Medical Device Directive 2007/47/EC What is New? Are we moving towards Drug Rules?

Medical Device Directive 2007/47/EC What is New? Are we moving towards Drug Rules? CEMO Congress, Paris, February 3rd, 2011 Dr. Martine Dehlinger-Kremer Vice President Global Regulatory Affairs

Agenda History What are Medical Devices Core Legal Framework Medical Device Directive 2007/47/EC - What is New? - Changes to definitions - Essential requirements - Technical documentation requirements - Classification rules - Bordeline Products - Requirements for clinical data - Authorized Representative - European Databank - Post Marketing Requirement Medical Device Directive 2007/47/EC Implementation Conclusion Page 2

History Some EU countries set up first specific regulations for medical devices in 1976 By mid- to late-1980s, most of the Western European countries required registration/pre- marketing approval (requirements differed among the countries) Harmonisation process during the 1990s - Mandatory essential requirements - Conformity assessment procedures - CE marking Page 3

What is a Medical Device? A medical device is defined as any health care product that does not achieve its primary intended purposes by pharmacological, immunological or metabolic means Medical Devices are separated into classes to include general controls and definition of risk Regulatory control increases as class or risk increases Classification or risk defines the regulatory requirements for device type Page 4

What is a Medical Device (continued) Life supporting or diagnostic with high risk Ventilators, dialysis machines, CT scanners, infusion pumps, implantable pacemakers, insulin pumps Combination products that have device as delivery system for drug Nebulizers, inhalers, nano disks In Vitro Diagnostic devices (IVDDs) Glucometers, pregnancy tests, devices for screening (Elisa screening), tumor markers or assays (DNA, genetic profiling) Software that runs equipment that carries significant risk Requires validation and assurance that failure will not occur Example: electronic medical records management systems Syringes, catheters, IV tubing, tampons, contact lenses, contact lens solutions, first aid bandages, dental, etc. Page 5

Core Legal Framework EU Directives (Directives are to be implemented into national law) Medical Devices Directive (MDD) 93/42/EEC Active Implantable Medical Devices Directive (AIMDD) 90/385/EEC In Vitro Diagnostic Devices Directive (IVDD) 98/79/EC Only one apply to one product Implemented in EU, Norway, Iceland, Liechtenstein, & Switzerland Page 6

Medical Devices Directive 2007/47/EC Directive 2007/47/EC amends Medical Devices Directive (MDD) 93/42/EEC and Active Implantable Devices Directive 90/385/EEC Aim is to regulate the broad range of medical devices (except in vitro diagnostics) Page 7

Medical Devices Directive 2007/47/EC Directive 2007/47/EC - Important dates Published Official Journal: 21 Sept. 2007 Entered into force on 11 October 2007 Transposition by Member States: 21 December 2008 Member States to apply the transposition measures from 21 March 2010 There is no clause in the Directive for a transition period Page 8

Changes to Definitions Software, included into the definition of Medical Devices (Article 1) Medical device means 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 for the purpose of Page 9

Changes to Definitions - Medical Software Software specifically for diagnostic/therapeutic use is a medical device however Software intended for general purposes, when used in a healthcare setting is not a medical device (Recital 6 of 2007/47/EC) Stand alone medical software is an active medical device (93/42/EEC,Annex IX) Page 10

Changes to Definitions- Medical Software For devices which incorporate software or which are medical software in themselves, the software must be validated according to the state of the art taking into account the principles of development lifecycle, risk management, validation and verification. (93/42/EEC, Annex I, ER 12.1a) Page 11

Essential Requirements Additional requirements (Annex I) Ergonomic design : reduce wherever possible the risk of use error due to the ergonomic features of the device and the environment in which the device is to be used (patient security) (ER 1) Information supplied by the manufacturer must take account of the knowledge and level of training of the user (ER 13.1) Requirement for conformity assessment to include a clinical evaluation (ER 6) Results of biophysical modelling used in device design to be appropriately validated (ER 7.1) Page 12

