EU Regulatory Environment—2008 Evangeline Loh, Ph.D., RAC Director Regulatory Affairs, Emergo Group Evangeline@Emergogrop.com © 2007 Emergo Group, Inc. Australia > Canada > China > The Netherlands > United States 1.800.956.6588

Medical Devices and CE Marking in 2008 © 2007 Emergo Group, Inc. Australia > Canada > China > The Netherlands > United States 1.800.956.6588

European Union in 2008 27 member states 490 million 23 languages © 2007 Emergo Group, Inc. Australia > Canada > China > The Netherlands > United States 1.800.956.6588

Recast of the Medical Devices Directives © 2007 Emergo Group, Inc. Australia > Canada > China > The Netherlands > United States 1.800.956.6588

Principle EU Market Four Freedom Principles: Movement of Services Capital People Products © 2007 Emergo Group, Inc. Australia > Canada > China > The Netherlands > United States 1.800.956.6588

New Approach Directives (provide for CE Marking) Medical Devices (MDD) – 93/42/EEC Active Implantable (AIMDD) - 90/385/EEC In-Vitro Diagnostics (IVDD) – 98/79/EC Machinery Safety - 2006/42/EC Personal Protective Equipment - 89/686/EEC Low Voltage - 2006/95/EC Electromagnetic Compatibility- 2004/108/EC © 2007 Emergo Group, Inc. Autralia > Canada > China > The Netherlands > United States 1.800.956.6588

© 2007 Emergo Group, Inc. Australia > Canada > China > The Netherlands > United States 1.800.956.6588

Basic Steps to Compliance Within the scope of which Directive? Classification Conformity Assessment Route Compliance to the Essential Requirements Harmonized standards Technical File © 2007 Emergo Group, Inc. Australia > Canada > China > The Netherlands > United States 1.800.956.6588

Basic Steps to Compliance Risk assessment Notified Body Authorized Representative and Competent Authority registration Vigilance system CE Marking Declaration of Conformity © 2007 Emergo Group, Inc. Australia > Canada > China > The Netherlands > United States 1.800.956.6588

Guidance Documents EU Commission Interpretative Fiche MEDDEV Manuals (Borderline and Classification Expert Group) NB-MED © 2007 Emergo Group, Inc. Australia > Canada > China > The Netherlands > United States 1.800.956.6588

How Classification is Determined Duration of contact: < 60 minutes Transient < 30 days Short term > 30 days Long term Degree of invasiveness: Application to body surface or into body orifice Surgically invasive Implantable © 2007 Emergo Group, Inc. Australia > Canada > China > The Netherlands > United States 1.800.956.6588

How Classification is Determined Degree of invasiveness Duration of contact Transient Class I Low risk Short term Class Iia Medium risk Long term Class Iib Medium risk Long term Class III High risk Class I non sterile and non measuring Class I sterile and measuring © 2007 Emergo Group, Inc. Australia > Canada > China > The Netherlands > United States 1.800.956.6588

Classification IVDD 98/79/EEC Annex II, List A Annex II, List B Self-test, Annex III, Section 6 Self-certify or self-declaration, Annex III © 2007 Emergo Group, Inc. Australia > Canada > China > The Netherlands > United States 1.800.956.6588

Annex II, List A Reagents and reagent products, including related calibrators and control materials, for determining the following blood groups: ABO system, rhesus (C, c, D, E, e) anti-Kell, reagents and reagent products, including related calibrators and control materials, for the detection, confirmation and quantification in human specimens of markers of HIV infection (HIV 1 and 2), HTLV I and II, and hepatitis B, C and D. © 2007 Emergo Group, Inc. Australia > Canada > China > The Netherlands > United States 1.800.956.6588

Annex II, List B - Reagents and reagent products, including related calibrators and control materials, for determining the following blood groups: anti-Duffy and anti-Kidd, - reagents and reagent products, including related calibrators and control materials, for determining irregular anti-erythrocytic antibodies, - reagents and reagent products, including related calibrators and control materials, for the detection and quantification in human samples of the following congenital infections: rubella, toxoplasmosis, - reagents and reagent products, including related calibrators and control materials, for diagnosing the following hereditary disease: phenylketonuria, - reagents and reagent products, including related calibrators and control materials, for determining the following human infections: cytomegalovirus, chlamydia, - reagents and reagent products, including related calibrators and control materials, for determining the following HLA tissue groups: DR, A, B, - reagents and reagent products, including related calibrators and control materials, for determining the following tumoral marker: PSA, - reagents and reagent products, including related calibrators, control materials and software, designed specifically for evaluating the risk of trisomy 21, - the following device for self-diagnosis, including its related calibrators and control materials: device for the measurement of blood sugar. © 2007 Emergo Group, Inc. Australia > Canada > China > The Netherlands > United States 1.800.956.6588

Conformity Assessment Route MDD 93/42/EEC Class I (sterile and measuring) Class IIa, Class IIb, Class III IVDD 98/79/EC Annex II, List A and List B Self-Test, Annex III, Notified Body required © 2007 Emergo Group, Inc. Australia > Canada > China > The Netherlands > United States 1.800.956.6588

