MassMEDIC: The European Medical Device Market – Re-Examined June 13, 2012 Securing the CE Mark for Your Medical Device Peter Rose – Managing Director High Edge Consulting Ltd www.highedge.co.uk © High Edge Consulting 2012 High Edge Consulting Quality Systems Sterilization Worldwide Regulatory Affairs Auditing Services Contamination Control & Microbiology Training Services www.highedge.co.uk © High Edge Consulting 2012 High Edge Authorized Rep European Union Authorized Representative www.highedge.co.uk © High Edge Consulting 2012 CE Marking • ‘Passport’ to legally place medical devices on the market in the EFTA & European Union (EU) (total 31 countries) • CE Marking on a product ensures the free movement of the product • CE Marking on a product permits the withdrawal of the nonconforming products by customs and enforcement/vigilance authorities www.highedge.co.uk © High Edge Consulting 2012 Countries of Europe www.highedge.co.uk © High Edge Consulting 2012 Why CE Mark Population • USA • Europe • UK 312 million 857 million 62 million (September 2011 – US census bureau) (2010, includes Russia & Turkey) (June 2011) Medical Device Market Size • USA US $ 105.8 billion (2010), world’s largest • Europe US $ 51.2 billion (2010) • Germany US $ 19.5 billion (2011), Europe’s largest • UK US $ 9.0 billion (2011), Europe’s #2 (rising to US $ 10.8bn by 2016) • France US $ 8.8 billion (2011), Europe’s #3 Source: Espicom www.highedge.co.uk © High Edge Consulting 2012 Route Map to CE Marking Determine that your product is a Medical Device Classify your product according to risk category Chose your conformity assessment route Document ISO 13485 Quality Management System Construct a Product Technical File Appoint a Notified Body (If applicable) Undergo Regulatory Audit and Approval www.highedge.co.uk © High Edge Consulting 2012 What is and is not a Medical Device In Vitro Diagnostic Medical Device Directive (IVDs) 90/385/EEC Medical Device Directive 98/79/EC 93/42/EEC 3 Medical Device Directives that define what is a Medical Device Active Implantable Medical Devices Directive (AIMDs) www.highedge.co.uk © High Edge Consulting 2012 Definitions - MDD Definition MDD: “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. Devices are to be used 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” www.highedge.co.uk © High Edge Consulting 2012 FDA Definition of Medical Device A medical device is "an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including a component part, or accessory which is: • recognized in the official National Formulary, or the United States Pharmacopoeia, or any supplement to them, • intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals, or • intended to affect the structure or any function of the body of man or other animals, and which does not achieve any of it's primary intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of any of its primary intended purposes." www.highedge.co.uk © High Edge Consulting 2012 Definition - Accessories ‘accessory’ means an article which whilst not being a device is intended specifically by its manufacturer to be used together with a device to enable it to be used in accordance with the use of the device intended by the manufacturer of the device; www.highedge.co.uk © High Edge Consulting 2012 Definitions – MDD Example Example: Hip replacement (Femoral Head & Cup) “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. Devices are to be used 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” www.highedge.co.uk © High Edge Consulting 2012 Definitions – MDD Example Example: Condom “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. Devices are to be used 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” www.highedge.co.uk © High Edge Consulting 2012 Definitions - IVDs • Definition IVD: “any medical device which is a reagent, reagent product, calibrator, control material, kit, instrument, apparatus, equipment, or system, whether used alone or in combination, intended by the manufacturer to be used in vitro for the examination of specimens, including blood and tissue donations, derived from the human body, solely or principally 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” www.highedge.co.uk © High Edge Consulting 2012 Definitions - IVDs • Specimen receptacles are considered to be in vitro diagnostic medical devices – “‘Specimen receptacles’ are those devices, whether vacuum-type or not, specifically intended by their manufacturers for the primary containment and preservation of specimens derived from the human body for the purpose of in vitro