Presentations by TGA and Industry (combined) to help sponsors and manufacturers better understand the regulation of medical devices and in-vitro diagnostic medical devices

1. Developments in medical device
regulation - 15 October 2015
John Skerritt
Deputy Secretary, Regulatory Services
Commonwealth Department of Health

2. This presentation
• Introducing the Devices Sponsor Information Day
• New Department of Health Regulatory Services Group and
changes to TGA structure
• Key facts and figures
• Expert Panel Review of Medicines and Medical Devices
Regulation
• International Collaboration
• Other changes made / anticipated to the IVD regulations
• Navigating the regulatory maze
• New Regulator Performance framework

3. The Devices Sponsor Information Day
• Today’s presentations are about the current regulatory
framework …although my presentation will look at emerging
trends and possible regulatory reforms
• Today is a great example of collaboration (in planning and
session delivery) between the Department of Health (TGA) and
four industry associations
• Two Streams
– Both - Conformity Assessment, GMP, Clinical Evidence (pre- and
post-market), Adverse events, Advertising and recalls
– Devices - Manufacturer evidence, ARTG inclusion, Audits, Lifecycle
– IVDs – Application processes, Technical File Reviews, Lifecycle

4. TGA’s role – part of the Department of Health
• Regulates therapeutic goods including prescription, over-the-
counter and complementary medicines, medical devices,
biologicals, blood and blood products
• Evaluates therapeutic goods before they are marketed and
monitors products once they are on the market
• Assesses the suitability of medicines and medical devices for
export
• Focuses on safety, efficacy and quality
• We do not make regulatory decisions based on value for money
or make decisions about which products receive Government
subsidy

5. Regulatory Services Group Structure
Medicines
Regulation
Medical
Devices and
Product Quality
Prescription
Medicines
Authorisation
Complementary
and OTC
Medicines
Pharmacovigilance
and Special
Access
Medical Devices
Laboratories
Manufacturing
Quality
Regulatory
Practice and
Support
Regulatory
Practice,
Education and
Compliance
Regulatory
Services and
Improvement
Regulatory
Engagement and
Planning
Office of
Chemical
Safety
Industrial Chemicals
(NICNAS)
AgVet Chemicals
Office of Gene
Technology
Regulator
Regulatory Practice
and Compliance
Evaluation
Scientific
Evaluation
Assistant
Minister for
Health
Regulatory Services Group
Deputy Secretary
Principal Medical
Adviser
Principal Legal and
Policy Adviser
Department of Health
Secretary
5

6. Medical Devices Branch
(Head: Dr Cheryl McRae)
Conformity Assessment (Dr Elizabeth McGrath)
Applications and Verification (Irina Tsyganova)
Devices Clinical (Dr Rona Hiam)
Devices Vigilance and Monitoring (Pamela Carter)
IVD Reforms (Michelle McNiven)
Business Improvement and Support (Rachel Croome)

7. Some key facts and figures
Did you know that as of 30 June 2015, there were:
47,458 medical devices on the ARTG
1,993 In vitro diagnostics on the ARTG
Compared with (only)….
15,425 prescription medicines ?

8. Conformity Assessment
Conformity
Assessment
Applications
Medical Devices IVDs
2012/13 2013/14 2014/15 2012/13 2013/14 2014/15
Received 190 195 141 34 40 19
Completed 188 245 161 18 41 40
- Successful 77 % 72 % 71 % 72 % 88 % 78 %
Main reason for rejections and applications withdrawn by the applicant is
errors in applications, the poor quality and/or unavailable data, including
clinical, engineering, biomaterials and quality management system
information

9. Inclusion in the ARTG
Applications
for Inclusion:
Medical Devices IVDs
2012/13 2013/14 2014/15 2012/13 2013/14 2014/15
Received
6500
(3700
assessed or
audited)
6300
(3400
assessed or
audited)
6100
(3600
assessed or
audited)
550 640 720
Completed 5850 (3050) 6700 (3800) 5900 (3400) 520 610 650
- Successfully
assessed or
audited
88 % 87 % 89 % 85 % 91 % 90 %
Applications for inclusion may be rejected or withdrawn due to incorrect
classification, or if information is not available such as clinical evidence
or information on conformity assessment procedures

