environmental impact on liquid handling...consumer healthcare we make a range of consumer healthcare...

© 2017 Artel1

© 2013 ARTEL

Environmental Impact

on Liquid Handling

Pascal Silversmet, GSK

Katie Haith, Tecan

George Rodrigues, Artel

GSK : Who we are

Pharmaceuticals

We develop and make

medicines to treat a range of

conditions including respiratory

diseases and HIV/AIDS

Vaccines

We research and make

vaccines for children and

adults that protect against

infectious diseases

Consumer Healthcare

We make a range of consumer

healthcare products in four

categories: Wellness, Skin

health, Oral health and Nutrition

2

2bnpacks of medicines

in 2016

833mdoses of vaccines

in 2016

5bnconsumer healthcare products

in 2016

Source: GSK 2016 Annual Report

Our global presence

3

Hamilton

Saint-Amand-Les-Eaux Dresden

Moscow

Nashik

Gödollö

Ste Foy

Wavre

Rixensart

Hamilton

Marietta

Marburg

Rosia/Siena

Tian Yuan (JV)

Shanghai

Singapore

Ankleshwar

Manufacturing

Facilities

Our global presence

4

Hamilton

Saint-Amand-Les-Eaux Dresden

Moscow

Nashik

Gödollö

Ste Foy

Wavre

Hamilton

Marburg

Tian Yuan (JV)

Shanghai

Singapore

Ankleshwar

Manufacturing

Facilities

Global R&D

Centers

Rockville

Rosia/SienaMarietta

Rixensart

EasyLab Global support to R&D

Global automation park

5

USA

BRA

CHN

CAN

- 450 users

- >80 running systems

- 7 countries, accross 3 continents

Marburg

RDC BelgiumEASyLab Centre of

Excellence

RDC US

RDC Italy

EasyLab : Engineering Automated Systems for Laboratory

Mission

6

Support Global R&D in :

Integrate Automated Solutions into Lab Processes with a

end-to-end service and harmonization mindset

Design Phase

Development Validation

LCMImplementation Phase

Project

EasyLab Expertise

• Liquid Handling (topic of today)Sample preparation & Predilution, Serial Dilution, Plate Filling & Reagent dispensing,

Aliquoting, Formulation and pH measurement, …

• Image AnalysisCells based assay reader: Seroneutralisation, Titration, Elispot, SRD, Bactericide,

Hemaglutination,…(Fluorescence, multiplex,…)

• Automated Label printing & Sample Management

• Customized Robotics solution

• Innovative technologies : Artificial Intelligence, Augmented Reality …

• Computer System Validation (Up to GMP level)

Main Technological Expertise Field

7

Liquid Handling : Precision/accuracy qualification

Case study : Laval 2015 (Canada)

8

Clinical Lab equipped with 6 TECAN Liquid handling systems

Systems are working days and night to produce Clinical results

Situation

•Nobody in the Lab the weekend STOP HVAC (air conditioning) in lab WE

•Canada winter -40°C and summer +40 ° extreme different environment conditions

Ecological initiatives in

2015

to save energy

•Suddenly, Assays performed on LH systems on Monday systematically out of range

•Consequence : No more testing on Monday decrease productivity & trust in automated systems

•After investigation : Humidity/pressure/temperature required all Monday to recover. No real human sensitivity but LH systems affected.

Issue

Liquid Handling : Environmental impact

As global organization EASyLab transfer system/protocol to other GSK sites and countries

different weather conditions and to workaround we need :

– Environment Automatic Liquid Handling parameters adjustment or

– At least monitor temperature/pressure/humidity for further investigation

Partnership between ARTEL-TECAN-GSK to Modelize impact of environment on LH

based on Design of Experiment approach where :

– GSK provided statistical design

– Tecan provided equipment and liquid handling expertise

– Artel provided environmental chamber, and conducted testing and data analysis

Partnership TECAN-ARTEL-GSK

9

xx

XX

Tecan QC Kit

February 2018

Katie Haith – Tecan US

11

Freedom EVO Series

Freedom EVO 150 equipped with AirLiHa, RoMa and MCA96

SOFTWARETEST MATERIALS

HARDWARE

QC Kit components

Freedom EVOware®

QC Kit Wizard

Barcode

Scanner

ShakerReaderCalibrator plate

12

QC Kit

Verification Plates

(96 well & 384 well)

QC Kit

Solutions

QC Kit Sample Solutions & Diluent

• Contain 2 dyes: Diluent and Range Solution

• Distinct absorbance maxima (520 & 730 nm)

