# Presentation: 024036

## Maria Judite Neves
MDEG, MSOG
INFARMED
Lisbon, Portugal 

- MDEG, MSOG
- INFARMED
- Lisbon, Portugal

- Study Group 1
**DEFINITION OF MEDICAL DEVICE**

## 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**

## 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**

## Slide 4

## Slide 5

## Low Risk and Reusable

**Low Risk and Reusable**

## Low Risk and Reusable

**Low Risk and Reusable**

## Low Risk and Sterile

**Low Risk and Sterile**

## Low Risk with Measure function

**Low Risk with Measure function**

## Medium Risk

**Medium Risk**

## Medium Risk

**Medium Risk**

## Medium Risk

**Medium Risk**

**High Risk**

## High Risk

**High Risk**

## High Risk

**High Risk**

## Custom made medical devices

## Medical Device Technologies

**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**

## Slide 17

## 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**

## MD

**MEDICAL DEVICE**_**Borderline Issues**_

**Other products**

**Cosmetics**

**Individual **
**protection **
**equipment**

**IVMD**

**Biocides**

**Medicinal**
**products**

## MD

**MEDICAL DEVICE**_**Borderline Issues**_

**Is this product a medical device ?**

**Medical purpose**
**Principal intended action**

## Analysing Tools

- Labelling / Instruction for use
- Technical documentation
- Pre-clinical and clinical studies
- Enquiries
- Classification/Demarcation guidelines

**MEDICAL DEVICE**_**Borderline Issues**_

## MEDICAL  DEVICE

- Low Risk

- Medium Risk

- High Risk

- 400.000 Medical Device Types
-             10.000 Families

**MEDICAL  DEVICE**

**Source, EUCOMED**

## MEDICAL DEVICES DEFINITION includes devices for “In Vitro” examination

**Reagent Product**
**Kit**
**Calibrator**
**Control Material **

**MEDICAL DEVICES DEFINITION ****includes devices for *****“In Vitro”***** examination**

**Instrument**
**Apparatus**
**Equipment**
**    ****or system**

## ... and sample collection, specimen receptacles and storage devices.

**MEDICAL DEVICES DEFINITION ****includes devices for “In Vitro” examination**

## MEDICAL DEVICE DEFINITION includes devices for “In Vitro” examination

**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**

## Thank You

**Thank You**

## Essential Principles

**Essential Principles**
**of**
**Safety and Performance**
**of Medical Devices**

- M. Gropp
- GHTF SG-1
- AdvaMed, Eucomed
- Guidant Corporation
- Brussels, Belgium

## Only medical devices that are safe and perform as

- 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**

## Presentation overview

**Presentation overview**
-  Introduction
-  Purpose
-  Overview of main points of Essential Principles guidance document

## http://www.ghtf.org/index.html

- GHTF SG-1:  Essential Principles of Safety and Performance of Medical Devices

## GHTF SG-1:  Essential Principles of Safety and Performance of Medical Devices

## GHTF SG-1:  Essential Principles of Safety and Performance of Medical Devices

## GHTF SG-1:  Essential Principles of Safety and Performance of Medical Devices

## Document history

**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. ...”

## Document history

**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.”

## Rationale

**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. ...”

## Rationale

**Rationale**
**“... **Moreover, eliminating differences between jurisdictions decreases the cost of gaining regulatory compliance and allows patients earlier access to new technologies and treatments.”

## Scope

**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.”

## GHTF SG-1:  Essential Principles of Safety and Performance of Medical Devices

***Source:***  GHTF

## Purpose

**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]

## Purpose

**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 ...

## Purpose

**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”

## Purpose

**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)

## GHTF SG-1:  Essential Principles of Safety and Performance of Medical Devices

***Source:***  GHTF

## General requirement 1

**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, ...”

## General requirement 1 (continued)

**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.”

## General requirement 2

**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*

## General requirement 2 (continued)

**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”

## General requirement 3

**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.”

## General requirement 4

**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.”

## General requirement 5

**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.”

## General requirement 6

**General requirement 6**
- “The benefits must be determined to outweigh any undesirable side effects for the performances intended”

## Conformity assessment

**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.”

## Summary

**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

## Summary

**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

## Questions?

**Questions?**

## STED

- GHTF SG-1
- COCIR
- Philips Medical Systems
- Best, The Netherlands

- Study Group 1
**STED**
*Summary Technical Documentation*

## 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*

## 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

## STED

- Remember, STED is a
**	****Summary** Technical Documentation,
- 	not ...

