Introduction to medical device regulation for

SMEs – John Skerritt, National Manager, TGA

The Australian Government Department of Health

(of which the TGA is a part): 1. advises that these presentation slides should not be relied upon in

any way as representing a comprehensive description of regulatory requirements

2. cannot guarantee, and assumes no legal liability or responsibility for, the accuracy, currency or completeness of the information contained in these presentation slides

The slides should not be taken to be statements of any law or policy in any way

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

What is a medical device?

4

“an instrument apparatus, appliance, material or other

article intended to be used for human beings for:

• diagnosis, prevention, monitoring, treatment or

alleviation of disease, injury or disability

• investigation, replacement or modification of the

anatomy or of a physiological process

• control of conception”

But sometimes the delineation between devices and

medicines under law is not obvious !

Bandages

Dental implant

Breast implant

Glucose monitor

Each year we receive very large numbers of

applications for devices

Medical Devices (non-IVD) IVDs

2012/13 2013/14 2012/13 2013/14

Received 6500 6300 550 640

Assessed or audited

(not auto-included)3700 3400

How does a medical device get to market?

Medical devices can not be tested like

medicines in a traditional clinical trial

Information on their performance and

safety is important prior to market authorisation

Most new devices are improvements of older

versions based on data collected from

real life use

A sponsor makes an application to include a device on the Australian Register of Therapeutic Goods(ARTG) so that it can be legally supplied in Australia

The applicant must have information available to demonstrate the quality, safety and performanceof the medical device

The device must undergo a Conformity Assessmentprocedure and comply with the Essential Principles

Benefit versus risk approach

7A device may be selected for review by TGA before, or once on the market

Risk classification is based on:

Intended use of the device

Risk to patients, users and other

persons (probability and

severity of harm)

Degree of invasiveness in the human body

Duration of use

The level of regulation is based on consideration of:

Risk classification rules – medical devices

Medical device classification Example

• Class I • Urine collection bottles

• Class Is (intended to be supplied sterile)

• Class Im (with measuring function)

• Sterile adhesive dressing

strips

• Clinical thermometer

• Class IIa

• Class IIb

• X-ray films

• Blood bags

• Class III

• AIMD (active implantable device)

• Biological heart valves

• Implantable pacemakersHigher risk

Lower risk

8

Have been regulated since July

2010 – to protect public and

personal health with a transition

period

By 2017 all IVDs – including

laboratory – developed “in

house” tests - will be regulated

In vitro diagnostic tests

Pregnancy test kits

Blood glucose meters

Blood screening

tests

Examples of IVDs

10

IVD classification Example

Class 1 IVD or Class 1 in-house IVD:

no public health risk or low personal risk

Glucose meter

Class 2 IVD or Class 2 in-house IVD:

low public health risk or moderate

personal risk

Pregnancy and fertility self-testing

kits

Class 3 IVD or Class 3 in-house IVD:

moderate public health risk or high

personal risk

Viral load and genotyping assays

Class 4 IVD or Class 4 in-house IVD:

high public health risk

IVDs used by the Australian Red

Cross Blood Service for the testing

of blood, HIV and Hepatitis C tests

Risk classification rules - IVDs

Higher risk

Lower risk

“Regulator-speak” is odd

Essential Principles Conformity

Assessment

Guidance documents

Essential principles that govern devices

• Use of medical devices not to compromise health and safety

• Design and construction of medical devices to conform to safety principles

• Medical devices to be suitable for intended purpose

• Long-term safety

• Medical devices not to be adversely affected by transport or storage

• Benefits of medical devices to outweigh any side effects

General principles

See the following slide for an example

Assessing benefits versus adverse effects

Complex medical devices used to assist with the ventricular flow of blood to the body in

patients with significant heart failure

Associated with known complications due to mechanical complexity and the patient groups

in which they are used

Clinical evidence generated by the manufacturer could demonstrate that the benefits outweigh the side effects of the device by offering significant

improvements in quality of life for users

Left ventricular assist device

Essential principles that govern devices

• Chemical, physical and biological properties

• Infection and microbial contamination

• Construction and environmental properties

• Medical devices with a measuring function

• Protection against radiation

• Medical devices connected to or equipped with an energy source

• Information to be provided with medical devices

• Clinical evidence

Principles about design and construction

Principle only applicable to IVDsSee the following slide for an example

Devices and energy sources

ECG patient monitor

Interprets the electrical activity of the heart using

electrodes attached to the surface of the skin

Manufacturer must design and produce the device in a way that ensures that when the device is used

correctly under normal conditions there is protection against faults

For example, patients and users are protected against the risk of accidental electric shock