• Different concentrations of Range (red dye)

for different volume ranges

• Diluent (blue dye) at same concentration for

all ranges

• Stable and traceable to the National Institute

of Standards and Technology, USA (NIST)

13

QC Kit Verification Plates

• Lot characterized plates

• Extensive testing of every plate lot

• Well dimensions traceable

to the National Institute of Standards

and Technology, USA (NIST)

• Bottom diameter (D) and taper angle ( )

are critical to volume calculations

• 2D barcode on plate boxes carries

necessary information about

performance, dimensions and lot

number

14

D

15

How it works - Overview of Dual-Dye Photometric

Method

• Photometric measurement of liquid volume

• Two dyes measured at two wavelengths

• Ratiometric calculation of results per well

• Simultaneous measurement of accuracy & precision per tip

• Artel’s patented dual-dye ratiometric photometry is included in ISO 8655:

Part 7 and the measurement results are NIST-Traceable

• The Tecan Infinite reader measures absorbance

at 520nm and 730nm

• Based on the optical density (OD)

measurements, the absolute volume of pipetted Range

Solution is calculated

• This calculation factors in data gathered from

the Calibration and Baseline steps

Patented dual-dye Ratiometric™ technology from Artel

16

QC Kit Software for EVOware

• Fully integrated with Freedom EVOware, enabling seamless, step-by-step control of the

entire workflow.

• A wizard controls pipetting, shaking, reading, data analysis and reporting, providing a

straightforward pass/fail result.

17

QC Kit Reporting

• Is designed to meet quality and regulatory needs with the following reporting

options:

• QC Kit report –one page summary of the verification test results and a

pass/fail analysis

• QC Kit extended data report – for more detailed, systematic analysis of

liquid handling verification results, to be used for troubleshooting and liquid

handling optimization

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QC Kit Report

19

OVERALL QC REPORT TO SATISFY

QUALITY AND REGULATORY

NEEDS

• Consists of:

• User Information

• Instrument information

• Software version information

• Pass/Fail requirements

• Average test results for all

channels

The reports can be printed or exported

to the PDF file format.

The data can also be exported as CSVs

for further analysis, such as trending

or data driven troubleshooting.

QC Kit Extended Data Report

20

THE AUTOMATICALLY GENERATED PRINTOUTS LISTS THE OVERALL ACCURACY AND

PRECISION (CV) AND GIVES VOLUME INFORMATION PER TIP

• Report shows the overall outcome (pass or fail)

• Color coding shows results for each individual well at a glance

• Easy to identify if a tip deviates from the expected volume

Reporting Module

PRINT ANY REPORT OR EXPORT TO .PDF OR .CSV FORMATS

21

Reliable Quality Control

QUALITY CONTROL ENSURES THAT YOUR INSTRUMENTATION’S PIPETTING RESULTS

ARE CONSISTENT AND COMPARABLE

• Consistent – Proves that your instrument is performing well over time,

whether that is weekly, monthly or annually

• Comparable – Shows that pipetting performance is similar to other

pipetting devices

• Demonstrates that your Freedom EVO® is performing as intended

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© 2017 Artel24

© 2013 ARTEL

DOE Basics

Process

Inputs

Responses

© 2017 Artel25

© 2013 ARTEL

Two Quantitative Responses

• Precision (percent CV)

• Trueness (percent systematic error)

© 2017 Artel27

© 2013 ARTEL

Some Constant Inputs

• One liquid handling system

• One liquid type (aqueous)

• One syringe size

• One dispense method

• One elevation (barometric pressure)

