Safety - global Harmonization task force Regulatory Framework

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Presentation at Malaysia Medical Device Regulatory ConferenceLangkawi, Malaysia - 24 Nov 2011

GE Healthcare

Global Harmonization Task Force Regulatory Framework

Alfred KWEKDirector, Regulatory Affairs, ASEAN

GE HealthcareMedical Device Regulatory Conference, Langkawi, Malaysia, 24 Nov 2011

Meeting Theme and Objectives

ThemeTransforming Malaysia as a Medical Device HubThrough Harmonized Regulatory Approach

Objectives

� To promote medical device industry in Malaysia

� To create awareness among stakeholders on policy and regulatory requirements

� To identify and overcome issues and challenges in medical industry

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Agenda

Global Harmonisation Task Force- Who is GHTF?- Current regulations in GHTF members- Understand recipient / importing market requirements

Harmonized Regulatory Approach- What is harmonization?

AgendaIdentify & Overcome Issues and Challenges

Tools – Common Dossiers- Common Submission Dossier Template (CSDT)- Global / 3rd party manufacturing sites- Quality management systems (QMS)

Tools – Grouping of Devices- Systems, Groups, Families, Spare Parts, Expendables- Registration of devices- Import and local supply of medical devices

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11/23/2011

GHTF Members

All Rights Reserved 2007 Health Sciences Authority6

USA� 1976 Medical Device Amendments to FFD&C Act

� The Safe Medical Device Act 1990

� FDA Modernisation Act 1997

� Medical Device User Fee & Modernisation Act 2002

EUROPEAN UNION� Active Implantable Medical Directive 1990

� Medical Devices Directive 1993

� In-Vitro Diagnostics Directive 1998

OTHERS� Therapeutic Goods Act 1989 (Australia)

� Therapeutic Goods (Medical Devices) Regulations 2002 (Australia)

� Medical Device Regulations 1998 (Canada)

� Pharmaceutical Affairs Law 1948,1960,1979,2002

Medical Device Regulations in GHTF Members

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USA


� Risk based classification

� Device classification depends on intended use and indications for use

� Devices are classified into 3 classes, based on the level of control

needed to assure the safety and effectiveness of the device:

� Class I (Low risk) – General controls

• With exemptions

• Without exemptions

� Class II (Moderate risk) – General controls and special controls

• With exemptions

• Without exemptions

� Class III (High risk) – General controls and premarket approval

Classification of Medical Devices

USA

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Premarket Requirements

� Classification determines type of premarket

submission required for market clearance

� Class I and II devices typically require premarket

notification (510k), unless exempt by regulation

� Class III devices require submission of premarket

approval (PMA)

USA


Class I

• General controls sufficient to provide reasonable assurance of safety

and effectiveness

• General controls:

� Establishment registration

� Medical device listing

� Labelling requirements

� Premarket notification (510k) submission

(unless exempted by regulations)

� Manufacture under GMP requirements

(Note: All classes are subject to general controls)

USA


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Class II

� General controls insufficient to provide reasonable

assurance of safety and effectiveness. In addition to

general controls, special controls are necessary

� Special controls:

� Special labelling requirements

� Mandatory performance standards

� Post market surveillance


USA


Class III

� General controls and special controls insufficient to

provide reasonable assurance of safety and effectiveness

� Premarket approval (PMA) is required : scientific review to

ensure safety and effectiveness

USA

Premarket requirements

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Premarket notification (510k)

� Premarket application to demonstrate that device is as safe and

effective i.e. substantially equivalent to a legally marketed device

(i.e. predicate device)

� A device is substantially equivalent to a predicate device if it

• Has the same intended use and technological characteristics as

the predicate device

OR

• Has the same intended use as the predicate device and different

technological characteristics that do not raise new questions of

safety and effectiveness

USA



Premarket Approval (PMA)

• Scientific review to evaluate the safety and effectiveness of

Class III devices.