## 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

## STED

- Global Regulatory Model

- SUMMARISED
- TECHNICAL INFORMATION

## STED

- Zoom-in on essential part ...

## STED

- Harmonised Regulatory Model

**SUMMARY **
**TECHNICAL DOCUMENTATION**

## STED

- Design Control Waterfall Model

**QUALITY SYSTEM DESIGN PROCESS GUIDELINE**

**Technical**
**Requirements**

**Device **
**Description**

**Verification and**
**Validation**
**Documents**

**Production,**
**Process & **
**Other docs****.**

**PROCESS OUTPUTS**

## STED

**STED**

- Source and Application

**QUALITY SYSTEM OUTPUT**

**SUMMARY**** ****DOCUMENTATION**

**USAGE**

**Technical**
**Requirements**

**Device **
**Description**

**Verification &**
**Validation**
**Documents**

**Production,**
**Process & **
**Other docs.**

**Data****Subset**

**Summary**
**Technical ****Documents**

**Data****Subset**

**Data****Subset**

**Data****Subset**

** ****Pre-market**
**Submitted **
**and/or **
**on file**

**Post-market**
**Available  **
**for audit**

## STED

**Summary Technical Documentation **
**Device description **
**Essential Principles****: ****evidence**** ****of conformity**
**Labelling**
**Risk analysis****    (**risk** **management**)**
**(p****re-****)****clinical design verification ****&**** validation **
**Manufacturing information**

**Notes:**
STED talks about Risk Analysis; I prefer to use the more integral approach of risk management, such as described in ISO 14971

## STED

**STED**

- STED & amount of information

## STED

- Again, STED is a
**	****Summary** Technical Documentation,
- 	not ...

## 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

## 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** **

## 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

## STED

-       Essential principles checklist

## 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

## 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.

## STED

**Risk analysis**

***Can you have full Risk ******Analysis (or****** Risk ******Management******)****** details in STED ???***

## 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?

## 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

## 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

## STED

**Summary documents of pre-clinical design verification and validation**

**7.3.1 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

## STED

**engineering tests**
**laboratory tests**
**biocompatibility tests**
**animal tests**
**simulated use**
**software validation**

