European Regulatory Affairs — Update on Medical Device Directives

UTC, Salt Lake City 20. September 2011

Michael Rinck MT Promedt Consulting GmbH

MT Promedt Consulting – Situated in the Heart of Europe

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500 miles

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Madrid www.mt-procons.com

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Agenda 

Changes and Trends and Changes in in European Medical Device Regulations



Changes of Directive 2007/47/EC



European Registration Requirements



Revision of RoHS Directive



Upcoming changes in IVD Directive 98/79/EC

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The European Union – An Economic Area of more than 490 Million People 29 different Member States, different cultures 21 different languages

EFTA

Different reimbursement systems

€ in 17 countries

?

EU members since 2004 Cyprus, Czech Republic Estonia, Hungary Latvia, Lithuania Malta, Poland Slovakia, Slovenia since 2007 Bulgaria, Romania

New EU Member July 2013 Croatia www.mt-procons.com

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The Principle of ―New Approach" 

1985: Single European Act: „…establish the internal market..“



EC-Directives take care of the basic health- and safety-requirements



Directives address Member States, national transpositions list Essential Requirements



The European Standardisation bodies (CEN and CENELEC) work out "Harmonised Standards", which concretise the Directives



These standards are recommendations and to follow them is voluntary



Compliance with standards will satisfy Essential Requirements

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Medical Device Directives cover entire Life Cycle of a Medical Device Transport Sterilization Manufacturing and Packaging

Final use and disposal

Transport

Storage

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Key Aspects of European Regulatory System in the Health Care Industry Medical Devices 90/385/EEC

• Active Implantable Medical Devices

93/42/EEC

• Medical Devices

98/79/EC 2000/70/EC

• In-vitro Diagnostics

2009/108/EC

• Common Technical Specification for IVD

2003/32/EC

• Animal Tissue

2005/50/EC

• Reclassification Hip implants

2007/47/EC

• Amendment MDD, AIMD, Biocidal Product Dir.

• Blood Derivatives

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European Regulatory System Key Directives and Regulations Further Directives to be considered by MD manufacturer 2001/95/EC

• Product Safety (umbrella)

94/62/EC

2002/95/EC

• Packaging and Packaging Waste Directive • Waste Electrical and Electronic Equipment (WEEE) • Hazardous Substances, RoHs Directive

2011/65/EU

• Recast of the RoHs Directive

85/374/EEC

• Product Liability

2006/42/EC

• Machinery Directive

89/686/EEC

• Personal Protective Equipment • REACH Regulation (Registration, Evaluation and Authorisation of Chemicals)

2002/96/EEC

EC 1907/2006 2006/114/EC

• Directive on misleading and comparative Advertising

2004/108/EC

• EMC Directive (covered by MDD and IVDD) www.mt-procons.com

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Implementation of Directive 2007/47/EC 18 months experiences Regulatory Environment with consequences for manufacturers 

Implemented March 21, 2010



Notified Body are reviewing Technical Files



Special Focus on Clinical Evaluation



Special Focus on Risk Management File and Post Market Surveillance



Increasing number of market surveillance activities by CA

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Revision of MD Directive 93/42/EEC Directive 2007/47/EC - Summary

Major changes of the European Medical Devices Directives

• • • • •

Classification / Reclassification Conformity assessment procedures Essential Requirements European Authorized Representative Clinical Evaluation

• Definition of Medical Devices (Software, SUD) • Labeling requirements (SUD, DEHP) • European Database (2012) • Custom made devices • Combination Devices (medicinal products and human blood derivatives) • Amendment to AIMDD • Updates Biocides Directives to remove IVD from scope

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Ways to the CE Mark – MDD and IVD Conformity Assessment Process Certification Audit Self Declaration

Conformity Assessment Procedure

Design Phase Harmonized Standards Essential Requirements

Classification

Annex IX Annex II and Article 9

CE

Annex I  Risk-Analysis (EN 14971)  Product Testing  Sterilization validiation  Compatibility Testing  Clinical Evaluation  Analytical Validation  Performance Evaluation (ISO 13612)

