This document provides an update on recent activities and ongoing reforms from the Scientific Evaluation Branch of the Therapeutic Goods Administration of Australia. It discusses implemented reforms such as streamlined variations for prescription medicines, utilizing evaluation reports from comparable overseas regulators, and biological and biosimilar medicines naming. Upcoming reforms addressed include improved labeling of neuromuscular blocking agents and regulation of fecal microbiota transplantation material. Approval times for different categories of medicines over the past years are also presented.

1. Update on recent activities
Scientific Evaluation Branch
Rochelle Christian
Assistant Secretary, Scientific Evaluation Branch (SEB)
Jenny Burnett
Director, Scientific Operations Management, SEB
Medicines Australia, Regulatory Affairs Working Group
18 April 2018

2. Presentation overview
Implemented and ongoing reforms
ü Variations to prescription medicines - notifications
ü Comparable Overseas Regulator (COR) reports and work-sharing
ü Biological and biosimilar medicines naming
ü Regulation of autologous human cells and tissues
ü Labelling – half-way through transition period
Upcoming reforms
ü Neuromuscular blocking agents (NMBA)
ü Faecal Microbiota Transplantation (FMT)
ü Continual improvement – generic medicines
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3. Prescription Medicines Variations e-Form
• Launched in mid-2017
• Since then > 2,000 submissions
• Changes to manufacturing information – current clearances needed for
all nominated manufacturers
• Modified December 2017
§ New change codes & descriptions added
§ Allow attachment of supporting data
§ Updated print preview
§ Introduction of notifications

4. Variations to prescription medicines
• Phase 1: Notifications for low risk changes to prescription medicines
– Launched 4 December 2017
– Must be submitted using the e-form
– c. 330 notifications submitted, affecting over 1,000 ARTG entries
• Phase 2: Investigating further improvements to our risk-based
approach for variations

5. Comparable Overseas Regulator (COR) report-based process
From 2 January 2018
• For prescription medicines with full marketing approval from a
COR following a de novo evaluation.
• Six overseas regulators identified as CORs.
• Unredacted COR evaluation reports must be provided by the
applicant.
• Two approaches*:
– COR-A 120 working days
– COR-B 175 working days
*depending on extent of TGA evaluation required.

6. Work-Sharing
• Simultaneous evaluation between multiple CORs
– Current work with ACSS partners
– Joint evaluation report
– Independent decision-making
– Creation of template documents, alignment between agencies
– Early stages

7. Biological and biosimilar medicines naming
• Consultation in 2017
– Improve collection of information on adverse events
• Government’s decision
– maintain existing convention i.e. continue using the Australian biological name
(without a suffix)
– mandatory reporting of product's trade name & non-proprietary name, when
reporting an adverse event to TGA

8. Regulation of autologous human cells & tissues
• Historically seen as medical practice and outside TGA’s regulatory oversight.
• Growing global concern with direct to consumer advertising of unproven autologous
stem cell interventions.
• Consultation on reforms in 2015 & 2016
• October 2017 government decision announced
• Level of regulation (as biologicals) determined by the risk posed to patient safety
• Drafting regulatory guidance & amendments to regulations

9. Labelling Reform
New TGO 91 implemented 2016
Four year transition period
We are half-way through!
All medicine labels must meet new
TGO requirements by 2020
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10. Key updates to medicine labels
• Prominence of active ingredient
– Immediately below the name of the medicine.
• Name of the medicine
– As it appears on the Certificate of Registration.
• Schedule 1 – Declarable substances
– New requirement for prescription medicines
– Includes declarations for substances that are not ingredients.
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11. Key updates to medicine labels
• Contrasting colours
§ Required for information on medicine label c.f. background.
• Machine readable code
§ May be used to include information such as batch number & expiry date.
• International Harmonisation of Ingredient Names
§ Australian approved names list, & formulation details for all affected ARTG entries updated
with new ingredient names
§ Transition period for labels & product information until 2020
§ Dual-labelled names ‘new name (old name)’ until 2023. 10

12. We all use medicine labels
• Frequent enquiries from consumers &
industry – interest level is high!
• New webpage for consumers
• New webpage for health professionals
• Input to newsletters
• Social media
• Update to labelling guidance published soon
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13. Changes to the labelling of Neuromuscular
Blocking Agents (NMBAs)
• NMBAs are paralysing agents.
• Administration errors involving NMBAs
§ Can cause serious harm
§ Linked to look-alike labelling & packaging.
• Sponsors, healthcare groups & TGA working together to introduce a visual cue
§ Warning statements
§ Colour coding.
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14. Regulation of donation, manufacture & supply of
Faecal Microbiota Transplantation (FMT) material
• ‘FMT material’ = donated human stool for application in humans
• Increasing attention on use of FMT for treatment of recurrent Clostridium
difficile infection
• Hospitals & clinics offering FMT material for the treatment of C. diff. & other disorders.
• No FMT material is entered as approved goods on ARTG
• Access as unapproved goods, e.g. clinical trial, SAS or authorised prescriber
• TGA is developing a position paper on regulatory status of current supply. 13

15. Regulation of donation, manufacture & supply of
FMT material
FMT material may often meet the definition of a ‘biological’ under Section 32A of the
Therapeutic Goods Act:
• It comprises, contains or is derived from human cells (e.g. colonocytes) or human
tissues.
FMT material that is banked:
• multiple donations are combined & processed for use in unrelated patients
• poses similar risks of infectious disease transmission as for other biological banks, e.g.
eye banks.
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16. Regulation of donation, manufacture & supply of
FMT material
• Biologicals are regulated by the TGA under the regulatory framework for biologicals
– different levels of regulation of products based on the risks associated with their use.
Possible changes for FMT material to address safety concerns:
1. New Standard specific to donor selection & screening for FMT material
2. Transition towards all manufacture of FMT material under GMP (exemption: phase 0 or
phase I clinical trials)
3. Information on TGA website to clarify requirements for supply & restrictions to
advertising unapproved therapeutic goods
Safety
First!
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17. Further reforms and improvements - Context
Government:
• MMDR reforms – new
pathways, shorter timeframes
• PBS expenditure – more
expensive drugs for smaller
populations
• Affordable & sustainable
health system, especially PBS
• Patient expectations for early
access to cheaper medicines
• Recruitment controls
Sponsors’ feedback:
• Generics take almost as
long as NCEs
• Milestones important for
predictability
• Appreciate cooperative
approach to get products
over the line
• Focus on material
aspects
Industry 4.0:
• Changing profile of
new medicines –
more complex
generics but fewer
overall
• Increase in NCEs &
biosimilars & shift to
immunotherapeutics
& personalised
medicines

18. Recent approval times
Category 1 (255 working days)
Jul-Dec 2017 Jan–Jun 2017 Jul-Dec 2016
Application Type Approved Mean Approval
Time
Range Approved Mean Approval
Time
Range Approved Mean Approval
Time
Range
New Chemical Entity 22 209 152-245 14 209 177-232 23 200 161-238
Fixed-dose
Combination
1 178 178 0 N/A N/A 4 204 179-218
Extension of
Indications
21 183 85-223 23 197 106-235 20 199 147-238
Generic medicine 55 190 123-254 59 186 109-254 53 177 124-253
Major Variation 21 195 155-254 22 181 139-226 24 195 134-224
PI Change 41 130 7-242 35 143 46-228 30 142 65-212

19. Approval times - Impact of stop clocks

20. Continual Improvement – generic medicines
Discussions with GBMA & other industry representatives:
• Dossier quality
– Common issues
– Options to address
• Options for accelerated review of some generic medicines

21. Questions?
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