Conformity assessmentIn

cre

asin

g le

ve

l o

f a

sse

ssm

en

tConformity assessments are all

about the manufacturer !

They are used to ensure the

essential principles and other

regulatory requirements are met.

The procedure for demonstrating

this varies depending on the

classification of the device.

Generally, the conformity

assessment procedure is more

rigorous the higher the risk class

Increasing risk classification

All medical devices supplied in Australia must be included in the ARTG

• Standard Class I devices are auto-included

• Applications for Class Is, Im, IIa and IIb are for a “kind” of device

– same classification, GMDN (Global Medical Device Nomenclature) code, manufacturer and sponsor

• Application for Class III or AIMD are only for a “kind” of device if

– it has the same Unique Product Identifier (UPI, unique identifier given by the manufacturer) and variants (to accommodate different patient anatomical requirements)

Sponsor Process Overview

Class I

Complete and submit eBS form, No application fee, Auto-inclusion

Class Is, Im, IIa or IIb

Preparation (and Manufacturer’s Evidence is accepted on eBS)

Complete and submit eBS form, fee payment processed

TGA reviews and may select for audit, approve or reject the application

Class III / AIMD

Preparation (and Manufacturer’s Evidence is accepted on eBS)

Complete and submit eBS form, fee payment processed

TGA selects for audit, Sponsor submits audit file and pays audit fee

TGA reviews audit file and may ask further questions, approve or reject the application

Mandatory audits required for:

• Class III devices (that have not been assessed under an MRA)

• Active implantable medical devices (AIMD)

• Certain contraceptives, device disinfectants, and intraocular devices

• Audits not required if the devices have TGA conformity assessment certification

A fee is payable for mandatory audits

Non-mandatory audits carried out for other devices when:

• Device classification appears incorrect or unclear

• Manufacturer’s Evidence may not clearly cover kind of device or meet

minimum Conformity Assessment requirements for the device class

• Product characteristics inconsistent with the intended purpose,

GMDN or classification

• Application appears to be for more than one kind of device

• Information provided with the application appears incorrect

No audit assessment fee is charged for these audits

Audit information that may be required

Level 1 audit

• Declaration of conformity

• Clarification of classification

• Labels, Instructions for use, Advertising material

Level 2 audit - documentation for a Level 1 audit plus

• Risk management report

• Clinical evaluation report or Notified Body audit report or Efficacy and

performance data (for devices that disinfect other devices)

Safety and performance – ongoing activitiesReviews of technical and clinical information to ensure that compliance with the essential principles and conformity assessment procedures is demonstrated

Testing to confirm compliance with the essential principles

Inspections of manufacturer or sponsor records and documentation

Audits of distribution records

Audits of the traceability of materials used in the manufacture of devices and tracking of component parts

Trend analysis and reporting to sponsors

Tools used in postmarket monitoring

Adverse event reporting

For an AIMD, Class

III or implantable

Class IIb device

Three consecutive

annual reports to the

TGA

Environmental scanning

(confidential advice from other regulators and review of medical literature, regulatory

news, media and other sources)

Managing risk

• Regulators work on a risk-benefit

assessment of products at a

population level

• The benefit of using the device

should be greater than the possible

adverse events

• Higher levels of risk may be

acceptable for a product used to

treat a terminal illness, but not for a

common or minor complaint

Definition of an adverse event

An event that resulted in, or could have resulted in, serious

injury, illness or death

A medical device adverse event can also be associated with the use (or misuse) of a device. This may include difficulties or malfunctions, such

as problems with getting the device to operate, need for repeated repairs, difficulty of use or with cleaning

The TGA is particularly interested in faults or problems with devices that

have resulted, or could have resulted, in adverse events

Recall actionsTaken to resolve a problem with a device supplied in the market when there

are issues in relation to safety, quality, performance or presentation.

