Update on regulatory reforms from the Scientific Evaluation Branch Jenny Burnett Scientific Operations Management Section Scientific Evaluation Branch Medicines Regulation Division, TGA ARCS August 2019, Sydney
Outline • The latest on variations • Generic Medicines Reform Program • Human cells and tissue regulation (excluded goods) • Faecal Microbiota Transplantation • 2D DataMatrix codes for medicines 1
The latest on variations 2
Variations to registered medicines Our philosophy is – Continuous improvement Thoughts from last year… • Possible new notifications • Enhancements to the e-form • More moves from paper to electronic applications So what happened next?? 3
Possible new notifications? • Requires amendment to the Regulations • Legislation changes require consultation • More complex situations … – Variations affecting Product Information Complex from regulatory perspective other projects affecting PIs already underway – Changes to low risk ingredients Requires an Act amendment Complexity = Time delay 4
Now the good news! Enhancements to the e-form for prescription medicines • Clarity on retaining existing AUST R number • ‘associated changes’ • Automated removal of manufacturers with invalid GMP Updated guidance • Multiple related changes • Multiple unrelated changes • Considerations prior to submission 5
“ We have multiple changes …” Associated New separate and changes New AUST R? distinct goods? Z codes An ‘event’ Any link between Consequential or the changes? related changes Same aspect of the goods 6
The importance of ‘conditions’ • Conditions listed under each variation type • Notification/ SAR conditions not met requires category 3 application Example LOTG: Label - changes to comply with current TGOs for labels that have previously been evaluated and approved by the TGA Conditions • There must be no other changes to the label made under this change request. • The changes must ensure continued compliance with the relevant TGO pertaining to labels and not contravene labelling best practice. If conditions not met LCDE: Label changes - any changes requiring data for evaluation 7
More good news!! More applications can be made using the e-form • Extension of Indications for generic medicines • Formulation changes - flavours, fragrances, inks 8
• The latest on variations • Generic Medicines Reform Program 9
A program of reforms Public consultation • Revised requirements for use of an overseas reference product • New templates for bioequivalence data • New process for ‘early advice’ • Incentives for medicines of special interest
Use of an overseas reference product • The overseas reference product must be identical to the Australian reference product • Evidence required includes: Product labels Dissolution data Physical Quantitative analysis characteristics of components What evidence should be provided to demonstrate identicality of reference products? 11
Consultation Outcomes Use of overseas reference product • Feedback – Reduce Australian-specific requirements – Harmonise with other regulators where possible – Must not adversely affect quality and safety of generic medicines supplied in Australia • Outcome – Develop a risk-based approach – Reduced requirements for simple, low risk products – All current requirements remain for higher risk medicines 12
New templates for bioequivalence (BE) data International templates • Internationally-used templates will: – Create greater consistency – Provide a checklist for applicants • We have identified the following international templates: – Bioequivalence study information – Biowaiver justification templates 13
Consultation Outcomes BE templates • Feedback – Some support for adopting internationally-used templates – Must not result in additional re-work of dossiers for submission to the TGA – Align with EU and ICH requirements, remove Australian-specific requirements • Outcome – Drafted 3 new templates based on those developed by comparable overseas regulators – Created new guidance material – Considered implications for dossier content 14
New process for ‘early advice’ Early advice on biowaiver justifications Aspects to be considered: • Explicit and limited number of technical issues specific to biowaiver justifications • No additional regulatory burden • Possible future broader use 15
Consultation Outcomes Early advice process • Feedback – All submissions were supportive – Advice needs to be ‘binding’ – Appropriate that a fee is charged – Should be available for a range of topics • Outcome – Amendment to the Therapeutic Goods Act 1989 – Restricted to biowaiver justifications (in the first instance) – Need industry involvement to ensure ‘fit for purpose’ 16
Generic medicines of special interest How to ensure robust supply? Encourage applications … – Faster evaluation time? – Queue jump? Case study 1. Medicine shortages Case study 2. Medicine expenditure 17
Consultation Outcomes … taking a different approach • Feedback – Mixed responses … with concerns – No clear benefit for either case study – More efficient TGA processes would be of greater benefit to all – Fast processing of manufacturer changes would assist with medicine shortages • Outcome – Consideration of further reform to the variations process for prescription medicines – Applies to all Rx medicines, therefore outside the Generic Medicines Reform Program 18
Next steps … Targeted consultation • Revised requirements for use of • Updated guidance an overseas reference product • New templates for • Draft templates and guidance bioequivalence data • New process for early advice • Confirm key concepts
• The latest on variations • Generic Medicines Reform Program • Human cells and tissues regulation (excluded goods) 20
Types of therapeutic goods Medicines • prescription medicines • over-the-counter medicines • complementary medicines • blood, blood components and plasma derivatives • gene therapies Medical devices • implants (artificial hips, breast implants) • in-vitro diagnostics (pregnancy tests, blood glucose monitors) • low risk medical devices (bandages, tongue depressors, condoms) Biologicals • tissue-based products (skin and bone) • cell-based products (MSCs) • viable animal cells and organs 2 1
What is an excluded good … Excluded vs exempt goods • Excluded – Not subject to the Therapeutic Goods Act 1989 Defined in a legislative instrument Not to be confused with… • Exempt – Some requirements are not applied Therapeutic Goods Regulations 1990 Schedule 5 – exempt from being on the ARTG Schedule 7 – exempt from GMP licence 22
Therapeutic Goods (Excluded Goods) Order - pre 2019 Autologous cells and tissues (Medical practice) • collected under the care of a medical practitioner • manufactured for treatment of a single indication • in a single course of treatment of that patient by the same medical practitioner , or by a person under their supervision –Not in alignment with most overseas regulators –Multiple concerns with this approach Review of this position was needed 23
Review of Excluded Goods Order • Concerns raised with current Order – Advertising claims for unproven therapies – Scope of activity and complexity of products has changed since 2011; increasing safety concerns – Scope of exclusion is not internationally aligned • Public consultation on options in 2015 and 2016 • Government agreement to an option supported by the majority of stakeholders in 2018 • 12 month transition period to allow operators to comply with the new regulations or cease supplying ended on 1 July 2019. 24
Autologous Human Cells and Tissues Excluded Goods Exempt Goods Full Regulation • Minimally • Manufactured and • Must be manipulated and used outside an manufactured and homologous use accredited hospital • Manufactured and • More than used in an accredited hospital used outside a minimally • Medical or dental hospital manipulated, or • Medical or dental • For non- practitioner practitioner homologous use 25
• The latest on variations • Generic Medicines Reform Program • Human cells and tissues regulation (excluded goods) • Faecal Microbiota Transplantation 26
Faecal Microbiota Transplantation (FMT) • Takes faecal material from a healthy individual for transplant to a patient • Hypothesis: ‘Healthy’ microbiota correct the underlying dysbiosis associated with disease state – Fresh, frozen, encapsulated Processing Donor Patient – Varying degrees of processing • Testing • Pre-screened • Administered • Processing under medical – Allogenic vs autologous supervision • storage – Stool banks 27
FMT – a new regulatory challenge • Medicine or biological? – Different regulatory requirements – Different safety considerations – Different approaches overseas UNAPPROVED • No goods on the Register BIOLOGICAL • Increasing use within Australia • Recognised treatment for Clostridium difficile infection 28
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