Study Group 1

IVD Medical Devices the GHTF Guidance Documents

Shelley Tang Therapeutic Goods Administration Australia

Petra Kaars-Wiele EDMA Representative/ Abbott Laboratories Germany

Study Group 1 March 2008 Kuala Lumpur

Overview of presentation
IVDs as a sub-set of medical devices Essential Principles Classification Summary Technical Documentation (STED) Conformity Assessment

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What is an IVD?
Medical device' means any instrument, apparatus, implement, machine, appliance, implant, in vitro reagent or calibrator, software, material or other similar or related article, 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 purposes by means of in vitro examination of specimens derived from the human body, and 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 function by such means.

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What is an IVD?
IVD medical device: A device, whether used alone or in combination, intended by the manufacturer for the in-vitro examination of specimens derived from the human body solely or principally to provide information for diagnostic, monitoring or compatibility purposes. This includes reagents, calibrators, control materials, specimen receptacles, software, and related instruments or apparatus or other articles. Note: In some jurisdictions, some IVD medical devices may be covered by separate regulations.

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GHTF documents on IVDs - General

SG1/N012 Role of Standards in the

Assessment of Medical Devices. SG1/N029 Information Document Concerning the Definition of the Term Medical Device. SG1/N041 Essential Principles of Safety and Performance of Medical Devices. SG1/N043 Labelling for Medical Devices.

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GHTF documents on IVDs - Specific

SG1(PD)/N045R13 Principles of In Vitro Diagnostic

(IVD) medical devices Classification SG1(PD)/N046R4 Principles of Conformity Assessment for In Vitro Diagnostic (IVD) medical devices SG1(PD)/N063 (early Draft) Summary Technical Documentation for Demonstrating Conformity to the Essential Principles of Safety and Performance of In Vitro Diagnostic Medical Devices (STED)

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The Roadmap
IVD Manufacturer
Class Conformity Assessment Procedures

Declaration of Conformity

PostMarket Responsibilities

Essential Principles

QMS ISO 13485

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Essential Principles

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Essential Principles
All IVDs must meet the Essential Principles for quality, safety and performance EPs underpin the regulatory framework Compliance with EPs may be demonstrated by use of standards see GHTF SG1-N012R10 Role of Standards in the Assessment of Medical Devices

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Essential Principles

Concept

ESSENTIAL PRINCIPLES
Supply/Use/Disposal Design/Development

Production
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Essential Principles
EPs cover design, manufacture, clinical performance, and overall safety to user and person being tested EPs define risks to be managed/ results to be achieved, but do not specify how Manufacturers determine which EPs are applicable Compliance with EPs is the manufacturers responsibility
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Essential Principles
GHTF document on Essential Principles includes IVDs in its scope. Six general EPs apply to all medical devices, including IVDs 11 specific EPs, which may or may not apply to a particular device, depending upon its type and construction

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General Essential Principles

Must not compromise health and safety Conforms to safety principles, taking into account the general state-of-the-art Suitable for intended purpose Performs as intended during determined shelf life under normal conditions of use Performs as intended when subjected to prescribed conditions of transport and storage Benefits outweigh risk

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Specific Essential Principles

Devices with a diagnostic or measuring function (5.10) Sensitivity, specificity, trueness, repeatability, reproducibility, control of interference, and limits of detection Traceability of controls and calibrators Self-Testing (5.15) Consider the user of the test - easy to use instructions/protocol Reduce risk of error in use and interpretation Design allows for verification by user
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Specific Essential Principles

(cont)

Performance evaluation (5.17) all data generated in support of performance evaluation should be obtained in accordance with the relevant requirements applicable in each jurisdiction Just what is required in relation to clinical evidence for IVDs not yet determined in GHTF guidance.

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Classification

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Classification

The GHTF framework proposes a risk based classification system for all IVDs The determination of classification will be based on a set of rules derived from those features that create the risk associated with an IVD

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Why classify?
Class determines the relevant conformity assessment procedures
Class determines level of regulatory oversight

The class is determined by applying a set of rules Rules based classification allows greater flexibility New diseases, emerging technologies Classification is the responsibility of the manufacturer

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How to determine class?

