Transcript Standardising NAT for clinical targets through SoGAT Clinical Diagnostics Jacqueline Fryer

Standardising NAT for clinical
targets through SoGAT Clinical
Diagnostics
Jacqueline Fryer
National Institute for Biological Standards and Control
Assuring the quality of biological medicines
Molecular Diagnosis of Clinical
Pathogens
• Many NAT assays developed in-house, methodology
varies significantly
• QC reagents often developed in-house, e.g. plasmids (not
extracted)
• Lack of standardised reference reagents (except for BBV)
makes it difficult to compare performance and develop
uniform patient management algorithms
• Results from EQA programmes and other studies indicates
variability in performance of testing, and highlights need
for standardisation
NIBSC/HPA/CVN Working Reagents
Organism
No. data
points
Mean Ct ±
2SD
Range (Ct)
Influenza A (H1)
252
31.29 ± 5.24
25.30 - 40.66
Influenza A (H3)
238
30.33 ± 5.40
24.30 - 37.88
Influenza B
265
28.14 ± 4.55
22.46 - 36.75
Norovirus
483
33.17 ± 9.00
23.00 - 44.03
HSV1
272
28.91 ± 7.72
18.73 - 39.23
HSV2
267
29.43 ± 6.27
20.83 - 39.00
HCMV
240
29.28 ± 5.51
24.87 - 37.40
EBV
139
28.03 ± 8.82
17.28 - 36.56
Aims of SoGAT Clinical Diagnostics
•
•
To plan and coordinate the development, evaluation and provision of
reference reagents, International Standards and reference panels for
qualitative and quantitative NAT assays for a range of clinical diagnostics
To exchange information on the technical and scientific aspects of NAT
assays for clinical diagnostics, between professionals in:
– Diagnostic and reference laboratories,
– Manufacturers of diagnostic kits and reagents,
– External Quality Assessment (EQA) providers
– Public health and regulatory authorities
•
•
To assist in the development of regulatory approaches
To provide support for new technologies, e. g. multiplex nucleic acid assays,
micro-arrays.
SoGAT Clinical Diagnostics I
• First meeting held 24th/25th June 2008
• NIBSC, UK
• Chaired by Dr Philip Minor (NIBSC)
SoGAT Clinical Diagnostics I
Programme - Day 1
Session 1:
Welcome address /Introduction to Clinical Diagnostics
Clinical NAT Bill Carman, West of Scotland Specialist Virology Centre, UK
Clinical Microbiology and Infection Control Brian Duerden, Department of Health, UK
Session 2:
Standardisation and aims of SoGAT
Aims of SoGAT and role of NIBSC Philip Minor, NIBSC, UK
Standardisation: calibration of International Standards, reference materials and working standards Micha Nübling, PEI,
Germany
Experience with Standardisation of blood virology NAT Clare Morris, NIBSC, UK
Session 3:
Standardisation for clinical diagnostics: part 1
WHO Collaborative Study to Establish WHO International Standards for Human Papillomavirus (HPV) Type 16 DNA and HPV
Type 18 DNA Nucleic Acid Amplification Technology (NAT)-Based Assays Dianna Wilkinson, NIBSC, UK
Development of clinical virology working standards for NAT Anna Gottlieb, NIBSC, UK
NAT Quality control for Chlamydia trachomatis (and Neisseria gonorrhoea) Joe Vincini, HPA, UK
Discussion on frequency of SoGAT Diagnostics Meetings and Aims
SoGAT Clinical Diagnostics I
Programme - Day 2
Session 4:
Standardisation for clinical diagnostics: part 2
MRSA - Practical aspects of standardization for a global controls manufacturer Frank Opdam, Acrometrix, USA
Controls for Chlamydia trachomatis and Neisseria gonorrhoea Mark Manak, SeraCare, USA
Standardization of full process nucleic acid testing controls Peter Trabold, ZeptoMetrix Corporation, USA
Session 5:
Assessment of laboratory performance and Calibration of EQAS panels
UK NEQAS schemes for CMV, HPV and mycobacteria Vivienne James, HPA, UK
QCMD molecular EQA past, present, and future Paul Wallace, QCMD, UK
Session 6:
Standardisation of CMV and EBV viral loads
Viral dynamics and the importance of viral load measurements in the management and prevention of HCMV disease Vincent
Emery, Royal Free and University College Medical School, UK
CMV and EBV standards Jutta Preiksaitis, PROVLAB, Canada
EBV viral load questionnaire responses Barbara Gärtner, Universitätsklinikum des Saarlandes, Germany
Proposals for WHO International Standards for CMV and EBV for NAT-based assays Jacqueline Fryer, NIBSC, UK
General Discussion
SoGAT Clinical Diagnostics I
Programme - Day 2
Session 7:
Standards for Bacteria and Parasites
Standardisation in meningococcal epidemiology Steve Gray, HPA, UK
Malaria and Toxoplasma standardisation of NAT assays David Padley, NIBSC, UK
Session 8:
Control and validation of commercial assays for Clinical Diagnostics
Control and validation of Roche clinical diagnostics John Saldanha, Roche, USA
Performance evaluation of standardized QIAGEN sample preparation methods for the artus CMV PCR Kit Volker Riemenschneider,
Qiagen, Germany
Session 9:
Regulation of clinical diagnostics
US regulation of IVDs Francisco Martinez-Murillo, FDA-CDRH, USA
CE-marking and regulation of clinical diagnostics in Europe Micha Nübling, PEI, Germany
Presentations available at www.nibsc.ac.uk/partners/SoGAT
Outcomes
• Highlighted the need for internationally-accepted reference standards
to improve the comparability of results
• Proposals developed for new standards for NAT-based assays for
clinical targets
– Proposed 1st WHO International Standard for human
cytromegalovirus (HCMV)
– Proposed 1st WHO International Standard for Epstein-Barr virus
(EBV)
• Proposals subsequently submitted to WHO ECBS and endorsed
October 2009
• Future meetings to be held annually, possibly linked with meetings of
relevant clinical societies
SoGAT Clinical Diagnostics II
• 30th September and 1st October 2009
• Harbiye Military Museum Istanbul,
TURKEY
• To follow directly 12th Annual Meeting
of the European Society for Clinical
Virology (ESCV)
• Further information
– www.nibsc.ac.uk/partners/SoGAT
– [email protected]
Proposed Discussion Topics
•
Update on the development of reference
reagents for clinical diagnostics (including
proposed 1st WHO International Standards for
HCMV and EBV)
•
Proposals for new references (1st WHO
International Standards for JC and BK viruses)
•
Assessing assay performance: EQAS and
proficiency studies, and data reporting
•
Technical aspects of assay variability
•
Regulatory and other standardisation issues
Abstract deadline 26 June 2009
Prioritising the development of
standards for clinical pathogens
• There is a need for internationally-accepted reference standards for
clinical pathogens:
– To improve the performance and comparability of results generated by
different assays
– To facilitate the development of uniform treatment strategies
• Need to prioritise the development of these standards on the basis of:
– Clinical need: where there is an intention to treat (BK and JC viruses,
adenovirus, HHV-6)
– Where studies indicate variability in assay performance
– Global disease prevalence