1. CE Marking for Medical Devices “Basic Steps to Compliance” Ján Petrík, PhD. EVPÚ, a.s. Nová Dubnica Medical Devices Branch Office Bratislava 4/27/06 EVPÚ, a.s., NB No. 1293

2. Basic Steps to Compliance Determining Whether or Not the Product is Within the Scope of the Directive Classification Conformity Assessment Routes Compliance to the Essential Requirements of the Directive Harmonized Standards Technical File Risk Analysis Notified Body Authorized Representative and Competent Authority - Registration Vigilance System CE Marking Declaration of Conformity 4/27/06 EVPÚ, a.s., NB No. 1293

3. Within the Scope of the Directive? Medical Device (MDD) 93/42/EEC Active Implantable Medical Device (AIMD) 90/385/EEC In-vitro Diagnostics (IVDD) 98/79/EC The definition will determine the scope 4/27/06 EVPÚ, a.s., NB No. 1293

4. What are Medical Devices? Medical devices are defined as all devices which according to the manufacturer are intended to be used in the treatment of humans, whether it concerns diagnosing, monitoring, prevention, treatment or alleviation. 4/27/06 EVPÚ, a.s., NB No. 1293

5. Annex IX 18 rules based on- intended use - duration of contact - degree of invasiveness - special situationsClassification All medical devices must comply with all relevant requirements of the Directive. Therefore the classification only serves to determine which conformity assessment procedure to apply and whether or not a notified body must co-operate. 4/27/06 EVPÚ, a.s., NB No. 1293

6. Classes Class I-low risk Class IIa -medium risk Classes IIb & III-high risk Classification The Directive divides the medical devices into four different classes (I, IIa, IIb and III). In addition, class I is subdivided into devices which are sold in a sterile condition and devices which are sold with a measuring function. The classification reflects the risks involved in the use of the product, the vulnerability of the parts of the body on which the devices are to be applied and the duration of use. 4/27/06 EVPÚ, a.s., NB No. 1293

7. Duration of Contact up to 60 minutes-‘transient’ up to 30 days-‘short term’ beyond 30 days-‘long term’ Classification

8. Classification Degree of Invasiveness  application to body surface or into body orifice (as far as pharynx)  surgically invasive  implantable 4/27/06 EVPÚ, a.s., NB No. 1293

9. Classification Invasive + Duration of Contact  ‘transient’-Class I  ‘short term’-Class IIa  ‘long term’-Class IIb 4/27/06 EVPÚ, a.s., NB No. 1293

10. Class I (Sterile and Measuring), Class IIa, IIb, and III require the intervention of a Notified Body which will be responsible for auditing the Manufacturer’s quality system Conformity Assessment Route 4/27/06 EVPÚ, a.s., NB No. 1293

11. "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". In-vitro Diagnostic Devices (IVDD) 4/27/06 EVPÚ, a.s., NB No. 1293

12. IVDD Classification Directive 98/79/EC divides in vitro diagnostic medical devices into the following four classes:  All devices except devices for self-testing and devices in Annex II  Devices for self-testing which are not included in Annex II  Devices in Annex II, List A  Devices in Annex II, List B 4/27/06 EVPÚ, a.s., NB No. 1293

13. IVDD Who Ensures that the Requirements Are Fulfilled? The manufacturers themselves to some extent assume the responsibility of complying with the requirements. With respect to general IVDD, except from devices for self- testing and devices in Annex II, it is the manufacturer alone who carries out the necessary evaluations. In the case of devices for self-testing and devices in Annex II, the manufacturer must always have the design and/or the production of the device approved by an independent third party, a notified body, before the product may be CE-marked and marketed. 4/27/06 EVPÚ, a.s., NB No. 1293

14. Technical File Technical File contains all the relevant information that is needed to demonstrate that the product meets the essential health and safety requirements of the Directive...information on e.g. product design, manufacture, testing, risk analysis and clinical evaluations must be included in the documentation. The purpose of the documentation is to enable the manufacturer to prove that his product complies with the "Essential Requirements" of the Directive. 4/27/06 EVPÚ, a.s., NB No. 1293