Essential Requirements Additional requirements (Annex I) Special attention to device constituents with carcinogenic, mutagenic, reproductive toxic potential (ER 7.5) Devices which contain phthalates, and which are intended to channel, transport or store medicines, body fluids or other substances for administration must be labelled to show presence of phthalates. If devices are for treatment of children or pregnant, nursing, women justification for use phthalate is required (ER 7.5) Page 13

Essential Requirements Additional requirements (Annex I) Devices incorporating human blood derivates must contain details of these derivates in the Instruction For Use (ER 13.6 (o)) Instruction for Use (IFU) must now be revision controlled The date of issue or latest revision of the IFU must be clearly indicated (ER 13.6 (q)) Page 14

Technical Documentation requirements (Annex II-VII) Technical documentation must Specify whether or not animal tissues are utilised in the manufacture of the device Include details on preclinical evaluation performed For conformity assessment, Notified Bodies will For Class III devices, include close examination of design For Class IIa devices, include assessment of TD of at least one representative sample for each device subcategory For Class IIb include assessment of TD of at least one representative sample for each generic device group Page 15

Technical Documentation requirements (Annex II-VII) Outsourced design or manufacturing Manufacturer must have a procedure (and records) which shows adequate controls in place to ensure the continued efficient operation of the quality Page 16

Data Retention (Annex II-VII) Records (including aspects of the technical documentation) must be maintained for inspection by the CA for the useful life of the product or 5 years from the date of manufacture, which ever is greater. For implantable devices, records are to be kept for 15 years from the time the last product was manufactured Page 17

Classification Rules (Annex IX) Amended definition of central circulatory system (Rule 1.7) Now includes the vessels aortic arch and descending aorta to the aortic bifurcation Any device that come in contact with these vessels is now Class III Amended definition of continuous use (Rule 2.6) Uninterrupted use Including discontinuation of use followed by immediate replacement with same or identical device Page 18

Classification Rules (Annex IX) Surgically invasive devices Transient use, surgically invasive devices for use in direct contact with the CNS are in Class III (Rule 6) (others are in Class IIa) Devices intended for disinfection Devices intended for disinfection invasive devices are in Class IIb (Rule 15) Page 19

Bordeline Products Classification for devices incorporating as an integral part a medicinal substance (as per Directive 2001/83/EC), is now determined by the Principal Mode of Action rather than by the Intended Use (Article 1, 5 (c)) Notified Body is responsible to verify the usefulness of medicinal substance, while medicine CA is responsible to verify the quality and safety of the medicinal product (Annex 1, ER 7.4) Medicine CA must provide its opinion on the medicinal substance within 210 days Page 20

Requirements for Clinical Data Clinical data are now required for ALL devices, including Class I clinical data is generally required for all devices regardless of classification Directive 2007/47/EC, Recital (8) Page 21

Requirements for Clinical Data - Article 1(k) Clinical Data defined clinical data means the safety and/or performance information that is generated from the use of a device. Clinical data are sourced from Clinical investigation(s) of the device concerned; or Clinical investigation(s) or other studies reported in the scientific literature, of a similar device for which equivalence to the device in question can be demonstrated; or Published and/or unpublished reports on other clinical experience of either the device in question or a similar device for which equivalence to the device in question can be demonstrated Page 22

Requirements for Clinical Data New Essential Requirement Addition in Annex I Section 6a Demonstration of conformity with the essential requirements must include a clinical evaluation in accordance with Annex X. The clinical evaluation and its outcome are to be included in the technical documentation Page 23

Requirements for Clinical Data Clinical Evaluation (Annex X) Conformity with the Essential Requirements for a device, including the acceptability of the clinical risk/benefit ratio, generally require clinical data Clinical evaluation must follow defined and methodologically sound procedure Clinical evaluation can comprise - Critical evaluation of relevant scientific literature on an equivalent device, or - Critical evaluation of the results of all clinical investigations with the device, or - A combination of both Page 24

Requirements for Clinical Data Clinical Evaluation (Annex X) For implantable devices and devices in Class III Clinical investigation to be performed unless it is duly justified to rely on existing clinical data Post Market clinical follow-up The clinical evaluation must be actively updated with data from the post market surveillance A documented rationale is to be provided if not performing post-market surveillance Page 25

