changes to the regulation of ivds in europe - bsi group...• new sections for software and...

Copyright © 2012 BSI. All rights reserved.

Changes to the Regulation of IVDs in Europe

Copyright © 2014 BSI. All rights reserved. 2

Caution

• The new regulations are draft and subject to change

• Further details will be added later pre and post application through implementing and delegating legislation


Structure of the IVDR

Chapters 10

Articles 90

Annexes 14

Annex I General Safety and Performance Requirements

• Equivalent to the current essential requirement

• Broadly similar with additional clarification

• New sections for software and requirements for use with mobile platforms

• Requirements for self tests are extended to include near patient testing

Annex II Technical documentation

• Significantly more detail regarding the expectations for technical documentation

Annex III Declaration of Conformity

Annex IV CE marking

Annex V Registration and UDI

Annex VI Requirements for Notified Bodies

Annex VII Classification

Annex VIII Conformity Assessment based on Full QA or Design Examination

Annex IX Conformity Assessment based on Type Examination

Annex X Conformity Assessment based on Production QA

Annex XI Notified Bodies Certificate content

Annex XII Clinical Evidence and Post Market Follow up

Annex XIII Interventional Clinical Performance Studies

Annex XIV Correlation table

More detailed consistent with the proposed Medical Device Regulation



When?


The IVDR Approval Timeline

General Agreement

Oct 2015

Informal Agreement

June 2016

First Reading Oct 2016

Accelerated Second Reading

Adoption Q4 2016



Transitional Arrangements

Entry into force Q4 2016/ 2017

Adoption + 6 months NB can

apply for Designation

5 Year Transition

Manuf can meet IVDD or IVDR

Date of application

(DoA) 2021/22


Class A IVDs under the IVDR can be placed

on market under IVDR

CE Certificates can be renewed during the transition

Max expiry DoA + 2 years


Notified Body Designation

• Details of NB designation will be in an Implementing Act prepared in the 6 months following the Entry into Force

• The implementing acts will define the details for designation, including a joint on-site audit with the Commission and at least one additional CA

• During this 6 month period manufacturers requiring a NB and those who can self declare will not be able to place product on the market using the IVDR they will have to use the IVDD.

• It could take up to 18 months to designate all NBs




Classification and Conformity


Change to scope of IVDR through MDR

• ‘medical device’ means any instrument, apparatus, appliance, software, implant, reagent, material or other article, intended by the manufacturer to be used, alone or in combination, for human beings for one or more of the specific direct or indirect medical purposes of:

• diagnosis, prevention, monitoring, prediction, prognosis, treatment or alleviation of disease,

• diagnosis, monitoring, treatment, alleviation of or compensation for an injury or disability,

• investigation, replacement or modification of the anatomy or of a physiological process or state,

• investigation, replacement or modification of the anatomy or of a physiological process or state,

• disinfection or sterilisation of any of the above-mentioned products,

• providing information concerning direct or indirect impacts on health,

and which does not achieve its principal intended action by pharmacological, immunological or metabolic means, in or on the human body, but which may be assisted in its intended function by such means.

Impact

Tests to predict the likelihood patients will develop cancer or heart disease will be included, Life

style tests for example tests to suggest dietary changes for health reasons will be included


Scope

'in vitro diagnostic medical device’ means any medical device which is a reagent, reagent product, calibrator, control material, kit, instrument, apparatus, equipment, software or system, whether used alone or in combination, intended by the manufacturer to be used in vitro for the examination of specimens, including blood and tissue donations, derived from the human body, solely or principally for the purpose of providing information:

• concerning a physiological or pathological state;

• concerning a physical or mental impairments; In vitro diagnostic medical devices used for DNA-testing shall be subject to this Regulation

• concerning the predisposition to a medical condition or a disease;

• to determine the safety and compatibility with potential recipients;

• to predict treatment response or reactions;

• to define or monitor therapeutic measures.


IVD Classification

27/04/2016

Application of the classification rules shall be governed by the intended purpose, novelty, complexity and inherent risk of the devices.


Class D

• High public health risk, high personal risk

Examples

• HIV 1/2,

• Hepatitis C virus,

• Hepatitis B virus

• HTLV I/II

• CHAGAS

• Syphilis (Used to screen blood donations)

• Blood grouping ABO, Rhesus (including RHW1), Kell, Kidd and Duffy systems


Class C

• High personal risk, moderate to low public health risk

Examples

• Syphilis (Used for diagnosis only)

• Neonatal screening for metabolic disorders e.g. PKU

• Rubella

• Cancer markers

• Genetic tests

• Companion diagnostics

• Blood glucose meters and strips

• Blood gas analysers

• Self tests


Class B

• Moderate to low personal risk, low public health risk

Examples

• Thyroid function

• Infertility assays

• Clinical chemistry


Class A

• Low personal risk, low public health risk

Examples

• Accessories

• Wash buffers

• Specimen receptacles

• Instruments


Classification

• It will continue to be the manufacturers responsibility to classify devices

• The Notified Body will verify the proposed classification for every application

