Regulation on CE Mark, ISO 13485 and other red tape stuff

1. Medical Electronics ELEC5650M
The Product Development Cycle in
the Medical Device Industry
Overview
• Context in which medical electronics products are used
• Implications for product development
• The Medical Devices Directive and other regulatory issues
• Practicalities and the product development cycle
• Practical examples
• A few comments on wider (business/marketing) issues

2. What is a medical device?
Any instrument, apparatus, appliance, software, material or other article,
whether used alone or in combination, including the software intended by its
manufacturer to be used specifically for diagnostic and/or therapeutic
purposes and necessary for its proper application, intended by the
manufacturer to be used for human beings for the purpose of:
• Diagnosis, prevention, monitoring, treatment or alleviation of disease
• Diagnosis, monitoring, treatment, alleviation of or compensation for an injury or
handicap
• Investigation, replacement or modification of the anatomy or of a physiological
process
• Control of conception
and which does not achieve its principal intended action in or on the human body by
pharmacological, immunological or metabolic means, but which may be assisted in
its function by such means.
EU Medical Devices Directive (93/42/EEC)
Simplified definition
Any product used for diagnosis, treatment or prevention of an
illness
But not drug-based…at least not solely
• Drug-device combinations exist and will increase in prevalence.
Includes software and software/hardware combinations.

3. Scope and examples
Devices used in the home
• Plasters, thermometers etc.
Devices used in hospitals and GP surgeries
• Diagnostic: ECG monitors, CT or MRI scanners,
stethoscopes, X-ray equipment etc.
• Therapeutic: surgical instruments, implants,
defibrillators etc.
• Hoists, beds, assistive aids etc.
Context is important – intended purpose.
A regulated market
A medical device cannot be ‘put on the market’ or ‘put into
service’ unless it has been checked and certified that it meets
the regulations for the country it is to be used in.
This applies whether the device is to be sold or used free of
charge.
• Within the EU, medical devices are regulated by the Medical Devices
Directive (CE mark)
• In USA, they are regulated by FDA (Food and Drug Administration)
• Other countries have their own systems

4. Principles of regulatory system
Risk management
• It must not cause any unnecessary risk to the patient, users, or anyone
else (eg. general public)
Verification
• It should ‘do what it says on the tin’
• In other words it should perform as claimed by the manufacturer
Validation
• It must be independently evaluated by a person with appropriate clinical
qualifications
• If necessary, clinical testing or trials should be done.
Product development
What does this mean for product development of medical
devices?

5. The context
Who uses it?
Under what conditions and
circumstances?
What could happen if
something goes wrong?
Could it give the wrong result?
How? What would happen?
How can it be designed, manufactured, labelled etc. to address all these points?
If something goes wrong…
Traceability is important.
If there is a problem, need to know
• Why?
• What caused it (design error, faulty components, manufacturing error,
not used correctly)?
• What can be done to prevent it happening again (This could include
withdrawal of the product certification and even prosecution)?
The regulatory bodies (MHRA, FDA etc) have extensive
powers of investigation and enforcement.

6. Product lifecycle
The whole product lifecycle is regulated by different bodies.
Key to next slide:
MHRA – Medicines and Healthcare products Regulatory Agency
(www.mhra.gov.uk)
NICE – National Institute for Health and Clinical Excellence
(www.nice.org.uk)
WEEE – Waste Electrical and Electronic Equipment Directive
Who regulates what?
Stage of product lifecycle Who regulates
Product design MHRA
Approvals testing, clinical MHRA
evaluation
User protocol development MHRA, NICE, NHS
Manufacturing MHRA
Use phase MHRA, NICE
Adverse incidents MHRA
Disposal – end of life Not currently regulated specifically for
medical devices – other regulations may
apply, eg. WEEE

7. Classification
How stringent is all this accreditation process?
It depends on
• The degree of ‘invasiveness’
• The level of risk
• Whether there is a measuring or diagnostic function
• Active or passive device
Each device is judged against a number of criteria to decide which class it is and
the rules are applied accordingly.
Class I Class IIa Class IIb Class III
Limited scrutiny, High scrutiny, more
simpler processes, clinical evaluation,
can self certify trials, testing,
closer monitoring.
What about medical electronic
devices?
Likely to be an active device
May include software
May have a measuring or diagnostic function
…so likely to be Class IIa or IIb

8. Medical Devices Directive
To be CE marked (under 93/42/EEC)
• The company (or ‘organisation placing the device on the market’) must
be ISO 13485 compliant (or occasionally some other equivalent)
• There should be a ‘technical file’ for each product showing how it
complies with the Medical Device Directive, performance requirements
and product standards (ISO etc).
• Information about the product’s development, acceptance testing and
information needed to manufacture, including user instructions and
labelling
Essential requirements
The main technical section of the directive
• A generic checklist of potential hazards
• Every device must be address all these points

9. Essential requirements -
electronics
Some example sections:
‘Devices incorporating electronic programmable systems must be designed to
ensure repeatability, reliability and performance of these systems according to the
intended use’
‘In the event of a single fault condition…appropriate means should be adopted to
eliminate and reduce …risks’
‘…the software must be validated according to the state of the art taking into
account the principles of the development lifecycle, risk management, validation
and verification’
‘Devices intended to monitor one or more clinical parameters of a patient must be
equipped with appropriate alarm systems to alert the user of situations which could
lead to death or severe deterioration of the patient’s state of health’
Focus on users and ‘use case’
A medical device is certified (CE marked) for a defined
‘intended purpose’
• The manufacturer is specifically responsible for it working if used (only)
in this way
A clinical evaluation is required to show that it works the way it
is described
• At the very least this must be a ‘critical evaluation of the relevant
scientific literature’
• Can be on similar products if you can demonstrate ‘equivalence’

