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Classification of Medical Devices –Clinical Evaluation and Conformity Assessment

Dr. Juliet M. DoranPre-market Evaluation AssessorHuman Products Authorisation & Registration

Committee for Advance Therapies (CAT) Presidency meeting

28th February 2013

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Presentation Content

• Definition of a Device

• Scope of MD legislation

• Medical device life-cycle

• Classification

• Clinical Evaluation

• Conformity Assessment

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Medical Device LegislationDefinition of a Medical Device (Article 1 93/42/EEC)

“‘medical device’ any instrument, apparatus, appliance, software, material or other article… intended …for… — diagnosis, prevention, monitoring, treatment or

alleviation of disease…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 onthe human body by pharmacological, immunological or metabolicmeans, but which may be assisted in its function by such means;”

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Medical Device Legislation-Definition of an Active Implantable Device (Article 1 90/385/EEC)

‘‘active implantable medical device’ …any device …intended to be totally or partially introduced, surgically or medically, into the human body or by medical intervention into a natural orifice, and which is intended to remain after the procedure;”

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“‘in vitro diagnostic medical device’ …any medical device which is a reagent… instrument, or system… intended …to beused in vitro for the examination of specimens,…for the purpose of providing information:— concerning a physiological or pathological state, or— concerning a congenital abnormality, or to determine the safety and compatibility with potential recipients, or— to monitor therapeutic measures.”

Medical Device Legislation-Definition of an In-Vitro Diagnostic Device (Article 1 98/79/EC

Scope of MD legislation (Directive 93/42/EC)

Does not apply to…

• IVDs, active implantable medical device

• MPs covered by 2001/83/EC

• Cosmetic products

• Human blood, blood products, plasma or blood cells of

human origin

• Transplants or tissues or cells of human origin

• Viable transplants or tissues or cells of animal origin.

Scope of MD legislation

Does apply to devices incorporating…

• a medicinal product, with an ancillary action

• a medicinal product derived from human blood or plasma, with an

ancillary action

• non-viable tissues of animal origin

Lifecycle of Medical Device

3. Registration with Competent Authority

Class I& Custom-made devices

Class IIa, Class IIb, Class III & Class I sterile or measuring

4. CE-marking

5. Post Market Surveillance

5. Post-market Clinical Follow-up

Prototype

1. Classification

3. Conformity Assessmentby Notified Body

2. Clinical Evaluation

4. CE marking & certificate issued XXXX

Post-market

Pre-market

1. ClassificationTo qualify as a medical device- must have medical purpose & primary physical mode of action.

4 device classes, based on risk:

Device class determined by 18 rules:• Rules 1-4- Non invasive devices • Rules 5-8- Invasive devices • Rules 9-12- Active devices • Rules 13-18- Special rules

These consider:Duration contact (e.g. 1second15years?)Degree invasiveness (e.g. intact surgery?)Anatomy affected (e.g. oral cavity CNS?)Active (i.e. uses a power source) Re-usable?

Device Class determines the route to CE marking.

Class Risk Examples

I Low

Wheelchairs, simple wound

dressings, Stethoscopes,

ECG electrodes, syringes

IIa Medium

Contact lenses, ECG

machines, electronic BP

monitors

IIb Medium – High

Peripheral Bare Metal Stents

(BMS), External Defibrillator

III High

Joint replacements, Drug-Eluting Stents (DES), Pacemakers,

Rule 13** Drug-Device Combinations (Class III)

If MD contains MP:1. Device aspect assessed under device legislation but general principles of other

MP legislation must apply2. Notified body must verify the ‘usefulness’ of the MP3. ‘Drug consultation’ required with a Competent Authority/EMA must give opinion on the

‘quality, safety and benefit/risk profile’.

**Rule 13 also covers human blood derivatives.

–Primary mode of action physical=> Medical Device (MD)e.g. Drug-Eluting Stent → MDe.g. Bone cement containing antibiotic → MD

–Primary mode of action pharmacological, immunological / metabolic => Medicinal Product (MP) e.g. Asthma inhaler → MPe.g. Patches for trans-dermal drug delivery → MP

1. Classification

1. Classification

Rule 17 Devices Containing Tissues of Animal Origin (Class III)

If MD contains Tissue of animal origin (relevant):1. (In addition to MDD) Manufacturer subject to Directive 2003/32/EC

(Regulation 722/2012 from 28th August 2013).2. If starting material has an EDQM CEP- considered by notified body in its

overall assessment.3. If starting material has no EDQM CEP, the notified body prepares a

Summary Evaluation Report (SER) (conduct risk assessment, review alternative materials, evaluate source of tissue)

4. SER circulated to all CAs for comments, considered by notified body.

1. Classification

The exception to the 18 medical device classification rules is….