Three distinct recall actions:

• Recall– e.g. product recalled due to possibility of containing a foreign substance

• Recall for product correction – e.g. insulin infusion sets recalled for product correction due to a potential safety issue if

insulin or other fluids came in contact with the set's connector

• Hazard alert– e.g. humeral resurfacing arthroplasty device, due to potential to break after implantation

You can search for recall actions via the

System for Australian Recall Actions (SARA) database.

Checking the quality of therapeutic goods

The TGA monitors and assesses manufacturers to ensure that therapeutic goods supplied in Australia are manufactured to a high standard

The emphasis and depth of manufacturer inspections, as well as the frequency of inspections, are guided by the inherent risks of the product and the method of manufacture. We also take into account the compliance and inspection history of the manufacturer

How do we do this

Quality manufacturing

On-site inspections of manufacturers and

compliance verifications (paper-based assessments)

Australian and overseas manufacturers are

assessed prior to supply of goods and are then

regularly reviewedInspections against the relevant Code of Good Manufacturing Practice (GMP) or Standard (for

devices) which describes the range of conditions required for the safe, sterile production of

goods

The manufacturer must:Have a quality management system in place under which manufacturing activities are controlled

Include in the system personnel involved in the control of therapeutic goods manufacturing and how they are trained

Provide information on how premises used in the manufacture of goods are designed, operated, maintained and controlled

Control manufacturing activities through the use of written procedures and instructions

Record manufacturing events through comprehensive record keeping practices

In Australia, the TGA manages

annually:

• ~400 licences for manufacturing,

supply and distribution sites

• ~450 sites

• ~250 inspections of sites

Inspecting Australian manufacturers

as of July 2013

0

10

20

30

40

50

60

70

80

90

good/average basic unacceptable

Perc

en

tag

e (

%)

Level of Compliance

Compliance Ratings

“ 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)

International regulatory

collaboration is a

requirement by government

International harmonisation

• International harmonisation of standards and inspections

allows for a shared workload with regulators in other

countries

• It may also include:

– joint inspections with overseas partners

– shared inspection scheduling

– sharing of information, reports and manufacturer

information

– mutual recognition of codes of GMP and standards

International Medical Device Regulators Forum (IMDRF) work program

• Medical Device Single Audit Program

• National Competent Authority Report

• Recognised Standards

• Regulated Product Submission

• Software as a Medical Device

• Integrating Patient Registries and Innovative

Tools for Enhanced Medical Device Evaluation

and Tracking

Navigating the regulatory maze

Regulatory guidance

• Australian regulatory guidelines for medical

devices – all 330 pages of it ….

• Currently developing simplified web linked

guidance…. but it’s still just guidance

• Device hotline: 1800 141 144 or

email devices@tga.gov.au

• www.tga.gov.au/sponsor-information-training-day

• ARCS, MTAA training sessions

Schemes run by other regulators

• Training days and workshops, hotlines, contact points

• Explanation of the regulatory framework as it applies to their product

• Scientific advice services (subsidised or charged)

What if I don’t agree with a TGA decision ?

You have appeal rights for most

decisions made about medical

devices but with some exceptions –e.g. selection of a device for an

application audit

See www.tga.gov.au/book/procedure

Mechanism for review of decisions

• Decisions made by TGA delegate of the Secretary, can be reviewed

under the Act if a person's interests are affected by the decision

• You may seek reconsideration by the Minister for e.g.:– a refusal to include a devices on the ARTG

– the variation or addition of conditions applying to inclusion

– suspension or cancellation of a registration or a listing

– revocation or suspension of a manufacturing licence

• The request should include a specific description and reasons why

parts of the decision are believed to be incorrect or in relation to which

you object and how your interests are affected by the decision

• The review will be dealt with by a separate delegate in the TGA

Still not satisfied ?

