RA C7 MEDICALDEVICES UeASPECTS Cae * 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MEDICAL DEVICES * A medical device is an instrument, apparatus, implant, in vitro reagent, or similar or related article that is used to diagnose, prevent, or treat disease or other conditions It does not achieve its purposes through chemical action within or 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 to advanced devices such as computers which assist in the conduct of medical testing, implants, and prostheses. The global medical device market reached roughly $209 billion in 2006.+ Population 500 million 03EU DIRECTIVES THAT IMPACT MEDICAL DEVICES * Medical Devices (MDD) 93/42/EEC + Covers the bulk of medical devices marketed in the EU + Examples: orthopaedic implants, heart valves, medical software + Active Implantable Medical Devices (AIMDD) 90/385/EEC * Covers devices that require external power sources in order to function properly + Examples: pacemakers, implantable defibrillators * InVitro 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OTHER EU DIRECTIVES THAT MAY APPLY TO WIEDICAL DEVICES + 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 + HumanTissue Products Directives 2004 & 2005 + Breast Implants Reclassification Directive 2003/12/EC + Hip, Knee, Shoulder Joint Replacement Reclassification Directive 2005/50/ECMEDICAL DEVICES ca AS DEFINED BYEUROPEAN UNION Medical Devices: Guidance Document MEDDEV 2.1/1 APRIL 1994 This guidance document under Directive 93/42/EEC on Medical Devices provides definition of Medical Devices to include the following: a. Devices —Accessory b. Medical Purpose c. Customizing d. Medical — Toiletry Purpose e. Aids for Handicapped Persons f. Software . Multipurpose ProductsCLASSIFICATION oF mepica Devices AS PEREUROPEAN UNION Medical Devices: Guidance Document MEDDEV 2.4/1 Rev.8 JULY 20014 MEDDEV 2.4/1 Rev.9 JUNE 2010 * The classification of medical devices is a ‘risk based’ system based on the vulnerability of the human body taking account of the potential risks associated with the devices. * This approach allows the use of a set of criteria that can be combined in various ways in order to determine classification, e.g. duration of contact with the body, degree of invasiveness and local vs. systemic effect. These criteria can then be applied to a vast range of different medical devices and technologies. * These are referred to as the ‘classification rules’ and are set out in Annex IX of Directive 93/42/EEC.THEC € CERTIFICATION cs * The CE mark, or formerly EC mark, is a mandatory conformity marking for certain products sold within the European Economic Area (EEA) since 1985. + The CE marking is also found on products sold outside the EEA that are manufactured in, or designed to be sold in, the EEA. * This makes the CE marking recognizable worldwide even to people who are not familiar with the European Economic Area. * It is in that sense similar to the FCC Declaration of Conformity used on certain electronic devices sold in the United States. + It consists of the CE logo and, if applicable, the four digit identification number of the notified body involved in the conformity assessment procedure. * The CE marking is the manufacturer's declaration that the product meets the requirements of the applicable EC directives.KEY PLAYERS wn te CE MARKING PROCESS (REGULATORY APPROVAL PROCESS FOR MEDICAL DEVICES) + Manufacturers and Subcontractors Glo) aa L-icclal UU La alol ela laty * Notified Bodies Sean gr te C)eNg Clg ed aN * DistributorsHORITIES * 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.NOTIFIED BODIES * 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* 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BASIC STEPS TO EU COMPLIANCE Identify Directives and Regulations appropriate for your device fl + Classify your device according to MDD Annex IX + Implement Quality System in compliance with ISO 13485. + Prepare Technical File or Design Dossier demonstrating compliance with MDD 93/42/EEC.| Appoint your Authorized Representative. = + Have Notified Body audit your Quality System and Technical File or Design Dossier. + Register your device with Competent Authorities if necessary. + Prepare Declaration of Conformity and affix CE Marking to your device.LASSIFICATION cs MDD DETERMINATION * 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 | Sterile Class | Measuringoa sTeRy CLASSIFICATION bd CONTINUED Class Ila Medium-risk, short-term invasive devices such as ( \ tracheal tubes and lancets Class IIb Higher-risk, often longer-term surgically invasive, sometimes implantable devices including intra-ocular lenses and surgical lasers Highest-risk devices, including all active implantable devices such as replacement heart valves and vascular stentsCONSIDERATIONS steF CLASSIFICATION * MDD 93/42/EEC Annex IX contains 28 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DETERMINATION ster CLASSIFICATION * 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.LASSIFICATION DETERMINATION