Annex II - VII Risk Evaluation QM-System Technical Product Dossier Annex III - VII Risk Evaluation QM-System Technical Product Dossier Design-Dossier

MDD IVDD www.mt-procons.com

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Product Classification European Medical Device Risk Classification  



One class under AIMD Four classes under MDD Four classes under IVD

-

Even though many regulations employ similar or same classification systems cultural perceptions of risks differ

-

Devices in one national regulation may have a different class in another

-

Classification is dynamic and may change over time

Classification defines the Conformity Assessment route for the CE-marking process www.mt-procons.com

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Classification Directive 93/42/EEC, Annex IX • Active/non-active

Classification Rules

• Location (Impact on critical organs) - Heart / central circulatory system (new vessels added) - Central nervous system

• Degree of Invasiveness - Intact Skin - Invasive by Body orifices - Surgical invasive • Duration of application new: consider here cumulative use - transient t < 60 minutes - short term t < 30 days - long term t > 30 days amended by Directive 2007/47/EC www.mt-procons.com

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Classification Guidance Documents European Commission provides Guidance Document for the Classification of Medical Devices MEDDEV 2.4/1 rev.09 June 2010 http://ec.europa.eu/health/medical-devices/files/meddev/2_4_1_rev_9_classification_en.pdf

and

Classification of Borderline products MANUAL ON BORDERLINE AND CLASSIFICATION IN THE COMMUNITY REGULATORY FRAMEWORK FOR MEDICAL DEVICES Version 1.10 (08-2011) (NEW) http://ec.europa.eu/health/medicaldevices/files/wg_minutes_member_lists/borderline_manual_ol_en.pdf

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Conformity Assessment Procedure – Medical Devices Class I

EC Declaration of Conformity (Annex VII)

Measuring / Sterile

Notified Body

Class II

Class IIb

EC Declaration of Conformity (Annex VII)

EC Typeexamination (Annex III)

EC Verification (Annex IV)

Production Quality Assurance (Annex V)

ABC

Product Quality Assurance (Annex VI)

Full Quality Assurance (Annex II) Notified Body (+ Medicine Board) EC Design Examination (Annex II, 4)

EC TypeExamination (Annex III)

Manufacturer’s option

Class III

Manufacturer’s option

ABC

Notification at Competent Authority

Product Class

Manufacturer’s option

Class IIa

Manufacturer’s option

Full Quality Assurance (Annex II)

EC Verification (Annex IV)

Production Quality Assurance (Annex V)

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ABC

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Technical Documentation Regulatory Requirements

• Required by Annexes of Directives and EN ISO 13485 • Required for all classes of devices

• Documentation to demonstrate conformity with Essential Requirements

Technical Documentation

• Complexity and risk of device determine level of detail • Availability within Europe (by European Authorized Representative) • To be updated by Manufacturer • Available for investigation by Competent Authority • Format depending from Notified Body

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Technical Documentation –

Content List (Example)

(1/2)

1

Introduction

2

Declaration of Conformity and Classification of the Device • 2.1 • 2.2 • 2.3

Results of Risk Analysis Essential Requirements Checklist Regulatory Documentation

3

Manufacturer’s Data

4

General Description and Intended Use • 4.1 • 4.2 • 4.3

5

Technical Data Specification/composition of the Device Specifications and Routine Tests

Toxicology and Biocompatibility / Electrical Safety • 5.1 Biocompatibility Tests of Device / Electrical Safety Tests • 5.2.1 Chemical, Physical and Toxicological Studies / EMC • 5.2.2 Expert Report www.mt-procons.com

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Technical Documentation –

Content List (Example) 6

(2/2)

Manufacturing, Flow Chart • 6.1 Manufacturing of Device • 6.2 Process Validation • 6.2.1 Sterilization Validation • 6.3 Control Procedures • 6.3.1 In process Control

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Test Specifications • 7.1. Type Tests • 7.2 Control Tests of Intermediate Product • 7.3 Control Tests of Finished Products

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Packaging and Labeling / Instruction for Use

9

Stability Tests

10

Clinical Evalution / Medical Efficacy / Clinical Data

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List of Relevant Standards www.mt-procons.com

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Essential Requirements – Annex I (MDD) I. • • • • • •

II.

