the roi of good quality & compliance
TRANSCRIPT
The ROI of Good Quality & ComplianceApril 19, 2016
2
2015
Expanded service offering and
geographical coverage
Changing Regulations in EU & US for Medical Devices Peter Rose, Managing Director Europe, Maetrics
Introduction to the Proposed EU Medical Device RegulationsMartin Penver, Head of Notified Body, LRQA
Integrating Quality with Corporate Compliance to Provide the Greatest ReturnSeth Whitelaw, President & CEO, Whitelaw Compliance Group
The Impact of a Good Quality Management System Carl Dover, Vice President – Quality Strategy & Process Improvement, DePuy Synthes
The Most Costly Problems and Why Continually Repeated Adrian Toutoungi, Commercial Partner, Eversheds
Maetrics Regulatory Event in Collaboration with ABHI
The ROI of Good Quality & Compliance
3
2015
Expanded service offering and
geographical coverageChanging Regulations in EU & US for Medical Devices
Peter RoseManaging Director EuropeMaetrics
Maetrics Regulatory Event in Collaboration with ABHI
The ROI of Good Quality & Compliance
Changing Regulations in the EU and US19th April 2016London, UK
Introduction 3
Timelines 12
Reclassification 18
Reprocessing of Single Use Devices 20
Unique Device Identification (UDI) 22
Clinical Evidence 27
The Cost of Compliance 30
Questions 32
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Presentation Topics
©2016 Maetrics. All Rights Reserved. 6
Introduction 3
Timelines 12
Reclassification 18
Reprocessing of Single Use Devices 20
Unique Device Identification (UDI) 22
Clinical Evidence 27
The Cost of Compliance 30
Questions 32
Presentation Topics
7
Introduction
The most important change to the regulation of medical devices since CE marking was first introduced Much is the same, or clarified
Many important changes
The new MDR is not news: First mooted as a Recast of the directive prior to 2007/47/EC
Process became politicised following high profile adverse publicity for the industry PIP fraud using non‐medical grade silicone, over a 16 year period
MoM hip implants, vigilance failures
Pelvic floor mesh issues
Inconsistencies across Notified Bodies
Modernise the CE marking legislation
Improve patient safety
Assisting innovation and trade across the EU
MDR Background
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8
Introduction
The future is now The future has already started Unannounced Inspections Clinical Evaluation Reports Joint audits of Notified Bodies by DA, CAs and FVO Reassessment of NBs by CA
Other key topics Notified Body Capacity EN ISO 13485:2016 OBL (on‐site QMS audit; TF, Unannounced Inspections at OEM, no chains of OBL) Changes to EUAR liabilities, need for QP Compulsory Liability Insurance for Manufacturers Surveillance Fees in the UK Apprentice Levy (0.5% >250 employees) REACH / SVHC (168 substances limit to 0.1% w/w, at component level)
Not just changes within the MDR
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9
Introduction
The best companies will act early
Notified Body capacity should be a major concern
Wise to start planning now
Nothing much will change, but anything can
Learn the lessons from 2007/47/EC
Book early to avoid disappointment
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10
Introduction
2015 Data
2082 company inspections
Of whom, 797 companies received one or more 483s (38%)
Totaling 1008 individual 483s
Leading to 95 Warning Letters (4.5%)
This is NOT probability it depends on your state of compliance
Top 483 citations
US – Compliance Trends
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Year #1 #2 #3 #4 #5
2015 CAPA ComplaintFiles
Purchasing Controls
Process Validation MDR
2014 CAPA ComplaintFiles
Design Controls
Purchasing Controls Receiving, In‐Process, Finished Device Acceptance
2013 CAPA ComplaintFiles
Design Controls
Receiving, In‐Process, Finished Device Acceptance
Purchasing Controls
11
Introduction
FDA have plans to change from the current 25 district and regional offices managing inspections to 3 offices for worldwide
FDA have ‘Program Alignment Medical Devices and Radiological Health FY2016 Action Plan’ – see also http://www.fda.gov/AboutFDA/CentersOffices/ucm477082.htm
A. Transition to Commodity‐Based and Vertically Integrated Regulatory Program (Specialization)
B. Training and Certification
C. Medical Devices and Radiological Health Program Work Planning
D. Quality Policy and Strategy
E. Imports
F. Laboratory Optimization
G. IT
US Issues
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12
Introduction
FDA are revising
CPGM – Compliance Program Guidance Manuals
IOM – Investigations Operations Manual
QSIT approach is under review with potential to be replaced by MDSAP (Medical Device Single Audit Plan) and within that context FDA has already announced plans to retire the voluntary ISO 13485 program in favour of MDSAP. Note: this is not a commitment at this time.
US Issues – Update of inspections Approach
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13
Introduction
A. Transition to Commodity‐Based and Vertically Integrated Regulatory Program (Specialization) More focussed approach
B. Training and Certification Many more highly trained resources, currently most inspectors have very general knowledge
C. Medical Devices and Radiological Health Program Work Planning Prioritise resources in line with the plan, and enforcement priorities
D. Quality Policy and Strategy FDA looking for 90% of their staff to have some connection with the public over the next 2 years to
understand the patients perspectiveE. Imports
More enforcement action on imports, especially Indian drugs hot topic Data integrity Increased foreign inspections. Proposals for increased funding, and headcount
F. Laboratory Optimization LDT – laboratory developed testing, validation and robustness
G. IT Focus on data integrity, documentation systems validation, altering of data
US Impact
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14
Introduction
No longer at an advantage during occasions where inspectors lack knowledge
More and more Inspectors will be specialist and individually know more as a result of extended training, e.g. electronics, software, 3D printing
Training from Industry means specialists will be able to keep up with new manufacturing methods and materials
Efficiencies in filing times due to better skills set within FDA
Conversely, will also be quicker action on compliance side, e.g. warning letters currently take months, anticipated to be much quicker
US Impact
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Introduction 3
Timelines 12
Reclassification 18
Reprocessing of Single Use Devices 20
Unique Device Identification (UDI) 22
Clinical Evidence 27
The Cost of Compliance 30
Questions 32
Presentation Topics
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Timelines
In the beginning
Final MDR expected to Enter into Force in Q2/2014
Always moving further away, but still ever closer
Latest expectations are Entry into Force will be around Q4/2016
Current status
5th October 2015 – Council agreed a full “General Approach”. Trilogues began with the Council, Parliament and Commission
Luxembourgish presidency (July – December 2015) – 5 Trilogues, progress slower than hoped
Dutch presidency (January – June 2016) – 3 Trilogues planned. Great expectations, for Q2/2016
Slovakian presidency (July – December 2016) – Q4/2016?
