Santiago de Chile, May 9 – 12, 2006 Maria Judite Neves MDEG, MSOG INFARMED Lisbon, Portugal Study Group 1 DEFINITION OF MEDICAL DEVICE

Santiago de Chile, May 9 – 12, 2006 MEDICAL DEVICE Why a harmonized definition ? GHTF/SG1/N29R16:2005 Harmonized definition offers significant benefits to the manufacturer, user, patient or consumer and to Regulatory Authorities; Supports global convergence of regulatory systems; Decreases the cost of regulatory compliance; Allows patients earlier access to new technologies and treatments

Santiago de Chile, May 9 – 12, 2006 MEDICAL DEVICE Definition which doesn’t achieve its primary intended action in or on the human body by pharmacological, immunological or metabolic means, but which may be assisted in its intended function by such means GHTF/SG1/N29R16:2005 Instrument Apparatus Implant Machine Appliance Software Material Other similar or related article Diagnosis Prevention Monitoring Treatment Alleviation Compensation Investigation, replacement, modification, or support of the anatomy or of a physiological process Supporting or sustaining life Control of conception Disinfection of medical devices disease / injury

Santiago de Chile, May 9 – 12, 2006 Low Risk

Santiago de Chile, May 9 – 12, 2006 Low Risk

Santiago de Chile, May 9 – 12, 2006 Low Risk and Reusable

Santiago de Chile, May 9 – 12, 2006 Low Risk and Reusable

Santiago de Chile, May 9 – 12, 2006 Low Risk and Sterile

Santiago de Chile, May 9 – 12, 2006 Low Risk with Measure function

Santiago de Chile, May 9 – 12, 2006 Medium Risk

Santiago de Chile, May 9 – 12, 2006 Medium Risk

Santiago de Chile, May 9 – 12, 2006 Medium Risk High Risk

Santiago de Chile, May 9 – 12, 2006 High Risk

Santiago de Chile, May 9 – 12, 2006 High Risk

Santiago de Chile, May 9 – 12, 2006 Custom made medical devices

Santiago de Chile, May 9 – 12, 2006 Neurological Conditions Ear, Nose & Throat Disorders Spinal Disorders Spasticity Chronic Pain Diabetes Management Cardiac Arrhythmias Heart Failure Sudden Cardiac Death Coronary Artery Disease Heart Valve Disease G/I Reflux Incontinence Peripheral Vascular Disease Medical Device Technologies

Santiago de Chile, May 9 – 12, 2006

New Medical Technologies Minimally invasive surgery High precision robotic surgery Telemedicine Targeted drug delivery systems Lab-on-a chip Regenerative Medicine In-vivo nano-imaging Cell therapies Artificial Organs Biological sciences Materials sciences Information Technology Imaging Technology

Santiago de Chile, May 9 – 12, 2006 MD MEDICAL DEVICE Borderline Issues Other products Cosmetics Individual protection equipment IVMD Biocides Medicinal products

Santiago de Chile, May 9 – 12, 2006 MD MEDICAL DEVICE Borderline Issues Is this product a medical device ? Medical purpose Principal intended action

Santiago de Chile, May 9 – 12, 2006 Analysing Tools Labelling / Instruction for use Technical documentation Pre-clinical and clinical studies Enquiries Classification/Demarcation guidelines MEDICAL DEVICE Borderline Issues

Santiago de Chile, May 9 – 12, 2006 Low Risk Medium Risk High Risk Medical Device Types Families MEDICAL DEVICE Source, EUCOMED

Santiago de Chile, May 9 – 12, 2006 Reagent Reagent Product Kit Calibrator Control Material MEDICAL DEVICES DEFINITION includes devices for “In Vitro” examination Instrument Apparatus Equipment or system

Santiago de Chile, May 9 – 12, 2006 … and sample collection, specimen receptacles and storage devices. MEDICAL DEVICES DEFINITION includes devices for “In Vitro” examination

