Meeting Customers Challenges - Waters Corporation

©2011 Waters Corporation 1

Dr Diego Rodriguez Cabaleiro, June 2012

Waters Europe

Meeting Customers Challenges Regulated Bioanalysis System Solution

Overview


Keen Understanding

BAN World Tour

Executive Technology Forums

Key customer visits

http://www.quotientbioresearch.com/�

http://www.yorkbio.com/�


Key Customer Challenges in Regulated Bioanalysis

Regulated Bioanalysis

Quality and Consistency

of results

Evolving analytical demands

Sensitive, Robust, meets

assay reqs

Increasing regulatory demands

->Up time <-Cost per

sample


Chemistry

ACQUITY Family

Xevo Family

Informatics

Current Individual Offerings


More Innovation Required

Sensitivity potential of the system not realized

Plenty of room to maximize

Existing platforms in place but with compromise

System Performance

Productivity

Validation & Security

System solution


Waters Regulated Bioanalysis System Solution

• Best in class

Sample Preparation Solutions

• The fastest and most resolving LC without compromise in robustness

ACQUITY UPLC® I-Class

• Different choices for best performance

ACQUITY UPLC Columns

• Most sensitive MS

® TQ-S

• Compliant, Interactive workflow-driven data platform

UNIFI

• Installation, maintenance & training • Compliance services

Service


Sample Preparation Solution

•Improves reproducibility & throughput vs LLE and PPT

•Combined PPT and superior phospholipid removal

•Highest sensitivity, selectivity and reproducibility

•Minimal matrix effects

•HLB and mix-mode & all formats available

•Straight forward method development strategy

•Specific biomolecules application kits

•Reduce sample handling vs classic PPT (no centrifugation…)

•Particulate free filtrate

•Automated, simple method development, easy workflow and high troughput (96 well plates)


Complex separation challenges require LC systems that are designed to maximize the benefits of sub 2µm particle columns. — Has minimized dispersion to enhance MS and

UV performance — Lowest carryover complementing MS sensitivity

and extending MS linear dynamic range — The system’s low dispersion, faster cycle-time

allows complex separations can be accelerated without compromising chromatographic fidelity

— Seamless method trasfer

— Robust, proven technology

ACQUITY UPLC I Class


ACQUITY UPLC and Column Choices

•Highest resolution and sensitivity (sub 2µm)

•Straigh forward method development and transfer

•Broad selection of selectivities

•Multiple dimensions

•Broad range of pH and temperatures

•High batch to batch reproducibility

Generic

Polar compounds

Basic compounds

Very polar compounds


Xevo TQ-S

• High Performance and information rich data

• Stepwave • Large increase in sensitivity (all acquisition modes) • Designed to be robust to sample matrix contamination

• Scanwave • Enhanced product ion spectra

• RADAR • Targeted MRM at the same time as full scan MS

• Versatility

• Ion Sources

• Simplicity of Operation

• Engineered Simplicity


UNIFI 1.5: Scientific Information System for Regulated Bioanalysis

Unites our end-to-end system solution

One software for Chromatography & MS

Workflow based design adjusts to roles and capabilities of users

Compliance-ready: Designed for Annex 11 & Part 11 compliance

Will grow with your needs


Waters Service and Support

•Project Management

•System Design & Configuration

•Installation Services

•Training

•Instrument Qualification

•Software Validation

•Repair & Maintenance

•Waters Quality parts

•Method validation

•Method transfer


Sensitive and Robust Data



of results



assay reqs


->Up time <-Cost

per sample



Sample Prep

•High selectivity

•High recovery

•Minimal matrix effects

•Batch-to-batch reproducibility

ACQUITY I Class & Columns

•Narrower peaks

•Lowest carryover

•Column selectivity choices

and MD protocol

•1 mm ID columns

•QC’d columns

•Broad pH and temperature

range

Xevo TQ-S

•Source design

•Minimal dwell time

•StepWave technology

•ScanWave technology

UNIFI

•IntelliStart

•Qualification center

SERVICE

•Compliance Services

•Performance Maintenance

•Application support

•Training


Fluticasone (1.0 pg/mL)