Malta presidency (January – June 2017)
United Kingdom presidency (July – December 2017)
Timelines change frequently
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Timelines
MDR ‐ An early timeline
2012 2013 2014 2015 2016 2017
Draft MDRSept 2012
Amendments agreedOct 2013
3 year transition period
Entry into force
June 2014
Date of Application June 2017
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Timelines
MDR ‐ Current Timeline Estimate
2012 2013 2014 2015 2016 2017
Draft MDRSept 2012
Amendments agreed
Sept 2016?
3 year transition period
Entry into force
Dec 2016?
Date of Application Dec 2019?
2018 2019 2020
NBs can apply +6 months for re‐designation
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Timelines
Entry into Force
The date the MDR is published in the OJ
The Date of Application
3 years after Entry into Force
6 months after Entry into Force, NBs may apply for Re‐designation under the MDR
Once granted NBs may begin to issue new certificates under the MDR and products may be legally placed on the market under the new rules
UDAMED database – timing remains unclear
UDI requirements – timing remains unclear
Total of 43 delegated acts that need to be implemented before the entire MDR can be fully implemented
MDR ‐ Entry info Force & Date of Application
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Timelines
The Date of Application is not necessarily the deadline
No requirement that devices must be re‐certified under the MDR by the Date Of Application of the new Regulation
Transitional provisions
Certificates issued before to the entry into force of MDR stay valid for the period indicated on the certificate
‒ Except certificates under Annex 4, Directive 90/385/EEC or Annex IV, Directive 93/42/EEC, which expire at the latest 2 years after the Date Of Application
Certificates issued during the 3‐year transition period stay valid for the period indicated on the certificate, BUT in any case will expire 4 years after the Date Of Application
Devices placed on the market under the current MDD before the Date Of Application may be made available for up to 4 years after that date
MDR ‐ Certificate Validity (– but commercial pressures may apply)
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Presentation Topics
Introduction 3
Timelines 12
Reclassification 18
Reprocessing of Single Use Devices 20
Unique Device Identification (UDI) 22
Clinical Evidence 27
The Cost of Compliance 30
Questions 32
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Reclassification
Classification rules are similar to before, but some significant examples of change:
In vitro contact with cells/embryos going back into the body to be Class III (or IIa)
Apheresis devices to be Class III
IVF and ART non‐invasive devices can be IIb
Spinal implants to be Class III
Total and partial joint replacements to be Class III
Devices recording diagnostic images to be IIa
Nanomaterial devices to be Class III
AIMD accessories to be Class III
Devices which are intended to be introduced into the human body via a body orifice, or applied on skin and that are absorbed by or locally dispersed in the human body are to be Class III
Reusable surgical Instruments are no longer class I
‒ (CAUTION) Rumour about Class I with NB input
Up‐Classification of Devices
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Introduction 3
Timelines 12
Reclassification 18
Reprocessing of Single Use Devices 20
Unique Device Identification (UDI) 22
Clinical Evidence 27
The Cost of Compliance 30
Questions 32
Presentation Topics
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Reprocessing of Single Use Devices
A sensitive subject for some, do these proposal enhance patient safety?
Still under debate
Allowed products list
Banned products list Default is that it is allowed and manufacturers must state why not (European Parliament)
Re‐processers become legal manufacturers
Member States can control within their own borders
In‐house (i.e. hospitals) can continue to operate outside of the MDR
Re‐processers must confine activities to OEM once used product or their own re‐processed products
Some debate over re‐processing vs fully refurbished
Still Under Debate
©2016 Maetrics. All Rights Reserved. 25
Presentation Topics
Introduction 3
Timelines 12
Reclassification 18
Reprocessing of Single Use Devices 20
Unique Device Identification (UDI) 22
Clinical Evidence 27
The Cost of Compliance 30
Questions 32
26
Unique Device Identification (UDI)
UDI System (Article 24)
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Article 24: A single system for UDI shall be put in place in the Union
1. Basic requirements for the UDI system
2. Issuing agencies for UDIs in Europe
3. Assignment of UDIs
4. Placing of UDIs on device labels / how UDIs should be used
5. Recording of UDIs
6. UDI database
7. Delegated acts related to running the UDI system
8. External factors
27
Unique Device Identification (UDI)
Benefits of UDI
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To enhance the post‐market safety of medical devices by:
Improving incident reporting and recall processes
Increased visibility for competent authorities
Reducing the likelihood of product related errors
Better stock‐management by healthcare facilities
Counterfeit devices
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Unique Device Identification (UDI)
FDA
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UDI system – Final Rule 21 CFR Parts 16, 801 and 803
Published September 2013
Implements IMDRF UDI
Timetable according to classification
29
Unique Device Identification (UDI)
Its not just a bar code!