‘Medical devices’ containing Advanced Therapy Medicinal Products (ATMPs)- combined ATMPs under ATMP Regulation No 1394/2007).

•Doesn’t matter if primary mode of action is physical (i.e. by a medical device)

2. Clinical Evaluation

• All medical devices require clinical evaluation: Class I, IIa, IIb, III & AIMD• Must be based on clinical data- 3 different routes:

• Clinical investigationClinical investigations “shall be performed unless it is duly justified” to rely on existing clinical data for (high risk devices):

» Implantable devices» Class III devices» Active implantable medical devices.

1. Scientific literature route 2. Clinical Investigation route

3. Combination route

Critical evaluation of the relevant scientific literature

•demonstration of equivalence between devices

•data adequately demonstrate compliance with Essential

Requirements

Critical evaluation of the results of clinical investigation(s)

Combination ofScientific literature route

+Clinical Investigation

route

3. Conformity Assessment (by a Notified Body)

• Notified bodies assess medium and high risk devices for conformity:

Notified bodies are- • Designated by their national Designating Authority as competent for particular device

types & • Notified to the European Commission as NANDO scope expressions. • Monitored routinely by Designating Authority.

• Currently 77 notified bodies for medical devices in Europe (http://ec.europa.eu/enterprise/newapproach/nando/).

0050 0123 0086 0124

Medical Devices Class I with a measuring or sterile function Class IIa, Class IIb & Class III

Active Implantable Medical Device

All

3. Conformity Assessment (by a Notified Body)

The number of (the 77) notified bodies designated to assess selected device types/technologies:

(Ref. http://ec.europa.eu/enterprise/newapproach/nando)

Medical Device Scope Expression No. of NBs

MD 0204- Non-active functional implants 39

MD 0204- Non-active soft tissue implants 38

MD 0300- Devices for wound care 48

MDS 7001- Medical devices incorporating medicinal substances, according to Directive 2001/83/EC

37

MDS 7002- Medical devices utilising tissues of animal origin, according to Directive 2003/32/EC

26

MDS 7003-Medical devices incorporating derivatives of human blood, according to Directive 2000/70/EC, amended

16

MDS 7008-Medical devices utilising nano-materials 22

Class III devices (assessed by a notified body under e.g. Annex II) would require…ANNEX I Essential Requirements review of device including…

GeneralRisk : benefit assessment (clinical & safety) and reduction (Risk EN ISO 14971)State-of-the-art design & constructionLifetime device performanceTransport& storage impactClinical evaluation (Clinical Investigation EN ISO 14155)Side effectsResidual risk information

Chemical, physical & biological propertiesMaterials of construction: toxicity, flammability Compatibility of materials of constructionBiocompatibility (EN ISO 10993) & Compatibility with other contact materialsDevice <-> MP compatibilityPre-clinical testing- animal, bench, computerDrug & blood consultationResidual material contamination, leaking & ingress

3. Conformity Assessment (by a Notified Body)

Infection & microbial contaminationAnimal tissues- SER/EDQM (TSE EN ISO 22442 )Sterility & packaging validation and stability (Sterilisation EN ISO 11135, 556)

Construction & environmental properties Combination safety & performance testingDevice ergonomics, usability & interference (Usability EN ISO 62366)

Measurement Accuracy & stability (Thermometers ISO EN 1060)

RadiationEnergy sources (Medical electrical equipment EN 60601)Labelling/IFU (Labelling EN ISO 980, IFU EN ISO1041)

Full Quality System (ISO13485) plus…Clinical data SOPs Design Control & Verification SOPs Post-market surveillance systemIn-process and Final QC release tests & SOPs Sterilisation, Purchasing, labelling SOPS

3. Conformity Assessment (by a Notified Body)

Design dossier review of deviceProduct description & Intended use Design Verification & ValidationRisk assessmentStandards applied

Sterilisation, Biocompatibility, Risk etc. Solution to Essential RequirementsPre-Clinical Testing

Bench Testing / simulationAnimal Model

Clinical Evaluation Literature reviewClinical Investigation (Human Model)

First In Man Acute In-Vivo Device Performance

Device labelling & IFUStability Testing Significant changesPerformance / Complaint Analysis

3. Conformity Assessment (by a Notified Body)

Declaration of Conformity by the manufacturerCE certificate issuedNotified body assessment of all Substantial ChangesAnnual surveillance, recertification- 3-5 years.

3. Conformity Assessment (by a Notified Body)