The ROI of Good Quality & Compliance

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


geographical coverageChanging Regulations in EU & US for Medical Devices

Peter RoseManaging Director EuropeMaetrics



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

©2016 Maetrics. All Rights Reserved. 5

Presentation Topics


Introduction 3

Timelines 12

Reclassification 18





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

©2016 Maetrics. All Rights Reserved.

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


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


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


Year #1 #2 #3 #4 #5

2015 CAPA ComplaintFiles

Purchasing Controls

Process Validation MDR


Design Controls

Purchasing Controls Receiving, In‐Process, Finished Device Acceptance


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


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


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


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



Introduction 3

Timelines 12

Reclassification 18





Questions 32

Presentation Topics


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


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


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


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


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)


Presentation Topics

Introduction 3

Timelines 12

Reclassification 18





Questions 32


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


Introduction 3

Timelines 12

Reclassification 18





Questions 32

Presentation Topics


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


Presentation Topics

Introduction 3

Timelines 12

Reclassification 18





Questions 32

26

Unique Device Identification (UDI)

UDI System (Article 24)


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


Benefits of UDI


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

28


FDA


UDI system – Final Rule 21 CFR Parts 16, 801 and 803

Published September 2013

Implements IMDRF UDI

Timetable according to classification

29


Its not just a bar code!


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


Presentation Topics

Introduction 3

Timelines 12

Reclassification 18





Questions 32

31

Clinical Evidence

Requirements


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

32

Clinical Evidence

Data Sources


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


Presentation Topics

Introduction 3

Timelines 12

Reclassification 18





Questions 32

34

The Cost of Compliance

Its not going to get cheaper


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


Presentation Topics

Introduction 3

Timelines 12

Reclassification 18





Questions 32

Maetrics

Maetrics Ltd Peter RoseBioCity Nottingham Managing Director, EuropePennyfoot Street [email protected] +44 7811 199 346NG1 1GFUnited Kingdom

+44 115 921 6200


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.


38

2015


geographical coverageIntroduction to the proposed EU Medical Device Regulations

Martin PenverHead of Notified BodyLRQA



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


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?)


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 -


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


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.


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.


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


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


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


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


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


– 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


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).


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 )


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


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


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


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)


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.


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


geographical coverageIntegrating Quality with Corporate Compliance to Provide the Greatest Return

Dr. Seth Whitelaw President & CEOWhitelaw Compliance Group



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


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

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Leading to Increased Enforcement

71

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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


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

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Quality & Compliance Not Keeping Pace

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CEO

Chief Quality Officer

ManufacturingQuality R&D Quality

Chief Compliance Officer

Compliance Operations


The Disconnect 74

External Regulations

Internal Audits

Quality Control

Quality Assurance

Quality

Corporate Compliance


How It Needs to Work 75

CEO

Chief Compliance Officer

Compliance Operations

Chief Quality Officer

Manufacturing Quality

R&D Quality


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

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It Isn’t Just TheoryINVACARE, VALEANT AND OTHER NOTABLE STORIES

77


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

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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

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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.

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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

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WhitelawComplianceGroup,LLC.helpingcompaniesgrowsustainableintegrity

www.WhitelawCompliance.com

+1.215.275.1556

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2015


geographical coverageThe Impact of a Good Quality Management System

Carl DoverVice President – Quality Strategy & Process ImprovementDePuy Synthes




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


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


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


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


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


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


Additional Benefits

Cost of Quality

Customer Satisfaction

Consolidation

Organizational Capability

Guaranteed Supply

EngagementIntegrationAgility

L&A

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2015


geographical coverageThe Most Costly Problemsand Why Continually Repeated

Adrian ToutoungiCommercial PartnerEversheds



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


− 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


− 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


− 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


− 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


− 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


− 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?


- 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


−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


− 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


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


−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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Europe01 London 24 Turku

02 Ipswich 25 Helsinki

03 Cambridge 26 Tallinn

04 Cardiff 27 Riga

05 Birmingham 28 Vilnius

06 Nottingham 29 Warsaw

07 Manchester 30 Budapest

08 Leeds 31 Vienna

09 Newcastle 32 Munich

10 Edinburgh 33 Zurich

11 Dublin 34 Berne

12 Belfast 35 Geneva

13 Paris 36 Madrid

14 Brussels 37 Milan

15 Rotterdam 38 Rome

16 Amsterdam 39 Bucharest

17 HamburgAfrica18 Berlin

19 Stockholm 40 Tunis

20 Pori 41 Durban

21 Tampere 42 Johannesburg (Bryanston)

22 Jyvaskyla 43 Johannesburg (Sandton)

23 Hameenlinna 44 Port Louis

Middle East45 Amman

46 Erbil

47 Baghdad

48 Riyadh

49 Doha

50 Abu Dhabi

51 Dubai

Asia52 Beijing

53 Shanghai

54 Hong Kong

55 Singapore

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Adrian Toutoungi

Partner - Eversheds LLP

+44 788 775 [email protected]

The ROI of Good Quality & Compliance

Presentations & Public Speaking

Transcript of The ROI of Good Quality & Compliance