SlideShare a Scribd company logo
Clare Morris, NIBSC, UK
Assay standardisation – how this
leads to improved patient results
2
National Institute for Biological
Standards and Control
-Establishment of biological standards and
reference materials
-Batch release of vaccines and blood
products
-Underpinning R & D
-Strategic alliances with major stakeholders
(eg USP, WHO)
A UK government funded laboratory with a statutory function in the control
and standardisation of biological medicines.
3
What are we trying to achieve?
Accurate measurement
More robust and reproducible diagnostic assays
Improved health – prevention and clinical
management
4
How can we achieve this?
• Biological medicines are more complex than chemically-
synthesised drugs and cannot be measured using
physicochemical means alone so their biological activity
must be measured using bioassays.
• Its hard to know if you’re correct without a reference to
compare with…..
5
Tick tock….
6
Biological standardisation
Providing laboratories with a means of comparison using the
same unit of measurement
 Improve comparability between different lab data regardless
of the assay
 In turn leads to better clinical management of patients.
Lack of standards…
No comparability between assays
• Patient movement between hospitals
• Clinical trial comparison
• Treatment implications
7
Types of standard and control
material
High level calibrators
For calibration of an assay or a
product
 International standards
 Secondary standards
 Primary reference
materials
Quality Control (QC) Materials
For regular assay monitoring
 Run controls
 External QC reagents
 CE marked control
8
Hierarchy of standards
WHO International standard (higher order,
international conventional calibrator)
Tertiary Standard (working reagent, Kit
control, run control)
Secondary Standard (calibrator for assays and
tertiary standards)
Traceability
Uncertainty of
measurement
9
Using External Quality Controls
Laboratories should use a
quality control material in
addition to the kit control
Provides intra-laboratory
consistency.
10
A NIBSC Study - a good lab
11
NIBSC Study - a less good lab
20
25
30
35
40
45
1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43
Ctvalue
12
NIBSC Study - a poor lab
20
25
30
35
40
45
50
55
1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 47 49
Ctvalue
Quality Manager started to
check assays here
13
Ensuring comparability
QC’s can help individual laboratories ensure quality and
accuracy but how to improve overall agreement between
laboratories, using different assays.
Same patient result
Assay A Assay B
14
Molecular testing is routinely used across diagnostic laboratories to
guide clinical decisions in the management of transplant recipients
Rapid and reliable
 Detection of opportunistic BKV infections is essential in the post-
transplantation period
 Persistent ≥ 4.0 log10 copies/mL viral load in plasma is
presumptive of disease progression
 Treatment threshold is recommended by clinical practice
guidelines to reduce immunosuppression to circumvent organ
damage/loss
BK virus molecular diagnostics in the
transplant setting
Blood
Plasma
Urine
Persistent high viral load
Reduce immune suppression
15
BK virus viral load estimate in copies/mL
Under quantification - increasing BKV lytic infection
- organ damage
Over quantification - immunosupressant reduced too soon
- potential graft rejection
ALL TESTS ARE NOT EQUAL!
Evaluation of a single BKV positive clinical sample by 28 laboratories
Are all tests equal?
A need for standardisation
16
In house
Commercial
Extraction Methods
ABBOTT (M2000SP)
Altona (AltoStar Automation System)
BioMérieux (Nuclisens easyMAG, Nuclisens miniMAG )
ELITech Group (ELITe GALAXY)
Roche ( MagNa Pure 96, MagNA Pure LC 2.0)
Siemens (VERSANT® kPCR Molecular System )
QIAGEN:(QIAcube, QIAcube HT, QIAGEN EZ1,
QIAsymphony)
Commerical Kits
QIAGEN Artus BK Virus QS RGQ kit
Biomerieux BK Virus R-gene
Altona Diagnostics RealStar BKV PCR 1.0
Epoch ASR (formerly Nanogen)
ELITechGroup S.p.A. BKV ELITe MGB® Kit
Luminex BK Primers MultiCode®-RTx Chemistry
Bosphore® BKV Quantification Kit v1 (Anatolia
Geneworks)
Euro-RTBKV kit Eurospital
Thermocycler
ABI Prism 7500 SDS, 7500 Fast, Step One
Eppendorf Mastercycle, 3M Integrated Cycler
Cephid Smart cycler, QIAGEN Rotorgene Q, Agilent
MxPro3000P, VERSANT kPCR Molecular System
Sacace Sacycler-96, Bio-Rad MyiQ, CFX96, QX100
ddPCR
ROCHE Lightcycler 480, 96
Methodology variations
17
Assay Standardisation
Bioassays use complex biological systems to test activity, they
are variable from test to test.
By using a biological reference material or standard of known
activity or potency, bioassay results can be compared and
calibrated to give a consistent result, no matter when or where
the bioassay is performed.
In the case of diagnostic tests, the use of control samples of
known activity allows the sensitivity and specificity of the test
system to be monitored and quality assured.
18
WHO International Standards
Highest order of reference for biological materials medicines
Allows direct comparison between different assays and methodologies
Quantify “relative potency” in a specific but arbitrarily defined International
Unit (IU)
Control all steps of the assay
Behave in similar way to clinical material
Stable over many years
Are quantified in International Units (IU’s) assigned following a multicentre
collaborative study using multiple assays
Intended for calibration of secondary references
19
Standardisation and Comparability
Standard Protocol
(Reference method)
• Allows same assays to
be compared
• Provides assurance of
data within assay
• Limits the
improvement of
assays
• Not practicable in
competitive market
Standard Reference
(Reference material)
• Allows different assays
to be compared
• Provides assurance of
data across hospitals
• Provides framework
for improving all
assays
20
PSA WHO IS – post 2000
Source: Dina Patel, UK NEQAS Immunology,
Immunochemistry & Allergy, Sheffield, UK
• Majority of assays recalibrated to the WHO IS.
• Both introduction of standard and assay improvements reduced variability
• Continued reports that methods are not interchangeable - issue for long
term screening and transfer between hospitals
• Cut-offs for biopsy not clear. PSA is not a perfect tumour marker. Accepted
4µg/L
21
EBV - NIBSC Inter-laboratory
comparison (Ct’s)
24
25
26
27
28
29
30
31
32
33
34
Crossingthreshold(Ct)
NIBSC laboratory code
Mean
Overall mean
Overall ± 2 SD
22
1.00E+03
1.00E+04
1.00E+05
1.00E+06
copies/ml
NIBSC laboratory code
Mean
Overall mean
Overall ± 2 SD
EBV - NIBSC Inter-laboratory
comparison (copies/ml)
23
1.00E+03
1.00E+04
1.00E+05
1.00E+06
IU/ml
NIBSC laboratory code
Mean
Overall mean
Overall ± 2 SD
EBV - NIBSC Inter-laboratory
comparison (IU/ml)
24
EBV - NIBSC Inter-laboratory
comparison (Ct’s)
24
25
26
27
28
29
30
31
32
33
34
Crossingthreshold(Ct)
NIBSC laboratory code
Mean
Overall mean
Overall ± 2 SD
25
Anyone for coffee?
5730 lira19.95 francs 498 pesetas 5.70 marks
Which coffee is the most expensive?
26
3 Euro
27
Assay harmonisation-
HCV RNA Detection
1st HCV RNA NAT study (copies/ml) 1996 5th HCV RNA NAT study (IU/ml) 2011
NumberofLaboratories
0
1
2
3
4
5
6
7
8
9
10
Log10 IU/ml
2 3 4 5 6 7
10 14 4
7
8
1a
1b
2
5
6
9
11
13
17a
18
12
17b
Quantitative Assays Qualitative Assays
3 Log10
1.5 Log10
28
Assay harmonisation-
HIV RNA Detection
Based on subtype B virus
29
Treating severe Adenosine deaminase
deficiency (ADA-SCID)
• First licensed medicine to treat rare inherited disease ADA-
SCID and clinical trial pipeline X-SCID, WAS, X-CGD, b-
thalassemia, ALD, MLD, are based on the platform
technology involving integrating vectors (RV or LV)
• Two CAR-T products have been approved into US and EU
markets and over 100 CAR-T therapies are at a late stage
of clinical trials
• Patients treated at small number of centers Europe, USA,
Australia, Japan.
• As diseases are rare, patients followed up worldwide
yuan.zhao@nibsc.org
30
Standardisation across technologies
(21 methods; ρC 0.995)
• KRAS mutations in colorectal cancer can lead to some drugs not being
effective.
• Important to understand sensitivities of mutation detection.
• Concordance (medians): MassARRAY<Sanger<Pyro<dPCR & NGS
Jennifer.boyle@nibsc.org
31
Challenges
Early IS’s
– blood borne viruses limited problem
– Plasma almost universal matrix of blood industry
– IS and other references diluted in plasma or equivalent
Clinical Virology markers
– Greater challenge much discussion at SoGAT
– Broader range of matrices tested in labs plasma/WB/CSF
– Too complex to include in initial collaborative study
– Efficiency of extraction of nucleic acid variable
– Evidence of non-commutability- assay or standard?
32
Adenovirus standardisation across clinical
matrices
Sample Plasma diluent Stool diluent Whole blood diluent
No. of
datasets
SD
absolute
SD relative No. of
datasets
SD
absolute
SD
relative
No. of
datasets
SD
absolute
SD
relative
Relative to A: 16/306
B: 16/324 (HAdV2) 15 0.49 0.14 12 1.03 0.38 14 0.70 0.29
C: HAdV1 TCS 15 0.42 0.27 11 1.01 0.31 14 0.92 0.50
D: HAdV5 TCS 15 0.46 0.30 11 0.96 0.20 14 0.72 0.33
E: HAdV14 TCS 15 0.79 0.50 11 1.05 0.81 13 0.98 0.75
F: HAdV1 Plasma 12 0.50 0.38
G: HAdV5 Stool 7 1.25 1.12
H: HAdV14 Whole blood 11 0.99 0.70
Relative to B: 16/324
A: 16/306 (HAdV2) 15 0.48 0.14 12 1.14 0.38 16 0.71 0.28
C: HAdV1 TCS 15 0.42 0.21 11 1.01 0.40 16 0.92 0.46
D: HAdV5 TCS 15 0.46 0.22 10 0.96 0.26 16 0.72 0.18
E: HAdV14 TCS 15 0.79 0.48 11 1.05 0.89 16 0.98 0.66
F: HAdV1 Plasma 12 0.50 0.45
G: HAdV5 Stool 7 1.25 1.27
H: HAdV14 Whole blood 11 0.99 0.76
F relative to C (both HAdV1) G relative to D (both HAdV5) H relative to E (both HAdV14)
12 0.50 0.37 7 1.25 1.21 11 0.99 0.48
33
Conclusions
• Different controls have different applications, but
they complement each other in the overall
assurance of a test result.
• The result provided by one assay is not
comparable with another unless they are
calibrated to a common standard.
• Patient outcomes can be affected by using
different assays
• The use of an international standard facilitates the
global harmonisation of assays >> patient results
34
Acknowledgements
Advanced therapies
Yuan Zhou
Jennifer Boyle
Biotherapeutics
Jackie Ferguson
Infectious Diseases
Neil Almond (Head)
Sheila Govind
Jacqueline Fryer
Graham Prescott
Rehan Minhas
Rob Anderson
David Padley
35
Forthcoming webinar
Internal and external controls
Is EQA sufficient
How frequently should you monitor controls
What are the Westgard rules
Ever used a Levey Jennings plot?
36
Webinar
Quality control materials: how best to
use them, why they can improve your
service, and what this means for your
laboratory accreditation
15 November 2018 | 11:30 - 13:00
The move from CPA to ISO 15189 has left laboratories with many more challenges to address, particularly
around the use of quality control materials.
The webinar will cover:
• ISO15189 and the use of quality control materials
• Types of control material and their use
• How to select the best control materials for your assay
• The benefits of regular monitoring, including the use of Westgard rules
https://nibscsogats.co.uk/home

