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 thalidomide
in 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 pacemakers
Higher
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)
Full Quality
Assurance
(TGA
Inspection)
Post-market
monitoring
system
Full Quality
Assurance
(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)
DesignProductionTGA Conformity Assessment Procedure Options

Conformity Assessment
• Quality management system in compliance
with ISO 13485 (except for Class I devices)
Quality Management
System
Quality Management
System
• Surveillance of product performance in the
market
Post market
surveillance
Post market
surveillance
• Technical documentation for the design of the
device (compliance with Essential Principles)
Technical
documentation
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:

Quality Management System
• 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

Quality Management System
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?

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
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 IVDs
See 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 Evidence
Essential 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

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.

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
stephanie.miles@hydrix.com
0422 001 723

Medical Device Regulation

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