Decide if the product is an IVD, based on intended use and using the definition
Responsibility of the manufacturer

Consider the Rules. An IVD with multiple intended purposes will be placed in the highest applicable class Determine that special national rules do not apply Where more than one Rule applies, the Rule which places the IVD in the highest class applies

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Classification
The intended use and indications for use Specific disorder, population, condition or risk factor for which the test is intended

Risk Factors

The technical/scientific/medical expertise of the intended user The importance of the information to the diagnosis Sole determinant or one of several The impact of the result (true or false)

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Risk Classes

Class D IVD - High Individual Risk and High Public Health Risk
E.G. HIV blood donor screening, HIV blood diagnostic

Class C IVD High Individual and/or Moderate Public Health Risk

E.G. Blood glucose self-testing, HLA typing, PSA screening, Rubella

Level of Risk

Class B IVD Moderate Individual and/or Low Public Health Risk

E.G. Vitamin B12, pregnancy self-testing, Anti-Nuclear Antibody, Urine test strips

Class A IVD Low Personal/No Public Health Risk

E.G. Clinical Chemistry Analyser, prepared selective culture media

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Class D IVD
Includes IVDs that are used for
High Public Health Risk and/or High Individual Risk

screening of the blood supply and organ and tissue donations for pathogens , eg IVDs used for screening for infection with HIV, HCV, HBV, HTLV Detecting the presence of a transmissible agent likely to cause a life-threatening illness with a threat to public health example as above Blood grouping or tissue typing to ensure compatibility where there is an individual high risk, eg ABO, rhesus, Kell, Kidd and Duffy

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Class C IVD
Includes IVDs that are used for
High Individual Risk and/or Moderate Public Health Risk

Blood grouping, tissue typing, not in Class D Detection of transmissible agents Sexually transmitted In CSF or blood (limited risk of propagation) Likely to cause death or severe disability Immune status in pregnancy Human genetic testing Detection of congenital diseases in the foetus

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Class C IVD

(cont)
Includes IVDs that are used for

High Individual Risk and/or Moderate Public Health Risk

Infective disease status in high individual risk situations Screening for selective therapy and management, for disease staging, or diagnosis of cancer Monitor levels of medicines etc, in high-risk patient management situations (cardiac markers, prothrombin time testing) Management of patients with life-threatening infectious disease (HCV/HIV viral load, genotyping or subtyping) Self-testing, in determining a medically critical status.
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Class B IVD
Includes IVDs that
Moderate Individual Risk and/or Low Public Health Risk are used for self-testing, where results are not

medically critical or require confirmation (pregnancy testing, fertility testing, urine test strips) Are not covered by other Rules (blood gases, hormones, vitamins, enzymes, metabolic markers) Are intended to be used as controls without a quantitative or qualitative assigned value (do not validate the decision on the release of patient results)

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Class A IVD
Includes IVDs that are
Low Individual Risk and/or Low Public Health Risk Reagents or other articles used in in vitro diagnostic procedures (selective/differential microbiological media, identification kits for cultured micro-organisms, wash solutions) Instruments intended by the manufacturer specifically to be used for in vitro diagnostic procedures Specimen receptacles

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STED-

Summary Technical Documentation

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Content of STED
Preface:
The STED does not represent the full technical documentation which is controlled under the Quality System STED should be in a language acceptable to the reviewing organization Depth and detail may be dependant on classification and risk, whether it is novel technology or already marketed

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Content of STED
General description and list of specified features Set of labels and list of language variants Summary of technical documentation concerning design and manufacturing Essential Requirement Checklist Summary of risk analysis and mode of control Summary of verification and validation studies Performance Evaluation
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Conformity Assessment

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SURVEILLANCE VIGILANCE

POSTMARKET

Regulatory Agency and Manufacturer Responsibility

Manufacturers responsibility
CLASS C

DESIGN
CLASS D

PREMARKET
RISK
CLASS A

CLASS B

PRODUCTION

Conformity Assessment Body oversight

ESSENTIAL REQUIREMENTS

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Conformity Assessment - Elements