More Related Content

What's hot

Thornton NAAT
Thornton NAATThornton NAAT
Thornton NAAT
DSHS
 
What can we learn from oncologists? A survey of molecular testing patterns
What can we learn from oncologists? A survey of molecular testing patternsWhat can we learn from oncologists? A survey of molecular testing patterns
What can we learn from oncologists? A survey of molecular testing patterns
Thermo Fisher Scientific
 
Resume_BB
Resume_BBResume_BB
Clinical biochemistry
Clinical biochemistry Clinical biochemistry
Clinical biochemistry
subramaniam sethupathy
 
The paradigm shift – central lab to point of care
The paradigm shift – central lab to point of careThe paradigm shift – central lab to point of care
The paradigm shift – central lab to point of care
jdyjdo
 
Antibiogram
AntibiogramAntibiogram
Antibiogram
DR.pankaj omar
 
Driving Point of Care Technology Development: Integrated Approach to Consensu...
Driving Point of Care Technology Development: Integrated Approach to Consensu...Driving Point of Care Technology Development: Integrated Approach to Consensu...
Driving Point of Care Technology Development: Integrated Approach to Consensu...
CFTCC
 
Review brochure
Review brochureReview brochure
Review brochure
St John's Laboratory Ltd
 
Results from a Interlaboratory exercise to evaluate NSP kits (C. Browning)
Results from a Interlaboratory exercise to evaluate NSP kits (C. Browning)Results from a Interlaboratory exercise to evaluate NSP kits (C. Browning)
Results from a Interlaboratory exercise to evaluate NSP kits (C. Browning)
EuFMD
 
Automation in blood banking
Automation in blood bankingAutomation in blood banking
Automation in blood banking
Shreya D Prabhu
 
It's More Fun Doing the Antibiogram
It's More Fun Doing the AntibiogramIt's More Fun Doing the Antibiogram
It's More Fun Doing the Antibiogram
Philippine Hospital Infection Control Society
 
Raamsdonk beijing immunoassay validation v2
Raamsdonk beijing immunoassay validation v2Raamsdonk beijing immunoassay validation v2
Raamsdonk beijing immunoassay validation v2
Rikilt (Wageningen UR)
 
Blueprints to blue sky – analyzing the challenges and solutions for IHC compa...
Blueprints to blue sky – analyzing the challenges and solutions for IHC compa...Blueprints to blue sky – analyzing the challenges and solutions for IHC compa...
Blueprints to blue sky – analyzing the challenges and solutions for IHC compa...
Candy Smellie
 
Cell Culture Media Filtration – Filter Selection and Sizing
Cell Culture Media Filtration – Filter Selection and SizingCell Culture Media Filtration – Filter Selection and Sizing
Cell Culture Media Filtration – Filter Selection and Sizing
MilliporeSigma
 
Revista new lab artigo 6 inglês
Revista new lab artigo 6 inglêsRevista new lab artigo 6 inglês
Revista new lab artigo 6 inglês
Terra Vivos
 
Point of care testing ( POCT)
Point of care testing ( POCT)Point of care testing ( POCT)
Point of care testing ( POCT)
binaya tamang
 
BK Virus Multi-Site Evaluation
BK Virus Multi-Site EvaluationBK Virus Multi-Site Evaluation
BK Virus Multi-Site Evaluation
Reina Karunaratne
 