Santiago de Chile, May 9 – 12, to provide information : Concerning a physiological or pathological state; Concerning a congenital abnormality; To determine the safety and compatibility with potencial recipients; To monitor therapeutic measures MEDICAL DEVICE DEFINITION includes devices for “In Vitro” examination

Santiago de Chile, May 9 – 12, 2006 Thank You

Santiago de Chile, May 9 – 12, 2006 Study Group 1 Essential Principles of Safety and Performance of Medical Devices M. Gropp GHTF SG-1 AdvaMed, Eucomed Guidant Corporation Brussels, Belgium

Santiago de Chile, May 9 – 12, 2006 GHTF SG-1: Essential Principles of Safety and Performance of Medical Devices Only medical devices that are safe and perform as intended should be allowed in the market  Agree  Disagree

Santiago de Chile, May 9 – 12, 2006 GHTF SG-1: Essential Principles of Safety and Performance of Medical Devices Presentation overview Introduction Purpose Overview of main points of Essential Principles guidance document

Santiago de Chile, May 9 – 12, 2006 GHTF SG-1: Essential Principles of Safety and Performance of Medical Devices

Santiago de Chile, May 9 – 12, 2006 GHTF SG-1: Essential Principles of Safety and Performance of Medical Devices

Santiago de Chile, May 9 – 12, 2006 GHTF SG-1: Essential Principles of Safety and Performance of Medical Devices

Santiago de Chile, May 9 – 12, 2006 GHTF SG-1: Essential Principles of Safety and Performance of Medical Devices

Santiago de Chile, May 9 – 12, 2006 GHTF SG-1: Essential Principles of Safety and Performance of Medical Devices Document history “The GHTF has identified as a priority the need to harmonize essential safety and performance criteria for a medical device that allow the manufacturer to demonstrate its product is suitable for its intended use. This goal was achieved through the publication of guidance on the subject entitled Essential Principles of Safety and Performance of Medical Devices (SG1/N020 of June 30, 1999) that applied to the majority of medical devices but not to in vitro diagnostic devices. …”

Santiago de Chile, May 9 – 12, 2006 GHTF SG-1: Essential Principles of Safety and Performance of Medical Devices Document history “…. This current document supersedes that earlier one. The major difference between them is the expanded scope; this document now includes medical devices for the in vitro examination of specimens derived from the human body.”

Santiago de Chile, May 9 – 12, 2006 GHTF SG-1: Essential Principles of Safety and Performance of Medical Devices Rationale “Consistent identification, selection and application of safety and performance principles to a medical device offers significant benefits to the manufacturer, user, patient or consumer, and to Regulatory Authorities since it allows its manufacturer to design, manufacture and demonstrate the device is suitable for its intended use....”

Santiago de Chile, May 9 – 12, 2006 GHTF SG-1: Essential Principles of Safety and Performance of Medical Devices Rationale “… Moreover, eliminating differences between jurisdictions decreases the cost of gaining regulatory compliance and allows patients earlier access to new technologies and treatments.”

Santiago de Chile, May 9 – 12, 2006 GHTF SG-1: Essential Principles of Safety and Performance of Medical Devices Scope “This document applies to all products that fall within the definition of a medical device that appears within the GHTF document Information Document Concerning the Definition of the Term “Medical Device”, including those used for the in vitro examination of specimens derived from the human body.”

Santiago de Chile, May 9 – 12, 2006 GHTF SG-1: Essential Principles of Safety and Performance of Medical Devices Source: GHTF

Santiago de Chile, May 9 – 12, 2006 GHTF SG-1: Essential Principles of Safety and Performance of Medical Devices Purpose “To describe six general requirements of safety and performance that apply to all medical devices. To provide a comprehensive list of design and manufacturing requirements of safety and performance, some of which are relevant to each medical device. …” [emphasis in original]

Santiago de Chile, May 9 – 12, 2006 GHTF SG-1: Essential Principles of Safety and Performance of Medical Devices Purpose “… These are grouped as: Chemical, physical and biological properties Infection and microbial contamination Manufacturing and environmental properties Devices with a diagnostic or measuring function Protection against radiation Requirements for medical devices connected to or equipped with an energy source Protection against mechanical risks …

