Laboratory Perspective: The challenge of standardisation · PDF file ·...
Transcript of Laboratory Perspective: The challenge of standardisation · PDF file ·...
Laboratory Perspective:
The challenge of standardisation
in the face of the revolution in
biotechnology and data
processing
Steven Edwards
Consultant Editor, OIE Manual of Diagnostic Tests and Vaccines for
Terrestrial Animals
Definition of a Standard
Oxford English Dictionary has 12 distinct
definitions. The most relevant today are:
A document specifying nationally or
internationally agreed properties for
manufactured goods etc.
“Written standard or procedure”
An object or quality or measure serving as a
basis or example or principle to which others
conform or by which the accuracy or quality of
others is judged
“Standard Reference Material”
OIE Written Standards
The principal written standards
Terrestrial Animal Health Code
Standards for international movements, disease
status and surveillance
Manual of Diagnostic Tests and Vaccines for
Terrestrial Animals
Standards for laboratories, laboratory tests and
reagents, and vaccine manufacture
Aquatic Animal Health Code
Manual of Diagnostic Tests for Aquatic Animals
OIE Quality Standard and Guidelines for
Veterinary Laboratories
The OIE Terrestrial Manual
First edition (1989-91) Loose leaf
Based on expert opinion (chapter authors)
Consensus approval by OIE Member Countries
Subsequent bound editions (every 4 years) Seventh edition 2012
Progressive development to broaden scope and increase rigour
Incorporation of new technologies
But only when the methods have been validated
Recognition
Widely used as a laboratory reference work
WTO sanitary & phytosanitary agreement
From the SPS Agreement
For animal health and zoonoses:
the standards, guidelines and recommendations developed under
the auspices of the OIE
The Validation Framework
Updated text in Manual
adopted 2013
Research provides
proof of principle
Supported by publication
Cannot be considered a
standard method at this
stage
Validation pathway
Fitness for purpose
Established as a
standard
Continual monitoring of
assay in use
Standard reference materials for diagnostic tests
1. Reference strains of pathogens
Should be representative of organisms circulating in the field
Maintained by Reference Laboratories in controlled repositories
Defined characteristics, including passage levels
Used to standardise diagnostic tests, or as standards for vaccines (eg specified in OIE Manual)
Complex for pathogens with multiple circulating types
Continual monitoring for changes in circulating field organisms
2. Serology – the hierarchical approach
Primary Standards Small quantities, use sparingly
Extensively evaluated in multiple laboratories
Defined activity level in a standard test protocol
Designated at international level (eg OIE)
Supplied to National Laboratories
Secondary Standards Prepared by National Laboratory
Calibrated against primary standards
Supplied to diagnostic laboratories in that country
Working standards (tertiary) Used by diagnostic laboratories as working controls
Standard reference materials for
diagnostic tests
FMD
SVD
Rinderpest
PPR
CBPP
Bluetongue
African horse sickness
Classical swine fever
Aujeszky’s disease
Rabies
Brucellosis
EBL
IBR/IPV
EIA
Equine influenza
EVA
Obtained from OIE Reference Laboratories
(see OIE website for details)
Currently available OIE-approved
International Standard Sera
(primary standards)
Important message
For many important diseases we still have
no OIE-designated primary reference
materials, even for serology
There are no OIE-designated primary
reference materials for molecular tests
Standard reference materials for
diagnostic tests
3. Molecular diagnostic methods
Written standards (OIE Manuals) can specify eg primer
sequences for PCR and related assays
Do we need physical standard reference materials?
Parallels with human medicine
Results need to be comparable across time and methods, either by
producing the same value across methods and test versions or by
using reliable and stable conversions. Universally available
standards and reference materials specific to quantitative molecular
technologies are critical to this process but are few in number.
One of the most important considerations in the development of
effective standards and reference materials is that the material be
commutable, ie, behave as closely as possible to the test samples in
the full range of measurement procedures expected to make use of
the material.
[Madej et al., 2010, Journal of Molecular Diagnostics 12: 133-143]
Considerations for nucleic acid
standards Target sequence, length of target sequence
Multiple or single genotypes
Method of preparation of standard Extraction, recombinant, synthetic
Activity level Should give comparable results to real samples
Matrix Should give comparable results to real samples
Should work with all the available technologies
Stability
Consistency
Evaluation and recognition
Availability (cost, shipment issues)
Based on a
WHO
consultation
meeting
An example from avian influenza:
Standard reference materials for
diagnostic tests
4. Mobile and hand-held methods
In effect a subset of traditional technologies
Immunoassay (detection of antigen or antibody)
Nucleic acid detection
Ease of use in the field is critical
Kit formulations – use of controls
Standardisation needs to be incorporated at
the development stage by manufacturer
Ongoing QC vital to ensure consistency and
accuracy
High throughput sequencing,
bioinformatics and computational
genomics (HTS-BCG)
A big challenge for standardisation
OIE ad hoc group identified opportunities and
challenges from this technology
The approach of agreed written standards still
applies
Technical standards for the OIE Manuals
Standard approaches for data processing
Consideration required on how to apply validation
principles to this technology
Criteria for the interpretation of HTS-BCG results
High throughput sequencing,
bioinformatics and computational
genomics (HTS-BCG)
Standard Reference Materials?
Traditional concepts don’t work here
Needs fresh thinking to ensure that when such
methods are used, the results and interpretation are
consistent, wherever or by whom the analyses are
done
High throughput sequencing,
bioinformatics and computational
genomics (HTS-BCG)
Ad hoc group report – challenges related to
standardisation Systems & infrastructure for data capture, handling, archiving
and access need to be optimised and standardised
Standards for HTS platforms need to be developed and
incorporated into the OIE Manuals
HTS-BCG needs to be fully validated and quality assured for use
as a diagnostic tool
High throughput sequencing,
bioinformatics and computational
genomics (HTS-BCG)
Ad hoc group report – recommendations related
to standardisation OIE should develop and adopt standards in the Manuals for
HTS-BCG
OIE should convene an ad hoc group which (inter alia) should
recommend standard approaches for harmonisation and
interpretation of HTS data
OIE should assess feasibility of extending WAHIS to incorporate
HTS data, with standards for data management.
Summary
Standardisation is essential for end-users to have
confidence in diagnostic test results
Great progress has been achieved with the
development of international written standards in
the OIE Manuals Work must continue, including incorporation of new technologies
Internationally recognised Standard Reference
Materials are few: We need more, but funding is difficult
May not apply to HTC-BCG technologies