1. New European Rules governing medical devices vigilance and combination products
Lincoln Tsang
May 2008

2. Topics Review of rules governing medical devices sector
Changes made in the new law
New framework governing novel combination products
11/21/2018

3. European regulatory landscape
Directives on devices adopted in 1990, 1993 and 1998 constitute the basic regulatory framework to harmonise practices in Member States
Placing on the market is linked to the need to undertake conformity assessment with essential requirements
Risk assessment
Risk management
Risk/benefit analysis
Standards
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4. Reviews Medical Devices Experts Group (June 2002)
Functioning of the Medical Devices Directive
Commission Communication to Council of Ministers and European Parliament (May 2003)
Enhancing the implementation of the New Approach Directives
Commission Communication to Council of Ministers and European Parliament (July 2003)
Medical devices
11/21/2018

5. Conclusion of Sector-specific Reviews
The basic framework remains appropriate
Room for improvement in a number of areas, including
Conformity assessment
Proper implementation of provisions on clinical data and quality assurance
Post-market Surveillance
Vigilance
Co-operation between Member States
International dimension
11/21/2018

6. What happened during the legislative process?
EP negotiated 141 amendments
definition of single use
proposal from Commission on “reprocessing of devices”
specific labelling requiring for SUD and devices containing DEHP
Council negotiated 90 amendments
17 out of 23 articles are changed
9 out of 12 annexes of MDD modified
Mixture of cosmetic changes and substantial major changes
Alignment of AMIDD with MDD
11/21/2018

7. Major changes to the regulatory framework
Refinement made:
clinical evaluation
classification and the corresponding conformity assessment
uniform application of rules and demarcation
reclassification issues
principle of design for patient safety
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8. Why clinical trials and monitoring?
Failure ex vivo to mimic clinical evaluation
Proof of concept
Modifications
New purpose
User issues
Efficacy
Safety for humans
Pharmacoeconomic considerations
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9. An example- treatment of abdominal aortic aneurysms
Design
Stress testing
Fatigue testing
X Fractures in vivo
X Endoleaks
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10. Clinical evaluation
In principle clinical evaluation is necessary for every device
In principle for Class III device and implantable devices a clinical investigation has to be performed
Documentation of clinical evaluation now part of the technical documentation
Notified bodies are required to assess clinical evaluation as part of conformity assessments (subject to classification of the device)
Principles of clinical evaluation clarified
11/21/2018

11. Clinical data in new law (amendment made to Annex X)
Information about safety and/or performance generated from use of device
Clinical investigations
Clinical investigations or other studies reported in literature or similar device (where equivalence to the device in question can be demonstrated)
Published and/or unpublished reports on other clinical experience of either the device or similar device
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12. Continuous monitoring
Clinical evaluation must be kept up to date
Implementation of post-market clinical follow up (PMCF) as part of PMS unless justification for absence
Exchange of information as regards clinical investigations between CAs
information on approval or non-approvals of clinical studies
information on termination of clinical trials
information on adverse events
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13. Essential requirements
Inclusion of design for patient safety
Consideration of
ergonomic features
mental, physical and health conditions of patients and users (home use devices for disabled and elderly patients)
Electronic labelling possible in the future (requires implementation)
Specific labelling requirements for SUD (risks on reuse)
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14. Read across to Machinery Directive
Machinery Directive excluded medical devices
Where the relevant hazard exists, devices which are also machinery…must also meet the essential health and safety requirements set out in Annex I of [Machinery Directive] to the extent that those essential health and safety requirements are more specific than MDD
lex specialis applies if Machinery Directive is more specific (moving parts, assembling of devices at point of care)
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15. Special labelling requirements
Devices intended to administer and/or remove medicines, body fluids or other substances to or from the body or devices intended for transport or storage of such body fluids or substances contain Phthalates
Devices including treatment of children or pregnant or nursing women, justification for use substances which are classified as carcinogenic, mutagenic or toxic to reproduction in technical documentation and instructions for use residual risks based upon precautionary principle
EP wanted to place prohibition of all dangerous substances
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16. Device Vigilance Most significant Changes made in amending Directive
basic framework not changed
collect, record, report
Parallel changes made to MEDDEV (Device Vigilance)
2.5 years consultation with CAs, Commission, industry and other interested parties
agreed position of best practice in interpretation
definitions
process
GHTF
11/21/2018

17. Reporting timescales Serious public health threat
immediately but not later than 2 calendar days after awareness by the manufacturer
Death or unanticipated serious deterioration in state of health
immediately after the manufacturer established a link between the device and the event but not later than 10 elapsed calendar days following the date of awareness of the event
Immediately means without delay that could not be justified
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18. Definitions Serious deterioration in state of health (expanded)
life threatening illness or deterioration in state of health
permanent impairment of a body function or permanent damage to a body structure
a condition required medical or surgical intervention to prevent
any indirect harm as a consequence of an incorrect diagnostic or IVD test results when used within IFU
foetal distress, foetal death or any congenital abnormality or birth defects
Serious public health threat
any event type resulting in imminent risk of death, serious injury, or serious illness that may require prompt remedial action
11/21/2018

19. Field safety corrective action
Replaced definition for recall
action taken by manufacturer to reduce a risk of death or serious deterioration in the state of health associated with the use of a medical device already on the market
action notified via a field safety notice
In assessing need for FSCA, use methodology described in harmonised standard EN ISO last edition
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20. FSCA Return of device to supplier Device modification Device exchange
Device destruction
Retrofit by purchaser of manufacturer’s modification or design change
Advice given by manufacturer regarding use of the device
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21. Exemption rules
Previous exemption rules 1-6 replaced by “conditions where under the vigilance system a report is usually not required”.
Summary reporting might be allowed for incidents described in FSNs and for common and well documented incidents (cfr old exemption rules 7 & 8)
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22. Enforcement National competence
effective
dissuasive
proportionate
Co-ordination and centralisation of information exchange
May be based upon consumer protection and/or general product safety regulation
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23. Challenges ahead: ancillary component to a device
Novel drug/device combination products
EMEA guidance on quality, safety and effectiveness of medicinal substance
Advanced therapy medicinal products
gene therapy
cell therapy
tissue engineered
specific risk management guidance
11/21/2018