1. The document summarizes recent developments and future options in medicines and medical devices regulation in Australia, as presented by John Skerritt from the Department of Health. 2. Key updates included planned changes to medicines labeling, reviews of programs for orphan drugs and recalls, and a new online system for clinical trial notifications. 3. The presentation also discussed an expert panel review that recommended modernizing approval pathways for new drugs and generics, adopting risk-based approaches, and reforms to schemes for unapproved products.

1. John Skerritt
Deputy Secretary for Regulatory Services
Department of Health
ARCS AGM Melbourne 26 Nov 2015
Medicines and Medical Devices
Regulation – current developments
and future options

2. This presentation
• Australia’s medicines regulatory environment – updates
– Planned medicines labelling changes
– Orphan drugs and options for regulatory reform
– Biosimilars
– Pharmacovigilance pilot inspection program
– Reviewing the URPTG (Recalls)
– Clinical trial notifications go online
• Update on the Expert Panel Review on the Regulatory
Framework for Medicines and Medical Devices

3. Medicines labelling – why reform?
Facilitate quality use of medicines by consumers and
health professionals by better labelling:
• reduce risk of prescribing, dispensing and self-
selection errors
• avoid consumer confusion and the inappropriate
use of medicines
• assisting the appropriate selection of OTC
medicines
• optimising identification and usability of necessary
information
• ensuring consumers know where to go for further
information about their medicine

4. • 15 year old regulations out of step with international
best practice
• Ageing population
• Growth of generic and complementary medicines
• Some more “powerful” medicines are now available
OTC
The process
• Multiple stakeholder consultations
• Several cycles of refinement
• Costing of regulatory burden of the proposed changes
to industry
• Drafting of TGO and guidance

5. Major proposed mandatory requirements
• Separate TGOs (regulations) to recognise different information requirements and
risks for prescription and OTC medicines
• Text sizes for active ingredients for registered medicines > 3 mm
– smaller if 4 or more active ingredients or medicine in a small container
• Prescription medicines to have names of the medicine on at least three non-opposing
sides of the carton and a machine readable code
• Certain excipients (e.g. allergens) and impurities to be declared
– Information can be on label or CMI for prescription medicines
• Registered OTC medicines require a Medicines Information Panel
• Required information must be in high colour contrast
• Specific requirements for some types of packaging and ingredients
• Warning statements related to use of medicines in pregnancy

6. Medicines labelling review - current status
• Extensive Stakeholder consultations conducted on
previous draft TGO during 2014
• Over 80 detailed submissions from industry, healthcare
professionals, consumer groups
• TGO extensively revised during 2015
• Guidance documents on mandatory and best practice
(non-mandatory) requirements developed
• More consultations during Oct-Nov 2015
• 4 year transition period proposed from 2016

7. Orphan drugs program review
Why review?
• The program objective is to help sponsors to market drugs used in the
treatment, prevention or diagnosis of rare diseases
• Support is by waiving fees for orphan evaluation and registration
– But because TGA is 100 % cost-recovered, the overall cost of NCE evaluation is
borne by other sponsors
• Change in medicines business models since 1998 – growth of highly
targeted treatments rather than “blockbusters”
• Discussion paper released early 2015

8. Program coverage and viability considered
• What reforms – if any – are required to ensure the program objectives are
continuing to be met?
• Orphan drug definition, i.e. who should be targeted with an orphan drugs
program?
– disease subgroups and stages
– first orphan indication vs all indications
• Is the current patient threshold appropriate?
• Program viability - are changes needed to the charging model?
• Government will soon consider options for any reforms

9. Biosimilars
• A version of an already registered biological medicine
that has a demonstrable similarity in physicochemical,
biological and immunological characteristics, efficacy and
safety, based on comprehensive comparability studies
• The claim is “similarity in all important aspects”
• The reference product must
– be registered in Australia by means of a full data
submission
– have been marketed for a sufficient duration
– have a volume of marketed use so that there is likely to
be a substantial body of data regarding safety and
efficacy for the approved indications
Similar …
but not the same..