10. Post Market reviews
Year
ARTG entries
reviewed
Reviews
completed
Cancelled by
sponsor
Cancelled by
TGA
2013 130 90 21 3
2014 226 168 34 13
Sponsor cancellations often due to device no longer being supplied, superseded,
manufacturer / sponsor changes.
TGA cancellations often due to non-response to s41JA requests for information,
inability to certify matters, non-compliance with class I auto-inclusion conditions.

11. Adverse event reports by class – 2014
245, 6%
1144, 26%
1757, 40%
480, 11%
35, 1%
291, 7%
7, 0% 38, 1% 77, 2% 253, 6% AIMD
Class III
Class IIb
Class IIa
Class 1
Sterile
Class 1
For Class II, III and AIMD devices this is roughly proportional to the
number of devices on the ARTG. Class I devices have few reports
despite representing around half of all devices on the ARTG.

12. Expert Panel Review of Medicine and
Medical Device Regulation
• Announced Oct 2014 to examine medicines and medical
devices regulation “to identify areas of unnecessary,
duplicative, or ineffective regulation and propose
opportunities to enhance the regulatory framework”
• First report on medicines and medical devices,
provided to government on 31 March and second report
on complementary medicines and advertising on 31 July
2015
• Devices stakeholder workshop run on 6 August 2015
• Next steps currently under consideration by the
Government

13. 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, as a sovereign entity,
retain responsibility for approving the inclusion of
therapeutic goods in the ARTG

14. 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

15. Review recommendations for Medical Devices
(also apply to IVDs)
• Multiple pathways are proposed for Class II, III, AIMD
devices and Class 2–4 IVD products:
– Conformity Assessment within Australia by either TGA or
a separate body designated by TGA; OR
– Utilisation of marketing approval for the device in an
overseas market where the device has been:
 Conformity Assessed by a body that has been designated by a
comparable overseas Designating Authority; or
 Approved by a comparable overseas regulatory authority
• Expedited approval process for devices in some
circumstances

16. Much further consultation will be needed as
implementation would be complex
• Few commercial conformity assessment bodies currently
exist in Australia
• International device/ IVD regulatory frameworks are quite
different to Australia and undergoing significant change, e.g.
– New European Device and IVD Regulations
– The US FDA system is very different - PMA vs 510(k), lack of clarity
around laboratory developed IVD tests
• Will need to define criteria and decision rights for expedited
approval of devices
• Approach to confidence building in notified bodies if there
are to be fewer application audits

17. Confidence building will require agreement
TGA accepts Conformity Assessment certification from Notified
Bodies, but highest risk devices currently have application audits
ARTG = 48,000
device entries
Highest risk
devices
(Class III and
AIMD) = 4,300
Manufactured
overseas=
4,250 (>98%)
Over 80% of highest risk
AIMDs/Class III devices are
included on the ARTG with
Conformity Assessment
certification from six Notified
Bodies:
• BSI (UK)
• TUV SUD (Germany)
• LNE/G-MED (France)
• Dekra (Netherlands)
• Lloyds LRQA (UK)
• Intertek (UK)

18. Other device / IVD recommendations
• Set binding timeframes for Conformity Assessment within
Australia or for device inclusion using an international approval
• Auto-inclusion of Class I devices to continue (unless if class
1 IVD selected for technical file review)
• Streamline access to medicines and medical devices
(including IVDs) that have not been approved in Australia
– Some SAS Category B applications could be subject to automatic
approval
– Online system for SAS notifications, approvals and reporting

19. Finally, a review of governance
arrangements was proposed by the Panel
• Comprehensive review of the
legislative framework to simplify its
structure and language
• Review and enhance TGA’s funding
model
• Alternative decision making
arrangements, including committees
• Greater collaboration with HTA
assessments (e.g. PBAC, MSAC)