• Sufficient valid scientific evidence to assure that the device is

safe and effective for its intended use must be submitted

• An approved PMA is, in effect, a private license granting the

applicant permission to market the device

USA


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Premarket Approval (PMA)

Review of a PMA is a 4 step review process consisting of:

• Administrative and limited scientific review by FDA staff to

determine completeness (filing review)

• In depth scientific and regulatory review by appropriate FDA

scientific and compliance personnel (in depth review)

• Review and recommendation by the appropriate advisory

committee (panel review)

• An FDA good manufacturing practices (GMP) inspection

USA



Quality System Requirements

� Quality system requirements are set out in the

Quality System Regulation

� FDA does not require a manufacturer to register a

quality system (a requirement of ISO and EN quality

systems)

� FDA inspects quality system requirements in the

course of regular inspections of a manufacturer’s

facilities

� Foreign manufacturers are also subject to FDA

inspections

USA

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Postmarket Requirements

� Requirements are set out in the Safe Medical Devices Act and FDA Modernisation Act:

� Manufacturers must submit medical device reports for device which caused death or serious injury, or, if the malfunction were to recur, would have cause death or serious injury

� User facilities must report device related deaths and serious injuries and submit a summary of all reports to FDA on an annual basis

� Manufacturers must have in place distribution records and other methods for tracking permanent implants or life sustaining/supporting devices used outside a facility

� Manufacturers and importers must report to FDA any removals and corrections of a device from the market

USA


European Union

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Medical Devices are regulated by three main Directives:

• Council Directive 90/385/EEC on Active Implantable Medical

Devices (AIMDD), 1990

• Council Directive 93/42/EEC on Medical Devices (MDD), 1992

• Council Directive 98/79/EC on In Vitro Diagnostic Medical Devices

(IVDMD), 1998

EU member states transpose these directives into their national

laws

EU

Regulatory Framework


Classification of medical devices

� Risk based and rules based classification

� Medical devices are classified into 5 categories:

� Class I (Low risk)

� Class IIA (Low-moderate risk)

� Class IIB (Moderate-high risk)

� Class III (High risk)

� Active Implantable Medical Devices (AIMD)

� Device class determines conformity assessment route

EU

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� Each member state appoints a competent authority

(CA) to act as the State’s regulator and the CA in turn

appoints notified bodies (NB) to implement the

requirements of the directives (certification of CE

marking and quality systems)

� NBs are typically test laboratories and quality

systems organizations

EU


Premarket Requirements� Directives define the essential requirements that devices have to

meet when they are put on the market or put into service (Annex I)

� Directives contain a number of conformity assessment procedures, which depend on the type of products and type of risks involved (Annex II – VII)

� Except for low risk devices, these procedures always involve independent bodies, so-called Notified Bodies, designated and monitored by national authorities. In a number of cases, authorities act themselves as Notified Bodies

� Compliance with harmonized European standards will provide a presumption of conformity with the relevant essential requirements

� Devices that meet the essential requirements and have undergone the appropriate conformity assessment procedures will be CE marked. The CE denotes a formal statement by the manufacturer of compliance with the Directives’ requirements.

EU

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� Quality system requirements are set out in the MDD

Annexes

� The MDD requires quality systems to be registered to

a particular Annex of the MDD

� Generally, notified bodies use ISO 13485 standard to

establish compliance with the quality system

requirements in a particular Annex

EU

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Postmarket Requirements

� Manufacturer is required to establish and maintain a

system for reporting and acting upon incidents

affecting health and safety of patient or user

EU


Canada

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� Risk based, rules based classification

� Medical devices are classified into 1 of 4 classes: I, II,

III or IV. Class IV represents the highest risk

Canada



� All classes of devices must meet the following requirements:

� Manufacturers must ensure that device meets safety and effectiveness requirements in the Regulations and maintain objective evidence as proof.

(Compliance with the safety and effectiveness requirements can be demonstrated through the use of Health Canada recognised standards.)

� Any person who imports or sells a medical device and any manufacturer who distributes directly to users must obtain an establishment licence

Canada

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� In addition,

� Class II, III or IV devices:

�Device licence required prior to import and sales in Canada

�Class III and IV devices require scientific and medical review of submitted evidence of safety and effectiveness

�Class II devices only require quality system audit

�Amount of information required to be submitted to obtain a device licence increases as the risk class increases.

