Medical Device Regulation

Medical Device Regulation

Stephanie Miles

Quality and Regulatory Specialist

MedTech’s Got Talent Workshop

9th January 2017

www.hydrix.com Commercial-in-Confidence

Hydrix

• Hydrix specialises in the design and development of high

technology devices for clients around the world

• Hydrix takes ideas and turns them into world class

medical devices

• We grow and develop the capabilities of our people to

make this possible


Hydrix: People and Processes


Agenda

• Why do we need regulation?

• Who regulates medical devices?

• Medical device definition

• Overview of regulatory framework

• Medical device regulation in Australia, Europe and

the USA

• Regulatory strategy


Why do we need regulation?

Australian doctor William McBride alerted

the world to the dangers of thalidomidein the 1960s which triggered the need for

an Australian regulator of therapeutic goods.

“In recent months I have

observed that the incidence of

multiple severe abnormalities

in babies delivered of women

who were given the drug

thalidomide (‘Distival’) during

pregnancy, as an anti-emetic

or as a sedative, to be almost 20%.”


What is a medical device?

Any instrument apparatus, appliance, material or other article

(whether used alone or in combination, and including the software

necessary for its proper application) intended to be used for human

beings for:

• diagnosis, prevention, monitoring, treatment or alleviation

of disease;

• diagnosis, monitoring, treatment, alleviation or

compensation for an injury or handicap;

• investigation, replacement or modification of the anatomy or

of a physiological process;

• control of conception; or

• an accessory to an instrument, apparatus, appliance,

material or other article mentioned above

It may not achieve its principal intended action by

pharmacological, immunological or metabolic means, but may be

assisted by such means

Bandages

Dental implant

Breast implant

Glucose monitor

Defined in s41BD of the Therapeutic Goods Act 1989


Articles declared not to be medical devices

Therapeutic Goods (Articles that are not Medical Devices) Order No. 1 of 2010

declares that the following are not medical devices:

� Chemical oxygen generators

� In-vivo imaging agents

� Product intended to deliver a medicine, where the medicine and device

are a single integral product (which is not reusable)

� Products incorporating tissues, cells, substances of human origin

� Products incorporating viable tissues, cells, substances of animal origin

� Hospital and household grade disinfectants


Software – is it a medical device?

A software product is a medical device if it meets the definition of a medical

device (s41BD of the Therapeutic Goods Act 1989)

Examples A software product that is

limited to managing and

presenting information

(e.g. records management

system or dosage

calculator) would not

normally meet the

definition unless it also

incorporates a therapeutic

or diagnostic function

• Mobile app used to measure blood glucose levels for

monitoring diabetes

• Software which analyses and interprets ECG signals

• Software running an infusion pump to control dose

delivery


Who regulates medical devices?

• Therapeutic Goods Administration (TGA)Australia

• Certification is obtained from a Notified BodyEurope

• Food and Drug Administration (FDA)USA

• Health CanadaCanada

• The State Food and Drug Administration (SFDA)China

• Ministry of Health Labour and Welfare (MHLW)Japan

• ANVISABrazil

*Determine your target markets*


Overview of Regulatory Framework

Intended use and device characteristics

Classification

Regulatory requirements

Regulatory submission process


Intended use

Intended use

The general purpose of the medical device or its function (what you “claim”

the medical device does)

Example:

…. is a diagnostic x-ray system for generation of x-rays for examination of various

anatomical regions


Medical Device Regulation in Australia


1. Classification

Determined by the rules in Schedule 2 and 2A,

Part 1 of the Therapeutic Goods (Medical

Device) Regulations 2002


1. Classification

The classification is risk based and determined by a set of rules in Schedule 2, Part 1 of the Therapeutic Goods (Medical Device) Regulations 2002. Rules for IVD medical devices are set out in Schedule 2A.

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

Power supply (active/non-active)

Location of use


Risk classification – 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

medical device)

• Biological heart valves

• Implantable pacemakersHigher

risk

Lower risk


IVD classification Example

Class 1 IVD or Class 1 in-house

IVD:

no public health risk or low

personal risk

Microbiological culture media,

Instruments/analysers


IVD:

low public health risk or moderate

personal risk

Pregnancy and fertility self-

testing kits


IVD: moderate public health risk

or high personal risk

Tests for sexually transmitted

diseases


IVD:

high public health risk

All tests used by the Australian

Red Cross Blood Service for

the testing of blood

Risk classification - IVDs

Higher risk

Lower risk


2. Regulatory requirements(Conformity Assessment)

Based on the classification, we can determine

the appropriate conformity assessment

procedure…

TGA Conformity Assessment Procedure Options

Part 1 Part 1 Part 2 Part 6

Full Quality Assurance

(TGA Inspection)

Type Examination

(Conducted by TGA)

Part 3

Device Verification

Statistical Verification

(Testing conducted

by TGA)

Declaration of

Conformity

Design Examination

(Part 1.6)

(Conducted by TGA)


(TGA Inspection)

Post-market monitoring

system


(TGA Inspection)

