AKSHAY ANAND MI Year – Master of Pharmacy

Pharmaceutical Regulatory Affairs

JSS College Of Pharmacy

Mysuru 570015, Karnataka

REGULATORYAPPROVALPROCESS FOR

MEDICALDEVICESIN EUROPEANUNION

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ASPECTS

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• Medical Devices – What are they?• European Union – An Overview• EU Directives that impact Medical Devices• Medical Devices as defined by EU• Classification of Medical Devices as per EU• The CE Certification• The Registration Process for MD• The Process Timeline for Registration

OF THIS PRESENTATION

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• A medical device is an instrument, apparatus, implant, invitro reagent, or similar or related article that is used todiagnose, prevent, or treat disease or other conditions

• It does not achieve its purposes through chemical action withinor on the body.

• Medical devices vary greatly in complexity and application.• The design of medical devices constitutes a major segment of

the field of biomedical engineering.• Examples range from simple devices such as tongue

depressors, medical thermometers, and disposable gloves toadvanced devices such as computers which assist in theconduct of medical testing, implants, and prostheses.

• The global medical device market reached roughly $209 billionin 2006.

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• 28 member states plus European Free Trade Association members.

• 24 languages.• Population of more than

500 million people.• GDP of $18.124 trillion.• Euro, the currency

equalling 71.47 Indian Rupee per unit.

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• Medical Devices (MDD) 93/42/EEC• Covers the bulk of medical devices marketed in the EU• Examples: orthopaedic implants, heart valves, medical software

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• Active Implantable Medical Devices (AIMDD) 90/385/EEC • Covers devices that require external power sources in order to

function properly• Examples: pacemakers, implantable defibrillators

• In Vitro Diagnostics (IVDD) 98/79/EC• Covers devices used for the examination of specimens taken from the

human body• Examples: pregnancy self-testing strips, blood glucose self-testing

strips

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• Personal Protective Equipment 89/686/EEC• Low Voltage 2006/95/EC• Electromagnetic Compatibility 2004/108/EC• Blood Product Directive 2002/98/EC• Animal Tissue Use in Medical Devices 2003/32/EC• Human Tissue Products Directives 2004 & 2005• Breast Implants Reclassification Directive 2003/12/EC• Hip, Knee, Shoulder Joint Replacement Reclassification

Directive 2005/50/EC

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This guidance document under Directive 93/42/EEC on MedicalDevices provides definition of Medical Devices to include thefollowing:

Medical Devices: Guidance Document

MEDDEV 2.1/1 APRIL 1994

a. Devices – Accessoryb. Medical Purposec. Customizingd. Medical – Toiletry Purposee. Aids for Handicapped Personsf. Softwareg. Multipurpose Products

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• The classification of medical devices is a ‘risk based’ system based on thevulnerability of the human body taking account of the potential risksassociated with the devices.

• This approach allows the use of a set of criteria that can be combined invarious ways in order to determine classification, e.g. duration of contactwith the body, degree of invasiveness and local vs. systemic effect. Thesecriteria can then be applied to a vast range of different medical devicesand technologies.

• These are referred to as the ‘classification rules’ and are set out in AnnexIX of Directive 93/42/EEC.

Medical Devices: Guidance Document

MEDDEV 2.4/1 Rev.8 JULY 2001

MEDDEV 2.4/1 Rev.9 JUNE 2010

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• The CE mark, or formerly EC mark, is a mandatory conformity markingfor certain products sold within the European Economic Area (EEA) since1985.

• The CE marking is also found on products sold outside the EEA that aremanufactured in, or designed to be sold in, the EEA.

• This makes the CE marking recognizable worldwide even to people whoare not familiar with the European Economic Area.

• It is in that sense similar to the FCC Declaration of Conformity used oncertain electronic devices sold in the United States.

• It consists of the CE logo and, if applicable, the four digit identificationnumber of the notified body involved in the conformity assessmentprocedure.

• The CE marking is the manufacturer's declaration that the product meetsthe requirements of the applicable EC directives.

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KEY PLAYERS IN THE

CE MARKING PROCESS(REGULATORY APPROVAL PROCESS FOR MEDICAL DEVICES)

• Manufacturers and Subcontractors

• Competent Authorities• Notified Bodies• Authorized Representatives• Distributors

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• Competent Authorities are entities enforcing Medical Device Directives at the national level in each EU member state.

• Member states and their Competent Authorities each have their own interpretations of how Directives should be carried out.

• Manufacturers seeking to sell in more than one EU member state should take this into account.

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• Notified Bodies are authorized to audit manufacturers’ quality systems and test/review devices for compliance with applicable EU Directives and standards.