Lisa_Grimm
Lisa_GrimmLisa_Grimm
Lisa_Grimm
Lisa (Prior) Grimm
 
Apvs2013 08 tee et al.-csf test kit comparison
Apvs2013 08 tee et al.-csf test kit comparisonApvs2013 08 tee et al.-csf test kit comparison
Apvs2013 08 tee et al.-csf test kit comparison
Merial EMEA
 
Management of health laboratory services
Management of health laboratory servicesManagement of health laboratory services
Management of health laboratory services
AhmadAlnatour5
 

What's hot (20)

Thornton NAAT
Thornton NAATThornton NAAT
Thornton NAAT
 
What can we learn from oncologists? A survey of molecular testing patterns
What can we learn from oncologists? A survey of molecular testing patternsWhat can we learn from oncologists? A survey of molecular testing patterns
What can we learn from oncologists? A survey of molecular testing patterns
 
Resume_BB
Resume_BBResume_BB
Resume_BB
 
Clinical biochemistry
Clinical biochemistry Clinical biochemistry
Clinical biochemistry
 
The paradigm shift – central lab to point of care
The paradigm shift – central lab to point of careThe paradigm shift – central lab to point of care
The paradigm shift – central lab to point of care
 
Antibiogram
AntibiogramAntibiogram
Antibiogram
 
Driving Point of Care Technology Development: Integrated Approach to Consensu...
Driving Point of Care Technology Development: Integrated Approach to Consensu...Driving Point of Care Technology Development: Integrated Approach to Consensu...
Driving Point of Care Technology Development: Integrated Approach to Consensu...
 
Review brochure
Review brochureReview brochure
Review brochure
 
Results from a Interlaboratory exercise to evaluate NSP kits (C. Browning)
Results from a Interlaboratory exercise to evaluate NSP kits (C. Browning)Results from a Interlaboratory exercise to evaluate NSP kits (C. Browning)
Results from a Interlaboratory exercise to evaluate NSP kits (C. Browning)
 
Automation in blood banking
Automation in blood bankingAutomation in blood banking
Automation in blood banking
 
It's More Fun Doing the Antibiogram
It's More Fun Doing the AntibiogramIt's More Fun Doing the Antibiogram
It's More Fun Doing the Antibiogram
 
Raamsdonk beijing immunoassay validation v2
Raamsdonk beijing immunoassay validation v2Raamsdonk beijing immunoassay validation v2
Raamsdonk beijing immunoassay validation v2
 
Blueprints to blue sky – analyzing the challenges and solutions for IHC compa...
Blueprints to blue sky – analyzing the challenges and solutions for IHC compa...Blueprints to blue sky – analyzing the challenges and solutions for IHC compa...
Blueprints to blue sky – analyzing the challenges and solutions for IHC compa...
 
Cell Culture Media Filtration – Filter Selection and Sizing
Cell Culture Media Filtration – Filter Selection and SizingCell Culture Media Filtration – Filter Selection and Sizing
Cell Culture Media Filtration – Filter Selection and Sizing
 
Revista new lab artigo 6 inglês
Revista new lab artigo 6 inglêsRevista new lab artigo 6 inglês
Revista new lab artigo 6 inglês
 
Point of care testing ( POCT)
Point of care testing ( POCT)Point of care testing ( POCT)
Point of care testing ( POCT)
 
BK Virus Multi-Site Evaluation
BK Virus Multi-Site EvaluationBK Virus Multi-Site Evaluation
BK Virus Multi-Site Evaluation
 
Lisa_Grimm
Lisa_GrimmLisa_Grimm
Lisa_Grimm
 
Apvs2013 08 tee et al.-csf test kit comparison
Apvs2013 08 tee et al.-csf test kit comparisonApvs2013 08 tee et al.-csf test kit comparison
Apvs2013 08 tee et al.-csf test kit comparison
 
Management of health laboratory services
Management of health laboratory servicesManagement of health laboratory services
Management of health laboratory services
 

Similar to Assay Standardisation - how this leads to improved patient results

Health economic modelling in the diagnostics development process
Health economic modelling in the diagnostics development processHealth economic modelling in the diagnostics development process
Health economic modelling in the diagnostics development process
cheweb1
 
25_Everson
25_Everson25_Everson
25_Everson
Bradley Everson
 
Preclinical Flow Cytometry
Preclinical Flow CytometryPreclinical Flow Cytometry
Preclinical Flow Cytometry
KCAS Bioanalytical & Biomarker Services
 
Nat Testing
Nat TestingNat Testing
Nat Testing
kabitachatterjee
 
C Diff
C DiffC Diff
2013-11-26 DTL FIH symposium, Leiden
2013-11-26 DTL FIH symposium, Leiden2013-11-26 DTL FIH symposium, Leiden
2013-11-26 DTL FIH symposium, Leiden
Alain van Gool
 
Automated hematology analyzer as a cost effective aid to screen and monitor s...
Automated hematology analyzer as a cost effective aid to screen and monitor s...Automated hematology analyzer as a cost effective aid to screen and monitor s...
Automated hematology analyzer as a cost effective aid to screen and monitor s...
nisaiims
 
L25 b met_complete_blood_count
L25 b met_complete_blood_countL25 b met_complete_blood_count
L25 b met_complete_blood_count
Shakeel Mujahid
 
Quality control chemical
Quality control chemicalQuality control chemical
Quality control chemical
Appy Akshay Agarwal
 
Invest to End TB. Save Lives
Invest to End TB. Save LivesInvest to End TB. Save Lives
Invest to End TB. Save Lives
Stop TB Italia Onlus
 
Molecualr diagnostics ,comparison with roche hbv kit
Molecualr diagnostics ,comparison with roche hbv kitMolecualr diagnostics ,comparison with roche hbv kit
Molecualr diagnostics ,comparison with roche hbv kit
grace tang
 
Choosing best laboratory practice
Choosing best laboratory practiceChoosing best laboratory practice
Choosing best laboratory practice
Charisma France Buenaventura
 
CVO+.pdf
CVO+.pdfCVO+.pdf
CVO+.pdf
BernardSudan1
 
MA114 Chapter 45 intro to clinical laboratory
MA114 Chapter 45 intro to clinical laboratoryMA114 Chapter 45 intro to clinical laboratory
MA114 Chapter 45 intro to clinical laboratory
BealCollegeOnline
 
Nucliec Acid Testing in Blood and solid organ Donor Screening by dr umair
Nucliec Acid Testing in Blood and solid organ Donor Screening by dr umairNucliec Acid Testing in Blood and solid organ Donor Screening by dr umair
Nucliec Acid Testing in Blood and solid organ Donor Screening by dr umair
Dr. Umair Manghrio
 
Lecture 2 diagnostic molecular microbiology bls
Lecture 2 diagnostic molecular microbiology blsLecture 2 diagnostic molecular microbiology bls
Lecture 2 diagnostic molecular microbiology bls
Bruno Mmassy
 
Turning up the Compen-DIAL: Rapid Test Methods for Cell & Gene Therapies
Turning up the Compen-DIAL: Rapid Test Methods for Cell & Gene TherapiesTurning up the Compen-DIAL: Rapid Test Methods for Cell & Gene Therapies
Turning up the Compen-DIAL: Rapid Test Methods for Cell & Gene Therapies
MilliporeSigma
 
Turning up the Compen-DIAL: Rapid Test Methods for Cell & Gene Therapies
Turning up the Compen-DIAL: Rapid Test Methods for Cell & Gene TherapiesTurning up the Compen-DIAL: Rapid Test Methods for Cell & Gene Therapies
Turning up the Compen-DIAL: Rapid Test Methods for Cell & Gene Therapies
Merck Life Sciences
 
uptodate on acute kidney injury
uptodate on acute kidney injuryuptodate on acute kidney injury
uptodate on acute kidney injury
Sherif Mohammed
 