General Requirements 1) Safety for patient and user 2) Risks (elimination, prevention, information) 3) Performance documentation 4) Performance during shelf life 5) Performance during transportation and storage 6) Undesirable side-effects / Clinical Evaluation

Requirements Regarding Design and Construction

• • • • • •

7) Chemical, physical und biological properties (use of phtalates) 8) Infection and microbiological contamination 9) Construction and environmental properties 10) Devices with a measuring function 11) Protection against radiation 12) Requirements for medical devices connected to an energy source (software validation) • 13) Information supplied by manufacturer (consider user, single-use, re-use, EAR, issue date of the IFU)

amended by 2007/47/EC

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Technical Documentation Focus on special aspects for File Review Process

Consider Special aspects  

    

Documentation of compliance with revised ER Biocompatibility strategy, tests and evaluation Clinical evaluation Sterilisation and packaging validation of sterile products Usability documentation Cleaning validation Compatibility aspects

Major areas of Notified Body audits as a result of the Notified Body TF review

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Essential Requirements – changes by Directive 2007/47/EC Additional requirements introduced by Directive 2007/47/EC 

Ergonomic features considered (Sect. 1)  

Usability aspects Qualification of users considered  devices for home care  for disabled or elderly patients

Standard EN IEC 62366 Usability (Usability Engineering Process) Experiences: NB requesting documentation for design phase Major deficiencies in Technical Files

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Usability Engineering Process - EN IEC 62366

Usability requirements to be considered

• Specify the application of the medical device • Identify the device's frequently used functions • Identify hazards and hazardous situations related to usability • Identify the device's primary operating functions • Develop the usability specification • Prepare the usability validation plan • Design and implement the user interface • Verify the user interface design • Validate the usability of the medical device Can be part of the Risk Management File www.mt-procons.com

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Essential Requirements – changes by Directive 2007/47/EC Additional requirements introduced by Directive 2007/47/EC 

Singe Use Devices (SUD)  Information to be provided on risks of reuse (sect. 13.6)  Specific labeling requirements  Foreseeable risks during unintended reuse has to be mentioned in IFU

Interpretation by Notified Bodies – Validation?



Instructions for use  must contain a date of issue or revision number

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Essential Requirements – changes by Directive 2007/47/EC Additional requirements introduced by Directive 2007/47/EC Evaluation of Leachables/Extractables (see Annex I, 7.4: Special attention shall be given to substances which are carcinogenic, mutagenic or toxic to reproduction, in accordance with Annex I to Council Directive 67/548/EEC of 27 June 1967 . Link to REACH Directive

Labeling Requirements for Phthalates containing devices Applies to phthalates classified as carcinogenic/mutagenic or toxic to reproduction (Annex I, Dir. 67/548, categories 1 or 2) intended to administer/remove medicines, body liquids or substances Intended to transport or store body fluids or substances

Devices intended for treatment of children or pregnant or nursing women must justify the use of phthalates & inform patients of residual risks in IFU www.mt-procons.com

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Consequence out of Directive 2007/47/EG New Symbols (e.g. Annex I, 7.5)

New Standard EN 15986:2011 published in May 2011 www.mt-procons.com

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Conformity Assessment requires intensive Technical File Review by Notified Body   

will cover “essentials” No differentiation between Class IIa and IIb Technical documentation should be reviewed for: 

classification



validity of essential requirements checklist risk management pre-clinical data (studies in animal models, biocompatibility, nanotechnology etc.)