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Requirements to record, and verify, UDI information on
Complaints forms & records
Adverse Incident / MDR forms & records
Corrections & Removals forms & records
DHR including QC Release forms & records
Service forms & records
Should have been implemented in 2013
Unlikely to yield a 483 if UDI is not yet a requirement
Should include a UPC (Universal Product code) if no UDI
Includes UDI requirements as part of Design History
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Presentation Topics
Introduction 3
Timelines 12
Reclassification 18
Reprocessing of Single Use Devices 20
Unique Device Identification (UDI) 22
Clinical Evidence 27
The Cost of Compliance 30
Questions 32
31
Clinical Evidence
Requirements
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Chapter 6 (12 articles)
Clinical evaluation and clinical investigation
Annex XIII: Clinical evaluation and PMCF
Annex XIV: Clinical Investigations
Clinical evidence
Must justify the level of clinical evidence used (e.g. risk class, intended use, device characteristics, etc)
Performance is not equivalence
More data will be required, CERs already under greater scrutiny
Greater expectation that clinical investigations will be required, especially for Class III devices
Equivalence for Class III devices should not be from other manufacturers
Clinical investigations
Greater emphasis on patient safety
Data robustness and protection of patients during clinical investigations
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Clinical Evidence
Data Sources
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Rule 8 Clinical data
Clinical studies
PMCF
Scientific literature
Engagement with KOLs
Clinician and patient focus groups
Registries
Ongoing data sources
Active post market surveillance, routed through Risk Management process
Use error and feedback
Complaints, vigilance reports and MDRs
Ongoing research by legal manufacturer
Competitor data
©2016 Maetrics. All Rights Reserved. 33
Presentation Topics
Introduction 3
Timelines 12
Reclassification 18
Reprocessing of Single Use Devices 20
Unique Device Identification (UDI) 22
Clinical Evidence 27
The Cost of Compliance 30
Questions 32
34
The Cost of Compliance
Its not going to get cheaper
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Rule 8 MHRA surveillance fees
Notified Body fees, including unannounced visits
Punitive damages – regulators
Compensation and punitive damages – courts and patients / patient groups
Remediation projects
Increased requirements CER
Risk
Up‐classification
New requirements UDI
Person responsible for regulatory compliance
Professional assistance
©2016 Maetrics. All Rights Reserved. 35
Presentation Topics
Introduction 3
Timelines 12
Reclassification 18
Reprocessing of Single Use Devices 20
Unique Device Identification (UDI) 22
Clinical Evidence 27
The Cost of Compliance 30
Questions 32
Maetrics
Maetrics Ltd Peter RoseBioCity Nottingham Managing Director, EuropePennyfoot Street [email protected] +44 7811 199 346NG1 1GFUnited Kingdom
+44 115 921 6200
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Contacts
37
The contents of this presentation are copyright ©2016 Maetrics. All rights reserved.
This presentation contains information in summary form and is intended for general guidance only. It is not intended to be a substitute for detailed research or the exercise of professional judgment. Maetrics cannot accept responsibility for loss occasioned to any person, firm, company or corporation acting or refraining from action as a result of any material in this publication. On any specific matter, reference should be made to the appropriate professional advisor.
©2016 Maetrics. All Rights Reserved.
38
2015
Expanded service offering and
geographical coverageIntroduction to the proposed EU Medical Device Regulations
Martin PenverHead of Notified BodyLRQA
Maetrics Regulatory Event in Collaboration with ABHI
The ROI of Good Quality & Compliance
Improving performance, reducing risk
Introduction to the proposed EU Medical Device Regulations
Martin PenverHead of Notified BodyLRQA
NEW Medical Device Regulation – 26/09/2012
Currently Medical Device Directives (60 pages)Proposal are MDD & IVDD Regulations (278+)
What is the difference (apart from 218 additional pages) ?
Brussels, 26.9.2012, COM(2012) 542 final
Proposal for a
REGULATION OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL
on medical devices, and amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009
Directive is not enforceable by law across Europe, but can be adopted by each country
Improving performance, reducing risk
A caveat: Discussions and documents are based on the Council General Approach agreed in October 2015 – prior to negotiations with the Parliament and the Commission. The final text of the Medical Devices Regulation will differ from those underlying this discussion in various respects.
The political timetable – September 2015
Jan2014
July2014
Jan2015
July2015
Jan2016
Greek Presidency
Italian Presidency
Rapporteurs appointed
Luxembourg Presidency
New Commissioners in place
Latvian Presidency
EP elections
Council partial General Approach
Triloguescommenced
Conclude trilogues?
Dutch Presidency
Parliament 1st reading
full General Approach
Entry into
force?
July 2016
Slovak Presidency
Started in 2012
The political timetable – March 2016
Jan2014
July2014
Jan2015
July2015
Jan2016
Greek Presidency
Italian Presidency
Rapporteurs appointed
Luxembourg Presidency
New Commissioners in place
Latvian Presidency
EP elections
Council partial General Approach
Triloguescommenced
Conclude trilogues?
Dutch Presidency
Parliament 1st reading
full General Approach
Entry into
force?
July 2016
Slovak Presidency
Another 6 Months
6 Month delay
Trilogues - State of the negotiations
• Council agreed a full ‘General Approach’ on 5 October 2015 – mandate for informal trilogue negotiations with European Parliament and Commission
• 5 trilogues under the Luxembourgish Presidency – progress not as fast as hoped
• Dutch Presidency (January-June 2016)– 3-4 political trilogues (17 Feb, 16 March, 7 April, ? May)– Informal political agreement by end of Dutch Presidency (June
2016?)– Slovak Presidency (July-December 2016)
– Council formal First Reading Position (October 2016?)– Accelerated 2nd reading by EP and adoption of final Regulations
(Autumn 2016?)
Improving performance, reducing risk
Council text
– Pre-market scrutiny• Expert Panels• Class III, implantable devices only• Notified Body retains final decision• Clinical Evaluation guidance & Common Specifications• Exemptions if NB judges conformity with the above, and for non-
substantial modifications
– LRQA – note some panels – NB abliged to use panel – may not need if similar products, may include renewals. This is only the council position, not yet definitive, expert panel will be available to manufacturers, could be 100’s of devices per year.