• Their responsibilities include:• Advising on device classification and Conformity Assessment routes• Pre-assessment of devices• Product and quality system evaluation• Concluding and evaluating manufacturers’ Corrective Actions• Issuance of certifications• Maintaining programmed surveillance of devices in the EU

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• Required for any firm without a location in the EU.• Their responsibilities include:

• Liaising between manufacturers and Competent Authorities• Listing their names on clients’ device labels and packaging• Notifying Competent Authorities of manufacturers’ and devices’ names• Keeping Technical Files/Design Dossiers available for review by

Competent Authorities• Participating in vigilance/post-market surveillance procedures

EC REP

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Identify Directives and Regulations appropriate for your device

Classify your device according to MDD Annex IX

Implement Quality System in compliance with ISO 13485.

Prepare Technical File or Design Dossier demonstratingcompliance with MDD 93/42/EEC.

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Appoint your Authorized Representative.

Have Notified Body audit your Quality Systemand Technical File or Design Dossier.

Register your device with Competent Authorities if necessary.

Prepare Declaration of Conformity and affix CE Marking to your device.

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• First, determine which Medical Device Directive (MDD, AIMDD or IVDD) applies to your device.

• Then determine device classification using Annex IX of MDD 93/42/EEC.

Class I Non-SterileClass I Non-Measuring

Class I SterileClass I Measuring

Low-risk, non-invasive devices such as non-sterilewound dressings and stethoscopes

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Class IIa

Medium-risk, short-term invasive devices such astracheal tubes and lancets

Class IIbHigher-risk, often longer-term surgically invasive,

sometimes implantable devices including intra-ocularlenses and surgical lasers

Class IIIHighest-risk devices, including all active

implantable devices such as replacement heartvalves and vascular stents

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• MDD 93/42/EEC Annex IX contains 18 rules for medical device classification based on factors including the following:

• Device’s intended use• Active versus non-active functionality• Device’s duration of contact with patient• Degree of invasiveness• Part of body contacted by device• Special situations

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• Duration of Contact Criteria• Less than 60 minutes = Transient• Less than 30 days = Short-term• More than 30 days = Long-term

• Degree of Invasiveness Criteria• Application to body surface versus an orifice• Surgically invasive or non-invasive• Implantable

Determining your device’s duration of contact and degree of invasiveness will help determine how to classify the device.

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Short Term

Long Term

Long Term

Transient

Transient

Medium-Risk

Medium-Risk

High-Risk

Low-Risk

Low-Risk

Class IIa

Class IIb

Class III

Class I Sterile/Measuring

Class I Non-Sterile/Non-Measuring

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Manufacturers of Class I sterile/measuring, IIa, IIb and III devices must implement quality management systems (QMS) (in compliance with Annex II or V of the MDD).

Most manufacturers meet this requirement using ISO 13485.

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Phase I: Quality system preparation and development• Management buy-in• Assign resources and staff• Conduct gap analysis• Develop quality manual and documentation controls

Phase II: Implementation• Employee training• Internal auditing• Corrective and preventative actions

Phase III: Registration• Registration audit performed by Notified Body• Final ISO 13485 certification

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• All Class I, IIa and IIb device manufacturers must prepare Technical Files containing data to demonstrate MDD 93/42/EEC compliance.

• Class III device manufacturers must prepare Design Dossiers to demonstrate compliance to MDD.

• All manufacturers must have clinical data to demonstrate compliance to MDD.

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1Description of product family and justification for why your device falls into that family

2 Device intended use

3Description of device components, specifications, packaging and literature

4 Device manufacturing Process

5 List of accessories to your device

6 Location of design responsibility and manufacturing facilities

7 Classification along with rationale for classification

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8 Chosen compliance route according to applicable Directive(s)

9Declaration of Conformity stating manufacturer’s compliance with applicable Directive(s)

10 Shelf life and environmental limitations of device

11Retention of quality assurance, Competent Authority and NotifiedBody records

12 Vigilance reporting and Medical Device Reporting procedures

13 How and when to contact Competent Authorities

14 Name of and contract with your Authorized Representative

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15 Subcontractor names and addresses if applicable

16 Essential Requirements

17 Design input specifications

18 Application and references to Standards and Guidelines

19 Testing results and clinical evaluations

20 Risk analysis

21 Instructions for Use and Labeling

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• EU regulators have increased their requirements for clinical data even for Class I medical devices in recent years.

• In many cases, manufacturers must submit Clinical Evaluation Summary Reports that verify the safety and performance of their products along with Technical Files or Design Dossiers.

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Manufacturers with no offices in the EU must appoint Authorized Representatives (EC REPs) to interact with regulators on their behalf.