10. The user in the design process
Iterative model (eg. Greenberg 1996)
Requirements
Design
Implementation
Verification
User evaluation Maintenance
ISO 13485
Quality management system for medical device
manufacturers/developers
Analogous to ISO 9000
Covers company processes for ensuring good practice
Must be applied to each product development project (also
covers purchasing, production, quality assurance, continuous
improvement, training etc)
States framework or policy – each company sets up own
procedures and documentation structure to comply

11. Product specific standards
If there is one (or more than one) for your product you need to
comply with it
• You can do a search for standards eg. on BSI Online
Other important standards
BS EN ISO 14971: 2001 Medical devices – application of risk management
to medical devices
• Includes flowcharts for risk analysis process, medical-specific hazard checklist
BS EN ISO 60601-1-1:2006 Medical electrical equipment – General
requirements for basic safety and essential performance
• More stringent specifications than for consumer products
BS EN ISO 60601-1-6: 2007 Medical electrical equipment – Usability
• Verification and validation requirements for user interfaces
BS EN ISO 60601-1-4: 1997 Medical electrical equipment – Programmable
electrical medical systems
• Risk management for software and embedded systems

12. Risk management
Must be built into all the company’s processes
Must be specifically addressed for each product
• Risk analysis
• Mitigation
• Regular reviews and updates of risk analysis
Comprehensive checklists in MDD Essential Requirements
and in Medical devices risk management standard 14971.
Patient involvement
If the product is to be used by/on a patient to assess the clinical benefits,
this is a clinical trial. It is usually best for device to be CE marked first
UNLESS you need to do the trials to validate it (in which case permission
from MHRA for a ‘clinical investigation’ is required)
Trials require ethical approvals
http://www.nres.npsa.nhs.uk/
Alternatively, patients may be asked to comment on a design in a focus
group, or through a questionnaire etc.
Nurses often have significant insights into patient behaviour. In the case of
certain patient groups (eg. children, patients with dementia) this may be
more reliable.
It is usually possible to observe clinics to get information about patient
behaviour.

13. Manufacturing stage
Compliance requirements continue
• Quality assurance – ensure products conform with own specifications
• Assessment of supplied components
• Test/inspection of own products
• Monitoring of customer feedback (post market surveillance) – root cause
analysis, corrective action, preventative action
• Periodic design review, updating
• Respond to external changes, eg. obsolete components, legislative changes
• Repeat risk analysis
• Decide action, implement, monitor
• Document everything
Practicalities
Manufacturers are audited and monitored by ‘notified bodies’
who are regulated by MHRA
The notified bodies are private sector bodies who charge a fee
to the manufacturer
• Initial accreditation to ISO 13485
• Annual audit to maintain certification
• Additional charges to CE mark each product

14. Exercise
Consider a medical electronic device
• What is its intended purpose? By what kind of user and in what context?
• What are the possible hazards in using it?
• Include general hazards and risks of it giving ‘wrong’ results
• How do these affect the product design?
• What are the design issues?
• How can some of the risks be managed?
• How can it be made easier to use?
Some more general issues
Product design is not all about regulations, even for medical
devices…

15. Product development in context
To develop a good product, it is necessary to understand the
use model
This is particularly true in medical device development
• Even more complicated for future e-health medical devices
And…we have not yet talked about marketing, business,
purchasing, financial issues.
A major target for the NHS is ‘efficiency’ – which tends to
mean ‘cost reduction’
Multiple stakeholders
Depending on the product, a number of people may be involved:
• Consultant clinician
• Senior nurse
• Allied health professionals – physiotherapists, occupational therapists etc.
• Patient (consumer/customer)
• Patient’s family/carers
• NHS procurement staff
• NHS managers and accountants
• Other service providers (public or private sector)
• Call centre
• Personal trainers/gyms
• Social services

16. Influencing opinion leaders
Risk averse market
But opinion leaders easy to identify
• Professional structures (BMA, RCN, other professional institutions)
• Conferences and journals
Clinical evaluation should be done by someone with good
reputation
Work with NHS procurement agency PASA
http://www.pasa.nhs.uk/PASAweb
NHS Technology Adoption Centre
The NHS Technology Adoption Centre, based in Manchester,
was launched in September 2007 with the following key aims:
• To increase the uptake of new technology in all areas of the NHS.
• To work with partners to identify excellent technologies which will
improve healthcare in the NHS.
• To promote greater cooperation between all organisations involved in
the development and use of healthcare technologies in the NHS.
http://www.technologyadoptioncentre.nhs.uk/home.html

17. Criteria for adoption
A set of criteria have been established by the Technology
Adoption Centre, against which all the technologies are
evaluated.
• Has to involve step change innovation.
• Has to have an adoption issue. The technology must have strong
independently reviewed evidence (possibly NICE, HTA, CEP) of
improved patient outcomes and / or systems efficiencies but still minimal
uptake in the NHS.
• Supports NHS national policy priorities.
• Should be in a clinical area of major focus for the NHS.
The private sector in UK
Conventional private healthcare sector (BUPA, Nuffield) offer
same services as NHS
• Major innovation will not be adopted
• May be more receptive to step change innovation
Growth in consumer healthcare may change this
• Sales direct to customer – self care, self diagnosis, self monitoring
• More freedom within allied professions – dentists, opticians,
audiologists?
• Products are there, service sector still immature