Step by Step, from Liquid Biopsy to a Genomic Biomarker: Liquid Biopsy Series...
Step by Step, from Liquid Biopsy to a Genomic Biomarker: Liquid Biopsy Series...Step by Step, from Liquid Biopsy to a Genomic Biomarker: Liquid Biopsy Series...
Step by Step, from Liquid Biopsy to a Genomic Biomarker: Liquid Biopsy Series...
QIAGEN
 

Similar to Assay Standardisation - how this leads to improved patient results (20)

Health economic modelling in the diagnostics development process
Health economic modelling in the diagnostics development processHealth economic modelling in the diagnostics development process
Health economic modelling in the diagnostics development process
 
25_Everson
25_Everson25_Everson
25_Everson
 
Preclinical Flow Cytometry
Preclinical Flow CytometryPreclinical Flow Cytometry
Preclinical Flow Cytometry
 
Nat Testing
Nat TestingNat Testing
Nat Testing
 
C Diff
C DiffC Diff
C Diff
 
2013-11-26 DTL FIH symposium, Leiden
2013-11-26 DTL FIH symposium, Leiden2013-11-26 DTL FIH symposium, Leiden
2013-11-26 DTL FIH symposium, Leiden
 
Automated hematology analyzer as a cost effective aid to screen and monitor s...
Automated hematology analyzer as a cost effective aid to screen and monitor s...Automated hematology analyzer as a cost effective aid to screen and monitor s...
Automated hematology analyzer as a cost effective aid to screen and monitor s...
 
L25 b met_complete_blood_count
L25 b met_complete_blood_countL25 b met_complete_blood_count
L25 b met_complete_blood_count
 
Quality control chemical
Quality control chemicalQuality control chemical
Quality control chemical
 
Invest to End TB. Save Lives
Invest to End TB. Save LivesInvest to End TB. Save Lives
Invest to End TB. Save Lives
 
Molecualr diagnostics ,comparison with roche hbv kit
Molecualr diagnostics ,comparison with roche hbv kitMolecualr diagnostics ,comparison with roche hbv kit
Molecualr diagnostics ,comparison with roche hbv kit
 
Choosing best laboratory practice
Choosing best laboratory practiceChoosing best laboratory practice
Choosing best laboratory practice
 
CVO+.pdf
CVO+.pdfCVO+.pdf
CVO+.pdf
 
MA114 Chapter 45 intro to clinical laboratory
MA114 Chapter 45 intro to clinical laboratoryMA114 Chapter 45 intro to clinical laboratory
MA114 Chapter 45 intro to clinical laboratory
 
Nucliec Acid Testing in Blood and solid organ Donor Screening by dr umair
Nucliec Acid Testing in Blood and solid organ Donor Screening by dr umairNucliec Acid Testing in Blood and solid organ Donor Screening by dr umair
Nucliec Acid Testing in Blood and solid organ Donor Screening by dr umair
 
Lecture 2 diagnostic molecular microbiology bls
Lecture 2 diagnostic molecular microbiology blsLecture 2 diagnostic molecular microbiology bls
Lecture 2 diagnostic molecular microbiology bls
 
Turning up the Compen-DIAL: Rapid Test Methods for Cell & Gene Therapies
Turning up the Compen-DIAL: Rapid Test Methods for Cell & Gene TherapiesTurning up the Compen-DIAL: Rapid Test Methods for Cell & Gene Therapies
Turning up the Compen-DIAL: Rapid Test Methods for Cell & Gene Therapies
 
Turning up the Compen-DIAL: Rapid Test Methods for Cell & Gene Therapies
Turning up the Compen-DIAL: Rapid Test Methods for Cell & Gene TherapiesTurning up the Compen-DIAL: Rapid Test Methods for Cell & Gene Therapies
Turning up the Compen-DIAL: Rapid Test Methods for Cell & Gene Therapies
 
uptodate on acute kidney injury
uptodate on acute kidney injuryuptodate on acute kidney injury
uptodate on acute kidney injury
 
Step by Step, from Liquid Biopsy to a Genomic Biomarker: Liquid Biopsy Series...
Step by Step, from Liquid Biopsy to a Genomic Biomarker: Liquid Biopsy Series...Step by Step, from Liquid Biopsy to a Genomic Biomarker: Liquid Biopsy Series...
Step by Step, from Liquid Biopsy to a Genomic Biomarker: Liquid Biopsy Series...
 

More from Walt Whitman

Webinar - Creating an SDMP for your NHS trust
Webinar - Creating an SDMP for your NHS trustWebinar - Creating an SDMP for your NHS trust
Webinar - Creating an SDMP for your NHS trust
Walt Whitman
 
NHS Sustainability Roadshow Cardiff
NHS Sustainability Roadshow CardiffNHS Sustainability Roadshow Cardiff
NHS Sustainability Roadshow Cardiff
Walt Whitman
 
NHS Sustainability Roadshow Manchester
NHS Sustainability Roadshow ManchesterNHS Sustainability Roadshow Manchester
NHS Sustainability Roadshow Manchester
Walt Whitman
 
Paul Dark - Biomarker guided duration of antibiotic treatment
Paul Dark - Biomarker guided duration of antibiotic treatmentPaul Dark - Biomarker guided duration of antibiotic treatment
Paul Dark - Biomarker guided duration of antibiotic treatment
Walt Whitman
 
Detecting, analysing and interpreting diagnostic devices
Detecting, analysing and interpreting diagnostic devicesDetecting, analysing and interpreting diagnostic devices
Detecting, analysing and interpreting diagnostic devices
Walt Whitman
 
Mike Wakeman - Case Study - CRP in community pharmacy
Mike Wakeman - Case Study - CRP in community pharmacyMike Wakeman - Case Study - CRP in community pharmacy
Mike Wakeman - Case Study - CRP in community pharmacy
Walt Whitman
 
UK Diagnostics
UK DiagnosticsUK Diagnostics
UK Diagnostics
Walt Whitman
 
Main Presentation UK Diagnostic Summit 2018
Main Presentation UK Diagnostic Summit 2018Main Presentation UK Diagnostic Summit 2018
Main Presentation UK Diagnostic Summit 2018
Walt Whitman
 
Real World Evaluation and implementation of a diagnostic test for pre-eclampsia
Real World Evaluation and implementation of a diagnostic test for pre-eclampsiaReal World Evaluation and implementation of a diagnostic test for pre-eclampsia
Real World Evaluation and implementation of a diagnostic test for pre-eclampsia
Walt Whitman
 
UK AMR Diagnositics Collaborative
UK AMR Diagnositics CollaborativeUK AMR Diagnositics Collaborative
UK AMR Diagnositics Collaborative
Walt Whitman
 
The State of the Nation
The State of the NationThe State of the Nation
The State of the Nation
Walt Whitman
 
Cancer detection therapy
Cancer detection therapyCancer detection therapy
Cancer detection therapy
Walt Whitman
 
Reducing Antimicrobial Prescribing
Reducing Antimicrobial PrescribingReducing Antimicrobial Prescribing
Reducing Antimicrobial Prescribing
Walt Whitman
 
In vitro Diagnostic Medical Devices
In vitro Diagnostic Medical DevicesIn vitro Diagnostic Medical Devices
In vitro Diagnostic Medical Devices
Walt Whitman
 
How diagnostics can drive efficiency within the NHS
How diagnostics can drive efficiency within the NHSHow diagnostics can drive efficiency within the NHS
How diagnostics can drive efficiency within the NHS
Walt Whitman
 
