Presentation on the latest on variations, Generic Medicines Reform Program, Human cells and tissue regulation (excluded goods), Faecal Microbiota Transplantation and 2D DataMatrix codes for medicines

1. 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

2. Outline
• The latest on variations
• Generic Medicines Reform Program
• Human cells and tissue regulation (excluded goods)
• Faecal Microbiota Transplantation
• 2D DataMatrix codes for medicines
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3. The latest on variations
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4. 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

5. 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
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6. 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
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7. “We have multiple changes …”
New separate and
distinct goods?
New AUST R?
Associated
changes
Z codes
Any link between
the changes?
An ‘event’
Consequential or
related changes
Same aspect of
the goods
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8. 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
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9. More good news!!
More applications can be made using the e-form
• Extension of Indications for
generic medicines
• Formulation changes -
flavours, fragrances, inks
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10. • The latest on variations
• Generic Medicines Reform Program
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11. 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

12. 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
characteristics
Quantitative analysis
of components
What evidence should be provided to demonstrate identicality of reference products?
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13. 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
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14. 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
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15. 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
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16. 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
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17. 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’
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18. 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
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19. 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

20. Next steps …
Targeted consultation
• Revised requirements for use of
an overseas reference product
• New templates for
bioequivalence data
• New process for early advice
• Updated guidance
• Draft templates and guidance
• Confirm key concepts

21. • The latest on variations
• Generic Medicines Reform Program
• Human cells and tissues regulation (excluded goods)
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22. 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

23. What is an excluded good …
Excluded vs exempt goods
• Excluded
– Not subject to the Therapeutic Goods Act 1989
Not to be confused with…
• Exempt
– Some requirements are not applied
Defined in a legislative instrument
Therapeutic Goods Regulations 1990
Schedule 5 – exempt from being on the
ARTG
Schedule 7 – exempt from GMP licence 22

24. 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

25. 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.
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26. Autologous Human Cells and Tissues
Excluded Goods
• Must be
manufactured and
used in an
accredited hospital
• Medical or dental
practitioner
Exempt Goods
• Minimally
manipulated and
homologous use
• Manufactured and
used outside a
hospital
• Medical or dental
practitioner
Full Regulation
• Manufactured and
used outside an
accredited hospital
• More than
minimally
manipulated, or
• For non-
homologous use
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27. • The latest on variations
• Generic Medicines Reform Program
• Human cells and tissues regulation (excluded goods)
• Faecal Microbiota Transplantation
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28. 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
– Varying degrees of processing
– Allogenic vs autologous
– Stool banks
Donor
• Pre-screened
Processing
• Testing
• Processing
• storage
Patient
• Administered
under medical
supervision
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29. FMT – a new regulatory challenge
• Medicine or biological?
– Different regulatory requirements
– Different safety considerations
– Different approaches overseas
• No goods on the Register
• Increasing use within
Australia
• Recognised treatment for
Clostridium difficile infection
UNAPPROVED
BIOLOGICAL
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30. The Biologicals Framework
Regulated as biologicals
Tissue-based products
(skin, bone, ocular,
cardiovascular)
Cell-based products (T cell
therapies, human stem
cells)
Combined cell and tissue
products (collagen
matrices for localised cell
delivery)
Living animal cells, tissues,
organs
(xenotransplantation)
Not regulated by the TGA
Fresh viable organs
Assisted reproductive
technologies
(in vitro fertilisation)
Fresh haematopoietic
progenitor cells
(bone marrow transplants)
Cells and tissues made in
an accredited hospital, by a
medical or dental
practitioner, for autologous
use in a single patient
under the care of that
medical practitioner
Regulated, but not as
biologicals
Animal tissue products
(non-viable)
Biological prescription
medicines (vaccines,
plasma derivatives)
Labile blood and blood
components
Haematopoietic
progenitor cells (non-
fresh transplants) 29

31. Critical considerations …
• Need for GMP
• Infectious disease transmission
– Donor selection and screening
– Current TGO 88
– In vitro diagnostic tests
• No advertising of biologicals
• Continued supply for existing
patient groups
• Rapid growth and evolution in
the sector
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32. Access to unapproved biologicals
Biologicals that, under the Regulations, are
exempt from some requirements
Special Access
Scheme
Authorised
prescriber
Personal
importation
For
experimental
use
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33. … for new regulatory scheme
Possible approaches
– Class 1 biologicals?
– Alignment with haematopoietic
progenitor cells?
– Alignment with autologous
human cell and tissue products?
– Self-regulation?
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34. • The latest on variations
• Generic Medicines Reform Program
• Human cells and tissue regulation (excluded goods)
• Faecal Microbiota Transplantation
• 2D DataMatrix codes for medicines
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35. Changing regulatory requirements
Overseas
• EU - Falsified Medicines Directive
• India – export requirements
• Track and trace models
– Turkey
– Argentina
– South Korea …
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36. In Australia …
TGO 91 for prescription medicines
–Machine readable code
–GTIN and product identifiers
– GS1 Linear barcode or 2D
DataMatrix
–Transition ends Sept 2020
How can these requirements align with
overseas requirements???
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37. Wide range
of
possibilities
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38. New Australian standard
Timeline for implementation
• Pre-consultation workshop
• Draft new standard and
supporting documentation
• Public consultation on draft
standard
• Finalisation of standard
• Target date – mid-2020
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39. Questions?
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