If not satisfied with the outcome of an internal

review, an application may be made to the

Administrative Appeals Tribunal

The AAT provides a merits review process, and

takes a fresh look at a decision and decides what

is the “best or preferable decision” - whether the

reviewable decision needs to be confirmed,

revoked or a substitute decision made

Affected parties may also appeal at any time to

the Federal Court on the legality of a decision

Expert Review of Medicine and Medical Device Regulation

• Review is examining medicines and medical devices regulation to

identify areas of unnecessary, duplicative, or ineffective regulation

and propose opportunities to enhance the regulatory framework

• A detailed discussion paper was released in Nov 2014 and the panel

have publicly indicated that the issues raised in the paper will also be

used to structure their report.

• First panel report was submitted to Government on March 31 2015 and

the next steps are under consideration by Government

Some issues raised in the devices chapter of the discussion paper – the regulatory framework

• Should accelerated or provisional device approvals be implemented ?

• Is the current system flexible enough to accommodate new and

emerging medical device technologies ?

• Do we have the balance right between pre-market and post-market

regulation of medical devices ?

• Far less information is publicly available about device evaluation than for

medicines. Should evaluation reports and other information about

regulatory decisions for devices be publicly available ?

Some issues raised in the devices chapter of the discussion paper – international convergence

• The Australian system is based on conformity assessment by Notified

Bodies. To manage concerns, should TGA undertake its own assessment of

the competence of notified bodies vs working with European oversight

processes ?

• Should a medical device be approved automatically for the same purpose by

a ‘trusted’ overseas regulator (presumably without further audit) ?

• Should Australia recognise other (non-European) regulatory systems ?

• Are there aspects of safety, quality or efficacy that need to be considered in

the Australian context ?

Clinical assessment guidance documents

• Their role will depend on Medicines and Devices Review

• Purpose is to clarify approaches to assessment of clinical

evidence for TGA/PLAC, industry and health care professionals

• Working with ASERNIPS (Aust. Safety and Efficacy Register of

New Interventional Procedures – Surgical) and Clinical Groups

• Need to consider – duration of clinical experience with the product, validation of endpoints

– whether ISO standards exist for the device group

– post market data duration, registries

– bench testing requirements, use of data from predicate devices

Some other TGA developments

• Customer Self Service Interface to provide better service / information

• Replacement of LVT with ACE (Annual Charge Exemption Scheme)

• Regulations amended to include definitions of total and partial shoulder,

hip or knee joint replacements and ancillary joint replacement devices

• Upcoming review of Uniform Recall Procedure for Therapeutic Goods – to increase transparency, include biologicals, communicate to private

hospitals and other stakeholders, clarify mandatory recalls

• Clearing backlogs of conformity assessment applications – no applications on hand > 200 TGA days -first time since 2007

TGA - wide Business Improvement Program

Easier engagement with TGA

• Continue to enable electronic submissions for device regulatory processes

• Strengthened guidelines and supporting information for sponsors and

manufacturers to enhance their interactions with TGA

Ensuring accurate and useful information available in real time

• Centralised data repository – single source of data

• New client portal for sponsors and manufacturers – to check application

status, receive invoices, and respond to requests for additional information

• Rollout of a client relationship management system within TGA

Annual charge exemption scheme – devices

• Annual charges exemption granted until first turnover (and for existing products that have not been sold since July 2013)

• No application required – self declaration through client portal

• No application fee – saving $2.4m in fees to industry

• Waiver of annual charge where a product in low supply is critical for public health

• Audit program to detect incorrect declarations

• Base annual charge rates reduce by 5 % for class II, III, AIMD devices

• Regulations anticipated to be formally approved in May

And some IVD regulatory reforms….

• Amended definition of a medical device to include tests

for predisposition and susceptibility to a disease

• Modified conformity assessment procedure for

manufacturers of in-house Class 4 IVDs based on

acceptance of third party evidence of a QMS certificate

• Alternative accreditation for manufacturers of class

1,2, and 3 in-house IVDs to remove need for labs to

provide TGA with a list of individual tests

• New guidance document on performance requirements

for self test, point of care and lab HIV tests

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