diagnostic examination. Products for general laboratory use are not in vitro diagnostic medical devices unless such products, in view of their characteristics, are specifically intended by their manufacturer to be used for in vitro diagnostic examination” www.highedge.co.uk © High Edge Consulting 2012 Definitions – IVDs Example Example: Blood Glucose Tests “any medical device which is a reagent, reagent product, calibrator, control material, kit, instrument, apparatus, equipment, or system, whether used alone or in combination, intended by the manufacturer to be used in vitro for the examination of specimens, including blood and tissue donations, derived from the human body, solely or principally 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” www.highedge.co.uk © High Edge Consulting 2012 Definitions – IVDs Example Example: Chorionic villus sampling (CVS) “any medical device which is a reagent, reagent product, calibrator, control material, kit, instrument, apparatus, equipment, or system, whether used alone or in combination, intended by the manufacturer to be used in vitro for the examination of specimens, including blood and tissue donations, derived from the human body, solely or principally 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” www.highedge.co.uk © High Edge Consulting 2012 Definition - AIMDs • Definition AIMD: “Any medical device which is 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” A device is ‘active’ if it relies for its functioning on a source of electrical energy or any source of power other than that directly generated by the human body or gravity. www.highedge.co.uk © High Edge Consulting 2012 Definition – AIMDs Example Example: implantable cardiac pacemakers “Any medical device which is 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” A device is ‘active’ if it relies for its functioning on a source of electrical energy or any source of power other than that directly generated by the human body or gravity. www.highedge.co.uk © High Edge Consulting 2012 Definition – AIMDs Example Example: cochlear implants “Any medical device which is 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” A device is ‘active’ if it relies for its functioning on a source of electrical energy or any source of power other than that directly generated by the human body or gravity. www.highedge.co.uk © High Edge Consulting 2012 What is and is not a Medical Device • If it does not meet any of the European Directives then it can be CE Mark Exempt • Check Intended Use ! www.highedge.co.uk © High Edge Consulting 2012 Intended Use • The intended use statement is the manufacturers stated intentions for the device and all claims and regulations hinge on that • Important to be consistent with the statement in marketing and literature including salespersons behaviour and website Cotton Buds: Intended to apply make up or medicine ? Walking Stick: Intended to compensate for an injury or handicap or just for a hill walker ? Surface Wipes: Intended to disinfect an endoscope or work surfaces? www.highedge.co.uk © High Edge Consulting 2012 Device Classification • Annex IX of the MDD sets out the classification rules to determine which class a device falls into according to its properties, function and intended purpose • Devices are assigned to one of three risk categories: – Class I for low-risk devices, – Classes IIa and IIb for medium-risk devices and – Class III for high-risk devices www.highedge.co.uk © High Edge Consulting 2012 Device Classification Example 1: Plasters & Wound Dressings • Section 1 - Non invasive • Rule 4 All non-invasive devices which come into contact with injured skin: – – – Normal plasters for superficial wounds. Class I Fly Larvae system for chronic or necrotic wounds. Class IIa Absorbent dressing for major trauma. Class IIb www.highedge.co.uk © High Edge Consulting 2012 Device Classification Example 2: Contact Lens • Section 2 – Invasive • Rule 5 All invasive devices with respect to body orifices, other than surgically invasive devices and which are not intended for connection to an active medical device or which are intended for connection to an active medical device in Class I: – – Short term use. Class IIa Long Term use. Class IIb www.highedge.co.uk © High Edge Consulting 2012 Device Classification Example 3: Heart Defibrillation Catheter • Section 2 – Invasive • Rule 7 All surgically invasive devices intended for short-term use are in Class IIa unless they are intended: — either specifically to control, diagnose, monitor or correct a defect of the heart or of