Conformity Assessment Routes MDD 93/42/EEC Class I – Non-Sterile, Non-Measuring Annex VII Class I - Sterile or Measuring Annex VII and Annex IV, V or VI. Class IIa Annex II (except Section 4, Design Dossier), or Annex VII plus IV, V or VI. Class IIb Annex II (except Section 4, Design Dossier), or Annex III plus IV, V or VI. Class III Annex II (plus Section 4, Design Dossier), or Annex III plus IV or V. © 2007 Emergo Group, Inc. Australia > Canada > China > The Netherlands > United States 1.800.956.6588

Conformity Assessment Routes Annex II – EC Declaration of Conformity (Full quality assurance system) Class I (Sterile and Measuring), IIa, IIb and III manufacturers can choose to follow Annex II and implement a full quality system that covers all classes of products. © 2007 Emergo Group, Inc. Australia > Canada > China > The Netherlands > United States 1.800.956.6588

Conformity Assessment Routes Annex III – EC Type Examination Class IIb and III manufacturers can elect to have a Notified Body do an audit using a representative sample of the company’s production to ascertain compliance with the directive. Used when Annex II is not the preferred route to compliance. Annex IV, V or VI must be used in conjunction with Annex III. © 2007 Emergo Group, Inc. Australia > Canada > China > The Netherlands > United States 1.800.956.6588

Conformity Assessment Routes Annex IV – EC Verification Requires the manufacturer to meet the applicable requirements of the MDD and other technical specifications. The Notified Body can sample up to 100% of the products, or may do statistical batch testing. If batch testing is done and accepted by the Notified Body, all products in the batch can bear the CE Marking. © 2007 Emergo Group, Inc. Australia > Canada > China > The Netherlands > United States 1.800.956.6588

Conformity Assessment Routes Annex V – EC Declaration of Conformity (Production quality assurance) This is much the same as Annex II but without design inspection. Often used by companies that manufacturer Class I sterile/measuring and Class IIa, and those that do not design their own products. © 2007 Emergo Group, Inc. Australia > Canada > China > The Netherlands > United States 1.800.956.6588

Conformity Assessment Routes Annex VI – EC Declaration of Conformity (Product quality assurance) This route is used by manufacturers of devices whose relevant properties can be determined during a final inspection. This means that this route to compliance cannot be used for devices that require special manufacturing processes such as sterilization. A Notified Body inspection is required. © 2007 Emergo Group, Inc. Australia > Canada > China > The Netherlands > United States 1.800.956.6588

Conformity Assessment Routes Annex VII – EC Declaration of Conformity Requires the manufacturer to compile a Technical File and conduct a risk assessment. Used by Class I non-sterile, non-measuring device manufacturers to self–certify their products. If the Class I device has a Sterile or Measuring function, Annex V may also apply. © 2007 Emergo Group, Inc. Australia > Canada > China > The Netherlands > United States 1.800.956.6588

Conformity Assessment Routes Annex VIII – Statement Concerning Devices for Special Purposes This Annex relates to custom made devices or devices for clinical investigation © 2007 Emergo Group, Inc. Australia > Canada > China > The Netherlands > United States 1.800.956.6588

Conformity Assessment Routes IVDD 98/79/EC Annex II, List A Annex IV or Annex V and Annex VII. Annex II, List B Annex IV or Annex V plus Annex VI or Annex VII. Self-test Annex III, Section 6 or procedures for Annex II, List A or Annex II, List B. Self-declaration or self-certification Annex III © 2007 Emergo Group, Inc. Australia > Canada > China > The Netherlands > United States 1.800.956.6588

Harmonized Standards Conformity to Standard Harmonized European Standards “Voluntary” application of Standards Presumption of Conformity (Article 5, MDD and IVDD) Conformity to Standard Conformity to Essential Requirements Hierarchy of Standards: > Harmonized – published in the Official Journal > EN > ISO > National (BS, DS, DIN, ASTM) > Industry-specific > Local, company-specific © 2007 Emergo Group, Inc. Australia > Canada > China > The Netherlands > United States 1.800.956.6588

Technical File & Design Dossier Contains all the relevant information to demonstrate that the product meets the Essential Requirements of the Directive = © 2007 Emergo Group, Inc. Australia > Canada > China > The Netherlands > United States 1.800.956.6588

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 © 2007 Emergo Group, Inc. Australia > Canada > China > The Netherlands > United States 1.800.956.6588

Risk Assessment ISO 14971:2007 is used to: Identify the product and describe the intended use Characteristics which could affect safety Identify possible hazards Estimate the risk, and… © 2007 Emergo Group, Inc. Australia > Canada > China > The Netherlands > United States 1.800.956.6588

Notified Body Third party organization appointed by a Member State to undertake prescribed activities Commercial contracts with manufacturers Who is responsible? © 2007 Emergo Group, Inc. Australia > Canada > China > The Netherlands > United States 1.800.956.6588

Authorized Representation Authorized Representative for Europe in the event the manufacturer is not established within the EEA Who to select? Who is responsible? © 2007 Emergo Group, Inc. Australia > Canada > China > The Netherlands > United States 1.800.956.6588