Powering Performance
Powering PerformancePowering Performance
Powering Performance
Walt Whitman
 
Sustainability in the NHS and leadership
Sustainability in the NHS and leadershipSustainability in the NHS and leadership
Sustainability in the NHS and leadership
Walt Whitman
 
Securing funding to deliver cost-saving energy efficient technologies
Securing funding to deliver cost-saving energy efficient technologiesSecuring funding to deliver cost-saving energy efficient technologies
Securing funding to deliver cost-saving energy efficient technologies
Walt Whitman
 
Quantum Waste Management Presentation
Quantum Waste Management PresentationQuantum Waste Management Presentation
Quantum Waste Management Presentation
Walt Whitman
 
Is care without carbon fit for the future
Is care without carbon fit for the futureIs care without carbon fit for the future
Is care without carbon fit for the future
Walt Whitman
 

More from Walt Whitman (20)

Webinar - Creating an SDMP for your NHS trust
Webinar - Creating an SDMP for your NHS trustWebinar - Creating an SDMP for your NHS trust
Webinar - Creating an SDMP for your NHS trust
 
NHS Sustainability Roadshow Cardiff
NHS Sustainability Roadshow CardiffNHS Sustainability Roadshow Cardiff
NHS Sustainability Roadshow Cardiff
 
NHS Sustainability Roadshow Manchester
NHS Sustainability Roadshow ManchesterNHS Sustainability Roadshow Manchester
NHS Sustainability Roadshow Manchester
 
Paul Dark - Biomarker guided duration of antibiotic treatment
Paul Dark - Biomarker guided duration of antibiotic treatmentPaul Dark - Biomarker guided duration of antibiotic treatment
Paul Dark - Biomarker guided duration of antibiotic treatment
 
Detecting, analysing and interpreting diagnostic devices
Detecting, analysing and interpreting diagnostic devicesDetecting, analysing and interpreting diagnostic devices
Detecting, analysing and interpreting diagnostic devices
 
Mike Wakeman - Case Study - CRP in community pharmacy
Mike Wakeman - Case Study - CRP in community pharmacyMike Wakeman - Case Study - CRP in community pharmacy
Mike Wakeman - Case Study - CRP in community pharmacy
 
UK Diagnostics
UK DiagnosticsUK Diagnostics
UK Diagnostics
 
Main Presentation UK Diagnostic Summit 2018
Main Presentation UK Diagnostic Summit 2018Main Presentation UK Diagnostic Summit 2018
Main Presentation UK Diagnostic Summit 2018
 
Real World Evaluation and implementation of a diagnostic test for pre-eclampsia
Real World Evaluation and implementation of a diagnostic test for pre-eclampsiaReal World Evaluation and implementation of a diagnostic test for pre-eclampsia
Real World Evaluation and implementation of a diagnostic test for pre-eclampsia
 
UK AMR Diagnositics Collaborative
UK AMR Diagnositics CollaborativeUK AMR Diagnositics Collaborative
UK AMR Diagnositics Collaborative
 
The State of the Nation
The State of the NationThe State of the Nation
The State of the Nation
 
Cancer detection therapy
Cancer detection therapyCancer detection therapy
Cancer detection therapy
 
Reducing Antimicrobial Prescribing
Reducing Antimicrobial PrescribingReducing Antimicrobial Prescribing
Reducing Antimicrobial Prescribing
 
In vitro Diagnostic Medical Devices
In vitro Diagnostic Medical DevicesIn vitro Diagnostic Medical Devices
In vitro Diagnostic Medical Devices
 
How diagnostics can drive efficiency within the NHS
How diagnostics can drive efficiency within the NHSHow diagnostics can drive efficiency within the NHS
How diagnostics can drive efficiency within the NHS
 
Powering Performance
Powering PerformancePowering Performance
Powering Performance
 
Sustainability in the NHS and leadership
Sustainability in the NHS and leadershipSustainability in the NHS and leadership
Sustainability in the NHS and leadership
 
Securing funding to deliver cost-saving energy efficient technologies
Securing funding to deliver cost-saving energy efficient technologiesSecuring funding to deliver cost-saving energy efficient technologies
Securing funding to deliver cost-saving energy efficient technologies
 
Quantum Waste Management Presentation
Quantum Waste Management PresentationQuantum Waste Management Presentation
Quantum Waste Management Presentation
 
Is care without carbon fit for the future
Is care without carbon fit for the futureIs care without carbon fit for the future
Is care without carbon fit for the future
 

Recently uploaded

CBO’s Economic Forecast: Understanding Productivity Growth
CBO’s Economic Forecast: Understanding Productivity GrowthCBO’s Economic Forecast: Understanding Productivity Growth
CBO’s Economic Forecast: Understanding Productivity Growth
Congressional Budget Office
 
Unlocking the Power of Matching Grants | North Texas Giving Day
Unlocking the Power of Matching Grants | North Texas Giving DayUnlocking the Power of Matching Grants | North Texas Giving Day
Unlocking the Power of Matching Grants | North Texas Giving Day
TechSoup
 
Celebrity Girls Call Navi Mumbai 🛵🚡9820252231 💃 Choose Best And Top Girl Serv...
Celebrity Girls Call Navi Mumbai 🛵🚡9820252231 💃 Choose Best And Top Girl Serv...Celebrity Girls Call Navi Mumbai 🛵🚡9820252231 💃 Choose Best And Top Girl Serv...
Celebrity Girls Call Navi Mumbai 🛵🚡9820252231 💃 Choose Best And Top Girl Serv...
902basic
 
Celebrity Girls Call Navi Mumbai 🎈🔥9920725232 🔥💋🎈 Provide Best And Top Girl S...
Celebrity Girls Call Navi Mumbai 🎈🔥9920725232 🔥💋🎈 Provide Best And Top Girl S...Celebrity Girls Call Navi Mumbai 🎈🔥9920725232 🔥💋🎈 Provide Best And Top Girl S...
Celebrity Girls Call Navi Mumbai 🎈🔥9920725232 🔥💋🎈 Provide Best And Top Girl S...
bellared2
 
The role of skills and geography in job changes for the green transition- Wes...
The role of skills and geography in job changes for the green transition- Wes...The role of skills and geography in job changes for the green transition- Wes...
The role of skills and geography in job changes for the green transition- Wes...
OECD CFE
 
Women's Empowerment in Agrifood Governance (WEAGov) training course
Women's Empowerment in Agrifood Governance (WEAGov) training courseWomen's Empowerment in Agrifood Governance (WEAGov) training course
Women's Empowerment in Agrifood Governance (WEAGov) training course
jkyle5
 
Rapport 2024 sur la richesse mondiale (UBS)
Rapport 2024 sur la richesse mondiale (UBS)Rapport 2024 sur la richesse mondiale (UBS)
Rapport 2024 sur la richesse mondiale (UBS)
bernarddetre2022
 
Lucknow Girls Call Kalyanpur 08630512678 Girls Call Service
Lucknow Girls Call Kalyanpur 08630512678  Girls Call ServiceLucknow Girls Call Kalyanpur 08630512678  Girls Call Service
Lucknow Girls Call Kalyanpur 08630512678 Girls Call Service
akarshkumar98776
 
Online Girls Call Delhi 9711199171 Provide Best And Top Girl Service And No1 ...
Online Girls Call Delhi 9711199171 Provide Best And Top Girl Service And No1 ...Online Girls Call Delhi 9711199171 Provide Best And Top Girl Service And No1 ...
Online Girls Call Delhi 9711199171 Provide Best And Top Girl Service And No1 ...
AK47
 