Santiago de Chile, May 9 – 12, 2006 GHTF SG-1: Essential Principles of Safety and Performance of Medical Devices Purpose “… These are grouped as: (continued) Protection against the risks posed to the patient by supplied energy or substances Protection against the risks posed to the patient for devices for self-testing or self-administration Information supplied by the manufacturer Performance evaluation including, where appropriate, clinical evaluation”

Santiago de Chile, May 9 – 12, 2006 GHTF SG-1: Essential Principles of Safety and Performance of Medical Devices Purpose “The manufacturer selects which of the design and manufacturing requirements are relevant to a particular medical device, documenting the reasons for excluding the others. The Regulatory Authority and/or Conformity Assessment Body may verify this decision during the conformity assessment process.” (or audit)

Santiago de Chile, May 9 – 12, 2006 GHTF SG-1: Essential Principles of Safety and Performance of Medical Devices Source: GHTF

Santiago de Chile, May 9 – 12, 2006 GHTF SG-1: Essential Principles of Safety and Performance of Medical Devices General requirement 1 “Medical devices should be designed and manufactured in such a way that, when used under the conditions and for the purposes intended and, where applicable, by virtue of the technical knowledge, experience, education or training of intended users, they will not compromise the clinical condition or the safety of patients, or the safety and health of users or, where applicable, other persons, …”

Santiago de Chile, May 9 – 12, 2006 GHTF SG-1: Essential Principles of Safety and Performance of Medical Devices General requirement 1 (continued) “… provided that any risks which may be associated with their use constitute acceptable risks when weighed against the benefits to the patient and are compatible with a high level of protection of health and safety.”

Santiago de Chile, May 9 – 12, 2006 GHTF SG-1: Essential Principles of Safety and Performance of Medical Devices General requirement 2 “The solutions adopted by the manufacturer for the design and manufacture of the devices should conform to safety principles, taking account of the generally acknowledged state of the art. When risk reduction is required, the manufacturer should control the risk(s) so that the residual risk(s) associated with each hazard is judged acceptable. …” Reference: ISO 14971:2001: Medical devices – Application of risk management to medical devices

Santiago de Chile, May 9 – 12, 2006 GHTF SG-1: Essential Principles of Safety and Performance of Medical Devices General requirement 2 (continued) “The manufacturer should apply the following principles in the priority order listed: identify known or foreseeable hazards and estimate the associated risks arising from the intended use and foreseeable misuse, eliminate risks as far as reasonably practicable through inherently safe design and manufacture reduce as far as is reasonably practicable the remaining risks by taking adequate protection measures, including alarms, inform users of any residual risks”

Santiago de Chile, May 9 – 12, 2006 GHTF SG-1: Essential Principles of Safety and Performance of Medical Devices General requirement 3 “Devices should achieve the performance intended by the manufacturer and be designed, manufactured and packaged in such a way that they are suitable for one or more of the functions within the scope of the definition of a medical device applicable in each jurisdiction.”

Santiago de Chile, May 9 – 12, 2006 GHTF SG-1: Essential Principles of Safety and Performance of Medical Devices General requirement 4 “The characteristics and performances …. should not be adversely affected to such a degree that the health or safety of the patient or the user and, where applicable, of other persons are compromised during the lifetime of the device, as indicated by the manufacturer, when the device is subjected to the stresses which can occur during normal conditions of use and has been properly maintained in accordance with the manufacturer’s instructions.”

Santiago de Chile, May 9 – 12, 2006 GHTF SG-1: Essential Principles of Safety and Performance of Medical Devices General requirement 5 “The devices should be designed, manufactured and packed in such a way that their characteristics and performances during their intended use will not be adversely affected under transport and storage conditions (for example, fluctuations of temperature and humidity) taking account of the instructions and information provided by the manufacturer.”

