abesson_poster_gyrolab user meeting
TRANSCRIPT
NovImmune SA, 14 Chemin des Aulx, 1228 Plan-les-Ouates, Switzerland
Contact: [email protected] , [email protected] * Presenting Author
Assay transfer context
June 8-9, 2015 Gyrolab User Seminar, London
Transfer and cross-validation of a pharmacokinetic (PK) assay
on the Gyrolab™ platform across three different sites
(Switzerland, UK, USA) Emilie Escoffier, Anaïs Moreau, Adeline Besson*, Sabrina Lory, Walter Ferlin, Maureen Deehan and Robert Nelson
Assay format
Conclusions
Table 1: Summary of validation parameters of PK assay at NovImmune
Assay technology
Case study: Transfer of a PK assay to 3 sites
www.novimmune.com
During the course of a drug’s development, it is often necessary to transfer assays
between laboratories. The reasons for transferring can be due to limited internal
resources, regulatory compliance or logistical issues.
For multi-site, global clinical trials, an assay may require validation and execution in
more than one site and even on different continents.
This case study describes the transfer and the cross-validation of a Gyrolab™
pharmacokinetic (PK) assay in three countries and on two continents in order to
achieve the goals of a clinical trial.
- Rare disease and pediatric population
- Rapid turnaround of data
- Multi-site global clinical study
sample analysis at the right time, in the right
place to satisfy data delivery requirement
Ensuring success in assay transfer
- Evaluate the expertise
- Ensure the ability to achieve a short data delivery turnaround time
- Check the technology availability
- Visit the CRO site
- Share skills and provide training
- Share information (e.g. characterization and documentation of critical reagents)
- Realistic timelines
- Follow-up with e-mails, teleconference calls, face-to-face meetings
- Flexibility
State your expectations clearly from the start
- Fast data turnaround capacity
- Suitable with low sample volume
- Good technical support from Gyros in case of troubleshooting
More challenging to transfer compared to simple ELISA methodology due to
platform expertise requirements
Why Gyrolab™ platform?
Overview
Validation summary (Step 1)
Validation successfully completed at NovImmune
Assessment of ruggedness of the assay across the 3 sites?
Working range of the method: 62.5-8000 ng/mL
* %RE ≤ ±20% and %CV ≤ 20%, except for LLOQ and ULOQ for which %RE ≤ ±25% and %CV ≤ 25%
Cross-validation at 3 sites (Step 4)
Establish inter-laboratory reliability: prepare and test 30 samples
Figure 2: Overview of the cross-validation at 3 sites
Figure 1: Steps performed for successful transfer and validation of the PK assay at 3 sites
A = Reference result (Mean result from NovImmune)
B = Observed result (at the CRO site)
Analysis:
Relative Percentage Difference (%) =
Target Criteria:
± 25% of the reference value for at least 80% of the
samples tested
Ruggedness assessment:
Figure 3: Concentration of 30 samples tested blinded at 3 sites
Figure 4: Relative percentage difference of 30 samples obtained for both CROs (UK and USA)
compared to the reference site (NovImmune)
87% of the samples within target criteria Ruggedness assessment passed
The PK assay was successfully validated at NovImmune (Switzerland) and at the two
CRO sites in the UK and USA
The assessment of ruggedness was successful, demonstrating the equivalence of
the assay across the three different sites
Successfully supported data delivery for clinical trial at the different bioanalytical
laboratory sites
Study requirement
Choose the CRO matching your project
Ensure good communication and partnership
𝐁 − 𝐀
𝐀 𝐱 𝟏𝟎𝟎
Abstract
Normal Atypical
Laser excitation of the AF
Emission measurement –
fluorescent profile
Streptavidin
Bead
Biotinylated
Drug
Bridging ADA
(reference material)
Alexa Fluor®
Conjugated Drug
Mixing
Chamber
Streptavidin Affinity
Capture Column
Volume Definition
Chambers
Drug (therapeutic mAb)
Biotinylated mouse
anti-idiotype mAb
Alexa Fluor (AF) mouse
anti-idiotype mAb
Gyrolab CD 200 nL
(With streptavidin
coated beads)
Streptavidin
Bead
Biotinylated
Drug
Bridging ADA
(reference material)
Alexa Fluor®
Conjugated Drug
Mixing
Chamber
Streptavidin Affinity
Capture Column
Volume Definition
Chambers
Volume Definition
Chambers
Mixing
Chamber
Streptavidin Affinity
Capture Column
<24 hours
Samplereceipt
Sampleanalysis
Data QC check
Data delivery
Automated nano-liter scale Gyrolab™ platform
Bridging immunoassay
Sequential format
Validation results
Passed
Passed up to 1 in 2000
No hook effect
Room temperature 24 hours
Freeze/Thaw Cycle 5 cycles
18 months stability at both -20°C and -80°C
Short term stability
Long Term Stability
Parameter
Matrix Effect
Normal matrices
Lipaemic and Haemolysed matrices
Passed
System suitability
Overall Intra- and Inter- accuracy and precision
within criteria*
Dilutional Linearity
Hook effect
1 2 3 4 5 6 7 8 910
11
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30
-4 0
-2 0
0
2 0
4 0
% R
ela
tiv
e d
iffe
re
nc
e
to r
efe
re
nc
e c
on
ce
ntr
ati
on
C R O in th e U K
C R O in th e U S A
50
S a m p le s s p ik e d w ith d if fe re n t le v e ls o f d ru g
* * *
* S a m p le s b e lo w L L O Q
1• Validation at NovImmune (Switzerland)
2
• Transfer at the 1st CRO (UK)
• Validation at the 1st CRO (UK)
3
• Transfer at the 2nd CRO (USA)
• Validation at the 2nd CRO (USA)
4• Cross-validation at 3 sites
1 2 3 4 5 6 7 8 910
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
0
4 0 0 0
8 0 0 0
1 2 0 0 0
4 0 0 0 0
8 0 0 0 0
1 2 0 0 0 0
2 0 0 0 0 0
4 0 0 0 0 0
6 0 0 0 0 0
Co
nc
en
tra
tio
n (
ng
/mL
)
N ovIm m une
C R O in th e U K
C R O in th e U S A
* S a m p le s b e lo w L L O Q
* * *
S a m p le s