• There will be borderline issues so it is best to try to classify devices early and identify any issues

• The IVD Technical Group will prepare guidance

• Borderline issues will be referred to the CA of the manufacturer or AR if this is different to the NB they will consult

• If there is more than one application for a test and the manufacturers intended use is the lower classification then there must be a specific exclusion in the labelling e.g. near patient not self test, syphilis screening v self-test



Conformity Assessment Routes

27/04/2016


Conformity Assessment Routes

4/27/2016

A B C D

EU Declaration of

Conformity

Annex III

Quality

Management

System Assurance

Annex VIII

Assessment of

Technical

Documentation for

each category of

device

Annex VIII 6.1

Quality

Management

System Assurance

Annex VIII

Type Examination

Annex IX

(includes Technical

Documentation)

Quality

Management

System Assurance

Annex VIII

Type Examination

Annex IX

(includes Technical

Documentation)

Assessment of

Technical

Documentation for

each generic

device class -

Annex VIII 6.1

Production Quality

Assurance

Annex X

Assessment of

Technical

Documentation for

each device

Annex VIII 6.1

Production Quality

Assurance

Annex X

For Companion

Diagnostics CA

consultation

For Companion

Diagnostics CA

consultationBatch Verification Batch Verification

All technical file reviews will be in depth BUT there is more sampling for D v C v B


Sampling

Class D

• Assessment of the technical documentation

Class C

• Assessment of the technical documentation of at least one device representative per generic device group

Class B

• Assessment of the technical documentation of at least one representative device for each category of devices

Class A

• Notified Body not required unless sterile

In choosing representative sample(s) the notified body shall take into account the guidance developed and published by the MDCG

• in particular the novelty of the technology,

• the potential impact on the patient and practice of medicine,

• similarities in design, technology, manufacturing and sterilisation methods, the

• intended purpose and the results of any previous relevant assessments that have been carried out in accordance with this Regulation.

• The notified body shall document its rationale for the sample(s) taken.


Sampling Plans

• All devices will now get an in depth review

• This is a significant change

• Low risk devices will get less sampling but will still receive and in-depth review


Additional Scrutiny for Class D devices

Pre Certification

• As part of the conformity assessment a reference laboratory will test the device to the Common Specification with specific focus on sensitivity. The notified body must take this into consideration the Reference lab has 60 days to respond

Post certification

• The NB informs the Commission of all Class D certificates

• A Competent Authority or the Commission can select a file for review following concerns outlined in the IVDR

• The Commission will create an electronic document exchange system with the Notified Body


Quantum Leap

Do not require a Notified

Body

80-90%

Require a Notified Body

80-90%

Require a Notified Body

Do not require a Notified

Body

IVD Directive IVD Regulation



Clinical Expectations


Clinical Requirements

• Increased expectation for clinical requirements

• Clinical evidence is to be kept up to date during the life time of the device

The GHTF documents now in the IMDRF archive best guidance

• Clinical Performance Studies for In Vitro Diagnostic Medical Devices

• Clinical Evidence for IVD Medical Devices – Key Definitions and Concepts

• Clinical Evidence for IVD Medical Devices – Scientific Validity Determination and Performance Evaluation

CLINICAL

EVIDENCE Analytical Performance

CLINICAL

UTILITY

SCIENTIFIC

VALIDITY

Clinical Performance


Scientific validity

Refers to the association of an analyte to a clinical condition or physiological state

Analytical

performance Refers to the ability of an IVD medical device to correctly detect and measure a particular analyte

Clinical performance Refers to its ability to yield results that relate to a particular clinical condition physiological state for the intended use and in accordance with target population and where applicable to the intended user

For established analytes, this may be from literature; but for companion diagnostics or novel analytes this needs to be established

Performance requirements similar to IVD Directive essential requirements

Data to support diagnostic accuracy compared to reference test; information related to expected values

Performance Evaluation

Clinical Evidence


Final Summary

• This is happening and is nearing completion

• Requirements and expectations are increasing

• Understand the impact to your organisations wider regulatory landscape

• Talk to notified bodies about their plans for designation and resource

• Classify your devices

• Look at the clinical data you have, is it enough how can you get what you need?

• Discuss at management reviews


Contact

Name: Sue Spencer

Title: Head IVD

Address: BSI

Kitemark Court,

Davy Avenue,

Milton Keynes, MK5 8PP, UK

Telephone: +44 (0)1908 814861

Email: [email protected]

Website: http://medicaldevices.bsigroup.com/

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