the central circulatory system through direct contact with these parts of the body, in which case they are in Class III, Note: Section 3 “Additional rules applicable to active devices” do not apply in this case www.highedge.co.uk © High Edge Consulting 2012 Device Classification Example 4: Breast Implant • Section 2 – Invasive • Rule 8 All implantable devices and long-term surgically invasive devices are in Class IIb unless they are intended…. www.highedge.co.uk © High Edge Consulting 2012 Classification IVDs • IVDs – Annex II List A – which includes test kits for HIV, HTLV and Hepatitis and some blood grouping products, including those used to test donated blood – Annex II List B – which amongst others includes test kits for rubella, toxoplasmosis and phenylketonuria test kits as well as self test kits for blood glucose – Self Testing – All others www.highedge.co.uk © High Edge Consulting 2012 Classification AIMDs • Active Implantable Medical Devices are considered unique and have no classification except for their designation as an AIMD www.highedge.co.uk © High Edge Consulting 2012 Conformity Assessment –Medical Devices Class I Class I Non sterile & Non measuring Sterile and/or measuring Comply with Essential Requirements Comply with Essential Requirements Document Product Technical File Document Product Technical File ECDC ECDC Self Declaration Self Declaration Notified Body certificate for sterility and/or metrology Class IIa Comply with Essential Requirements Annex VII with Annex IV EC verification Examination & testing of each product or homogenous batch by Notified Body Submit RG2 to MHRA CE Mark CE Mark Annex VII with Annex V Annex VII with Annex VI Annex II Audit of the production quality assurance system ISO 13485:2003 (excluding design) by Notified Body Audit of final inspection and testing ISO 13485:2003 (excluding design & Manufacture) by Notified Body Audit of the full quality assurance system ISO 13485:2003 by Notified Body Declaration of Conformity CE Mark CE Mark CE Mark CE Mark www.highedge.co.uk © High Edge Consulting 2012 Conformity Assessment –Medical Devices Annex III Type examination by Notified Body With Annex IV Every Device/batch verified by NB (non sterile only) Class IIb Class III Comply with Essential Requirements Comply with Essential Requirements Annex III Type examination by Notified Body With Annex V Production QA ISO13485: 2003 (excl design) by NB Annex III Type examination by Notified Body With Annex VI Inspection QA (non sterile only) ISO13485:2003 (exl design & manufacture) Annex II Audit of the full quality assurance system ISO 13485:2003 by Notified Body Submit Design Dossier to Notified Body Annex II Audit of the full quality assurance system ISO 13485:2003 by Notified Body Declaration of Conformity CE Mark CE Mark CE Mark CE Mark CE Mark www.highedge.co.uk © High Edge Consulting 2012 Conformity Assessment – IVDs Self-testing General List B Products List A products Annex III Excluding Section 6 Annex III Including Section 6 Annex IV Self Certification Design examination by Notified Body Full Quality system audited by Notified Body CE Mark CE Mark CE Mark Annex V EC type examination by Notified Body Annex V EC type examination by Notified Body Annex VII Annex VI Section 5 Production quality system audit by Notified Body Batch verification by Notified Body CE Mark CE Mark www.highedge.co.uk © High Edge Consulting 2012 Conformity Assessment - AIMDs Active Implantable Medical Devices • There are no classifications for AIMDs, either devices fall into this definition or they do not Comply with Essential Requirements Annex 3 EC Type Examination by Notified Body with Annex 4 EC verification Annex 3 EC Type Examination by Notified Body with Annex 5 EC Declaration of conformity (Production Quality) Annex 2 EC Declaration of Conformity Audit of the complete quality assurance system ISO 13485:2003 by Notified Body Declaration of Conformity CE Mark CE Mark CE Mark www.highedge.co.uk © High Edge Consulting 2012 The Regulators • Competent Authorities – Government Organisations – 1 per country – 32 Competent Authorities – http://ec.europa.eu/health/medical-devices/files/list-of-contactpoints-within-the-national_en.pdf • Notified Bodies – Commercial Organisations – Currently 77 NBs – http://ec.europa.eu/enterprise/newapproach/nando/index.cfm?fusea ction=directive.notifiedbody&sort=name www.highedge.co.uk © High Edge Consulting 2012 Role of Competent Authority • The organisation appointed by each national government to enforce compliance with the directive in that country www.highedge.co.uk © High Edge Consulting 2012 Role of the Notified Body • Agents of Competent Authority • Independent but commercial organisations • Provide services for conformity assessment as required by the MDDs for CE marking • Conformity assessment may include inspection, quality assurance, type examination or design examination, or a combination of the above www.highedge.co.uk © High Edge Consulting 2012 Typical Technical File Section 1 Section 2 Section 3 Section 4 Section 5 Section 6 Device Description Labelling Design & Manufacturing Essential Requirements Risk Analysis & Control Product Verification & Validation www.highedge.co.uk © High Edge Consulting 2012 Device Description • General description • Product variants and configurations • Accessories, other medical devices and other products that to be used with • Intended use statement: – Medical condition is to be treated – Intended patient population – Contraindications • Description of how the device works including unique features and performance claims www.highedge.co.uk © High Edge Consulting 2012 Device Description • Product specification • List of components and their materials – Materials of Animal Origin statement – Human cells/tissue products/derivatives statement • Previous generations or similar competitor devices • Device classification • Conformity assessment route www.highedge.co.uk © High Edge Consulting 2012 Labelling • All labelling associated with the device – labels on the device itself – labels on the primary pack – labels on the packaging, etc • IFU (Instructions for Use) • Sales / Promotional Literature • A list of countries where the device will be marketed, and corresponding official languages www.highedge.co.uk © High Edge Consulting 2012 Design & Manufacturing • Description of the design stages applied to the device • Technical drawings • Further detail on product design • General overview of the manufacturing process • Manufacture, assembly, in process and final product testing, device packaging – Documentation comprising the Device Master Record – Critical suppliers including sub-contracted manufacturing processes • Product Release process www.highedge.co.uk © High Edge Consulting 2012 Essential Requirements • EC Declaration of Conformity • Full details for product Classification • Completed Essential Requirements Checklist • List of Applied Standards www.highedge.co.uk © High Edge Consulting 2012 Risk Management • Risk Management according to EN ISO 14971:2009 – Risk Management Plan – dFMEA – pFMEA – uFMEA Risk Analysis Risk Evaluation Risk Control Evaluation of overall residual risk acceptability Risk Management Report Production & Post Production Info www.highedge.co.uk © High Edge Consulting 2012 Product Verification & Validation • Summary of the results of verification and validation activities typically: – Engineering tests – Laboratory tests – Pre-clinical test data – Published literature inc. relevant competitor products • Biocompatibility data • Medicinal substances • Animal or human cells, tissues or their derivatives • Sterilization www.highedge.co.uk © High Edge Consulting 2012 Product Verification & Validation • Software verification and validation • Pre-clinical data related to clinical safety and performance of the device. • Clinical Evaluation • Shelf Life with supporting data • Other relevant data www.highedge.co.uk © High Edge Consulting 2012 ISO 13485 • 21 CFR 820 is a great starting point • ISO 13485 is based on the ISO 9001 format but with additional requirements for medical devices relating to: – Design – Special Processes – Environmental Control – Traceability – Documentation records – Regulatory actions www.highedge.co.uk © High Edge Consulting 2012 ISO 13485 EN ISO 13485:2012 • Medical Devices Quality Management Systems- Requirements for Regulatory Purposes • Requirements section identical to ISO 13485:2012 ISO/TR 14969:2005 • Medical Devices Quality Management Systems Guidance on the Application of ISO 13485: 2003 www.highedge.co.uk © High Edge Consulting 2012 ISO 13485 Overview 0 1 2 3 4 5 6 7 8 Introduction Scope Normative References Terms & Definitions Quality Management System Management Responsibility Resource Management Product Realization Measurement Analysis & Improvement www.highedge.co.uk © High Edge Consulting 2012 Questions www.highedge.co.uk © High Edge Consulting 2012 Thank You High Edge Consulting Ltd BioCity Nottingham Pennyfoot Street Nottingham NG1 1GF United Kingdom www.highedge.co.uk info@highedge.co.uk Office: +44 115 921 6200 @HighEdgeConsult www.highedge.co.uk © High Edge Consulting 2012