Part 3

Device Verification

100% Verification

(Testing conducted

by TGA)

Surveillance Audit

Surveillance Audit

Part 4

Production Quality

Assurance

(TGA Inspection)

Surveillance Audit

Part 5

Product Quality

Assurance

(TGA Inspection

Surveillance Audit

Class III & AIMD Class IIb or below Class AIMD, III, IIb Class IIa, I(s), I(m) & I

Class AIMD, III, IIb, IIa, I(m) & I(s)

Class IIb, IIa & I(m)

Class AIMD, III, IIb, IIa, I(m)

Class III, IIb, IIa & I(m)

Desig

nP

roduction

TGA Conformity Assessment Procedure Options


Conformity Assessment

• Quality management system in compliance with ISO 13485 (except for Class I devices)

Quality Management System


• Surveillance of product performance in the market

Post market surveillancePost market surveillance

• Technical documentation for the design of the device (compliance with Essential Principles)

Technical documentation


• Declaration that the device complies with the regulatory requirements

Declaration of Conformity

Declaration of Conformity

The Conformity Assessment Procedures require the following elements:



• ISO 13485 specifies requirements for a Quality Management System

(QMS) for the design, development, production, installation and

servicing of medical devices

• Requirements include:

• Documentation requirements (written procedures, as well as

document and record control)

• Management responsibility

• Resource requirements

• Design control

• Purchasing requirements

• Control of production and service

• Monitoring processes and product

• Used to demonstrate an organisation can provide medical devices that

consistently meet customer and regulatory requirements


Conceived by Research Improved by Marketing Designed by Engineering

Built by Manufacturing Installed What the user needs

If you don’t know where you’re going you might not get there!

Yogi Berra

Design and Development PlanningDesign and Development PlanningDesign and Development PlanningDesign and Development Planning



Design Control

Image taken from the FDA Design Control Guidance For Medical Device Manufacturers

www.fda.gov/RegulatoryInformation/Guidances/ucm070627.htm


Good design or bad design?


Good design or bad design?


What is the cost of bad design?

A report by the FDA shows a 97% increase in recalls of medical devices between fiscal years 2003 and 2012.

FDA researchers found that software design failures accounted for the most common recall causes, making up about 15% of all device recalls between 2010 and 2012.

The cost of rework, re-design and re-submission can kill companies!



Technical documentation for the design of the device must be

held by the manufacturer and may be reviewed by the TGA for

compliance with the Essential Principles


Essential principles that govern devices

1. Use of medical devices not to compromise health and safety

2. Design and construction of medical devices to conform to safety principles, having regard to the generally acknowledged state of the art

3. Medical devices to be suitable for intended purpose

General principles

We’ll discuss this further


Standards

State-of-the-art

• ISO 14971 Medical devices – Application of risk

management to medical devices

• IEC 62304 Medical device software – Software life

cycle processes

• IEC 62366-1 Medical devices – Part 1: Application of

usability engineering to medical devices

• IEC 60601-1 Medical electrical equipment – Part 1:

General requirements for basic safety and essential

performance

• ISO 10993-1 Biological evaluation of medical devices

– Part 1: Evaluation and testing within a risk

management process

• There are many other product specific standards


Standards - ‘State of the art’

29

If a patient’s natural heart valve fails, an artificial heart valve may be used to replace it

ISO 5840:2005 is an international standard for the design and manufacture of heart valve substitutes.

It includes tests to assess the physical, chemical, biological and mechanical properties of the device

This testing is one way of demonstrating compliance with the state of the art

(Essential Principle 2)

Artificial heart valve

‘Artificial heart valves (450128462)’ by Patrick J. Lynch,

https://commons.wikimedia.org/wiki/File:Artificial_heart_valves_(450128462).jpg

Licence at http://creativecommons.org/licenses/by/2.0


Risk Management

• ISO 14971:2007 Medical Devices - Application of risk management to

medical devices

• Process to identify the hazards associated with medical devices,

estimate and evaluate the associated risks, to control these risks, and

to monitor the effectiveness of the controls

• Structured process and team effort

Clinician

Software

Electronic

Systems

Service

Tech Nurse

Manufacturing


Example - Risk Analysis Tools

� Hazard Analysis

� Fault Tree Analysis (FTA)

� Failure Mode and

Effects Analysis (FMEA)

Figure sourced from http://asq.org/quality-

progress/2002/03/problem-solving/what-is-a-fault-

tree-analysis.html


Risk control/mitigation

Inherently safe design

Protection measures including alarms

Inform users of residual risks e.g. labelling & instructions for use

Eliminate or

reduce risks

Warn users of risks

Document risks



4. Long-term safety

5. Medical devices not to be adversely affected by transport or storage

6. Benefits of medical devices to outweigh any side effects

General principles

See the following slide for an example


Assessing benefits versus known side effects

34

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

with significant heart failure

Associated with a number of known complications due to their 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



7. Chemical, physical and biological properties

8. Infection and microbial contamination

9. Construction and environmental properties

10.Medical devices with a measuring function

Principles about design and construction

Principle only applicable to IVDsSee the following slide for an example


Biological safety

36

Local effects e.g. cell death, irritation

Systemic effects e.g. sensitisation, toxicity, genotoxicity

Does the medical device come into direct contact with the patient’s body?