– Panel will be a commission led process -
Improving performance, reducing risk
Council text
– In-house manufacturing exemption (IVD)• Largely positive inclusion but some concerns• Class C & D• Publication of in-house practices and justification• ‘Quality Management Systems’• ‘Within health institutions’
– LRQA note: lists ISO15189 is stated or national provisions, some tests are not applicable to this standard. Large discussion “on an industrial scale” TERMINOLOGY
– Reprocessing of single-use devices• Member State discretion• EU minimum standard – no less than in-house manufacturing,
and reflect Common Specifications
– LRQA note: this means re-CE marking required, plus CTS’s, some question on whether a NB is required
Improving performance, reducing risk
Council text
– Eudamed & unique device identification (UDI)– Single Registration Number (SRN) for economic operators– Manufacturers, Importers, Distributors required to store UDI– Healthcare institutions not required but some system needed
Software– Not an active device– Classification concerns– CE marking Laboratory Information Management Systems
(LIMS)
LRQA note: Eudamed current design does not take into account UDI, so complete overhaul required, logic wrong.
Improving performance, reducing risk
Council text
– Clinical investigations– Coherence with Clinical Trials Regulation– Clinical evidence & equivalence
LRQA note: “clinical” taken from IVD performance has been requested to be added back into the defined term. Has impact on ethics approval, to be brought up during technical discussions on technical regulation.– Post-market surveillance
– Clearer requirements– Regular reporting for higher risk devices
Classification rules– Further clarification during implementation
LRQA note: 19 & 21 rules out class I, all surgical instruments will become class IIa.
Improving performance, reducing risk
Council text
Non-medical medical devices – Annex XV
LIST OF PRODUCTS COVERED BY THE LAST SUBPARAGRPAH OF THE DEFINITION OF ‘MEDICAL DEVICE’ REFERRED TO IN NUMBER (1) OF ARTICLE 2(1)
1. Contact lenses;2. Implants for modification or fixation of body parts;3. Facial or other dermal or mucous membrane fillers;4. Equipment for liposuction;5. Invasive laser equipment intended to be used on the human body;6. Intense pulsed light equipment.
Products can be continual addedCommon specifications as a trigger – What’s the problem here? (ER6)
Cosmetic only - No medical benefit only risksImproving performance, reducing risk
Implementation - priorities
• Pre-market scrutiny - Expert Panels• Re-processing – national law & guidance• In-house Manufacturing – guidance• Genomics & companion diagnostics – guidance• Software – guidance • UDI & Eudamed – IT system & guidance• Reference labs/expert panels – composition• Notified Body Operations Groups (NBOG) codes
LRQA note:- more codes to be generated especially on IVD further discussions
3 year transition for MDD will it happen? it will take 2 years just to re-designate at Notified bodies, plus all the above. Plus the Implementing / delegated acts (43 in total), common specifications and guidance
Improving performance, reducing risk
Lets go back to the current - Trilogues
• Negotiations between European Parliament, Council and Commission
So why since the Brussels, 26.9.2012 publication, has a final version not yet been agreed?• Politics?– Large differences still exist for scrutiny procedure and reprocessing of medical devices as well as the (compulsory) requirement
for all manufacturers to have liability insurance (proposed by Parliament), which was rejected by Council.
– The rapporteur for MDR - Glenis Willmott (S&D) - will be strongly bound in the coming months because of the referendum in the UK regarding the remaining in the EU. It is therefore questionable whether the planed timeframe can be adhered.
– Maybe till June, there will be only a compromise regarding the main points of the Regulations. The details will then be regulated later on.
• 3 versions of the MDR now exist
• Immediate Actions following Dalli Stress Test (European Commission)The new regulation (920/2013) and recommendation (2013/473/EU which were published on the 24 September 2013
LRQA opinion is no immediate rush, and therefore the debate will continue
Improving performance, reducing risk
Delegated and Implementing Acts MDR
I = Implementing Act D = Delegated ActRelevance to NB : ++ very important, + important, o not so important
Act Article Content Commission
Parliament
Council
Relevance
D 42 (11) -Conformity assessment procedures
In the light of technical progress and any information which becomes available in the course of the designation or monitoring of notified bodies set out in Articles 28 to 40, or of the vigilance and market surveillance activities described in Articles 61 to 75, the Commission shall be empowered to adopt delegated acts in accordance with Article 89 amending or supplementing the conformity assessment procedures set out in Annexes VIII to XI.
X
++In the light of technical and scientific progress and any information which becomes available in the course of the designation or monitoring of notified bodies set out in Articles 28 to 40, or of the vigilance and market surveillance activities described in Articles 61 to 75, the Commission shall be empowered to adopt delegated acts in accordance with Article 89 amending or supplementing the conformity assessment procedures set out in Annexes VIII to XI.
X
D 45 (5) -Certificates
In the light of technical progress, the Commission shall be empowered to adopt delegated acts in accordance with Article 89 amending or supplementing the minimum content of the certificates set out in Annex XII. X X X ++
D 89 (1) - Exercise of the delegation
The Commission shall, in drafting delegated acts, seek the advice of the MDCG.
X o
I 94 (4) -Transitional provisions
By way of derogation from Directives 90/385/EEC and 93/42/EEC, conformity assessment bodies which comply with this Regulation may be designated and notified before its date of application. Notified bodies which are designated and notified in accordance with this Regulation may apply the conformity assessment procedures laid down in this Regulation and issue certificates in accordance with this Regulation before its date of application if the relevant delegated acts and implementing acts have been implemented.
X ++ *
Interpretation of text – will be difficult
Lets look at one already implemented in Regulation 920 – 2013
All Nofitied Bodies shall– (a) the necessary administrative, technical, clinical and scientific personnel with technical
and scientific knowledge and sufficient and appropriate experience relating to medical devices and the corresponding technologies to perform the conformity assessment tasks, including the assessment of clinical data;
The MHRA interpret this asA GMC registered & practising clinician, employed by the Notified Body
Other Competent Authorities see this as having access to a medical person.
Some of the Commission interpret this as Sufficient Clinicians to have specific knowledge of the full scope of devices that the Notified body certify, including Class III & AIMD products but also for ALL Class IIa & IIb medical devices. This includes the clinician peer reviewing all certificates already issued and re-check the clinical data.
LRQA have asked for published guidance from the Commission – nothing yet.
Published in 2013, with at least 3 interpretations, which affect the consistency of all notified bodies completing the same assessments and therefore the same reviews on clients across the world
(Interpretation of 278 pages plus implementing and delegating acts) – not good for Manufacturers or Notified Bodies and will it make improve product performance and safety ?