 

  

clinical data (review as per MEDDEV 2.7.1) declaration of conformity, and other technical documentation based on product risks (Guidance from NBOG)

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Special Focus Clinical Evaluation

Clinical Evaluation

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Clinical Evaluation Regulatory Requirements Annex I: Essential Requirements

“Demonstration of conformity with the essential requirements must include a clinical evaluation in accordance with Annex X” MDD, Annex 1 ER 6a

Annex X: General Provisions – “… confirmation of conformity with the requirements …. of Annex I …. and the evaluation of the side-effects and of the acceptability of the benefit/risk ratio (Section 6 of Annex I), must be based on clinical data. “clinical evaluation”, … , must follow a defined and methodologically sound procedure … on:

A new understanding of ―clinical evaluation‖ www.mt-procons.com

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Clinical Evaluation demonstrates compliance with Essential Requirements Clinical Investigation vs. Clinical Evaluation Clinical Investigation

Clinical Evaluation

any designed and planned systematic study in human subjects undertaken to verify the safety and/or performance of a specific device (ISO 14155-1:2009)

Demonstration of conformity with the essential requirements must include a clinical evaluation in accordance with Annex X - Data from scientific literature - Results of clinical investigations

Clinical Evaluation CI

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Revision of MD Directive 93/42/EEC Directive 2007/47/EC • Clinical Evaluation is mandatory for all products and risk classes

Clinical Evaluation

• Clinical Investigation mandatory for implants and Class III devices • Documentation of Clinical Evaluation is part of TD • Updates as part of PMS activities (Annex X, sect. 1.1)

Follow MEDDEV 2.7.1 guideline www.mt-procons.com

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Clinical Evaluation Experiences of 12 months dossier audits Expectations of Notified Bodies Clinical Evaluation to comply with MEDDEV 2.7.1.

Experience of clinical experts selection criteria of scientific literature conclusive risk-benefit evaluation

missing QM process annual update process (link to PMS procedure)

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Quality Systems

FDA QSR (21 CFR part 820)

The implementation of a comprehensive Quality Management Systems allows access to the major markets

CAMDCAS PAL

ISO CE MDD EN ISO 13485:2003/ AC:2009 www.mt-procons.com

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Directive 2007/47/EC Changes in Quality System Requirements Directive 2007/47 introduces changes to the assessment of QA modules:   

Documentation of control of subcontractors Procedure for clinical evaluation Pro-active post market surveillance

Recommendation: Consider NB-MED/2.12/Rec1 “Post-Marketing Surveillance (PMS) post market/production; vigilance” Establish annual program for PMS, update of Clinical Evaluation (MEDDEV 2.7/1) and Risk Management File

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The Declaration of Conformity

Required Minimum Contents (Annex II, V, VI) • • • •

Written Declaration of Conformity (DOC) • issued by the • manufacturer • •

Name and address of the manufacturer and his representative within the EC Name and type of the product Must cover one or more medical devices manufactured Relevant EC-directive(s) Harmonized standards used Date and signature Function of the signatory

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CE Mark

Class I devices

XXXX 

 

 

Notified Body Number

required for devices of Class I s/m Class IIa or IIb Class III

CE = “Conformité Européenne“ (French) CE Marking indicates conformity with all applicable directives. CE Marking must be shown on the device or its sterile pack, in user manual and on the packaging and/or sales packaging (Article 17, MDD). CE Marking must be accompanied by the number of the Notified Body (if a Notified Body was involved). Form and dimensions are described in Annex XII. www.mt-procons.com

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Marketing and Product Registration in Europe

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European Device Marketing Requirements Prior to placing on the market…..

in

Product Notification by EAR  

Database notification Europe wide notification (EUDAMED database) 

 

Specific national notification requirements

Notification for other Directives (WEEE) Translation of IFU and labeling requirements

Reimbursement Notification   

Product Codes for Technical Aids In-patient and out-patient use National notification requirements

Vigilance System www.mt-procons.com

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Authorized European Representative



Required by MDD and IVD for Non-European Manufacturers



First contact for the CA



Responsibilities:  

  

Interaction with distributor, manufacturer and CA Representing the manufacturer in all European Regulatory Affairs Interaction with CA in Medical Device Vigilance System Notification of incidents and Recalls Cooperation with the manufacturer in the reporting process

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Position of European Authorised Representative German Competent Authorities consider EAR as „the European representative of the legal manufacturer“ • Holds all responsibilities as being the legal manufacturer • Contact point for all communications during market surveillance • Has to appoint the Safety Officer according §30 MPG