10. Biosimilars – TGA’s role in evaluation
• As for all registered medicines, biosimilars must meet acceptable standards of
quality, safety and efficacy
• Additionally, TGA assesses whether the scientific and clinical data warrant a
biosimilar designation
• Biosimilar naming - WHO consultation still to be concluded
– In the interim, use the Australian biological name without a specific biosimilar identifier
suffix, e.g. a biosimilar to Neupogen filgrastim would be named 'TRADENAME' filgrastim
• A comprehensive Risk Management Plan developed by the sponsor
– taking into account identified and potential risks for the reference product
– as well as any risks associated with biosimilarity and anticipated patterns of use (including
immunogenicity in humans)

11. Pharmacovigilance pilot inspection program
• Responsibilities of Sponsors are specified in the TG Act and
Regulations, including:
– Reporting of serious adverse drug reactions and safety issues
– Notification of a staff member responsible for pharmacovigilance
– Responding to TGA requests for information
– Compliance with conditions of registration, such as submission of PSURS, RMPs,
updating of PI/ CMI, retention of records
• Pilot inspection program will assess compliance
• Eleven sponsors agreed to take part in pilot program
– First inspection was undertaken in October 2015
– Will assess feasibility and seek feedback on value for the sponsor

12. Reviewing the Uniform Recall Procedure for
Therapeutic Goods
• Consultation closed 23 November
• Now drafted as interlinking webpages to enhance navigation and usability
• Includes a step-by-step guide through the recall procedure
– examples of different classes of recall actions
– Sponsor’s Hazard Alert customer letter requirements
– Mandatory recall actions
• Includes requirements for recalling biologicals and greater clarity on the
requirements for device/ IVD recall actions

13. Reviewing the Uniform Recall Procedure for
Therapeutic Goods
• Changes to recall terminologies
– Product Defect Correction
– Hazard Alert (implanted medical devices and biologicals)
– Product Defect Alert (new terminology)
• Includes probability aspects in Classification of Recalls
• Clarifies the requirements of safety alerts (non-recall action)
• Updates publication of safety alerts (non-recall action) and publication of
recall letters on a case by case basis in SARA
• Includes the outcomes of the review of recall actions

14. TGA Clinical Trial Notifications go online
• From October 2015 TGA Clinical Trial Notifications
moved from a paper-based database to a new online
system
– reduced administrative burden
– online Sponsor declaration replaces requirement for
submitting original signatures can manage and track
notifications via an online dashboard
– can directly amend submitted information
– online invoice generation and payment
• After December 2015, pre-July 2015 CTN data will be
posted to the online system

15. Expert Panel review of Medicines and Medical
Devices regulation …..
• First report on medicines and medical devices, provided to government
31March and the second report on complementary medicines and
advertising submitted on 31 July 2015
• Review process included submissions in response to discussion papers and
interviews with key stakeholders
• Both reports now publicly released, some stakeholder workshops held and
more planned
• The Report is a report from a Review panel to Government and has not yet
been formally considered by Government

16. Overarching principles for regulation as
recommended by the Expert Panel
• Australia maintain the capacity to undertake assessments of therapeutic
goods for safety, quality and efficacy
• The Australian Government retain responsibility for approving the
inclusion of therapeutic goods in the ARTG
• 32 recommendations in the first report cover six main areas:
– principles for regulation
– pre-market approvals
– post-market monitoring
– access to unapproved therapeutic goods
– structure/ decision making; and
– broader reviews

17. Some proposed initial reform bundles
• Reforms to registration of New Chemical Entities
• Reforms to generics and biosimilar medicines
registration
• Risk based approaches to variations of medicines
on the ARTG
• Reform to schemes for unapproved medicines and
devices (i.e. the Special Access and Authorised
Prescriber Schemes)
• Establish criteria and mechanisms for expedited
approval of (very) novel medical devices

18. Pathways proposed for registration of a new chemical
entity (prescription medicine)
1. Submission of a complete dossier for full assessment by the TGA
(current process)
2. Expedited approval based on submission of an un-redacted evaluation
report from a comparable overseas regulator, with a copy of the dossier
and an Australian-specific module one
3. Accelerated approval based on transparent criteria
4. Potential for provisional approval/ adaptive licensing, if time-limited
and subject to public advice that the medicine is (only) provisionally
approved