Impact of Short Term Changes to the System
Discovery of a 16 year fraud in PIP breast implants using low quality “industrial grade” silicon oil
Stress test performed by EU Commission
Determined that changes were needed to improve early detection and prevent this type of incident
Other high profile vigilance cases with hips, pelvic floor meshes, pacemaker leads, etc.
Outcome: short term changes to the system – Safety & PerformanceImmediate Actions– Commission Regulation: How Competent Authorities control Notified Bodies– Commission Recommendation: How Notified Bodies audit Manufacturers
Improving performance, reducing risk
The new regulation (920/2013) and recommendation (2013/473/EU which were published on the 24 September 2013
MDR & IVDR Proposal
Addit ional ENVI
Proposals
920/2013
2013/473/EU
Implemented Sept 2013
Improving performance, reducing risk
COMMISSION IMPLEMENTING REGULATION (EU) No 920/2013of 24 September 2013 on
the designation and the supervision of notified bodies
– Re-assessment of qualifications and scope of activities of NBs
– Joint Audits of NBs by Designating Authority, Commission (FVO) plus two other CA’s
• NBs and Designating Authorities under scrutiny
• Highlights different approaches in Member States
• More scrutiny of competency requirements, in-house clinicians, qualifications: NBOG Codes.
• Processes and procedures clarified
IMPACT – 83 down to 61 (so far – not yet finished)
Impact of Com. Recommendation (2013/473/EU) on audits and assessments performed by NBs – Items to be verified by NB during an audit
Improving performance, reducing risk
– Annex III: Unannounced visits to manufacturers, "critical subcontractors" or “crucial suppliers”, in addition to planned audits
• Completely new requirement needing extra product and QMS assessors• Significant increase in NB workload and resources• First 3 year cycle to be completed by March 2017
LRQA on-track and demonstrated this at our re-designation audit
Sharing of UV’s for CS or CS – discussions ongoing with NB’s but 1 UV not sufficient
What is required within an unannounced visit (UV)? – Your Notified Body must have already communicated
– Additional visit to normal LRQA assessments – not take less than one day and should be executed by at least two auditors
– Sample devices belonging to at least three different device types
– Verifying conformity of a recently produced adequate sample (product, batch, lot) of an approved device type
– Traceability audit (device history record and reconciliation of stock)
– Witness selected tests – sampling criteria and testing procedures should be identified in advance
– Review two critical processes
Improving performance, reducing risk
Annex II . 2 Critical subcontractors and crucial suppliersCritical – risk based approach by NB’s
– Key processes may not be done at the main site, and may involve subsidiaries or OEM’s– LRQA needs to know who are the critical suppliers / subcontractors– LRQA use the logic provided by IVD working group
Experience gained from Un-announced Visits
– Preparation is key, create a client pack for the assessment team, with an identification of what products are on our wish list.
– Clients shock when auditors arrive – various reactions, key is to have the list of 4 or 5 contacts (if people are on vacation)
– The team will need to categorize non-conformities into either (a) “Product” – may affect CE certificate –immediate action required(b) “QMS” – can be followed up at normal surveillance visit
– Robust refusal policy required, 30 day resolution timescale before CE certificate is suspended – this is a product audit. Worst case is another PIP.
Note: visit charged to client for refusal. So lose / lose scenario.One refusal so far by a critical subcontractor who does supply other major clientsTwo clients require additional visits as key processes done at “other sites”One certificate suspension after visiting a Critical Subcontractor
– Clients are doing what they have always told us they were doing – no real surprises (except one).
Improving performance, reducing risk
What is in the recommendation that is different/new?– OBL requirement for Technical files
Recommendation 2013/473/EU, was issued to facilitate consistent application of conformity assessments contained within the Medical Directives.
Page 2 of recommendation
(9) Subcontractors or suppliers cannot fulfil in the manufacturers’ place crucial obligations of manufacturers, such as keeping available the full technical documentation, as this would void the concept of the manufacturer as responsible in accordance with Directive 90/385/EEC, Directive 93/42/EEC and Directive 98/79/EC. Therefore, the notified bodies should be advised on what they need to verify in case of outsourcing.
Page 3 of recommendation under Annex I – Product assessment
7. Notified bodies should verify all documentation related to the device’s conformity assessment. To that end, they should verify that the technical documentation is correct, consistent, relevant, up-to-date and complete ( 4 ) and that it covers all variants and trade names of the device. They should furthermore verify that the manufacturer’s device identification. ( (4) refers to a STED )
Improving performance, reducing risk
Meeting with the MHRA in February 2016
– The MHRA have provided all UK notified bodies with a guidance document covering own Brand Labelling.
1. OBL is not a term within the Medical Directive, there are only legal manufacturers – Clients are Virtual Manufacturers
2. Notified Bodies must complete an onsite QMS visit at an OBL company3. Notified bodies must sample the FULL technical file. 4. MHRA are producing further Guidance in April 2016
5. OBL companies need to change their contracts with the OEMa. To allow full access to propriety information for the OBL’s Notified Body.b. To allow un-announced audits by the OBL notified bodyc. OEM should make a declaration that they manufacture the product and not
outsource it to another OEM.
Experience gained from reviewing OBL technical file requirements
– Why are you an OBL? Why not a distributor ?– MHRA have agreed to publish guidance on this
– No NB costs & no un-announce visits
Improving performance, reducing risk
MDR Proposals – 1
• Strengthened Designation Criteria• Joint Audits: Three Member States and
Commission (FVO)• Unannounced Inspections
Notified Bodies
• Less Equivalence, More Data for High Risk Devices
• Publish Safety and Performance Data• Post Market Clinical Follow-up
Clinical Evidence
• Scrutiny for High Risk Devices• Common Technical Specifications• Qualified Person for Manufacturers and Authorised
Representatives
Pre-market
Improving performance, reducing risk
MDR Proposals – 2
• Central Database and Co-ordination• Trend Reporting• Enforcement Activities
Post-Market Surveillance and Vigilance
• Devices and Economic Operators Registered Centrally
• Unique Device Identification (UDI)• Implant Cards
Transparency and
Traceability
• Central Committees: Scientific Advice, Harmonised Implementation
• Expert Panels• JRC, Reference Laboratories
Governance and Oversight
Improving performance, reducing risk
LRQA Conclusion
– Where are the possible risks
To Much Focus?– Duplication of visits on OEM’s Critical Subcontractors and Crucial subcontracts with multiple
Notified Body un-announce visits with no additional benefit – does not add value, but is a requirement of the recommendation.