Santiago de Chile, May 9 – 12, 2006 GHTF SG-1: Essential Principles of Safety and Performance of Medical Devices General requirement 6 “The benefits must be determined to outweigh any undesirable side effects for the performances intended”

Santiago de Chile, May 9 – 12, 2006 GHTF SG-1: Essential Principles of Safety and Performance of Medical Devices Conformity assessment “Refer to … Principles of Conformity Assessment for Medical Devices and the work of GHTF Study Group 5 for further information on the use of clinical evaluation to demonstrate compliance with these Essential Principles.”

Santiago de Chile, May 9 – 12, 2006 GHTF SG-1: Essential Principles of Safety and Performance of Medical Devices Summary Essential Principles form foundation of harmonised global regulatory model Comprehensive in scope Cover safety and performance Define design requirements Do not define methods of achieving, demonstrating, or documenting conformity Often covered by international standards

Santiago de Chile, May 9 – 12, 2006 GHTF SG-1: Essential Principles of Safety and Performance of Medical Devices Summary Flexible to accommodate advances in the state of the art and new medical devices / technologies / intended uses Recognise risks and benefits associated with medical devices Are founded on risk management principles Intimately linked to manufacturer’s quality system for design, manufacture, and risk management

Santiago de Chile, May 9 – 12, 2006 GHTF SG-1: Essential Principles of Safety and Performance of Medical Devices Questions?

Peter W.J. Linders GHTF SG-1 COCIR Philips Medical Systems Best, The Netherlands Study Group 1 STED Summary Technical Documentation

Santiago de Chile, May 9 – 12, 2006 STED  What is STED ?  How is STED developed ?  What’s in STED ?  Use of standards (brief) Inspired by Johan Brinch & Ed Woo, APEC Bangkok 2005

Santiago de Chile, May 9 – 12, 2006 STED  STED=Summary Technical Documentation  Used for demonstrating conformity to the Essential Principles of …  Safety & Performance of Medical Devices  STED=information considered sufficient for regulatory agency to confirm conformity

Santiago de Chile, May 9 – 12, 2006 STED  Remember, STED is a Summary Technical Documentation, not …

Santiago de Chile, May 9 – 12, 2006 STED GHTF identified the need to harmonize documentation of evidence of conformity to regulatory requirements  MD manufacturers increasingly global  Differences in documentation requirements  Necessitate additional work for the same device  Hinder timely access to medical devices  May pose barriers between countries  Increase cost  International standardization good for all parties

Santiago de Chile, May 9 – 12, 2006 STED SPECIFY DEVICE’S INTENDED USE DEVICE CLSSSIFICATION IDENTIFY RELEVANT ESSENTIAL PRINCIPLES of SAFETY & PERFORMANCE DESIGN & MANUFACTURE DEVICE TO MEET ESSENTIAL PRINCIPLES DEMONSTRATE COMPLIANCE THROUGH TESTING, MEETING REQUIREMENTS OF STANDARDS, OR THROUGH CLINICAL EVALUATION etc. RISK ANALYSIS/ MANAGEMENT PLACE SAFE DEVICE ON THE MARKET FULL TECHNICAL DOCUMENTATION SUMMARISED TECHNICAL INFORMATION MANUFACTURER’S POST-MARKET SURVEILLANCE VIGILANCE REPORTS VERIFICATION THROUGH INDEPENDENT AUDIT (if required) REGULATORY OVERSIGHT AND ENFORCEMENT Source: GHTF website (amended) Global Regulatory Model SUMMARISED TECHNICAL INFORMATION

Santiago de Chile, May 9 – 12, 2006 STED Global Regulatory Model FULL TECHNICAL DOCUMENTATION SUMMARISED TECHNICAL INFORMATION PLACE SAFE DEVICE ON THE MARKET Zoom-in on essential part …

Santiago de Chile, May 9 – 12, 2006 STED Quality System Audit Quality System Postmarket vigilance Pre-market approval Design Verification/ Validation ManufactureMarket Harmonised Regulatory Model SUMMARY TECHNICAL DOCUMENTATION

