Changing medical device regulations in Europe and the U.S

Changing Regulations in the EU and US19th April 2016London, UK

2

Introduction 3

Timelines 13

Reclassification 19

Reprocessing of Single Use Devices 21

Unique Device Identification (UDI) 23

Clinical Evidence 28

The Cost of Compliance 31

Questions 33

©2016 Maetrics. All Rights Reserved.

Presentation Topics

3©2016 Maetrics. All Rights Reserved.

Introduction 3

Timelines 13

Reclassification 19





Questions 33

Presentation Topics

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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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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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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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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 Complaint Files

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

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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


http://www.fda.gov/AboutFDA/CentersOffices/ucm477082.htm

http://www.fda.gov/AboutFDA/CentersOffices/ucm477082.htm

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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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Introduction

A. Transition to Commodity-Based and Vertically Integrated Regulatory Program (Specialization)

More focussed approachB. Training and Certification

Many more highly trained resources, currently most inspectors have very general knowledgeC. Medical Devices and Radiological Health Program Work Planning

Prioritise resources in line with the plan, and enforcement prioritiesD. 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 perspective

E. 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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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 13

Reclassification 19





Questions 33

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 agreed

Oct 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 13

Reclassification 19





Questions 33


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 13

Reclassification 19





Questions 33

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 13

Reclassification 19





Questions 33

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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

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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

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FDA


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

Published September 2013

Implements IMDRF UDI

Timetable according to classification

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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 13

Reclassification 19





Questions 33

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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

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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 13

Reclassification 19





Questions 33

31

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 13

Reclassification 19





Questions 33

33

Maetrics

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

+44 115 921 6200


Contacts

Thank You!

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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.


Presentations & Public Speaking

Changing medical device regulations in Europe and the U.S