� Class I devices:

�Exempt from device licensing requirements

Canada


Quality system requirements

� Manufacturers of Class II medical devices must have their devices manufactured in accordance with the National Standard of Canada CAN/CSA-ISO 13488-98, Quality Systems —Medical devices — Particular requirements for the application of ISO 9002,

� Manufacturers of Classes III and IV medical devices must have their devices designed and manufactured in accordance with the National Standard of Canada CAN/CSA-ISO 13485-98, Quality systems — Medical devices — Particular requirements for the application of ISO 9001, as amended from time to time.

� Quality system certificates to be issued by third party audit organizations accredited by Standards Council of Canada and recognized by Health Canada

Canada

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Postmarket requirements

Postmarket requirements apply to all classes of

devices:

• Maintaining distribution records of each device

• Mandatory problem reporting

• Recall

• Implant registration

Canada


Australia

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� Risk based, rules based classification

� There are five classes of medical devices:

• Class I

• Class IIa

• Class IIb

• Class III

• Active Implantable Medical Devices (AIMD)

Australia



� The classification of a medical device determines the conformity assessment procedure(s) a manufacturer can choose to ensure that the device is adequately assessed to conform to the essential principles of safety and performance defined in Australian legislation

� Higher class devices undergo a more stringent form of conformity assessment than lower class devices

� Depending on the procedure chosen, assessment of the final design, the controls implemented for production and the manufacturer’s courses of action may have to be assessed by the TGA or another appropriate conformity assessment body.

Australia

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The following kind of medical device manufacturers are required under

Australian Legislation to obtain a Conformity Assessment Certificate

issued by TGA before the medical device can be included in the

ARTG:

� All Australian manufacturers

� Any manufacturer who manufactures medical devices containing

materials derived from animal, microbial or recombinant origin.


medicinal substances


blood plasma derivatives.

Australia

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� Overseas manufacturers not belonging to one of the categories

described above and who hold current EC certification issued by

an EU Notified Body under the EU Medical Devices Directive

93/42/EEC (MDD) or the EU Active Implantable Medical

Devices Directive 90/385/EEC (AIMDD) are allowed, under

certain conditions, to use EC certificates to support an

application for inclusion in the ARTG. These manufacturers do

not require a Conformity Assessment Certificate to be issued by

the TGA prior to making an application to include the device in

the ARTG.

Australia



� Quality system requirements are set out in the

Regulations, under the various conformity

assessment routes

Australia

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Postmarket Requirements� Vigilance System - Mandatory reporting system for adverse events

involving all medical devices. Based on recommendations of GHTF

� Sponsors are required to report any problem to the manufacturer of the device. Manufacturers are required to report the problem to the TGA.

� The Vigilance System comprises:

• penalties and time frames

• recall and seizure provisions

• voluntary reporting provisions for medical device users

• international information exchange between conformity assessment bodies

• information exchange between inter governmental agencies within Australia (such as Health Care Complaints Commission and coronial inquests)

Australia


Common & Uncommon Features

� Devices classified according to risk- level of

regulatory scrutiny on a device depends on

the risk of harm that the device presents.

Higher risk class; higher level of control

� Safety and effectiveness of the device can

be assured through a balance

• Quality system requirements

• Pre-market requirements & scrunity

• Post-market surveillance system &

obligations

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All Rights Reserved 2007 Health Sciences Authority

Harmonized Approach


11/23/2011

Harmonization

� Quality Management System (QMS)

� Post-market Surveillance

� Technical Documentation

� Declaration of Conformity

� Registration of manufacturers, distributors and their devices

? What is harmonization ?

? What are we harmonizing ?

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? What is harmonization? ? What are we harmonizing?

Harmonization is NOT:-

• A clone of each other’s regulations; and

• Recognition of each other’s regulations or approval.

Harmonization is:-

• A process of sharing;

• Agreeing (and disagreeing) on best practices within regulatory control regime for MD; and

• Achieving a least burdensome regulatory pathway to market(s) as a desired outcome.