Lack of Focus?– Mean while who is reviewing Class 1 non sterile or non Measuring? CA’s – no resource
ALL Manufacturers still need a Declaration of Conformity as per Annex VII of the MDD 93/42/EEC Annex VII requires technical documentation
(Instrument sets)(incontinence pads) Annex VII requires conformance with Annex I (essential requirements)
( biocompatibility, state of the art, risk, clinical)
Interpretation of text?– Clinician requirements are different– Un-announced visits – are all NB’s doing the same level? No CA witnessing (YET)– OBL will nearly become consistent 3 years after publication
( 1 member state still going to use OBL)
Improving performance, reducing risk
Lloyd’s Register and variants of it are trading names of Lloyd’s Register Group Limited, its subsidiaries and affiliates.Copyright © Lloyd’s Register Quality Assurance Limited 2014. A member of the Lloyd’s Register group.
Improving performance, reducing risk
Martin PenverT 0800 783 2179E [email protected] www.lrqa.co.uk/medical
1 Trinity Park,Bickenhill Lane,Birmingham, B37 7ES, United Kingdom
Contact Us
LRQA
T +44 (0)330 4141244E [email protected]
General Enquiries to Business Support staffT +44 (0)330 4141348E [email protected]
67
2015
Expanded service offering and
geographical coverageIntegrating Quality with Corporate Compliance to Provide the Greatest Return
Dr. Seth Whitelaw President & CEOWhitelaw Compliance Group
Maetrics Regulatory Event in Collaboration with ABHI
The ROI of Good Quality & Compliance
1 is the Loneliest Number
Integrating Quality & Corporate Compliance To Provide the Greatest
Return MaetricsThe ROI of Good
Quality & Compliance
LondonApril 19, 2016WhitelawComplianceGroup,LLC.
Copyright © 2015 Whitelaw Compliance Group LLC. All rights reserved
The “Heart of Darkness” 69
1‐Press Release by Senator Charles Grassley (February 1, 2013)2‐Eric Campbell et al., A National Survey of Physician‐Industry Relationships, 356 N Engl. J. Med. 1742, 1746‐47 (2007)3‐Martin Roland, et al., Professional values and reported behaviors of doctors in the USA and UK: quantitative survey, Brit. Med. J. Quality & Safety at 3 (2011), http://qualitysafety.bmj.com/content/early/2011/02/07/bmjqs.2010.048173.full4‐David Grande, et al., Pharmaceutical Industry Gifts to Physicians: Patient Beliefs and Trust in Physicians and the Health Care System, J. Gen. Intern. Med. (Jun. 14, 2011), available at http://www.ncbi.nlm.nih.gov/pubmed/21671130
NEED FOR TRANSPARENCY
Only 78.7% of U.S. physicians believe in putting a patient’s interest above their own.2
64% of surveyed physicians said that disclosure for doctors should be mandatory.3
83% supported mandatory disclosure for researchers.3
Physician Perspective
“We want our doctors … to rely on evidence that is real and true and accurate and not partial or affected some way by a money interest behind it.”1
“The case has clearly been made for requiring industry to report payments to physicians, especially those conducting highly influential research, often with taxpayer support. Operating with transparency sends a message that there’s nothing to hide.”2
Congressional Perspective
94% of U.S. physicians have had a relationship with a life sciences company2
Life Science Perspective
55% of patients believe their doctor receives industry gifts4
Patient Perspective
Copyright © 2016 Whitelaw Compliance Group LLC. All rights reserved
Causing Pressure for Reform to Build
Intractable quality issues are dominating the global news Indian API debacle
Chinese reform efforts
Price and quality are in the forefront of the U.S. election Unsupported price increases
Value-based pricing
70
Copyright © 2016 Whitelaw Compliance Group LLC. All rights reserved
Leading to Increased Enforcement
71
05000
100001500020000
2008
2009
2010
2011
2012
2013
2014
2015
FDA Warning LettersFiscal Years 2008 – 20151
0500
10001500
2010 2011 2012 2013 2014
Federal Criminal Healthcare Fraud Prosecutions (FY10-FY14)2
1http://www.fda.gov/downloads/ICECI/EnforcementActions/UCM384647.pdf
2HHS & DOJ Annual Reports on Healthcare Fraud and Abuse Control Program
Copyright © 2016 Whitelaw Compliance Group LLC. All rights reserved
While Regulators Struggle with Dated Frameworks
Off-label vs. 1st Amendment
Software as a medical device
Genetic testing and dietary supplements
Drug shortages
Opioid misuse
72
Copyright © 2016 Whitelaw Compliance Group LLC. All rights reserved
Quality & Compliance Not Keeping Pace
73
CEO
Chief Quality Officer
ManufacturingQuality R&D Quality
Chief Compliance Officer
Compliance Operations
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The Disconnect 74
External Regulations
Internal Audits
Quality Control
Quality Assurance
Quality
Corporate Compliance
Copyright © 2016 Whitelaw Compliance Group LLC. All rights reserved
How It Needs to Work 75
CEO
Chief Compliance Officer
Compliance Operations
Chief Quality Officer
Manufacturing Quality
R&D Quality
Copyright © 2016 Whitelaw Compliance Group LLC. All rights reserved
Achieving An Integrated Team
Securing commitment At all organizational levels
Establishing an agreed upon framework Objectives of integrating
Speaking the same language Defining the key terms (e.g., “risk”)
Identifying combined compliance/quality expertise
76
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It Isn’t Just TheoryINVACARE, VALEANT AND OTHER NOTABLE STORIES
77
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Invacare
2012 Consent Decree
Last 3 years lost money
Latest Inspection (12/2015) 5 months duration
11 page FDA-483
Consent decree non-compliance
CEO asserting strong compliance culture is top priority
78
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Valeant
Virazole microbial contamination recall
Accusations of improper relationship with PBM Philidorto recommend Valeant drugs
Hedge fund loses >$1B in single day (3/15/16)
Former CEO subpoenaed to testify before Senate on drug pricing
79
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OtisMed Corp.