Oasis, UPLC, Xevo TQ-S



ACQUITY UPLC I Class IS the Inlet of Choice for MS

Low Carryover: 5 ng/mL injection of Fluticasone followed

by blank

Fast cycle time Analysis time as low as 45 s


Increasing Regulatory Demands



of results



assay reqs


->Up time <-Cost

per sample


Increasing Regulatory Demands: GLP and 21 CFR 11 Compliance

UNIFI

•Embedded relational database

•Workgroup

•Comprehensive Audit trail

•Electronic signature

•Built-in Qualification Center

•Central repository of work-flow based SOP’s

•Fileless connection to Watson LIMS

•Structurally Validated calculation of ISR

•Automatic calculation and comparison of Matrix Effect Factor

WATERS SERVICES

•Compliance service and consultancy

•Instrument Qualification & Software Validation


Reducing Software Validation Barrier

Present Future Desire

Barriers

SO

FTW

AR

E

VA

LID

ATIO

N

GAMP 5 for COTS Leverage Vendor testing Test Summary document Vendor Quality systems Supplier Audit

Built in Tools for Qualification Qualification Centre to manage IQ and OQ of Software and Instrument Portal installation on Clients

Built in Tools for Verification Development of common Validation Scripts Built in tools to automate running and documenting scripts

Validation Consulting Integrate common scripts into a complete validation package customised to Customer protocols


Leveraging Vendor Services

IQ

IQ

Simple OQ

Extended OQ PQ or UAT’s

PQ or UAT’s

IQ Comprehensive Validation Services

IQ Simple OQ

PQ or UAT’s PQ or UAT’s Vendor Factory Testing


Step 1 Step 2 Step 3 Step 4 Step 5

Create Analysis from LIMS Sample List

Review Results and Verify Quality Measures

Electronically approve the batch result report

Select batch result analysis for export

Verify batch selection then export

UNIFI Workflow with Watson LIMS



Create Analysis Then Pick a Sample List

Click

Select



Review Results and Verify Quality Measures

Evaluate



Electronically Approve the Batch Result Report


Select the Batch Result Analysis for Export

Export




Verify Batch Selection Then Export

Click

Export


Increasing Regulatory Demands - Matrix Interference

•Nature

•Is sample dependent: gender, age, diet, life style, metabolites and co-administered therapies

•Due to endogenous or exogenous materials

•Very common is in matrix effects are the phospholipids not resolved from analytes

•Impact

•Influences ionization process

•Bad sensitivity and irreproducibility

•Causes batch failures



Sample Prep •Cleanest sample

•Minimized matrix effect

•Method development

ACQUITY I Class & Columns •Lower dispersion •Broad column selectivity choices •Broad pH and temperature range •Highest resolution •Method development&transfer

Xevo TQ-S •RADAR

UNIFI •Matrix factor calculator

•Comparison within batch

SERVICE •Application support

and troubleshooting

•Method Validation

•Method Transfer



Protein Precipitation

MRM

Full Scan (Extracted

Interference)

Protein precipitation Monitor Alprazolam MRM 309->281 7.03e6

SPE Monitor Alprazolam MRM 309->281 1.56e6

SPE Background ms scan 2.61e7

Protein precipitation Background ms scan 2.44e8


TargetLynx

New Capabilities Integrate Into the Environment to Create New Workflows

Automatic calculation Of matrix

factor

UNIFI Meets Expectations


Increasing Regulatory Demands - Incurred Sample Reanalysis Defined

• Incurred Sample Reanalysis (ISR) discussions at Crystal City Meeting, February, 2008; followed by CVG (Canada), EBF (Europe)

• Focused upon improving assay reproducibility and monitoring storage, shipping & handling of samples

• Requires the reanalysis of a percentage of the samples from a study, typically 5-15%. 2/3 of the repeat samle concentrations must be within 20% of the original