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• Registering your device with Competent Authorities before commercialization• Serving as primary point of contact with all EU Competent Authorities• Keeping a current copy of your Technical File/Design Dossier available for

inspections by Competent Authorities• Authorizing you to place EC REP name and address on your device labels,

packaging and instructions for use• Handling Incident and Field Safety Corrective Action (FSCA) reporting to

Competent Authorities• Representing you before the European Commission in the event that your

product is withdrawn in a member state• Protecting the confidentiality of your product information• Maintaining reports on clinical evaluation data for review by Competent

Authorities• Communicating with Competent Authorities on serious device incidents or FSCAs

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Following appointment of your EC REP, your quality system and Technical File/Design Dossier must be audited by a Notified Body. Upon Successful completion of your audit, the Notified Body will

issue a CE Certificate.

Manufacturers of Class I Non-sterile/Non-measuring devices self-declare MDD conformity and do not require CE Marking certificates.

Class IIa Class IIb Class IIIClass I S/M

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Class I device manufacturers must register with the Competent Authority of the country where their EC REPs are based.

Class I S/MClass I NS/NM

Class IIa Class IIb Class III

Some EU member states do not require registration of Class IIa, IIb or III devices with Competent Authorities. Other countries do

not require registration of devices.

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• In order to complete the CE Marking process, all manufacturers must prepare a Declaration of Conformity stating their device is in compliance with all applicable Directives.

• Upon completion of your Declaration of Conformity, you may affix CE Marking to your product.

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Product Identification

Manufacturer Identification

EC REP Information

Applicable Directives

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• EU member states MAY require labelinginformation be made available in their local languages or another European Community language to patients and users in accordance with Annex I, point 13 of the MDD.

• All languages subject to subsidiarity All EU member states require device labeling in their official languages Label information in your Technical File should only appear in ONE language

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Source: EmergoGroup.com

Device

Classification in

Europe

Wait Time after

submission until

approval is

granted

Validity

Period for

CE Marking

Certificate

Advance Start

Time for

Registration

Renewal

Complexity of

Registration

Process

Overall Cost of

gaining

Regulatory

Approval

Class I NS/NM <1 Month No Expiry Not Applicable

Class I S/M 3-5 Months 3 Years 2 Months

Class IIa 3-5 Months 3 Years 2 Months

Class IIb 3-6 Months 3 Years 2 Months

Class III 6-9 Months 3 Years 2 Months

Simple Complex Low High

Simple Complex Low High

Simple Complex Low High

Simple Complex Low High

Simple Complex Low High

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• PMS required for all medical devices sold in the EU• Manufacturers are required to develop proactive plans for PMS• PMS plans should include reviews of market and field data, complaints and

corrective actions• Systematic records of PMS findings must be kept

• Purpose of Vigilance Requirements:• Protecting public health and safety• Evaluating incidents to prevent recurrence• Determining effectiveness of corrective actions taken• Monitoring and learning from experience

• Vigilance Requirements for Manufacturers:• Establish and maintain systematic procedures to review experience

gained from devices in the post-production phase• Implement appropriate means to apply any necessary corrective actions

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• https://en.wikipedia.org/wiki/Medical_device - Wikipedia article on Medical Devices• http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CONSLEG:1993L0042:20071011:en:PDF – Official EU

Document : Council Directive 93/42/EEC• http://ec.europa.eu/health/medical-devices/documents/guidelines/index_en.htm - Guidance MEDDEVs Online

Directory• http://ec.europa.eu/health/medical-devices/files/meddev/2_1-1___04-1994_en.pdf - Guidance Document

MEDDEV 2.1/1 April 1994• http://ec.europa.eu/health/medical-devices/files/meddev/2_2_4-1part1_07-2001_en.pdf - Guidance Document

MEDDEV 2.4/1 Rev.8 July 2001• http://ec.europa.eu/health/medical-devices/files/meddev/2_4_1_rev_9_classification_en.pdf - Guidance

Document MEDDEV 2.4/1 Rev.9 June 2010• https://en.wikipedia.org/wiki/CE_marking- Wikipedia article on CE Certification• http://www.lne-gmed.com/pdf/en/annex9-directive-93-42-amended.pdf - Official EU Document : Annex IX of

Council Directive 93/42/EEC• http://ec.europa.eu/health/medical-devices/faq/market_en.htm - Information about the Medical Device

Registration on the Official Website of European Commission• http://medicaldevices.bsigroup.com/en-GB/our-services/ce-marking/ - Information about CE Marking Approval

for Medical Devices in Europe• http://www.emergogroup.com/resources/europe-process-chart - Europe CE Approval Process for Medical

Devices – Charts & Timelines

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thankyou!axayanand@gmail.com