Requirements for Clinical Data Clinical Evaluation (Annex X) Where a manufacturer determines that clinical evaluation is not required for demonstration of conformity with Essential Requirements Adequate justification is to be provided, based on risk management output, performance evaluation, bench testing and preclinical evaluation Page 26

Requirements for Clinical Data Clinical Studies Clinical Trial Application (Article 15, Annexes VIII and X) For Class III, long-term and invasive implantable MDs (Class IIa or IIb) CA: implicit approval; wait 60 days or explicit max. 60 days EC: explicit approval; timeline not specified Parallel or sequential is not specified Other devices CA: as above or notification only EC: explicit approval; timeline not specified Parallel or sequential is not specified Trials with devices with CE mark No approval from / notification to CA required, if device used in accordance with intended use and information for user EC: explicit approval; timeline not specified Page 27

Requirements for Clinical Data Clinical Studies Submission documents to CA Name of sponsor / manufacturer Reference to earlier submission, if applicable List of other Member States participating in the trial List of investigators Detailed Investigator Brochure, incl. risk-benefit-assessment Statement that the device complies with the essential requirements except with regard to those aspects to be investigated in the trial Informed consent documentation Patient insurance Clinical Trial Protocol Copy of EC approval, when available Some countries may request additional country specific documents Page 28

Requirements for Clinical Data Clinical Studies Article 15 Clinical studies performed with non-ce Marked devices, CAs of MS to inform ALL MS on decision To refuse clinical trial approval To terminate an approved clinical trial earlier on safety grounds Involving significant modification or temporary interruption of an approved trial Page 29

Requirements for Clinical Data Clinical Studies End of Trial notification No timeline provided in the MDD For early termination justification to be included If early termination due to safety, all MSs and the Commission have to be informed Clinical trial report to be kept at the disposal of the competent authorities Page 30

Requirements for Clinical Data Clinical Studies Annex X SAE to be immediately reported to all National Competent Authorities (NCAs) where the clinical investigation has commenced Page 31

Authorized Representative (Article 14.2) Manufacturer based outside the EU must appoint a single European Authorized Representative (AR) The AR to act and be contacted in lieu of the manufacturer in terms of meeting the obligations of the Directives The AR to cover at least all devices of the same model Page 32

European Databank (Article 14a) Implementation of Centralised European database on Medical Devices including Data on clinical trials, registration, manufacturer and authorised representative, certificates and safety Timelines To be implemented by 5 September 2012 Commission to evaluate its functionality by 11 October 2012 Page 33

Post Marketing Requirement Need to have a system in place that proactively monitors how the devices are being used and are performing in the field (Annex VIII) More emphasis placed on post- market clinical followup as part of the post- market surveillance plan Page 34

Medical Devices Directive 2007/47/EC - Implementation Application of Directive 2007/47/EC Devices put on the market or in use after 21 March 2010 must comply with the new Directive Products which were on the market prior March 2010 will remain Manufacturers are to indicate in the declaration of conformity that the products comply with the amended directives if statement was prior 21 March 2010 Proof to get conform is to be documented For products which changed in Class verification by Notified Bodies was due prior 21 March 2010 For the other products the Notified Bodies will verify compliance during the inspections of design documentation Page 35

CONCLUSION Directive 2007/47/EC represents a considerable revision for devices even though Directive 98/79 for the in vitro diagnostics is not yet affected There is a move towards a European harmonisation There is a move towards a legislation similar in certain ways to the legislation for drugs Clinical trials Safety surveillance Communication between Member States Page 36

Medical Devices Directive 20007/47/EC Documents of Interest http://eur-lex.europa.eu/lexuriserv/lexuriserv.do?uri=consleg: 1993L0042:20071011:en:PDF http://eur-lex.europa.eu/lexuriserv/lexuriserv.do?uri=consleg: 1990L0385:20071011:EN:PDF MEDDEV 2.7/1, Dec 2009, Rev.3 MEDDEV 2.7/3 (Dec 2010) http://www.mddionline.com/article/best-both-worlds-sops-device-trialseurope-part-1 http://www.mddionline.com/article/best-both-worlds-sops-device-trialseurope-part-2 Page 37

Thank you Page 38

Questions Page 39