• This places greater emphasis on the quality of the methodology


Increasing Regulatory Demands - Incurred Sample Reanalysis (ISR)

Sample Prep •Minimized matrix effect

•Reproducibility: well-to-well, plate-to-plate, lot-to-lot

ACQUITY I Class & Columns •Column batch-to-batch reproducibility •Instrument repeatability (ex: APH)

Xevo TQ-S •RADAR

UNIFI •Database to retrieve original data

•Critical quality criteria automatically checked

SERVICE •Application support and

•troubleshooting


0

50

100

150

200

250

300

Amitriptyline

Original Assay (ng/mL)

Repeat Analysis (ng/mL)

N

CH3

CH3

Amitriptyline MW 277.4 pKa = 9.4

0

50

100

150

200

250

300

350

400

Nortriptyline

Original Assay (ng/mL)

Repeat Analysis (ng/mL)

N

CH3

CH3

Nortriptyline MW 263.3 pKa = 9.7

Increasing Regulatory Demands - Incurred Sample Reanalysis (ISR)


Increasing Regulatory Demands - Metabolites in Safety Testing (MIST)

• Requirement to control metabolites at >10% of the drug substance

in blood

• Need for identification those metabolites

• Need for development and validation of quantitative methods


ACQUITY UPLC I Class

& Columns

•Minimized metabolite

co-elution

•Low dispersion

•Column selectivity

•Broad pH and

temperature range

Xevo TQ-S

•Stepwave

• RADAR

• Enhanced PIC

(Product Ion Confirmation)

Sample Prep •Recovery

UNIFI •Database to retrieve original data

•Critical quality criteria automatically checked

•IntelliStart

SERVICE •Application support and troubleshooting

Increasing Regulatory Demands - Metabolites in Safety Testing (MIST)


Benefits Metabolites detected

with maximum sensitivity

Spectra acquired in the time scale of UPLC peak

Data acquired in one analytical run, no need for confirmatory experiment

Time0.50 1.00 1.50 2.00 2.50

%

0

100

18_4_022 5: MRM of 1 Channel ES+ 458.195 > 339.845 (AZ1_Hydroxylation)

3.77e5

m/ z1 00 12 0 1 40 1 60 18 0 2 00 2 20 24 0 2 60 28 0 30 0 3 20 34 0 36 0 3 80 40 0 42 0 4 40 46 0

%

0

1 00

18 _4 _0 23 3 ( 2. 07 8) 5: Pro du c t I on s o f 4 58 ES+45 8. 19 5 > 3 39 .84 5 (AZ1_ Hy dro x y la tion )

1.9 2e 5326

315

340

354

m/ z1 00 12 0 14 0 16 0 18 0 2 00 2 20 2 40 26 0 28 0 30 0 3 20 3 40 3 60 38 0 40 0 42 0 44 0 4 60

%

0

1 00

18 _4 _0 25 5 ( 2. 14 0) 3: Pro du c t I on s o f 4 42 ES+44 2.2 > 32 5. 84 7 ( AZ 1_ Par en t)

8.9 8e 6326

313

340

425

Time0.50 1.00 1.50 2.00 2.50

%

0

100

18_4_025 3: MRM of 1 Channel ES+ 442.2 > 325.847 (AZ1_Parent)

1.08e8

Time0.50 1.00 1.50 2.00 2.50

%

0

100

18_4_022 1: MRM of 1 Channel ES+ 416.148 > 325.847 (AZ1_Dealkylation)

5.66e6

m/ z1 00 1 20 14 0 16 0 1 80 20 0 22 0 2 40 2 60 28 0 30 0 3 20 340 36 0 3 80 4 00 42 0

%

0

1 00

18 _4 _0 23 4 ( 1. 97 6) 1: Pro du c t I on s o f 4 16 ES+4 16 .1 48 > 32 5. 84 7 ( AZ1 _D ea lk y la tion )

5.5 6e 5326

313298

340

Time0.50 1.00 1.50 2.00 2.50

%

0

100

18_4_022 2: MRM of 1 Channel ES+ 428.184 > 325.829 (AZ1_Demethylation)

