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

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

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

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

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

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)

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 ?

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

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

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.

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 1SterileClass 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.

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

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

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

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

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

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)

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

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)

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

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 !

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)

• 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

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

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 !

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

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

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

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)

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

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

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

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

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

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

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 !