20. IVD regulatory framework
• From 1990 to 2010 a limited number of
IVDs were regulated in Australia
including HIV and Hepatitis C virus
(HCV) tests
• In 2010 Australia introduced a more
comprehensive regulatory framework for
IVDs under the Therapeutic Goods
(Medical Devices) Regulations 2002
• New framework covers both commercial
and in-house (laboratory developed)
IVDs but not research use only or
analyte-specific reagents

21. Some current IVD regulatory reforms….
• Amended definition of a medical device to
include tests for predisposition and
susceptibility to a disease
• Modification to Classification for Class 3
IVDs that detect pathogens to remove
reference to National Notifiable Disease
Surveillance System list to instead use risk-
based classification principles (some IVDs may
be down classified to Class 2)
• Timeframe for submission of applications
for inclusion in the ARTG for commercial
IVDs had been extended but is now over !

22. International regulatory
collaboration now a formal
requirement by government
“ if a system, service or product has been approved under a
trusted international standard or risk assessment, then our
regulators should not impose any additional requirements
for approval in Australia, unless it can be demonstrated that
there is a good reason to do so…..
……. As an important first step, the Government will enable
Australian manufacturers of medical devices the option
of using EU certification in place of TGA certification.”
(media release 14 Oct 2014)

23. • Aims to accelerate international device
regulatory harmonisation and
convergence
• Established in 2012 to build on foundational
work of GHTF (Global Harmonization
Taskforce on Medical Devices)
• Members: Australia, Brazil, Canada, China,
EU, Japan, Russia and USA
• Asian Harmonization Working Party and
PAHO are affiliates and WHO and APEC are
observers

24. IMDRF Medical Device Single Audit Program
Pilot from Jan 2014 for 3 years to:
• Promote greater alignment of regulatory
approaches and technical requirements
• Develop a standard set of requirements for third
party organisations performing audits of
manufacturers’ QMS on behalf of regulators
• Standardise oversight practices and
procedures of participating regulators over third
party auditing organisations, and the auditing
organisations themselves
• Enable TGA resources to be focused on
problematic devices, manufacturers that are not
in compliance with regulations, and oversight of
third party auditors

25. IMDRF Medical Device Single Audit Program
Mid-pilot report released recently
• Third party Canadian auditing
organisation “registrars” assessed,
undergoing MDSAP recognition
requirements, comprehensive MDSAP QA
system established
• By end July 2015: several witnessed
audits conducted, 10 audits of
manufacturers conducted, 45
manufacturing sites requested participation
in the MDSAP program
• Initial progress is good – but greater
manufacturer participation will be vital to
success !

26. Other IMDRF projects
• Table of Contents pilot
– Will develop a comprehensive submission structure as an
international format for device premarket evaluation
– Greater uniformity and reduced regional divergence will reduce
burden on sponsors and increase efficiency of review
– TGA current seeking applications from sponsors to trial
• National Competent Authority Report review
– Facilitates exchange of post market safety information
• Software as a Medical Device
– Definitions document, Framework for Risk Categorization
– Harmonized vocabulary and considerations for manufacturers,
regulators and users to address unique challenges with SaMD

27. Other IMDRF projects
Completed
• Use of recognised Standards for devices to increase consistency
• Roadmap for UDI implementation
Recently initiated
• Integrating Patient Registries and Innovative Tools for Enhanced
Medical Device Evaluation and Tracking
• Medical device adverse event terminology
• Good regulatory review practice

28. Draft medical device clinical assessment
guidance documents
• Developed as drafts together with ASERNIPS (Australian Safety and
Efficacy Register of New Interventional Procedures – Surgical)
• These guidance documents do not intend to change regulatory
requirements but rather document the current situation
• Purpose is to clarify approaches to assessment of clinical
evidence for TGA evaluators, and help industry through providing
consistent advice
• No internationally accepted standards exist for clinical evidence for
many types of devices, so much interest from IMDRF members
• Consultation with PLAC, clinical craft groups and the device industry
will be the next step

