04/19/23

Activities in Quality Management and Accreditation of Genetic Testing Services

Ros Hastings

EUROGENTEST: Activities in Quality Management and Accreditation of Genetic Testing Services

Unit Leaders: Els Dequeker, Ros Hastings

www.eurogentest.org

WP1.5Biochemical

EQA

WP1.4Cytogenetics

EQA

WP1.3Molecular

EQA

WP1.9QM of EQAschemes

HarmonizationDequeker, Hastings

Qualitymanagement

Dequeker, Morris

EQA SchemesElles, Fowler, Hastings, Müller

Reference systems & proceduresBarton, Gancberg

Validationof diagnostic tests

Matthijs, Macek

Quality Management and Accreditation

WP1.8Technical

aspects of QAu

WP1.2QAu database

WP1.6Referencematerials

WP1.7Diagnostic validation

WP1.1Website, overall

activities

Overall Objective

To measurably improve the quality

of management and provision

of genetic testing services

for the benefit of the patients,

laboratory accreditation considered to be the norm.

Quality Assurance Database

Aims:• Create and maintain a QAu database of European genetic testing

laboratories and make it available to the public• Identify closest accredited laboratory that offers a specialist

genetic test • To develop a framework for sustainability of the database• Harmonization and collaboration between database providers

http://www.eurogentest.org/web/qa/basic.xhtml

Quality Assurance Database

Progress:Release of the QAu database of European genetic testing laboratories

• Evaluation / validation of the QAu data:• Summary test data• Quality managers• EQA participation• Accreditation and licensing: scopes

• Modification of the internal EUGT QAu database search engine for public use and to include Orphanet activity data.

• Register and update lab data online• Automated validationAdditional benefits

•Publicize and reward effort and investment in QA•Educate public and regulators on the

importance of quality issues

QAu database: How to find it

www.eurogentest.org www.orpha.net

Workshops - Training on QAu and accreditation

Aims:• to support and encourage implementing and improving

quality systems• to collaborate with accreditation bodies and other interested

parties Progress: • 3 workshops and 2 round table discussions

• Guidance document for preparing for accreditation • A glossary of QAu terms on EUGT website and evaluation

report• Meeting with chair of EA to plan further collaboration

Future: • More workshops and round table discussions (ESHG)

Participation over 3 years:

• 8 different workshops, 3 topics • 5 x accreditation and quality systems

• 2 x internal audit

• 1 x IT support

• 27 different countries

participated• Europe: 24

• North-America: 1

• South-America: 1

• Australia: 1

• 85 different institutes

participated

• 156 different participants, • 29 of them participated more than once

Workshops - Training on QAu and accreditation

participated 8 xparticipated 6 xparticipated 5 xparticipated 4 xparticipated 3 xparticipated 2 xparticipated 1 x

no participation

http://www.eurogentest.org/unit1/workshops.xhtml

Aims: Harmonizing existing EQA schemes for genetic testing in Europe:

• Expand opportunities for genetic testing laboratories in Europe to participate in EQA

• Link Internal Quality Control and EQA through consensus guidelines in genetic practice

• Accreditation of EQA schemes

Genetics External Quality Assessment (EQA)

Progress:Assisting National and European EQA Schemes to achieve accreditation:

• Generic Quality Manual

• EQA providers Forum

• Standard EQA checklist

• Formal EQA umbrella organisation for all genetic disciplines – ESHG

Quality Committee

• EMQN, CEQA and ERNDIM all preparing for accreditation

EQA

Biochemical7 schemes centres9 EQAs2 pilot EQAs266 labs18 countriesNew national representatives

MolecularNew EQA: MODY

2 pilot EQAs: MD & mutation screening Inclusion of CF synthetic control

materials 464 labs41 countries

CytogeneticsCEQA scheme- 2 full EQAs + 2 pilotsInternet based EQA and registration70+ labs28 European countriesNational schemes expanding repertoire

Genetics External Quality Assessment (EQA)

Progress:• EQA expansion through EUGT• New Participants for all EQAs

Biochemical ERNDIM Guidelines• Guidelines for investigation of hyperammonaemia• White cell preparation for cysteine• 5 guidelines in preparation

Guidelines• Published: ERNDIM & EUGT website

Genetics External Quality Assessment (EQA)

Detail:• Best practice guidelines

CytogeneticsEuropean Cytogenetic Guidelines and Quality Assurance: A common European framework for quality assessment for constitutional and acquired cytogenetic investigations• EJHG – a summary, March 2007

Microarray Best Practice• EJHG – Summer 2007

MolecularBest Practice Guidelines• 3 Best Practice meeting in 2007• MODY Guidelines published• Draft SCA & BRCA guidelines

EQA

Progress:• International symposia on RM in genetic testing • Guidance document for use of RMs in Genetic Testing

• Guidelines for the production of further CRMs• Field trials (in collaboration with EU CF Network) for 2

different commercial multiplex RMs for CF testing • Workshop on the implications of the IVD Directive

Quality Control Materials

Aims:

• Support development of certifiable reference materials

for a wide range of genetic tests

• Build an enduring network, involving all the key

stakeholders in RM development and use

Diagnostic Validation

Aims:

• Diagnostic validation of available methods, with the

aim of facilitating their implementation

• Evaluation of the performance of commercial kits and /

or technologies

• Define criteria for and establish a standard procedure

for analytical / technical evaluation of test methods

• Establish a draft guideline “Minimum acceptable

standards for diagnostic validation” of molecular tests

and commercial kits

• Provide training in validation by experts

Progress: • Validation report: MLPA (Multiplex Ligation dependent Probe

Amplification) • Diagnostic use and variability of the MLPA procedures

• IT tools for MLPA analysis

• Precision and performance evaluation

• Chemagen DNA extraction for large volumes of blood• Validation report

• Performance evaluation: CFTR commercial kit • Publication ‘Variability in the use of commercial CFTR assays’

Future: • New diagnostic method validation projects

• HRMCA (high resolution melting curve analysis) • CSCE (conformation sensitive capillary electrophoresis)

Diagnostic Validation

Benefit to Labs:• Contacts for other labs• Accredited labs for referring specialised tests• Positive and negative controls for assays• Validated SOPs• Generic SOPS for new technologies• Validation technologies/methods• Access to EQA schemes• Accreditation courses/advice

Benefits patients too:• Assurance of quality results• Which labs offer a service in my area?

Quality Assurance Summary

The team

Quality Control Materials

Aims:

• Support development of certifiable reference materials

for a wide range of genetic tests

• Guidelines for the production of further CRMs

• Build an enduring network, involving all the key

stakeholders in RM development and use

• Inform stakeholders of the implications of the IVD

Directive for Genetic Tests

The EUGT – Orphanet QAu database

Why should I use it? Find a lab to perform tests that are not available in my area Identify the labs investing in QAu Watch the uptake of QAu in Europe.

Why should I be in it? Public window for your tests Publicize your efforts and investment in QAu.

How do I put my lab in it? Add or update your QAu data via the online form

at www.eurogentest.org/web/qa/basic.xhtml → Or contact your national Orphanet partner.

What does it cost me to join? Nothing.

More questions ? Contact qausurvey@eurogentest.org

The EUGT – Orphanet QAu (quality assurance) database

What does it contain? Validated data including :

Quality managers Accreditation Licensing EQA participation data for 2004 and 2005

for about 100 schemes from 29 providers

2006 - 2007 update underway

Full integration with Orphanet test and contact data

Comprehensive search engine for QAu, contact and test data.

Availability ? V1 online and publicly available since July

2007 Over 230 laboratories from 32 countries Basic search page has received over

5000 unique visits in the last 6 months.

Who is it for? Consumers

to facilitate an informed choice of a quality partner for genetic testing;

Laboratories and QAu institutions to publicize and reward their efforts and

investment in quality assurance;

General public and regulators to educate them about the importance given to

quality issues by our profession.

Plans for 2008:• Practitioners meeting in Prague: in search of consensus of

• Draft of guideline “Minimum acceptable standards for diagnostic validation” • for molecular tests and commercial kits

• Several annexes * Instructions MLPA

* Instructions CFTR kit, FRAX kit * Generic SOP

• Priority list of diagnostic tests for validation in the different core-labs

• Validation of other DNA extraction platforms (e.g. Gentra)• Complete the additional diagnostic method validation projects:

• HRMCA (high resolution melting curve analysis) • CSCE (conformation sensitive capillary electrophoresis)

• Workshop on validation (link to QAu workshops)

• Website: user guide on validation, glossary of terms, useful guidelines…

Diagnostic Validation

Plans for 2008:

• Further trial of CF multiplex RMs (if company supports it)

• Support for RMs for New Technologies (Molecular Cytogenetics

etc.)

• Design for development of a plasmid-based generic mutation

detection RM in collaboration with NGRL Wessex

• Follow-up workshop with key regulators and stakeholders

• Continued networking with RM developers and producers

• Discussions with PHGU to look at Best Practice world-wide and

find a balance to strengthen oversight but preserve test

availability

• Collaboration with SAFE on RMs for NIPD

Quality Control Materials

Genetics External Quality Assessment (EQA)Plans for 2008:

Establish a governance structure for CEQA, EMQN and ERNDIM

Determine poor performance criteria

Organize Best Practice Meeting on Quality Management of EQA schemes

Prepare for accreditation: draft guide to accredit EQA schemes relating to existing standards

Cytogenetics EQA Molecular EQA Biochemical EQANew schemes for - Acute leukaemia - PIDPilot resulted in two full EQA schemes (prenatal and postnatal)

New schemes for - Von Hippel Lindau- Connexin 26

New Pilot schemes for - Lysosomal enzymes- CDG syndromes

Establish a Steering Committee Best Practice Guidelines- Cardiac genetics- 2 others (open call)

Best Practice Guidelines Organisation of testing services at a national level

Open cytogenetic EQA to all labs. Discussions with German EQA scheme for future collaborations

Development of standard methodologies and reporting procedures

Prepare for accreditation in 2009 Accreditation in 2008 Training workshops

Pilot a self-assessment system online (for CPD)

Link directory analytes to diseases in Orphanet database

Workshops - Training on QAu and accreditation

Plans for 2008:Workshops / training

• Workshops on:• Motivation and change• Laboratory accreditation• Diagnostic validation• Internal audit

• Round-table session at the ESHG• Training of experts • Pilot Training on national level – initially Belgium • Benchmarking and business plan

Monitoring improvements in quality assurance• Define key elements and barriers when implementing a quality

system in genetic testing laboratories • Study the evolution of quality improvement after implementing

key elements• Comparison of different standards and requirements for

quality management