**Summary documents of pre-clinical design verification and validation**

## STED

**7.3.2 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**

## 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

## 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**

## STED

**USA - ****FDA**** / Canada - ****HC**** / Europe - ****NB’s**** /**
**Australia - ****TGA**** / Japan - ****MHLW**** / other - ****?**
**FDA: ****	**_**[http://www](http://www.fda.gov/cdrh/ode/guidance/1347.html)**__**[.](http://www.fda.gov/cdrh/ode/guidance/1347.html)**__**[fda](http://www.fda.gov/cdrh/ode/guidance/1347.html)**__**[.](http://www.fda.gov/cdrh/ode/guidance/1347.html)**__**[gov](http://www.fda.gov/cdrh/ode/guidance/1347.html)**__**[/](http://www.fda.gov/cdrh/ode/guidance/1347.html)**__**[cdrh/ode/guidance/1347.html](http://www.fda.gov/cdrh/ode/guidance/1347.html)**_ ** **
**HC: ****	**_**[http://www](http://www.hc-sc.gc.ca/dhp-mps/md-im/activit/int/ghtffs_gthmfd_e.html)**__**[.](http://www.hc-sc.gc.ca/dhp-mps/md-im/activit/int/ghtffs_gthmfd_e.html)**__**[hc-sc.gc.ca/dhp](http://www.hc-sc.gc.ca/dhp-mps/md-im/activit/int/ghtffs_gthmfd_e.html)**__**[-](http://www.hc-sc.gc.ca/dhp-mps/md-im/activit/int/ghtffs_gthmfd_e.html)**__**[mps](http://www.hc-sc.gc.ca/dhp-mps/md-im/activit/int/ghtffs_gthmfd_e.html)**__**[/](http://www.hc-sc.gc.ca/dhp-mps/md-im/activit/int/ghtffs_gthmfd_e.html)**__**[md](http://www.hc-sc.gc.ca/dhp-mps/md-im/activit/int/ghtffs_gthmfd_e.html)**__**[-](http://www.hc-sc.gc.ca/dhp-mps/md-im/activit/int/ghtffs_gthmfd_e.html)**__**[im](http://www.hc-sc.gc.ca/dhp-mps/md-im/activit/int/ghtffs_gthmfd_e.html)**__**[/](http://www.hc-sc.gc.ca/dhp-mps/md-im/activit/int/ghtffs_gthmfd_e.html)**__**[activit/int/ghtffs](http://www.hc-sc.gc.ca/dhp-mps/md-im/activit/int/ghtffs_gthmfd_e.html)**__**[_](http://www.hc-sc.gc.ca/dhp-mps/md-im/activit/int/ghtffs_gthmfd_e.html)**__**[gthmfd_e.html](http://www.hc-sc.gc.ca/dhp-mps/md-im/activit/int/ghtffs_gthmfd_e.html)**_
- 	_[http://www](http://www.asiahwp.org/Canada_ghtf_sted_guide_e.pdf)__[.](http://www.asiahwp.org/Canada_ghtf_sted_guide_e.pdf)__[asiahwp](http://www.asiahwp.org/Canada_ghtf_sted_guide_e.pdf)__[.](http://www.asiahwp.org/Canada_ghtf_sted_guide_e.pdf)__[org/Canada_ghtf](http://www.asiahwp.org/Canada_ghtf_sted_guide_e.pdf)__[_](http://www.asiahwp.org/Canada_ghtf_sted_guide_e.pdf)__[sted](http://www.asiahwp.org/Canada_ghtf_sted_guide_e.pdf)__[_](http://www.asiahwp.org/Canada_ghtf_sted_guide_e.pdf)__[guide_e.pdf](http://www.asiahwp.org/Canada_ghtf_sted_guide_e.pdf)_
**EU:****	**_**[no format specified](http://tga.health.gov.au/docs/pdf/tganws/tganews35.pdf)**_
**TGA:****	**_**[http://](http://tga.health.gov.au/docs/pdf/tganws/tganews35.pdf)**__**[tga](http://tga.health.gov.au/docs/pdf/tganws/tganews35.pdf)**__**[.health.](http://tga.health.gov.au/docs/pdf/tganws/tganews35.pdf)**__**[gov](http://tga.health.gov.au/docs/pdf/tganws/tganews35.pdf)**__**[.au/docs/](http://tga.health.gov.au/docs/pdf/tganws/tganews35.pdf)**__**[pdf](http://tga.health.gov.au/docs/pdf/tganws/tganews35.pdf)**__**[/](http://tga.health.gov.au/docs/pdf/tganws/tganews35.pdf)**__**[tganws](http://tga.health.gov.au/docs/pdf/tganws/tganews35.pdf)**__**[/tganews35.](http://tga.health.gov.au/docs/pdf/tganws/tganews35.pdf)**__**[pdf](http://tga.health.gov.au/docs/pdf/tganws/tganews35.pdf)**_
**MHLW: **_**[no specific ](http://tga.health.gov.au/docs/pdf/tganws/tganews35.pdf)**__**[url ](http://tga.health.gov.au/docs/pdf/tganws/tganews35.pdf)**__**[available](http://tga.health.gov.au/docs/pdf/tganws/tganews35.pdf)**_

**Regional tailoring**

## STED

## STED

## 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**

## STED

## Building blocks for harmonized regulatory processes

**International Standards**

## 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

## 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

## 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 !!

## 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 60601-1: *Safety & Essential Performance for medical electrical equipment

## 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

**Notes:**
To be practicable, the transition period should allow manufacturers to respond in an appropriate manner. The maximum transition period should not exceed 5 years unless there are exceptional circumstances that would justify a longer transition period.

## 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

## 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 ...**

## STED

- Thank you for your attention