Quality Management System Documentation (STED= Summary Technical Documentation) Declaration of Conformity Registration of Manufacturer and their Products Systematic Post-Market Surveillance System

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Type of Quality System

ISO 13485 ISO 13485
Certified full Quality System with design Control Certified full Quality system except design control (alternative for Class A and B products only)

In assessing the Quality Management System for Class B to D IVDs, the Regulatory Authority or Conformity Assessment Body will take into account relevant existing certification and conduct on-site audit only with reasoned justification.
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STED =

Summary Technical Documentation

Technical documentation is to be prepared for all IVDs according SG1(PD)/N063 (early draft) Submission and review by the authorities not required for Class A and B, but if in justified cases may be submitted on request. Review by the authorities for Class C and D, based on risk of the products and experience of the manufacturer

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Declaration of Conformity
A declaration made by the manufacturer Name and address of the responsible manufacturer Identification of the device (product name, product number, GMDN code) Statement that the device complies with
The Essential Principles of Safety and Performance The Classification and Conformity Assessment Procedure List standards used in the Conformity Assessment Procedure

Dated and signed by the manufacturer (appropriate senior personnel)

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Registration of Manufacturer and Their IVD Products

At minimum the Regulatory Authority maintains a registrar of products marketed in their country (manufacturer and product listing, and maybe importers)

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Systematic Post-Market Surveillance

Manufacturer holds a complaint handling systems and initiates appropriate investigations Manufacturer captures information learnt from the market and the users and takes actions if required Manufacturer reports any potential medical events to the authority, where the event occurred Regulatory Authority may request information or audit the manufacturer in justified cases

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Quality System or Surveillance Audits

It is not passing an exam!!!! Demonstration of continual operation and compliance Supports continuous improvement of products and processes

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Conformity Assessment
Considerations for Regulatory Authorities
Public health protection priorities (risked based, not every product has the same risk) Proportionality of methods to public health benefits Access to market to ensure efficient diagnosis of patients and state-of-the-art products Relevant existing certification Resources
Funding Expertise Efficient use Timeliness (eg - impact on market viability)

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In Practice
Class D
The manufacturer has a full Quality System certificate which includes design control according ISO 14835 Submission of the STED and Declaration of Conformity Pre-Market Review by the Regulatory Authority or the Conformity Assessment Body (3rd party) of documentation and performance of the product to ensure that the Essential Principles are fulfilled and the claims of the products are met Review Adverse Event Reporting process and procedure Open questions to be discussed with the manufacturer and/ or representative Add product to registrar

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In Practice
Class C
The manufacturer has a full Quality System certificate which includes design control according ISO 14835 Submission of the STED and Declaration of Conformity Review by the Regulatory Authority or the Conformity Assessment Body (3rd party) of documentation and performance of the product to ensure that the Essential Principles are fulfilled and the claims of the products are met (maybe done during a pre-market audit on-site) Review Adverse Event Reporting process and procedure Open questions to be discussed with the manufacturer and/ or representative Add product to registrar
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In Practice
Class B
The manufacturer has a Quality System certificate according ISO 14835, which need not include design control Preparation of STED and maintained by the manufacturer, pre-market submission is not required, but in justified cases may be reviewed Declaration of Conformity is prepared by the manufacturer and submitted to the Regulatory Authority Verify that Declaration of Conformity is appropriate Ensure Adverse Event Reporting process and procedure is in place Add product to registrar

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In Practice
Class A
The manufacturer has a Quality System certificate according ISO 14835, which need not include design control Preparation of STED and maintained by the manufacturer, pre-market submission is not required, may be reviewed during surveillance audits or if there are regulatory concerns Declaration of Conformity is prepared by the manufacturer, not submitted to Regulatory Authorities Ensure Adverse Event Reporting process and procedure is in place Add product to registrar

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Any Questions?

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