New Girls Call Noida 9873940964 Provide Best And Top Girl Service And No1 in ...
New Girls Call Noida 9873940964 Provide Best And Top Girl Service And No1 in ...New Girls Call Noida 9873940964 Provide Best And Top Girl Service And No1 in ...
New Girls Call Noida 9873940964 Provide Best And Top Girl Service And No1 in ...
AK47 AK47
 
OECD Survey on the Drivers of Trust in Public Institutions: 2024 Results
OECD Survey on the Drivers of Trust in Public Institutions: 2024 ResultsOECD Survey on the Drivers of Trust in Public Institutions: 2024 Results
OECD Survey on the Drivers of Trust in Public Institutions: 2024 Results
OECD Governance
 
New Girls Call Mumbai 👀 9820252231 👀 Cash Payment With Room DeliveryDelivery
New Girls Call Mumbai 👀 9820252231 👀 Cash Payment With Room DeliveryDeliveryNew Girls Call Mumbai 👀 9820252231 👀 Cash Payment With Room DeliveryDelivery
New Girls Call Mumbai 👀 9820252231 👀 Cash Payment With Room DeliveryDelivery
87tomato
 
Lucknow Girls Call Telibagh 08630512678 Girls Call Service
Lucknow Girls Call Telibagh 08630512678  Girls Call ServiceLucknow Girls Call Telibagh 08630512678  Girls Call Service
Lucknow Girls Call Telibagh 08630512678 Girls Call Service
annarivihqrika
 
Day care centers for poor children kurnool
Day care centers for poor children kurnoolDay care centers for poor children kurnool
Day care centers for poor children kurnool
SERUDS INDIA
 
Pune Girls Call Pune 0X0000000X Payment On Delevery Cash Hot Premium Genuine ...
Pune Girls Call Pune 0X0000000X Payment On Delevery Cash Hot Premium Genuine ...Pune Girls Call Pune 0X0000000X Payment On Delevery Cash Hot Premium Genuine ...
Pune Girls Call Pune 0X0000000X Payment On Delevery Cash Hot Premium Genuine ...
seenaoberoi
 
How to Save a Place: Understand Local, State, and Federal Preservation Groups
How to Save a Place: Understand Local, State, and Federal Preservation GroupsHow to Save a Place: Understand Local, State, and Federal Preservation Groups
How to Save a Place: Understand Local, State, and Federal Preservation Groups
National Trust for Historic Preservation
 
About Bridge of Hope
About Bridge of HopeAbout Bridge of Hope
About Bridge of Hope
Jamie Ritbalt
 
Lucknow Girls Call Mohanlalganj 08630512678 Girls Call Service
Lucknow Girls Call Mohanlalganj 08630512678  Girls Call ServiceLucknow Girls Call Mohanlalganj 08630512678  Girls Call Service
Lucknow Girls Call Mohanlalganj 08630512678 Girls Call Service
akarshkumar98776
 
Girls Call Surat 000XX00000 Provide Best And Top Girl Service And No1 in City
Girls Call Surat 000XX00000 Provide Best And Top Girl Service And No1 in CityGirls Call Surat 000XX00000 Provide Best And Top Girl Service And No1 in City
Girls Call Surat 000XX00000 Provide Best And Top Girl Service And No1 in City
gargruksana71
 
UNEP Report: Navigating New Horizons 2024
UNEP Report: Navigating New Horizons 2024UNEP Report: Navigating New Horizons 2024
UNEP Report: Navigating New Horizons 2024
Energy for One World
 

Recently uploaded (20)

CBO’s Economic Forecast: Understanding Productivity Growth
CBO’s Economic Forecast: Understanding Productivity GrowthCBO’s Economic Forecast: Understanding Productivity Growth
CBO’s Economic Forecast: Understanding Productivity Growth
 
Unlocking the Power of Matching Grants | North Texas Giving Day
Unlocking the Power of Matching Grants | North Texas Giving DayUnlocking the Power of Matching Grants | North Texas Giving Day
Unlocking the Power of Matching Grants | North Texas Giving Day
 
Celebrity Girls Call Navi Mumbai 🛵🚡9820252231 💃 Choose Best And Top Girl Serv...
Celebrity Girls Call Navi Mumbai 🛵🚡9820252231 💃 Choose Best And Top Girl Serv...Celebrity Girls Call Navi Mumbai 🛵🚡9820252231 💃 Choose Best And Top Girl Serv...
Celebrity Girls Call Navi Mumbai 🛵🚡9820252231 💃 Choose Best And Top Girl Serv...
 
Celebrity Girls Call Navi Mumbai 🎈🔥9920725232 🔥💋🎈 Provide Best And Top Girl S...
Celebrity Girls Call Navi Mumbai 🎈🔥9920725232 🔥💋🎈 Provide Best And Top Girl S...Celebrity Girls Call Navi Mumbai 🎈🔥9920725232 🔥💋🎈 Provide Best And Top Girl S...
Celebrity Girls Call Navi Mumbai 🎈🔥9920725232 🔥💋🎈 Provide Best And Top Girl S...
 
The role of skills and geography in job changes for the green transition- Wes...
The role of skills and geography in job changes for the green transition- Wes...The role of skills and geography in job changes for the green transition- Wes...
The role of skills and geography in job changes for the green transition- Wes...
 
Women's Empowerment in Agrifood Governance (WEAGov) training course
Women's Empowerment in Agrifood Governance (WEAGov) training courseWomen's Empowerment in Agrifood Governance (WEAGov) training course
Women's Empowerment in Agrifood Governance (WEAGov) training course
 
Rapport 2024 sur la richesse mondiale (UBS)
Rapport 2024 sur la richesse mondiale (UBS)Rapport 2024 sur la richesse mondiale (UBS)
Rapport 2024 sur la richesse mondiale (UBS)
 
Lucknow Girls Call Kalyanpur 08630512678 Girls Call Service
Lucknow Girls Call Kalyanpur 08630512678  Girls Call ServiceLucknow Girls Call Kalyanpur 08630512678  Girls Call Service
Lucknow Girls Call Kalyanpur 08630512678 Girls Call Service
 
Online Girls Call Delhi 9711199171 Provide Best And Top Girl Service And No1 ...
Online Girls Call Delhi 9711199171 Provide Best And Top Girl Service And No1 ...Online Girls Call Delhi 9711199171 Provide Best And Top Girl Service And No1 ...
Online Girls Call Delhi 9711199171 Provide Best And Top Girl Service And No1 ...
 
New Girls Call Noida 9873940964 Provide Best And Top Girl Service And No1 in ...
New Girls Call Noida 9873940964 Provide Best And Top Girl Service And No1 in ...New Girls Call Noida 9873940964 Provide Best And Top Girl Service And No1 in ...
New Girls Call Noida 9873940964 Provide Best And Top Girl Service And No1 in ...
 
OECD Survey on the Drivers of Trust in Public Institutions: 2024 Results
OECD Survey on the Drivers of Trust in Public Institutions: 2024 ResultsOECD Survey on the Drivers of Trust in Public Institutions: 2024 Results
OECD Survey on the Drivers of Trust in Public Institutions: 2024 Results
 
New Girls Call Mumbai 👀 9820252231 👀 Cash Payment With Room DeliveryDelivery
New Girls Call Mumbai 👀 9820252231 👀 Cash Payment With Room DeliveryDeliveryNew Girls Call Mumbai 👀 9820252231 👀 Cash Payment With Room DeliveryDelivery
New Girls Call Mumbai 👀 9820252231 👀 Cash Payment With Room DeliveryDelivery
 
Lucknow Girls Call Telibagh 08630512678 Girls Call Service
Lucknow Girls Call Telibagh 08630512678  Girls Call ServiceLucknow Girls Call Telibagh 08630512678  Girls Call Service
Lucknow Girls Call Telibagh 08630512678 Girls Call Service
 
Day care centers for poor children kurnool
Day care centers for poor children kurnoolDay care centers for poor children kurnool
Day care centers for poor children kurnool
 
Pune Girls Call Pune 0X0000000X Payment On Delevery Cash Hot Premium Genuine ...
Pune Girls Call Pune 0X0000000X Payment On Delevery Cash Hot Premium Genuine ...Pune Girls Call Pune 0X0000000X Payment On Delevery Cash Hot Premium Genuine ...
Pune Girls Call Pune 0X0000000X Payment On Delevery Cash Hot Premium Genuine ...
 