Consequence: • German CA consider EAR as being responsible for Product documentation and Product Quality • Position of German CA represents „worst-case“ scenario for EAR • EAR should be able to take over these responsibilities www.mt-procons.com

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Authorized European Representative Requirements for Notification Action performed by MT Promedt Consulting



Plausibility Check of Technical Documentation Completeness of Checklist ER, Risk Management File, Clinical Evaluation Declaration of Conformity Samples of Labels IFU



Notification at DIMDI database

   

UMDNS vs. GMDN

Action performed by Competent Authority 

Approve notification, issue notification code (DE/CA 70/ xxxxxxx) GMDN = Global Medical Device Nomenclature UMDNS = Universal Medical Device Nomenclature System

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EUDAMED Database  

 

Eudamed use is mandatory since May 2011. Eudamed is a web-based portal for information exchange between national competent authorities and the Commission. Eudamed is not publicly accessible. Use of the Global Medical Device Nomenclature GMDN in Eudamed. 

The GMDN is a comprehensive, regularly updated web-based nomenclature accessible to manufacturers against license fees.

Source: http://ec.europa.eu/consumers/sectors/medical-devices/market-surveillance-vigilance/eudamed/index_en.htm

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EUDAMED Database 

Eudamed contains data on: 







registration of manufacturers, authorized representatives and devices, data relating to certificates issued, modified, supplemented, suspended, withdrawn or refused, data obtained in accordance with the vigilance procedure and data on clinical investigations.

Source: http://ec.europa.eu/consumers/sectors/medical-devices/market-surveillance-vigilance/eudamed/index_en.htm

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Changes and Updates

Revision RoHs www.mt-procons.com

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RoHS and WEEE-Directives 



RoHS and WEEE (Waste Electrical and Electronic Equipment) Directives cover the entire life cycles of devices RoHS is closely linked to the WEEE Directive

Intentions:  The RoHS Directive is intended to eradicate certain hazardous substances from new electrical and electronic equipment  The WEEE Directive is intended to reduce the amount of waste of electrical and electronic equipment

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RoHs Directive 2011/65/EU Implementation until 02. January 2013 RoHS Directive 

The new Directive – 2011/65/EU will take effect on January 3rd, 2013 and the 2002/95/EC will be superseeded



Scope for 11 product categories (Annex 1)



Medical Device are included



No new compounds or changed concentrations



EU conformity declaration (Annex VI) required



Directive is implemented in national laws (ie. German “Elektrogesetz”, together with WEEE) www.mt-procons.com

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Directive 2011/65/EU (RoHS) Annex I Categories of EEE covered by this Directive 1. Large household appliances 2. Small household appliances

3. IT and telecommunications equipment 4. Consumer equipment 5. Lighting equipment 6. Electrical and electronic tools

7. Toys, leisure and sports equipment 8. Medical devices (including IVDs, but not AIMDs) 9. Monitoring and control instruments including industrial monitoring and control instruments 10. Automatic dispensers 11. Other EEE not covered by any of the categories above www.mt-procons.com

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Directive 2011/65/EU Timelines (Article 4 point 3) 

RoHS Directive will apply 

to medical devices and monitoring and control instruments which are placed on the market from 22 July 2014



to in vitro diagnostic medical devices which are placed on the market from 22 July 2016 …



Not applicable for Active Implantable Medical Devices

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RoHs Directive 2011/65/EU Implementation until 02. January 2013 RoHS Directive 

Implement and document production control



Archive documentation for 10 years 

Documentation:

Product description  Applicable standards  Test reports 



New definition of “homogenous materials”

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Directive 2011/65/EU Provides a list of Restricted Substances Max Concentration Values of the restricted substances (Annex II):     



Lead (0,1 %) Mercury (0,1 %) Cadmium (0,01 %) Hexavalent chromium (0,1 %) Polybrominated biphenyls (PBB) (0,1 %) Polybrominated diphenyl ethers (PBDE) (0,1 %) ―By weight in homogeneous materials..shall be tolerated.‖ (uniform composition)

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Directive 2011/65/EU Definition of Homogeneous Materials 

Article 3 (20) Directive 2011/65/EU “homogeneous material means one material of uniform composition throughout or a material, consisting of a combination of materials, that cannot be disjointed or separated into different materials by mechanical actions such as unscrewing, cutting, crushing, grinding and abrasive processes.”