Class Ila Class IIbrequire pieUALITY SYSTEM mea nies SQ13485 Phase |: 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 Ill: Registration Registration audit performed by Notified Body Final ISO 13485 certificationECHNICAL FILE DESIGN DOSSIER PREPARATION * All Class |, lla and IIb device manufacturers must prepare Technical Files containing data to demonstrate MDD 93/42/EEC compliance. * Class Ill device manufacturers must prepare Design Dossiers to demonstrate compliance to MDD. All manufacturers must have clinical data to demonstrate compliance to MDD.Te Se ea Description of product family and justification for why your device Re CR cosa acc LaLh A Device intended use Description of device components, specifications, packaging and Srey DevemeuM ete taba rte List of accessories to your device Location of design responsibility and manufacturing facilities Classification along with rationale for classificationTECHNICAL FILE COMPONENTS Chosen compliance route according to applicable Directive(s) Prencmateencummen ca harun cee acntleues with applicable Directive(s) Shelf life and environmental limitations of device Retention of quality assurance, Competent Authority and Notified Body records Vigilance reporting and Medical Device Reporting procedures Taleo AVIA UR coReers ieee Golan) ole Cee nh cy Name of and contract with your Authorized RepresentativeTECHNICAL FILE COMPONENTS EWU oleo ln agotacolmel- lance lure lele lg coma] eye) fede y Perdana CTnL ey Design input specifications Application and references to Standards and Guidelines Braue meses tee ae at Ceol NII Leon Ree Instructions for Use and LabelingECHNICAL FILE CLINICAL DATA REQUIREMENTS + EUregulators have increased their requirements for clinical data even for Class | medical devices in recent years. + Inmany cases, manufacturers must submit Clinical Evaluation Summary Reports that verify the safety and performance of their products along with Technical Files or Design Dossiers.AUTHORIZED cd REPRESENTATION Manufacturers with no offices in the EU must appoint Authorized Representatives (EC REPs) to interact with regulators on their behalf.EC REP Ed RESPONSIBILITIES Registering your device with Competent Authorities before commercialization Serving as primary point of contact with all EU Competent Authorities Keeping a current copy of yourTechnical 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 amember 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NO UD iT AA 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 | Non-sterile/Non-measuring devices self-declare MDD conformity and do not require CE Marking certificates.REGISTRATION WITH COMPETENT AUTHORITIES Class I device manufacturers must register with the Competent Authority of the country where their EC REPs are based. Class Ila Class IIb Some EU member states do not require registration of Class lla, IIb or Ill devices with Competent Authorities. Other countries do not require registration of devices.Led ca DECLARATION OF CONFORMITY sTEPA THE PARTS Product Identification ee A 5 5 janufacturer Identification Applicable DirectivesLABELING AND LANGUAGE cad RQUIREMENTS + EU member states MAY require labeling information be made available in their local languages or another European Community at language to patients and users in ~_ accordance with Annex |, point 13 of the MDD. cnacn6o 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35 Device AEE Cis Validity ERC ice-l Clad ON heals eee uC meer creteces ee a Pernt eee ana ic) ae Tete TTS ere Cone ame Cel roel Class | NS/NM No Expiry Not ApplicablePOST-MARKET SURVEILLANCE (PMS) AND VIGILANCE 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IN THE ORDER OF APPEARANCE hitpslien.wikipedia.org/wiki Wikipedia article on Medical Devices leurlex europa eulle«UriServ/L exUaSenv do?uri=CONSLEG;19931.0042:2007s0431¢n:PDF ~ Offical EU Document : Councl Directive 93/42/EEC htip:/ec. evropa.eulhealth/medical-devices/documents/guidelines/index en.htm - Guidance MEDDEVs Online Directory http:ifec.europa.eu/health medical-devicesffilestmn n.pdi- Guidance Document MEDDEV 2.2/1 Aprilag9q, hrrpillec europa eujhealth/medical-devicesifiles/meddev/2 2 4-sparts 07-2001 en.ndf - Guidance Document MEDDEV 2.4/1 Rev.8 July 2002 httpullec europa eujhealthimedical-devicesifilesimeddevi2 4 1 rev g classification en pdf -Guidance Document MEDDEV 2.4/1 Revg June 2010 https:/lenswikipedia.orgjikilCE marking Wikipedia article on CE Certification http: |faww.Ine-gmed,com/pdfjen/annexa-directive-93-42-amended.pdf - Offical EU Document : Annex IX of Council Directive 93/42/EEC http:l/ec.europa.eu)health/medical-devices/faq/market_en.hitm - Information about the Medical Device Registration on the Official Website of European Commission, htipslimedicaldevices.bsigroup,com/en-GB/our-services/ce-marking! - Information about CE Marking Approval for Medical Devices in Europe hitos/buiww.emergoaroup.com/resourceslevrope-process-chart - Europe CE Approval Process for Medical Devices ~Charts& Timelines