How to Save a Place: Understand Local, State, and Federal Preservation Groups
How to Save a Place: Understand Local, State, and Federal Preservation GroupsHow to Save a Place: Understand Local, State, and Federal Preservation Groups
How to Save a Place: Understand Local, State, and Federal Preservation Groups
 
About Bridge of Hope
About Bridge of HopeAbout Bridge of Hope
About Bridge of Hope
 
Lucknow Girls Call Mohanlalganj 08630512678 Girls Call Service
Lucknow Girls Call Mohanlalganj 08630512678  Girls Call ServiceLucknow Girls Call Mohanlalganj 08630512678  Girls Call Service
Lucknow Girls Call Mohanlalganj 08630512678 Girls Call Service
 
Girls Call Surat 000XX00000 Provide Best And Top Girl Service And No1 in City
Girls Call Surat 000XX00000 Provide Best And Top Girl Service And No1 in CityGirls Call Surat 000XX00000 Provide Best And Top Girl Service And No1 in City
Girls Call Surat 000XX00000 Provide Best And Top Girl Service And No1 in City
 
UNEP Report: Navigating New Horizons 2024
UNEP Report: Navigating New Horizons 2024UNEP Report: Navigating New Horizons 2024
UNEP Report: Navigating New Horizons 2024
 

Assay Standardisation - how this leads to improved patient results

  • 1. Clare Morris, NIBSC, UK Assay standardisation – how this leads to improved patient results
  • 2. 2 National Institute for Biological Standards and Control -Establishment of biological standards and reference materials -Batch release of vaccines and blood products -Underpinning R & D -Strategic alliances with major stakeholders (eg USP, WHO) A UK government funded laboratory with a statutory function in the control and standardisation of biological medicines.
  • 3. 3 What are we trying to achieve? Accurate measurement More robust and reproducible diagnostic assays Improved health – prevention and clinical management
  • 4. 4 How can we achieve this? • Biological medicines are more complex than chemically- synthesised drugs and cannot be measured using physicochemical means alone so their biological activity must be measured using bioassays. • Its hard to know if you’re correct without a reference to compare with…..
  • 6. 6 Biological standardisation Providing laboratories with a means of comparison using the same unit of measurement  Improve comparability between different lab data regardless of the assay  In turn leads to better clinical management of patients. Lack of standards… No comparability between assays • Patient movement between hospitals • Clinical trial comparison • Treatment implications
  • 7. 7 Types of standard and control material High level calibrators For calibration of an assay or a product  International standards  Secondary standards  Primary reference materials Quality Control (QC) Materials For regular assay monitoring  Run controls  External QC reagents  CE marked control
  • 8. 8 Hierarchy of standards WHO International standard (higher order, international conventional calibrator) Tertiary Standard (working reagent, Kit control, run control) Secondary Standard (calibrator for assays and tertiary standards) Traceability Uncertainty of measurement
  • 9. 9 Using External Quality Controls Laboratories should use a quality control material in addition to the kit control Provides intra-laboratory consistency.
  • 10. 10 A NIBSC Study - a good lab
  • 11. 11 NIBSC Study - a less good lab 20 25 30 35 40 45 1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 Ctvalue
  • 12. 12 NIBSC Study - a poor lab 20 25 30 35 40 45 50 55 1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 47 49 Ctvalue Quality Manager started to check assays here
  • 13. 13 Ensuring comparability QC’s can help individual laboratories ensure quality and accuracy but how to improve overall agreement between laboratories, using different assays. Same patient result Assay A Assay B
  • 14. 14 Molecular testing is routinely used across diagnostic laboratories to guide clinical decisions in the management of transplant recipients Rapid and reliable  Detection of opportunistic BKV infections is essential in the post- transplantation period  Persistent ≥ 4.0 log10 copies/mL viral load in plasma is presumptive of disease progression  Treatment threshold is recommended by clinical practice guidelines to reduce immunosuppression to circumvent organ damage/loss BK virus molecular diagnostics in the transplant setting Blood Plasma Urine Persistent high viral load Reduce immune suppression
  • 15. 15 BK virus viral load estimate in copies/mL Under quantification - increasing BKV lytic infection - organ damage Over quantification - immunosupressant reduced too soon - potential graft rejection ALL TESTS ARE NOT EQUAL! Evaluation of a single BKV positive clinical sample by 28 laboratories Are all tests equal? A need for standardisation
  • 16. 16 In house Commercial Extraction Methods ABBOTT (M2000SP) Altona (AltoStar Automation System) BioMérieux (Nuclisens easyMAG, Nuclisens miniMAG ) ELITech Group (ELITe GALAXY) Roche ( MagNa Pure 96, MagNA Pure LC 2.0) Siemens (VERSANT® kPCR Molecular System ) QIAGEN:(QIAcube, QIAcube HT, QIAGEN EZ1, QIAsymphony) Commerical Kits QIAGEN Artus BK Virus QS RGQ kit Biomerieux BK Virus R-gene Altona Diagnostics RealStar BKV PCR 1.0 Epoch ASR (formerly Nanogen) ELITechGroup S.p.A. BKV ELITe MGB® Kit Luminex BK Primers MultiCode®-RTx Chemistry Bosphore® BKV Quantification Kit v1 (Anatolia Geneworks) Euro-RTBKV kit Eurospital Thermocycler ABI Prism 7500 SDS, 7500 Fast, Step One Eppendorf Mastercycle, 3M Integrated Cycler Cephid Smart cycler, QIAGEN Rotorgene Q, Agilent MxPro3000P, VERSANT kPCR Molecular System Sacace Sacycler-96, Bio-Rad MyiQ, CFX96, QX100 ddPCR ROCHE Lightcycler 480, 96 Methodology variations
  • 17. 17 Assay Standardisation Bioassays use complex biological systems to test activity, they are variable from test to test. By using a biological reference material or standard of known activity or potency, bioassay results can be compared and calibrated to give a consistent result, no matter when or where the bioassay is performed. In the case of diagnostic tests, the use of control samples of known activity allows the sensitivity and specificity of the test system to be monitored and quality assured.
  • 18. 18 WHO International Standards Highest order of reference for biological materials medicines Allows direct comparison between different assays and methodologies Quantify “relative potency” in a specific but arbitrarily defined International Unit (IU) Control all steps of the assay Behave in similar way to clinical material Stable over many years Are quantified in International Units (IU’s) assigned following a multicentre collaborative study using multiple assays Intended for calibration of secondary references
  • 19. 19 Standardisation and Comparability Standard Protocol (Reference method) • Allows same assays to be compared • Provides assurance of data within assay • Limits the improvement of assays • Not practicable in competitive market Standard Reference (Reference material) • Allows different assays to be compared • Provides assurance of data across hospitals • Provides framework for improving all assays