Are there any unwanted biological effects?

ISO 10993 includes tests for biological evaluation of medical devices

Essential Principle 7 requires the manufacturer to

consider the biological properties of the device



11. Protection against radiation

12. Medical devices connected to or equipped with an energy source

13. Information to be provided with medical devices

14. Clinical evidence

15. Principles applying to IVD medical devices only

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

IEC 60601 is a series of standards related to the safety and performance of medical electrical equipment


Clinical EvidenceEssential Principle 14

Clinical evidence demonstrating safety and performance is a requirement for

every medical device. The level of clinical evidence required varies depending

on the use and classification of the device.

Clinical evidence may comprise:

� Full clinical study report

� Literature review

� Post market data


3. Pre-market submission


How does a medical device get on the ARTG?

• Determine the device classification

• The manufacturer must demonstrate that the device complies with the Essential Principles and Conformity Assessment Procedures have been applied

• The manufacturer makes a Declaration of Conformity

• The manufacturer applies for a Conformity Assessment Certificate (with the exception of Class I medical devices)

• A sponsor submits Manufacturer’s Evidence (Conformity Assessment Certificate) using the TGA online eBS system

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


Fees

* Reference https://www.tga.gov.au/book-page/medical-devices

Current as of January 2017


Medical Device Regulation in Europe


European Regulations

� Medical Device Directive 93/42/EEC

� IVD Medical Device Directive 98/79/EEC

� Active Implantable Medical Devices Directive 90/385/EEC

Other directives to consider:

� 2011/65/EU Restricted Hazardous Substances (RoHS II)

� 2012/19/EC on Waste and Electrical and Electronic Equipment (WEEE II)

� Regulation No. 1907/2006 REACH

� 2006/66/EC on Batteries

� 94/62/EC on Packaging and Packaging Waste


Overview of EU Regulatory Process

• Determine the device classification* and applicable conformity assessment procedure

• Implement a Quality Management System (ISO 13485)

• Prepare a Technical File which demonstrates compliance with the Essential Requirements and any other applicable directives

• Appoint an Authorised Representative (EC Rep) located in Europe and ensure their name and address is included on the device labelling

• Prepare a European Declaration of Conformity

• Employ a Notified Body to audit the manufacturer’s Quality Management System and Technical File or Design Dossier. If successful, then the manufacturer is issued with a European CE Certificate

• Affix the CE mark to the device

* Classification rules in Annex IX of MDD 93/42/EEC and IVD MDD 98/79/EEC


Medical Device Regulation in the USA


1. Device Classification

Medical Devices are regulated by the US Food and Drug

Administration (FDA).

• FDA classification database:

https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cf

pcd/classification.cfm


2. Regulatory requirements

Class Regulatory requirements

Class I (low risk) General controls*

Class II (moderate risk) General controls*

Special controls:

- Performance standards

- Post-market surveillance

- Patient registries

- Special labelling

- Pre-market data requirements

- Guidelines

Class III (high risk) General controls*

Premarket Approval (PMA)

* General controls include, but are not limited to: establishment

registration and device listing, records and reports, and Quality System

Regulation (QSR) defined in 21 CFR Part 820.


2. Regulatory requirements

Determine the type of submission required

Premarket Notification 510(k)

- Applicable to some Class I and most Class II devices

- A submission is made to demonstrate a device is at least as safe and effective (substantially equivalent) to a legally marketed or predicate device

- Predicate devices can be found by searching the FDA 510(k) database (http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm)

Premarket Approval (PMA)

- Applicable to most Class III devices

- Most stringent type of submission. It involves an in-depth assessment to determine there is sufficient valid scientific evidence to assure the device is safe and effective

De Novo

- Novel devices not previously classified are automatically Class III, regardless of the risk they pose

- The De Novo pathway allows the FDA to re-classify low to medium risk devices from Class III to Class I or Class II

Humanitarian Device Exemption

- Applicable to Class III devices intended to benefit patients with rare diseases or conditions, that is, affecting less than 4,000 individuals in the United States per year


3. Pre-market submission process

• Determine the classification and regulatory requirements

• Implement a Quality Management System which meets the FDA QSR (21 CFR Part 820)

• Prepare information for submission and organise pre-submission meeting if required

• Submit pre-market submission to the FDA for approval. If successful, the FDA issues clearance or approval letter

• If you have no local presence in the US, appoint an FDA US Agent representative as a local point of contact with the FDA

• Complete the establishment registration and device listing


Fees

*Reference http://www.fda.gov/ForIndustry/UserFees/MedicalDeviceUserFee/ucm452519.htm


Regulatory Strategy


Questions?


Contact

Stephanie Miles

Quality and Regulatory Specialist

[email protected]

0422 001 723

Small Business & Entrepreneurship

Medical Device Regulation