© 2017 Artel28

© 2013 ARTEL

Three Controlled Input Variables

• Temperature – quantitative

• Relative Humidity - quantitative

• Volume Arrangements - categorical

© 2017 Artel29

© 2013 ARTEL

Three Tip Sizes

Code Tip Size Volume

V1 1000 200

V2 200 100

V3 200 25

V4 200 10

V5 50 25

V6 50 10

Configuration

© 2017 Artel30

© 2013 ARTEL

Four Test Volumes


V1 1000 200

V2 200 100

V3 200 25

V4 200 10

V5 50 25

V6 50 10

Configuration

© 2017 Artel31

© 2013 ARTEL

Nine Environments

• Temperature Three Levels

• 15, 22.5, 30 °C

• Relative Humidity Three Levels

• 30, 55, 80 %RH

© 2017 Artel32

© 2013 ARTEL

Nine Environments

© 2017 Artel33

© 2013 ARTEL

Six Volumes at Each Environment

V1V2V3V4V5V6

V1V2V3V4V5V6

V1V2V3V4V5V6

V1V2V3V4V5V6

V1V2V3V4V5V6

V1V2V3V4V5V6

V1V2V3V4V5V6

V1V2V3V4V5V6

V1V2V3V4V5V6

© 2017 Artel34

© 2013 ARTEL

Plus Replicates

V1V2V3V4V5V6

V1V2V3V4V5V6

V1V2V3V4V5V6

V1V2V3V4V5V6

V1V2V3V4V5V6

V1V2V3V4V5V6

V1V2V3V4V5V6

V1V2V3V4V5V6

V1V2V3V4V5V6

V1V2V3V4V5V6

V1V2V3V4V5V6

V1V2V3V4V5V6

V1V2V3V4V5V6

V1V2V3V4V5V6

V1V2V3V4V5V6

V1V2V3V4V5V6

V1V2V3V4V5V6

V1V2V3V4V5V6

© 2017 Artel35

© 2013 ARTEL

Should We Randomize?

© 2017 Artel36

© 2013 ARTEL

Fixed Navigation

© 2017 Artel37

© 2013 ARTEL

Example of one QC Kit test result

199 1 2 3 4 5 6 7 8 9 10 11 12

A 202.3 202.1 202.2 202.6 202.5 202.3 202.7 202.4 201.9 201.9 201.7 199.9

B 203 203.1 202.7 202.5 202.6 202.8 202.4 202.8 202.3 202.5 202.1 202

C 202.2 202.2 202.2 202.4 202.3 202.6 202.4 202.6 202.1 202.4 201.7 202.3

D 201.1 200.6 200.5 200.8 201 200.9 201.3 201.3 201.1 200.7 200.5 200.8

E 201.6 201.5 201.5 201.7 201.9 202.5 202 202 202.1 202.1 201.3 202.5

F 201.6 201.3 201.5 201.7 202.1 202.1 202.6 201.8 201.8 201.6 201.5 202.2

G 202.6 202 201.9 202.8 203.1 202.8 203.1 203.4 202.7 202.9 201.8 203.3

H 201.3 200.9 200.7 201.3 201.2 201.9 201.5 200.9 201.1 201.7 201.3 201.7

PrecisionStd Dev = 0.71 µL

CV = 0.35%

TruenessMean Volume = 201.93 µL

Systematic Error = + 0.97%

© 2017 Artel38

© 2013 ARTEL

Precision

© 2017 Artel39

© 2013 ARTEL

1000 µL tips delivering 200 µL

© 2017 Artel45

© 2013 ARTEL

Trueness

© 2017 Artel56

© 2013 ARTEL

Calculate Evaporation Potential

Temp P sat RH P vap P evap

C kPa % kPa kPa

30 0.51 1.20

55 0.94 0.77

80 1.37 0.34

30 0.82 1.92

55 1.50 1.23

80 2.19 0.55

30 1.28 2.98

55 2.34 1.92

80 3.41 0.85

1.71

2.74

4.26

15

22.5

30

© 2017 Artel68

© 2013 ARTEL

Sensitivities in order


V2 200 100 -1.0%

V5 50 25 -1.6%

V1 1000 200 -1.7%

V6 50 10 -2.6%

V3 200 25 -2.8%

V4 200 10 -3.7%

Configuration Sensitivity

per kPa

© 2017 Artel69

© 2013 ARTEL

Conclusions1) Environmental conditions impact any pipetting that incorporates air.

2) Precision was found to be insensitive to temperature and humidity over the

testing range.

3) Trueness was found to depend on the environmental conditions

a. Trueness should be optimization under the local environmental conditions

b. A linear correlation was found between the trueness and the evaporation

potential

c. Fuller tips are less sensitive

c. A stable environment will minimize impact on the business process

4) The QC Kit is unaffected by the environmental conditions.

© 2017 Artel70

© 2013 ARTEL

Final NoteThe precision of the Tecan Freedom EVO ® was found to be

insensitive to environmental conditions and performed within

manufacturer’s limits over the entire range tested in this

study (15 °C to 30 °C and 30% to 80% relative humidity).

Note: Tecan specifies the pipetting behavior of the Freedom

EVO ® under controlled environment conditions (T = 20 °C

to 27 °C; relative humidity at 25 °C between 30% and 60%).

Volumetric performance specifications apply to this

controlled limit. For operation outside these limits meeting

the manufacturer's specifications for volumetric performance

is not guaranteed.

environmental impact on liquid handling...consumer healthcare we make a range of consumer healthcare...

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