19. Generic and Biosimilar medicines
• The Panel recommended that there be two pathways
to seek registration of a generic medicine or
biosimilar:
1. Submission of a complete dossier for full assessment by
TGA
2. Submission of an un-redacted evaluation report from a
comparable overseas regulator (together with the
dossier)
• The opportunity for a range of other business
process improvements for generics in the reforms is
also being considered

20. Other Prescription Medicine Recommendations
• Adopt a risk-based approach to management of variations:
– Notification of variations where the variation does not impact the quality,
safety or efficacy
– Assessment of the variation if the variation could impact safety, quality or
efficacy
• Streamline access for consumers and health professionals to medicines
and medical devices that have not been approved in Australia through the
Special Access Scheme

21. Subsequent bundles proposed
• Comprehensive medical device reforms
• More comprehensive post-market reforms
• Adaptive licensing of medicines
• Further studies proposed for:
– The Medicines Scheduling Policy Framework
– Schedule 3 medicine advertising Guidelines
– Lower-risk goods to determine whether they may best
regulated under other frameworks or better regulated
according to risk

22. Post market monitoring recommendations
• Better integration and timely analysis of available
datasets including matched de-identified data from
PBS and MBS
• Implement an alert scheme that a medicine is newly
registered and to encourage reporting of adverse
events
• Electronic reporting of adverse events
• Enhanced information-sharing with overseas
regulators
• Will require enhancement if accelerated and/or
provisional licensing is adopted

23. The Second report of the panel
• Publicly released on 19 November 2015
• Focussed on options for regulation of
– complementary medicines and
– advertising (all categories of therapeutic goods)
• Concluded that TGA should remain the regulator for both areas
– While Complementary Medicines are low risk, it is appropriate to regulate
products that make therapeutic claims within the therapeutic goods
framework
– This has also underpinned the reputation of Australian Complementary
Medicines in the export market

24. Recommendations –
Complementary Medicines
Some recommendations for reducing particular pre-market requirements are
conditional on strengthening aspects of postmarket regulation and enforcement
1. Streamline transparency and predictability of regulation:
– Better regulatory guidance materials
– Introduce permitted indications for Complementary Medicines
– Adopt/ develop evidence monographs
– Allow review rights for ingredients
– Establish ingredient assessment timeframes
– Stakeholder input through an advisory committee

25. Recommendations –
Complementary Medicines
2. Increasing the transparency of evidence of efficacy for particular
indications
– Requirement to publish efficacy evidence
– Establishment of an evidence hierarchy, with a new class of complementary
medicines proposed that would be allowed to make higher-level claims than listed
medicines
– Closer linkage to advertising claims
3. Greater utilisation of overseas assessments for new ingredients
4. Increase in postmarket monitoring and compliance powers,
including ability to refuse to list particular products

26. Recommendations –
Advertising of therapeutic goods
1. Advertising of therapeutic goods to the public continues to be
regulated by TGA under a framework which includes an advertising code
2. Abolish pre-approvals of advertising, and move to a self-regulatory
regime
3. Requirements for advertising to the public are made consistent for all
medicines and medical devices
– currently sponsors of medical devices are responsible for ensuring that advertisements are
consistent with the intended purpose for the device
– but they are not subject to a pre-vetting process prior to publication

27. Recommendations –
Advertising of therapeutic goods
4. Advertising to the public continues to be prohibited for prescription
medicines and most pharmacist only medicines
5. New mechanism for managing complaints managed through a single
agency (either TGA, another government agency, or an external one)
6. Consideration be given as to whether the current range of investigation and
enforcement powers around advertising should be broadened
7. TGA to run a sponsor education programme to assist in achieving
compliance with advertising requirements

28. A review of a number of governance arrangements
were proposed by the Panel in the first report
• A comprehensive review of the legislative framework to simplify its structure
and language
• Review and enhance TGA’s funding model
• Review TGA’s Decision making arrangements including the role and number of
committees
• Explore integrated collaboration with HTA assessments

29. Next Steps
• Government consideration of recommendations from both reports, including
those in the second report on complementary medicines and advertising
• Once Government decisions on the proposed reforms are known,
implementation planning will be firmed up
• We will also consult closely with stakeholders in developing the finer
detail on implementation, including assessment of regulatory impacts and
fees and charges