29. Draft medical device clinical assessment
guidance documents: content
• General clinical evidence guidelines/ legislative requirements
– clinical dossiers, evaluation report and evaluation of clinical data
• Demonstrating substantial equivalence - guidance on use of
clinical evidence from predicate devices
• Guidance on specific high-risk device groups
– Total and partial joint prostheses
– Cardiovascular devices (that promote patency or functional flow)
– Electrical impulse generators
– Heart valve prostheses
– Supportive devices – meshes, patches and tissue adhesives
– Demonstrating MRI safety of active implantable medical devices
(e.g. cardiac pacemakers)

30. International inspection harmonisation
• About 90 % of overseas inspections are avoided
by TGA’s use of desktop clearances based on
information provided by other regulators
• International collaboration also includes:
– joint inspections with overseas partners
– Involvement in MDSAP
– shared inspection scheduling
– sharing of information, reports and manufacturer
information
– mutual recognition of codes and standards

31. Navigating the regulatory maze
• Australian regulatory guidelines for medical
devices – all 330 pages of it ….
• Currently developing simplified web linked
guidance….
• Device hotline: 1800 141 144 or
email devices@tga.gov.au
• SME workshops and contact points are
under consideration

32. Subscribe to the
TGA information
services to stay
up-to-date:
www.tga.gov.au
Receive information on:
• Safety alerts
• Recall actions
• Medical Devices Safety Update
• Consultations
• Publications
More specific information
• Therapeutic Goods Act 1989
(especially Chapter 4)
• Therapeutic Goods (Medical
Devices) Regulations 2002
• Australian Regulatory Guidelines for
Medical Devices

33. TGA Business Improvement Program
• Continue to enable electronic
submissions for device regulatory
processes
• Strengthened guidelines and
supporting information for sponsors
and manufacturers
• Centralised data repository – single
source of data a client relationship
management system
• New client self-service portal for
sponsors and manufacturers to
− check application status
− receive invoices
− respond to requests for information

34. Development underway of a new application form for
conformity assessment certificates
• Industry working group identified ways to improve the application form:
– See only what is applicable to your application
– Pre-population of information the TGA already has
– Guides the applicant with the information required
– Ability for TGA to push the form back to the client for more information
– Access to TGA issued CA certificates within the application
– Clear explanations and examples to assist with providing information
BIP Conformity Assessment Workflow tool
• Being further developed to remove problem issues
– Will support the CA process through: a CA Application eForm, workflow automation
for the administrative process, a CA Certificate Repository and Reporting Capability
• In 2016 work will commence on integrating other device business processes
into BIP, but will depend on changes to regulation that flow out of the MMDR

35. Regulator Performance Framework (from July 2015)
• Encourages regulators to have the minimum impact necessary to
achieve objectives and to effect positive ongoing and lasting change
• Six KPIs articulate the Government's expectations:
– Regulators do not unnecessarily impede the efficient operation of
regulated entities
– Communication with regulated entities is clear, targeted and effective
– Actions undertaken by regulators are proportionate to risk managed
– Compliance and monitoring approaches are streamlined and
coordinated
– Regulators are open and transparent in dealing with regulated entities
– Regulators actively contribute to continuous improvement of the
regulatory framework
• KPIs are supported by measures of good regulatory performance

36. Next steps for regulatory reform
• The MMDR recommendations (if accepted by Government) will
provide an opportunity to implement many welcome changes
• Government consideration of recommendations still to take place
• Once Government decisions on the proposed reforms are known,
implementation planning will be firmed up
• We need to agree a governance plan and timeline, resource
allocation, and the roles and responsibilities of different parts of TGA
• Reforms outside the Expert Panel Review continue (e.g. business
process reforms, in-house IVDs, Business Improvement Program)
• But today’s sessions are about the current regulatory framework !