Distributed product after FDA refused to approve their application.
Company acquired by Stryker.
Company paid more than $80 million dollars in civil and criminal fines.
Its CEO pled guilty to criminal charges, and was sentenced this year to serve 24 months in prison, 1 year supervised release and a $75,000 fine.
80
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Olympus Corporation of America
3 separate regulatory actions FDA Anti-kickback and False Claims
Act violations FCPA
3 separate regulatory outcomes Warning Letters and Recalls Corporate Integrity Agreement Deferred Prosecution Agreement
Total settlement - $646 million Chief Compliance Officer was
the whistleblower
81
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WhitelawComplianceGroup,LLC.helpingcompaniesgrowsustainableintegrity
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83
2015
Expanded service offering and
geographical coverageThe Impact of a Good Quality Management System
Carl DoverVice President – Quality Strategy & Process ImprovementDePuy Synthes
Maetrics Regulatory Event in Collaboration with ABHI
The ROI of Good Quality & Compliance
The ROI of Good Quality & Compliance
The Impact of a Good Quality Management System
Carl DoverVice President, Quality Strategy & Process Improvement
DePuy Synthes
Maetrics Regulatory Seminar by ABHI:
The ROI of Good Quality & Compliance19th April 2016
The ROI of Good Quality & Compliance
Quality Management Systems Development
Quality is COMPLIANCE
Quality is a DISCIPLINE
Quality is an INTEGRATED CAPABILITY COMPETENCY
Proactive Quality is a
CORE COMPETENCY
Proactive Quality is a
DIFFERENTIATOR
The ROI of Good Quality & Compliance
Quality is Compliance
• The Starting Point
• Foundational Systems
• Market Access
Opportunity Areas:
• More Reactive than Proactive
• Internal Complexity
• Higher Cost of Quality
• Internally Focused
• Sustainability Issues
The ROI of Good Quality & Compliance
Quality is a Discipline
• > Compliance Outcomes
• Enhanced Technical Capabilities
• Capability Risk Reduction Focus
• Reduced Cost of Non Conformance
Opportunity Areas:
• Goal Alignment
• Governance
• Speed to Market
• External Focus
• Customer Satisfaction
The ROI of Good Quality & Compliance
Quality is an Integrated Capability
• Reduced Complexity• Cross Functional Engagement• Organizational Capability• > Design, LEAN, QE Outcomes• Robust External Manufacturing• Faster Cycle Times• Reliable, Predictable Supply• Cost Of Quality Improvement
Opportunity Areas:
• Proactive Quality
• Triple Aim
• Field Action Trend
• Quality Culture & Sustainability
Cost of Non-Conformance
Internal Failures
External Failures
Cost of Conformance
PreventionAppraisal
The ROI of Good Quality & Compliance
Proactive Quality : A Core Competency + Competitive Differentiator
• Predictive Analytics
• Reduced Complexity - Agile, Scalable, Integrated Quality Systems
• Higher Investment in Prevention
• Patient Centric Solutions – Triple Aim – Satisfaction/Outcomes/Costs
• Higher Reinvestment in Breakthrough Innovation
• Anticipating & Shaping the External Environment
• Recognized Sustainable Culture of Quality
Compliant, quality products & services
Reliable supply of high quality products & services
Innovative, high quality products & services through customer insights
PROACTIVE QUALITY delivers BUSINESS GROWTH and CUSTOMER VALUE
Cost of Quality measured
COMPLIANT
Achieve top quartile COQ benchmark
INTEGRATED
Reinvestment of cost savings in Innovation
PROACTIVE
The ROI of Good Quality & Compliance
Additional Benefits
Cost of Quality
Customer Satisfaction
Consolidation
Organizational Capability
Guaranteed Supply
EngagementIntegrationAgility
L&A
91
2015
Expanded service offering and
geographical coverageThe Most Costly Problemsand Why Continually Repeated
Adrian ToutoungiCommercial PartnerEversheds
Maetrics Regulatory Event in Collaboration with ABHI
The ROI of Good Quality & Compliance
The most costly problems (and why continually repeated)?
Adrian Toutoungi
Partner - Eversheds LLP
19 April 2016
1. Data privacy
2. Borderline issues
3. Unharmonized issues− advertising and promotion of medical devices− registration requirements− enforcement
4. Beyond regulatory compliance
On the Agenda – Traps for the unwary
1. Data Privacy
Eversheds LLP | 19/04/2016 |
− An increasing problem for medical device manufacturers
− Conventional devices
− e-health (Internet of Things)
− m-health
Data privacy
Eversheds LLP | 19/04/2016 |
− Local, variable implementation− Personal data
• information which on its own on when combined with other information held, identifies or relates to a living individual
− Processing• any use, including storing or reading
− Sensitive personal data − Data Protection principles
• fair and lawful use• security• export
− Maximum fine in UK: £500,000
Data Protection Directive 95/46/ECThe existing regime
Eversheds LLP | 19/04/2016 |
− Direct effect from 2018− More detailed rules and obligations− Privacy by design and default− Tightened rules
• notice• consent• lawful use
− Mandatory reporting of breaches− Enforcement
• potential fines of up to 4% of global turnover
General Data Protection RegulationThe upcoming regime
Eversheds LLP | 19/04/2016 |
− Medical imaging technology• MRI scanner• Database of scanned images• Access by device supplier• Impact on market launch?