3.58e6

m /z10 0 12 0 140 1 60 1 80 20 0 22 0 24 0 260 2 80 3 00 3 20 34 0 36 0 380 4 00 4 20

%

0

1 00

18_ 4_ 023 3 (1 .87 1) 2 : Pro du ct I ons of 428 ES+42 8.1 84 > 3 25 .82 9 ( AZ1 _De me thy la tio n)

3. 92 e4326

147235

176

340

Dealkylation Demethylation

Dosed Compound

MRM 442.2>326

HydroxylatedMetabolite

MRM 458.2>340

PIC Spectrum

PIC Spectrum

PIC Spectrum

PIC Spectrum

Increasing Regulatory Demands Metabolites in Safety Testing (MIST)


Quality and Consistency of Results



of results



assay reqs


->Up time <-Cost

per sample


Quality and Consistency of Results

Sample Prep

•Minimized matrix effect

•15 years of proven reproducibility

ACQUITY I Class & Columns

•Lot-to-lot column reproducibility

•Holistic instrument design

Xevo TQ-S

•Harmonized performance between instruments

•Engineered simplicity

UNIFI

•One method to transfer

•Sharing of methods and results via client/server

•IntelliStart


•Buit-in tool for change control/Audit trail

SERVICE •Instrument Qualification

•Software Validation

•Method Validation

•Method Transfer


System Uptime & Cost per Sample



of results



assay reqs


->Up time <-Cost

per sample


Maximize System Up Time Minimize Cost per Sample

Sample Prep •µElution plate

•Cost of plates vs cost of entire process

•Cost of plates vs cost of risk on data quality

ACQUITY I Class&Columns •Proven UPLC

•Faster analysis

•Solvent reduction

•Better utilization of MS resource

•Proven column life time

Xevo TQ-S •Robust source design

•Source versatility

•RADAR

•PIC

•Engineered simplicity

UNIFI •Tailored workflow and user interface

•Watson LIMS connection

•Secure and compliant


•Electronic signature

•Built-in tool for change control

•Client/server ↑ sharing ↓ error/redundancy

SERVICE •Award-winning service

•Performance Maintenance

•Application support

•Training


Evolving Analytical Demands - Bioanalysis of Peptides



of results



assay reqs


->Up time <-Cost

per sample


• Importance

• Promissing drugs counting for 15-20% of the drug development pipeline

• Biomarkers for many disease states

• Limitations of current instrumentation

• Appropriate mass range not addressed by SCIEX

• Challenging separation from protein plasma matrix

• Manual and slow LC/MSMS method development

• Carryover

•Succesful customers using Waters Solution

•Johnson & Johnson (Europe), SGS (France), Lundbeck(Denmark), York (UK)…



Sample Prep •PST plates & protocol

•µElution plate

•No evaporation & reconstitution

•15x concentration

ACQUITY UPLC I Class & Columns •Lower dispersion •Dedicated PST columns •Longer columns if needed •Lowest carryover

Xevo TQ-S •Stepwave •Mass range •Minimal dwell time •RADAR •PIC

SERVICE •Application support and troubleshooting

UNIFI •IntelliStart and BioLynx functionalities

•Multiple charge precursor ions



Evolving Analytical Demands - Peptide Biomarker

Amyloid β 0.1 ng/mL Oasis (MCX µ-elution), UPLC, Xevo TQ-S


Evolving Analytical Demands - Peptide Therapeutics

Desmopressin 1 pg/mL Oasis, UPLC, Xevo TQ-S


Regulated Bioanalysis System Solution Summary

No compromises — Total solution for the best in sensitivity, data quality and productivity, while

meeting compliance demands

Focus where it belongs – on the science — Spend time being scientists…not systems integrators

Leverage technology in real time — Take advantage of the latest technologies as they happen

An investment for today and the future — Immediate success, and ready to evolve with future analytical demands

Partnering for the complete solution — Expert service and support maximizes your return on investment

Documents

Meeting Customers Challenges - Waters Corporation