15. Technical File 4/27/06 EVPÚ, a.s., NB No. 1293 Application for the conformity assessment Notified Body Type of certification (e.g. CE marking...) Device classification (product + specified Directive, Rule used for the devices classification) Conformity assessment route

16. Technical File 4/27/06 EVPÚ, a.s., NB No. 1293 General description of the product Intended Use (intended use of MD should be stated) Principle of the Assay / Test / Function (exact description of the MD’s function) Device / Kit Content (description of the content of a pack, set, etc.) Shelf-life of the Device (the duration of shelf-life should be specified, validity testing – references to relevant standard(s), the place where the expiration date is stated (label and its location, etc….)) Storage & Stability of the Product / Material / Reagent (description of conditions in the raw material, semi finished products and devices finished storerooms: temperatures and other physical conditions, stability of material, semi products and devices at defined conditions..etc.) Assay / Testing Procedure Criteria of Acceptability of the Test Results Calculation & Interpretation of the Results Assay / Test Performance – Sensitivity, Specificity, Reproducibility, Stability

17. Technical File 4/27/06 EVPÚ, a.s., NB No. 1293 Regulatory standards applied List of the Standards Applied (list of all applied standards / regulations (usually EN and/or harmonized ones). Add relevant standards for sterilization, testing for biological safety, etc – if applicable) Check List in Respect to the Directive (Essential Safety Requirements) @@ Correlation among Technical Documents (references, links) Risk Analysis (Application of the Risk Management to Medical Devices according with EN ISO 14971) Clinical Evaluation (copies of completed clinical studies)

18. Technical File 4/27/06 EVPÚ, a.s., NB No. 1293 List of documents Labelling Package content Instruction for use Product technical sheet (product description, manufacturer – name & address, technical features, in case of set give its content with description of individual parts, shelf-life, storage and stability, testing – type of test, results, protocols, standards used) Material safety data sheet (identification of raw materials: physical/chemical properties, supplier, relevant tests – required quality of materials, hazard identification, health measures (if applicable during handling with materials/components), storage - conditions, quality check, exposure control/ personal protection, stability, toxicological information, ecological effects, disposal info, transport information, directives & standards)

19. Technical File 4/27/06 EVPÚ, a.s., NB No. 1293 Project Description History of the product (description of the device manufacture with respect to its (respective) development (modifications) if applicable, over the years) Customer Complaints (list of professional complaints to the device according to complaint date, description of complaint/problem, name of customer, list of investigations to relevant complaints and solutions) Detailed list of raw material(s) Strategic Raw Material / Reagents (the system of checking of raw material and its components (references to standard, GMP manual, QS manual should be stated) Material of Human Origin (if applicable) Information on Substances & Dangerous Materials

20. Technical File 4/27/06 EVPÚ, a.s., NB No. 1293 Specification of the Product (description of product characteristics (e.g. by the references to documents given in other part of the TF) Compatibility with other MDs (if applicable) Evaluation Results (if applicable) Electric Safety, EMC, etc. Data of Stability (references to the relevant tests of device stability should be stated)

21. Technical File 4/27/06 EVPÚ, a.s., NB No. 1293 Production Method of Manufacture & Procedure Standards Validation of the Production/Manufacturing Processes List of Equipments (description of purpose of individual equipment + its location in the manufacture facility) Maintenance & Control Program

22. Technical File 4/27/06 EVPÚ, a.s., NB No. 1293 Quality System Documenation Control of Production (reference to GMP(QS) manual chapter(s), paragraph(s), etc.) Equipments (list of equipments used for QC. References to standards/directives/technical procedures according to which is the control performed) Product Maintenance (If applicable. reference(s) to internal manuals (GMP, QS…) according to which is maintenance provided) Characteristic of the Environment (description of manufacture facilities & premises. Description of individual floors/ rooms, give dimension, type of activity, equipments installed…etc.) Declaration of Conformity Declaration of Agreement with a Notified Body

23. Essential Requirements - General Requirements - Design & Construction Requirements - Chemical, Physical and Biological Properties - Infection and Microbial Contamination - Construction and Environmental Properties - Information Supplied by the Manufacturer on the Label and in the Instructions for Use 4/27/06 EVPÚ, a.s., NB No. 1293