemical substances) Method 2B (biowaiver or not requiring biopharmaceutic studies)
Full literature search ✓ ✓ ✓ Published studies or clinical study reports ✓ finished product ✓ each active ✓ each active Biopharmaceutic and pharmacokinetic evidence X not normally required ✓ bioequivalence or comparative dissolution ✓ in vitro dissolution or PK studies demonstrating in vivo release of actives Formulation All methods must provide justification of the use of the particular combination of ingredients, including potential interactions between ingredients
Refer to AUST L(A) Evidence guidelines – Table 5
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Category A Category B Category C Category D
Double-blind, randomised, controlled trials (including cross-over trials) Observational studies e.g. cohort and case control studies Non-systematic, generalised reviews (including databases) Traditional reference text Systematic reviews Comparative studies (non-control) Publicised international regulatory authority articles Herbal monograph Evidence based reference text - scientific Herbal pharmacopoeia Scientific monographs Materia medica Publicised international regulatory authority articles (traditional only)
Refer to AUST L(A) Evidence guidelines – Table 6
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Indication Primary (intermediate) Secondary (low level) Indication type Scientific Scientific Traditional Required evidence Minimum of one from Category A OR Minimum of two sources from Category B and one from Category C Non-specific indications Minimum of two sources from Category B or Category C Non-specific indications Minimum of two sources from Category D to support the tradition of use Specific indications Minimum of one from Category A OR Minimum of one from Category B and two from Category C Specific indications Minimum of two sources from Category D to support the tradition of use PLUS Additional evidence from Category C or D to support the specificity of the traditional indication
Refer to AUST L(A) Evidence guidelines – Table 7
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e.g. 1968 phenytoin intoxication
studies
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Pre-submission
meeting Submission Screening Evaluation Decision Implementation
ebs.tga.gov.au
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‒ Ingredients ‒ Indications ‒ Mandatory requirements ‒ Evidence Guidelines ‒ Application category
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format.
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– Mandatory requirements – Evidence guidelines – TGO 92 and Advertising Code (label)
– Clock will stop
required
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