Authorized Representation Listed on the label and/or packaging Name of the manufacturer and the device must be notified to the Competent Authority Keeps the Technical File available for review by Competent Authorities Plays an essential role in vigilance procedures and Post-market Surveillance © 2007 Emergo Group, Inc. Australia > Canada > China > The Netherlands > United States 1.800.956.6588

Post Marketing Surveillance Required for all devices Review of market, field data, complaints, investigation, corrective actions Systematic records kept © 2007 Emergo Group, Inc. Australia > Canada > China > The Netherlands > United States 1.800.956.6588

Vigilance, MEDDEV 2.12.1, Rev. 5 The manufacturer must: Institute and keep up to date a systematic procedure to review experience gained from devices in the post-production phase and; Implement appropriate means to apply any necessary corrective actions © 2007 Emergo Group, Inc. Australia > Canada > China > The Netherlands > United States 1.800.956.6588

CE Marking Implies conformance with all European Directives Inspection Authorities Preempts all other marks for same requirements Not a quality mark! Measurement Affixing Labeling © 2007 Emergo Group, Inc. Australia > Canada > China > The Netherlands > United States 1.800.956.6588

Language Member States required the labeling information to be in their official language 23 languages to date – will increase as new Member States join the EU Label copy should only appear in one language in the Technical File © 2007 Emergo Group, Inc. Australia > Canada > China > The Netherlands > United States 1.800.956.6588

Declaration of Conformity Product identification Identification of the manufacturer Directives complied with Standards used Signature by authorized person Language requirements © 2007 Emergo Group, Inc. Australia > Canada > China > The Netherlands > United States 1.800.956.6588

Registration or Notification Class I, AR register where they are established (MDD 93/42/EEC, Article 14.1) Member states latitude to transpose the directive to require “to be informed of all data allowing for identification” Class IIb and III All IVDDs need to be registered in member states where they are to be marketed, including where the AR is established (IVDD 98/79/EEC, Article 10.6) © 2007 Emergo Group, Inc. Australia > Canada > China > The Netherlands > United States 1.800.956.6588

Certificate Free Sale (CFS) Issued by the member state’s Competent Authority or Ministry of Health to their member state-based manufacturers (or Authorized Representatives) for all devices which possess CE Marking including Class I self-certified medical devices or in vitro diagnostics devices. Each CFS can only reference one country, but there is no limit to the number of devices listed. © 2007 Emergo Group, Inc. Australia > Canada > China > The Netherlands > United States 1.800.956.6588

OBL and PBL Original Equipment Manufacturer (OEM) or Original Equipment Supplier (OES) Own Brand Labeler (OBL) or Private Brand Labeler (PBL) EU Commission Interpretative Document* * http://ec.europa.eu/enterprise/medical_devices/guide-stds-directives/interpretative_fiche_obl.pdf © 2007 Emergo Group, Inc. Australia > Canada > China > The Netherlands > United States 1.800.956.6588

EU Device Regulations – Green Dot Packaging Packaging Waste Directive 94/62/EC German Green Dot Program Licensed to Pro-Europe – other national organizations “Green Dot” Current Membership 28 European Countries Alliance: UK, The Netherlands, Italy Other: Canada © 2007 Emergo Group, Inc. Australia > Canada > China > The Netherlands > United States 1.800.956.6588

EU Device Regulations – Green Dot National Organization are Non-profit – pays regional / local waste management companies Green Dot licenses – applied in each country License fees determined on the basis of materials, weight and number of units © 2007 Emergo Group, Inc. Australia > Canada > China > The Netherlands > United States 1.800.956.6588

EU Device Regulations - WEEE Waste Electrical and Electronic Equipment Directive (WEEE) Into effect August 2005 Aims to reduce electrical and electronic waste through collection, recovery, recycling and treatment of electrical products at the end of their useful life © 2007 Emergo Group, Inc. Australia > Canada > China > The Netherlands > United States 1.800.956.6588

EU Device Regulations - WEEE Applies to medical equipment Excluded: Implants and “infected” devices; Devices designed for a voltage rating exceeding 1000 Volts AC and 1500 volts DC © 2007 Emergo Group, Inc. Australia > Canada > China > The Netherlands > United States 1.800.956.6588

EU Device Regulations - WEEE Producer pays principle Producer prepare data on their device – instructions for recycle and disassembly and locations of dangerous substances Producer responsible for take back - Two options: Submit your individual take back plan to the relevant authorities Become a member of a collective take back system in each Member State! © 2007 Emergo Group, Inc. Australia > Canada > China > The Netherlands > United States 1.800.956.6588

EU Device Regulations - WEEE Labeling Requirement – Wheelie Bin Disposal Instruction Requirements EN 50419 © 2007 Emergo Group, Inc. Australia > Canada > China > The Netherlands > United States 1.800.956.6588

EU Device Regulations A Work in Progress… © 2007 Emergo Group, Inc. Australia > Canada > China > The Netherlands > United States 1.800.956.6588