  • 20. 20 PSA WHO IS – post 2000 Source: Dina Patel, UK NEQAS Immunology, Immunochemistry & Allergy, Sheffield, UK • Majority of assays recalibrated to the WHO IS. • Both introduction of standard and assay improvements reduced variability • Continued reports that methods are not interchangeable - issue for long term screening and transfer between hospitals • Cut-offs for biopsy not clear. PSA is not a perfect tumour marker. Accepted 4µg/L
  • 21. 21 EBV - NIBSC Inter-laboratory comparison (Ct’s) 24 25 26 27 28 29 30 31 32 33 34 Crossingthreshold(Ct) NIBSC laboratory code Mean Overall mean Overall ± 2 SD
  • 22. 22 1.00E+03 1.00E+04 1.00E+05 1.00E+06 copies/ml NIBSC laboratory code Mean Overall mean Overall ± 2 SD EBV - NIBSC Inter-laboratory comparison (copies/ml)
  • 23. 23 1.00E+03 1.00E+04 1.00E+05 1.00E+06 IU/ml NIBSC laboratory code Mean Overall mean Overall ± 2 SD EBV - NIBSC Inter-laboratory comparison (IU/ml)
  • 24. 24 EBV - NIBSC Inter-laboratory comparison (Ct’s) 24 25 26 27 28 29 30 31 32 33 34 Crossingthreshold(Ct) NIBSC laboratory code Mean Overall mean Overall ± 2 SD
  • 25. 25 Anyone for coffee? 5730 lira19.95 francs 498 pesetas 5.70 marks Which coffee is the most expensive?
  • 27. 27 Assay harmonisation- HCV RNA Detection 1st HCV RNA NAT study (copies/ml) 1996 5th HCV RNA NAT study (IU/ml) 2011 NumberofLaboratories 0 1 2 3 4 5 6 7 8 9 10 Log10 IU/ml 2 3 4 5 6 7 10 14 4 7 8 1a 1b 2 5 6 9 11 13 17a 18 12 17b Quantitative Assays Qualitative Assays 3 Log10 1.5 Log10
  • 28. 28 Assay harmonisation- HIV RNA Detection Based on subtype B virus
  • 29. 29 Treating severe Adenosine deaminase deficiency (ADA-SCID) • First licensed medicine to treat rare inherited disease ADA- SCID and clinical trial pipeline X-SCID, WAS, X-CGD, b- thalassemia, ALD, MLD, are based on the platform technology involving integrating vectors (RV or LV) • Two CAR-T products have been approved into US and EU markets and over 100 CAR-T therapies are at a late stage of clinical trials • Patients treated at small number of centers Europe, USA, Australia, Japan. • As diseases are rare, patients followed up worldwide yuan.zhao@nibsc.org
  • 30. 30 Standardisation across technologies (21 methods; ρC 0.995) • KRAS mutations in colorectal cancer can lead to some drugs not being effective. • Important to understand sensitivities of mutation detection. • Concordance (medians): MassARRAY<Sanger<Pyro<dPCR & NGS Jennifer.boyle@nibsc.org
  • 31. 31 Challenges Early IS’s – blood borne viruses limited problem – Plasma almost universal matrix of blood industry – IS and other references diluted in plasma or equivalent Clinical Virology markers – Greater challenge much discussion at SoGAT – Broader range of matrices tested in labs plasma/WB/CSF – Too complex to include in initial collaborative study – Efficiency of extraction of nucleic acid variable – Evidence of non-commutability- assay or standard?
  • 32. 32 Adenovirus standardisation across clinical matrices Sample Plasma diluent Stool diluent Whole blood diluent No. of datasets SD absolute SD relative No. of datasets SD absolute SD relative No. of datasets SD absolute SD relative Relative to A: 16/306 B: 16/324 (HAdV2) 15 0.49 0.14 12 1.03 0.38 14 0.70 0.29 C: HAdV1 TCS 15 0.42 0.27 11 1.01 0.31 14 0.92 0.50 D: HAdV5 TCS 15 0.46 0.30 11 0.96 0.20 14 0.72 0.33 E: HAdV14 TCS 15 0.79 0.50 11 1.05 0.81 13 0.98 0.75 F: HAdV1 Plasma 12 0.50 0.38 G: HAdV5 Stool 7 1.25 1.12 H: HAdV14 Whole blood 11 0.99 0.70 Relative to B: 16/324 A: 16/306 (HAdV2) 15 0.48 0.14 12 1.14 0.38 16 0.71 0.28 C: HAdV1 TCS 15 0.42 0.21 11 1.01 0.40 16 0.92 0.46 D: HAdV5 TCS 15 0.46 0.22 10 0.96 0.26 16 0.72 0.18 E: HAdV14 TCS 15 0.79 0.48 11 1.05 0.89 16 0.98 0.66 F: HAdV1 Plasma 12 0.50 0.45 G: HAdV5 Stool 7 1.25 1.27 H: HAdV14 Whole blood 11 0.99 0.76 F relative to C (both HAdV1) G relative to D (both HAdV5) H relative to E (both HAdV14) 12 0.50 0.37 7 1.25 1.21 11 0.99 0.48
  • 33. 33 Conclusions • Different controls have different applications, but they complement each other in the overall assurance of a test result. • The result provided by one assay is not comparable with another unless they are calibrated to a common standard. • Patient outcomes can be affected by using different assays • The use of an international standard facilitates the global harmonisation of assays >> patient results
  • 34. 34 Acknowledgements Advanced therapies Yuan Zhou Jennifer Boyle Biotherapeutics Jackie Ferguson Infectious Diseases Neil Almond (Head) Sheila Govind Jacqueline Fryer Graham Prescott Rehan Minhas Rob Anderson David Padley
  • 35. 35 Forthcoming webinar Internal and external controls Is EQA sufficient How frequently should you monitor controls What are the Westgard rules Ever used a Levey Jennings plot?
  • 36. 36 Webinar Quality control materials: how best to use them, why they can improve your service, and what this means for your laboratory accreditation 15 November 2018 | 11:30 - 13:00 The move from CPA to ISO 15189 has left laboratories with many more challenges to address, particularly around the use of quality control materials. The webinar will cover: • ISO15189 and the use of quality control materials • Types of control material and their use • How to select the best control materials for your assay • The benefits of regular monitoring, including the use of Westgard rules https://nibscsogats.co.uk/home

Editor's Notes

  1. Ask the time…..
  2. Molecular testing is routinely used across diagnostic laboratories to guide clinical decision making in the management of transplant recipients They allow for rapid and reliable detection of opportunistic BKV infection post-transplantation to predict and diagnose disease course A persistent viral load of 4.0 log10 copies/mL in plasma is presumptive of BKV disease progression, and is recommended by clinical practice guidelines to reduce immunosuppression Since there is no effective anti-viral treatment against BK virus, reduction of immunosuppressive drugs allows the reconstitution of the immune response to clear the virus and prevent lytic infection and kidney damage or potential organ loss
  3. However not all tests are equal as illustrated by this evaluation of a single BKV positive sample by 28 labs and detection in some labs may result in under quantification of BK virus, this would permit BK induced lytic infection to proceed undetected and increase the likelihood of organ damage. And over-quantification BK virus could result in the removal of immunosuppressive treatment too soon and risk the likelihood of graft rejection.
  4. There is no single reference method for BKV viral load determination, instead there is variation in extraction methods, amplification methods, laboratory developed or commercial assays, targeting different regions of the BKV genome and using different thermocyclers and of course different primer probe sequences and chemistries.
  5. Clear spread of data. Clearly not able to consider all results as one data set MassARRAY poor (semi-quantitative only) NGS, dPCR & pyrosequencing excellent, but several outliers with pyrosequencing NGS & dPCR with strongest concordance (n= 21 methods; Lin’s concordance correlation coefficient ρC 0.995 ) and NGS as most common, increasingly used; dPCR as gold standard Mutations in KRAS can mean that some drugs will not be effective…. Colorectal cancer