Distilling and harmonizing technical elements within Regulations


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GHTF Definition of a Medical Device (current)

“Medical device” means any instrument, apparatus, implement, machine,

appliance, implant, in vitro reagent or calibrator, software, material or

other similar or related article:-

a) intended by the manufacturer to be used, alone or in combination, for

human beings for one or more of the specific purpose(s) of:

· diagnosis, prevention, monitoring, treatment or alleviation of disease,

· diagnosis, monitoring, treatment, alleviation of or compensation for an

injury,

· investigation, replacement, modification, or support of the anatomy or of a

physiological process,

· supporting or sustaining life,

· control of conception,

· disinfection of medical devices,

· providing information for medical or diagnostic purposes by means of in

vitro examination of specimens derived from the human body;

Reference: GHTF/SG1/N29R16:2005, Information Document Concerning the Definition of the Term

"Medical Device"

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“Medical device” means any instrument, apparatus, implement, machine,

appliance, implant, in vitro reagent or calibrator, software, material or

other similar or related article:-

and

b) which does not 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.

The definition of a device for in-vitro examination includes, for example,

reagents, calibrators, sample collection and storage devices, control

materials, and related instruments or apparatus. The information

provided by such an in-vitro diagnostic device may be for diagnostic,

monitoring or compatibility purposes.

Reference: GHTF/SG1/N29R16:2005, Information Document Concerning the Definition of the Term

"Medical Device"

GHTF Definition of a Medical Device (current)

Identify & Overcome Issues & Challenges

Tools - Common Dossiers

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Elements of CSDT (non-exhaustive)

• Executive Summary

• Essential Principles

• Use of Standards

• Classification rules for MDs

• Labelling

• Verification & Validation

• Risk Analysis

• Manufacturer Information

Manufacturer Information

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Globalized manufacturing sites

USAMonitor B888

Monitor C124

Milwaukee, USA

Mexico

Helsinki, Finland

Wuxi, China

FinlandMonitor AB12

Monitor B82

MexicoMonitor V2B8

ChinaAccessories manufacturing


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• LNE certifies….• GE Medical Systems• For the activities• Design and configuration of cardiology equipment…• Performed on the location of• GE Medical Systems• Complies with the requirements of the international standards• ISO 9001:2008 – ISO 13485:2003• This certificate is issued according to the rules of G-Med certification• G-Med Notified Body for Medical Devices

ISO 13485 Certificate


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• EC Certificate• Approval full Quality Assurance System• Annex II section 3 Directive 93/42/EEC concerning medical devices• Manufacturer• GE Hangwei Medical Systems• Device category• CT Scanners – MRI systems• G-Med certifies that, on the basis of the results contained in the file

referenced J018084-R, the quality system – for design, manufacturing, and final inspection – of medical devices listed here above complies with the requirements of the Directive 93/42/EEC, annex II section 3.

EC Certificate


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What’s Does it Mean?

As an example

• What are the meanings behind the wordings of the certificate?

• Notified Body (CE XXXX) issues a certificate. It means that:-

�manufacturer has maintained a QMS that meets the ISO 13485:2003 standard;

and �meets EU Medical Device Directive (93/42/EEC)

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Harmonization (revisit)



o Technical Documentation

o Declaration of Conformity

o Registration of manufacturers, distributors and their devices

Conformity Assessment Bodies (CABs)

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GHTF Definition of CABs

GHTF Definition of Conformity Assessment Body (CAB):

a body engaged in the performance of procedures for determining whether the relevant requirements in technical regulations or standards are fulfilled. A CAB is authorisedto undertake specified conformity assessment activities by a Regulatory Authority (RA) that will ensure performance of the CAB is monitored and if necessary withdraw designation


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Conformity Assessment of QMS & Device

Conformity Assessment of Manufacturer’s QMS• Audits of the QMS

• Audits of the Post Market Surveillance process

Conformity Assessment of the Device Safety and Performance

• Review of device product technical documentation in dossier

�Review of Declaration of Conformity

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Accreditation of Conformity Assessment Bodies

For example: Assessment of Technical

Competence

� Product knowledge

� Clinical experience

� Regulatory knowledge

� Auditing experience


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Ensuring Competency

Conformity Assessment

Bodies

Upstream Manufacturers

Midstream Distributors

Downstream Hospitals, clinics, retail

Accreditation of Conformity Assessment Bodies

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o Technical Documentation



Identify & Overcome Issues & Challenges

Tools – Grouping of Medical Devices

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Wide Range of Device Types – Different from Drugs

Orthopedic

General & Plastic Surgery

Cardiovascular

Radiology

General Hospital

Dental

Clinical Chemistry

Anesthesiology

Gastroenterology / Urology

Neurology

Microbiology

Physical Medicine

Ob / Gyn

Ophthalmic

Immunology

Hematology

Ear Nose & Throat

Toxicology

Pathology


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Clinical breadth & depth of device use in the hospital