Santiago de Chile, May 9 – 12, 2006 STED Design Control Waterfall Model QUALITY SYSTEM DESIGN PROCESS GUIDELINE Technical Requirements Device Description Verification and Validation Documents Production, Process & Other docs. PROCESS OUTPUTS

Santiago de Chile, May 9 – 12, 2006 STED Source and Application QUALITY SYSTEM OUTPUTSUMMARY DOCUMENTATIONUSAGE Technical Requirements Device Description Verification & Validation Documents Production, Process & Other docs. Data Subset Summary Technical Documents Data Subset Pre-market Submitted and/or on file Post-market Available for audit

Santiago de Chile, May 9 – 12, 2006 STED Summary Technical Documentation Device description Essential Principles: evidence of conformity Labelling Risk analysis (risk management) (pre-)clinical design verification & validation Manufacturing information

Santiago de Chile, May 9 – 12, 2006 STED Detail of the Contents of Data Novelty of Medical Device Class D （Ⅳ） Class C （Ⅲ） Class B （Ⅱ） Require Clinical data Assess the Conformity to Standards Assess Validity and Safety from the Examination Results etc. STED & amount of information

Santiago de Chile, May 9 – 12, 2006 STED  Again, STED is a Summary Technical Documentation, not …

Santiago de Chile, May 9 – 12, 2006 STED Device description 7.2 Device description  functional purpose  general description of the device  the intended patient population(s)  contraindications  an explanation of any novel features  the accessories  the variants of the device  comparisons to other devices

Santiago de Chile, May 9 – 12, 2006 STED Device description (2)  materials and their physical properties  functional characteristics  technical performance specifications  chemical, physical, electrical, mechanical, biological, software, sterility, stability, storage and transport, and packaging

Santiago de Chile, May 9 – 12, 2006 STED Essential Principles and evidence of conformity 7.1 Essential Principles For ease of use in a global situation, it is recommended that the evidence of conformity be provided in tabular form with supporting documentation available for review as required

Santiago de Chile, May 9 – 12, 2006 STED Essential principles checklist

Santiago de Chile, May 9 – 12, 2006 STED Labelling 7.4 Labelling  Labels on the device and its packaging  Instructions for use  Other literature or training materials  Instructions for installation and maintenance  Any information and instructions given to the patient, incl. instructions for any procedure the patient is expected to perform

Santiago de Chile, May 9 – 12, 2006 STED Risk analysis 7.5 Risk analysis The STED should summarize or reference or contain (as determined by need for a submission and the option selected by the manufacturer in Section 6.2) the results of the risk analysis. This risk analysis should be based upon international or other recognized standards, and be appropriate to the complexity and risk class of the device.

Santiago de Chile, May 9 – 12, 2006 STED Risk analysis Can you have full Risk Analysis (or Risk Management) details in STED ???

Santiago de Chile, May 9 – 12, 2006 STED Risk analysis Risk analysis/mgt dossier is BIG No prescribed format Links to many other documents Decisions made by manufacturer (How to) interpret all information?

Santiago de Chile, May 9 – 12, 2006 STED Risk analysis For the manufacturer Include process description in STED dossier Give actual RM process data for the device For the regulator Verify that RM process IS in place

Santiago de Chile, May 9 – 12, 2006 STED Risk analysis For the manufacturer Include process description in STED dossier Give actual RM process data for the device For the regulator Verify that RM process IS in place

Santiago de Chile, May 9 – 12, 2006 STED Summary documents of pre-clinical design verification and validation General on design V&V declarations/certificates of conformity to the “recognized” standards listed as applied by the manufacturer and/or … summaries or reports of tests and evaluations based on other standards, manufacturer methods and tests, or alternative ways of demonstrating compliance

Santiago de Chile, May 9 – 12, 2006 STED engineering tests laboratory tests biocompatibility tests animal tests simulated use software validation Summary documents of pre-clinical design verification and validation