− m-Health software apps
Examples
2. Borderline issues
Eversheds LLP | 19/04/2016 |
− Qualification of a product can be uncertain• medical device v medicinal product• medicinal product v cosmetic product• others
− Increasingly sophisticated products• technical advances outpacing legislation and guidance• combination products (incorporate or designed to administer a
medicinal product)
− Qualification may be vital• commercial viability (cost, timing to market)• to gain a competitive advantage
Borderline issues
Eversheds LLP | 19/04/2016 |
− Article 1(2) of Directive 2001/83/EC• Any substance or combination of substances presented as having properties for treating or preventing disease in human beings;• Any substance or combination of substances which may be used in or administered to human beings either with a view to restoring, correcting or modifying physiological functions by exerting a pharmacological, immunological or metabolic action, or to making a medical diagnosis’.
− Consider both presentation and function
− Definition has evolved over the years
Definition of medicinal product
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’
Definition of ‘Medical Device’, Article 1.2 of Directive 93/42/EEC
Eversheds LLP | 19/04/2016 |
− Article 2(2) Directive 2001/83/EC• in cases of doubt, where, taking into account all its characteristics, a
product may fall within the definition of a medicinal product and within the definition of a product covered by other Community legislation the provisions of this Directive shall apply”
− Borderline MEDDEV
− European Commission Manual on Borderline and Classification in the Community Regulatory Framework for Medical devices, Version 1.16 (07-2014)
− Further guidance from national regulators • Guide to What is a Medicinal Product• MHRA Borderline Guidance
A uniform approach?
Eversheds LLP | 19/04/2016 |
- Gynocaps capsule• for correcting bacterial imbalances in
the vagina• lactobacillus, lactose and magnesium
stearate in a gelatine capsule• Marketed as a Class III device since
2006 in AU, DE, ES, FIN, FR• reclassified in FIN as a medicinal
product in November 2008
- CJEU confirmed that MS are not bound by decisions of other MS
- Major adverse commercial impact
Laboratoires Lyocentre case (Case C-109/12,
Overview of different MS
Member State Legal Framework Borderline Products
Belgium Assessment of border products is carried out by a specific body in the Federal Agency for Medicines and Health Products (FAFMP) – the joint committee
France Classification is carried out by French Agency of Sanitary Security of Health Products (AFSSaPS). Case law prefers a broad view of the term “medicinal product”
Germany Extensive civil and administrative case law on classification of borderline products
Italy The Italian Ministry of Health is the Competent Authority on borderline issues. It follows the borderline MEDDEV and Guidance
The Netherlands Assessment is carried out by the CIBG
Sweden There is some civil case law on classification of borderline products
UK MHRA’s Borderline section offers advice. The MHRA also publishes its own guidance
− Review the applicable legislation and guidance
− Check precedent cases and competent authority decisions
− Consider the method by which the principal action is achieved
− Consider the intended purpose of the product, taking into account the presentation• careful positioning of the product may be required• ensure consistency of labelling, claims and advertising
− Consider limiting marketing of the product to selected MS
− Don’t assume that the US classification will apply, or even be persuasive
Practical tips on dealing with borderline questions
Eversheds LLP | 19/04/2016 |
−Mouthwash• purpose of the product was to reduce bacterially-caused dental
plaque and to protect from gingivitis• “pharmacological means” = interaction between molecules of the
substance and a cellular constituent (usually referred to as a receptor) which either results in a direct response or blocks the response to another agent (borderline MEDDEV)
• CJEU clarified that the cellular constituent must be present in the user’s body, but does not need to be a cellular constituent of the user’s body.
−Hyaluronic acid and sodium pre-filled syringe• natural compound of joint fluid, which provides the viscosity and
elasticity required for protection of joints• principal means of action was physical
−Stand-alone software• a different type of borderline issue
Examples
3. Unharmonized issues
Eversheds LLP | 19/04/2016 |
− Do not overestimate the degree of EU harmonization• take local law advice
− Aim of New Approach• No further conformity assessments should be required• But Article 14 allows MS to require notification by manufacturer of marketing
of Class IIa, IIb and III devices;• other issues are unharmonized (e.g. enforcement, transfers of value to HCP)
− Advertising/promotion is not harmonized• Directive 2006/114/EC, concerning misleading and comparative advertising • Directive 2005/29/EC concerning unfair business-to-consumer commercial
practices• Eucomed Code of Ethical Business Practice • National laws and guidance may be more stringent• Careful clearance of advertising campaigns is required
Lack of regulatory harmonization across the EU
Eversheds LLP | 19/04/2016 |
Member State Provisions relating to medical device marketing
Belgium No advertising of non-CE marked devices (Royal Decree). Limited exemption for trade fairs, exhibitions and demonstrations
France No specific regulation. French Consumer Code prohibits false or misleading advertising. Enforced by DGCCRF
Germany Strict provisions on advertising medical devices can be found in the Law on Advertising of Medicinal Products. Also Code of Conduct of trade bodies
Italy Advertising to general public of prescription devices or devices only used with the assistance of an HCP is prohibited; other advertising requires prior consent of Ministry of Health. Some regional regulations too, and provisions in the Assobiomedica Code of Conduct
The Netherlands Few specific provisions. The self-regulatory Code on Public Advertising of Medical Devices 2009 applies. Medical device advertising is however subject to pre-approval by the council of Inspection of Public Advertising of Medicinal Products (KOAG)
Spain FENIN Code of Conduct (Association of manufacturers of medical devices) regulates advertising of medical devices
UK No specific regulation. ABHI Code of Conduct.
Advertising medical devices in the EU
regulation
4. Beyond regulatory compliance
Eversheds LLP | 19/04/2016 |
−Procurement • failing to challenge tender processes and unfavourable awards
−Product liability• intended use, device description, instructions for the user
−Pricing and reimbursement• failing to challenge unfavourable Health Technology Assessments
− Patent infringement issues• Unified Patent Court and Unitary Patent
A wider perspective on costly problems in the sector Beyond regulatory compliance
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Adrian Toutoungi
Partner - Eversheds LLP
+44 788 775 [email protected]