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Cables and Spare Parts

Reference: Onrust, MedTeC 2011, Stuttgart

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Directive 2011/65/EU 

Article 4 (1) “Member States shall ensure that EEE placed on the market, including cables and spare parts for its repair, its reuse, updating of its functionalities or upgrading of its capacity, does not contain the substances listed in Annex II.”

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Changes and Updates

Coming Changes and Revision IVDD 98/79/EEC

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Development General 

Directives 90/385/EEC and 93/42/EEC have been supplemented over time with a number of modifying or implementing Directives. The latest being Directive 2007/47/EC (implemented in March 2010)



Directive 98/79/EC on in vitro diagnostic medical devices (IVDs) has not been substantially amended since its adoption.

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European Commission - Roadmap 

This indicative roadmap is provided for information purposes only and is subject to change



1. Proposal for a Directive of the European Parliament and of the Council concerning medical devices and repealing Directives 90/385/EEC and 93/42/EEC (recast); 2. Proposal for a Directive of the European Parliament and of the Council concerning in vitro diagnostic medical devices and repealing Directive 98/79/EC (recast)





Expected date of adoption of the initiative: 1st quarter 2012 Source:

http://ec.europa.eu/governance/impact/planned_ia/docs/2011_sanco_036_medical_devices_en.pdf

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Public Consultation IVD Directive 





European Commission’s public consultation of the Recast of the Medical Devices Directive launched in 2008 This public consultation was mainly focused on horizontal issues regarding the revision of the legal framework for medical devices. Many responses received to the public consultation underlined the need to revise some specific aspects of Directive 98/79/EC.

Public Consultation: Revision of Directive 98/79/EC Source: Revision of Directive 98/79/EC of the European Parliament and of the Council of 27 October 1998 on in vitro diagnostic medical devices; Summary of responses to the public consultation, 23 February 2011

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European Regulatory System for IVD Upcoming Regulations 

Revision of Directive 98/79/EC  

  

Public consultation, about 200 reactions received Risk based product classification Summary published in March 2011 Final draft expected 2012 Transposition not before 2015

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Summary



Major changes in MDD with impact on manufacturers



Control your CE compliance by regular Standard Evaluations



Understand auditing process by Notified Bodies



Regulatory system of IVD directive will be adapted



Upcoming changes in RoHS Directive



Understand CE marking requirements and marketing requirements

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The European Market represents an interesting opportunity for medical device manufacturers 

European Union - a unique patchwork of markets – provides challenges and possibilities for international exporters of medical devices



Vibrant economies with high levels of healthcare spending and large populations are fertile ground for medical device producers



Fast market access for innovative products



Favorable regulatory climate – CE certification CE Mark is basis for international product registration



Different conditions across the region make local intelligence of market factors key to success

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Cooperation with a German Regulatory Partner Benefits for a successful market entry in Europe 

Understanding the regulatory landscape of Europe’s biggest market



Safety Officer (§30 MPG) with defined responsibilities assures working vigilance system



Notification of products of all Risk Classes (Class I, IIa, IIb and III) results in Notification approval by Competent Authorities with Approval Code



Preparation of Certificates of Marketability on the basis of product Notifications is basis for international product marketing



Our multi-cultural and multi-lingual regulatory team provides capacity and know-how for European Market to 

control your registration projects and



get access to the European customers, distributors and authorities

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For further information please contact us

MT Promedt Consulting GmbH

Germany Office

US Office

Altenhofstrasse 80 D-66386 St. Ingbert Phone: +49 6894 581020 Fax: +49 6894 581021 E-Mail: [email protected]

41 North Rio Grande Street #100 Salt Lake City, UT 84101 Phone: +1 (801) 699 07 65 Fax: +1 (801) 546 29 17 Email: [email protected]

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