Santiago de Chile, May 9 – 12, 2006 STED Clinical Evidence The STED should indicate how any applicable requirements of the Essential Principles for clinical evaluation of the device have been met. Where applicable, this evaluation may take the form of a systematic review of existing bibliography, clinical experience with the same or similar devices, or by clinical investigation Summary documents of (pre-)clinical design verification and validation

Santiago de Chile, May 9 – 12, 2006 STED Manufacturing information 7.6 Manufacturer information The STED should summarize or reference or contain documentation related to the manufacturing processes, including quality assurance measures, which is appropriate to the complexity and risk class of the device

Santiago de Chile, May 9 – 12, 2006 STED From 2.0: Regional tailoring As an interim measure until full global harmonization of documentation requirements is achieved, the precise content of the STED … will need to be augmented by documentation required by country-specific regulations and regulatory guidance USA - FDA / Canada - HC / Europe - NB’s / Australia - TGA / Japan - MHLW / other - ? Regional tailoring

Santiago de Chile, May 9 – 12, 2006 STED USA - FDA / Canada - HC / Europe - NB’s / Australia - TGA / Japan - MHLW / other - ? FDA: HC: EU: no format specified no format specified TGA: MHLW: no specific url available no specific url available Regional tailoring

Santiago de Chile, May 9 – 12, 2006 STED

Santiago de Chile, May 9 – 12, 2006 STED

Santiago de Chile, May 9 – 12, 2006 STED USA - FDA / Canada - HC / Europe - NB’s / Australia - TGA / Japan - MHLW / other - ? Regulators and industry should jointly evaluate progress towards harmonization and adapt processes accordingly: “continual improvement” Regional tailoring

Santiago de Chile, May 9 – 12, 2006 STED

Santiago de Chile, May 9 – 12, 2006 Building blocks for harmonized regulatory processes International Standards

Santiago de Chile, May 9 – 12, 2006 Use of Standards in conformity assessment (another GHTF SG1 document) Compliance to “Recognized Standard” gives “Presumption of compliance” with Essential Principles Voluntary except when deemed mandatory Manufacturer is free to select alternative solutions to demonstrate compliance –National and International standards –Industry standards –Internal SOP –Current state of art techniques related to performance, material, design, processes

Santiago de Chile, May 9 – 12, 2006 Standards in STED In STED, in lieu of technical doc. submission Declarations, certificates, summary test report Retain documentation to demonstrate device compliance to selected standard or other means to meet Essential Principles –How standard was applied with test results. –Deviations other means to compliance when not applicable

Santiago de Chile, May 9 – 12, 2006 Standards in development ISO, IEC, … are global bodies Use defined consensus mechanism All stakeholders involved Stepwise development process:  NWIP / CD / CDV or DIS / FDIS / IS Maturation process, usually > 3 years Voting process includes national committees Great help in global convergence !!

Santiago de Chile, May 9 – 12, 2006 Standards in development A few well known examples: ISO 13485: Quality Mgt. System for medical device manufacturers ISO 14971: Risk Mgt. for medical devices IEC : Safety & Essential Performance for medical electrical equipment

Santiago de Chile, May 9 – 12, 2006 Revision or Replacement of Recognized Standards Updated standard becomes “recognized” too Transition Period –Should allow for manufactures to implement –Max < 5 years; unless exceptional circumstances During Transition Period –Both versions give presumption of conformity to EP –Unless safety implication, devices on market is OK After Transition Period –Superseded document may be withdrawn –Manufacturer using superseded version may do so but should perform & document risk assessment on differences

Santiago de Chile, May 9 – 12, 2006 Summary on standards Standards compliance is one means to demonstrate compliance to Essential Principles Transition to revised version important Standards enforcement flexibility should be allowed International standards key in harmonization Economies may want better participation in development and use of international standards

Santiago de Chile, May 9 – 12, 2006 STED Final comments  STED is a compilation of a subset of documents normally generated during the design process  Size of the STED dossier is proportional to the risk class of the device  Some regional tailoring is still here …

Santiago de Chile, May 9 – 12, 2006 STED