EmergencyEmergency RadiologyRadiology PerioperativePerioperative Critical CareCritical CareProgressive

Care

Progressive

Care

Maternal-

Infant

Maternal-

InfantOutpatientOutpatient

Doctor

Office

Doctor

Office

Patient

Monitors

Patient

Monitors

Supplies &

Accessories

Supplies &

Accessories

Networking Systems

& Interfacing

Networking Systems

& Interfacing

CIS & Mgt.

Software

CIS & Mgt.

Software

Critical Care

Ventilators

Critical Care

Ventilators

Telemetry

ED Cath/EP Lab OR ICU

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Total Knee Replacement System –Different from Drugs

• Femoral component (various size)

• Tibial plate (various size)

• Tibial insert (various size)

• Instrumentation (e.g. retractors)

Femoral

component

Tibial insert

Tibial plate

Dental Burrs Dental Anchors

Med Devices & Accessories

Dental Hand Piece Source: HSA, Singapore


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Med Dev & Accessories in Use

Close to the Patient(Modules)

Near the Bedside(Displays)

Where Convenient(CPU)

Patient Specific(Supplies & Accessories)

Monitor Needs Accessories to Function

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Copyright: The Straits Times, SPH

Medical

Devices:

Spare

Parts for

Ourselves

Medical Devices Requires Spare

Parts too!

X-Ray tube Source: http://www.hcstarck.com/

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Globalized manufacturing sites

USAMonitor B888

Monitor C124

Milwaukee, USA

Mexico

Helsinki, Finland

Wuxi, China

FinlandMonitor AB12

Monitor B82

MexicoMonitor V2B8

ChinaAccessories manufacturing

Globalization: A necessary pain


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Hospitals / Clinics / Users

Device RegulatorsNon-MOH Regulators

Manufacturers

People

Stakeholders

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Facts About MD & the Industry

• Wide range of device types

• Many different areas of clinical use

• Accessories (sometimes disposable) critical to device use

• Import of spare parts / expendables

• Globalization and global manufacturing sites

• Physician’s influence on clinical outcome

• Risk sharing during device use


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� Technical Documentation� - review sample device label



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Implement MD regulatory system

� Declaration of Conformity (legal attestation)

� Registration of manufacturers, distributors and their devices (MD regulatory control regime)

Meeting Theme and Objectives (revisit)

ThemeTransforming Malaysia as a Medical Device HubThrough Harmonized Regulatory Approach

Objectives

� To promote medical device industry in Malaysia

� To create awareness among stakeholders on policy and regulatory requirements

� To identify and overcome issues and challenges in medical industry

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Least Burdensome Regulatory Pathway

Import of Medical Devices

� Harmonized System (HS) Codes mapped to medical device registrations / product codes

� Licensed entities permitted to import devices (incl. accessories/spare parts) they have registered


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Least Burdensome Regulatory Pathway

Import of Accessories

� Import of accessories separately from main device permitted as part of the approved license; no separate import license for accessories needed� Facilitation of separate import of accessories

Import of Spare Parts

� Import permitted as part of the approved medical device license; no separate import license for spare parts needed

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ConclusionGlobal Harmonization Task Force

- What is GHTF & their current regulations?

Harmonization

- What is / what is not harmonization?

Tools of Harmonization – Common Dossiers, Grouping- Tools to be used for registration

- Tools to be used for designing a regulatory

framework that is least burdensome

Conclusion

Tools of Harmonization – Common Dossiers, Grouping

- Use of international Standards / local standards)

- Outsourced / 3rd party manufacturing sites

- Clarity in grouping rules (affects registration fees)

- Grouping affects multi-country use of CSDT

- Inclusion of accessories codes into CSDT (affects Import and supply of accessories)

- Import and supply of spare parts / expendables (affects local supply)

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Conclusion

Recommendations

- Aware of need to map against other regulatory elements and guidance documents for setting up a harmonized regulatory framework (e.g. registration of manufacturers and listing of medical device, definition of MD, classification of MD, definition of manufacturers, authorized representatives)

Thank You

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