Data Management and Electronic Publication (SDMS/VP)...o Decrease document storage costs. ... — Electronic COA, eCTD submission process, LIMS, eNotebooks, Next Step: Electronic Worksheets

Data Management and Electronic Publication Data Management and Electronic Publication Data Management and Electronic Publication Data Management and Electronic Publication (SDMS/VP)(SDMS/VP)

Chris Chris StumpfStumpf, Ph.D., Ph.D.Senior Product Marketing ManagerSenior Product Marketing Manager

©2010 Waters Corporation | COMPANY CONFIDENTIAL

Corporate Business ObjectivesCorporate Business Objectivesp jp j

Increase Market Share

o Increase Market Coverage

o Increase New Product Offerings

Reduce Time to marketReduce Time to market

o Optimize Operations

o Decrease Development /Cycle Time

Increase asset utilization

o Decrease R&D or Lab Space

o Utilize 3rd Party Resouceso Utilize 3rd Party Resouces

o Do more with less/minimize duplication

Decrease Costs

©2010 Waters Corporation | COMPANY CONFIDENTIAL 2

o Decrease record review

o Decrease document storage costs

Strategic Operational NeedsStrategic Operational Needsg pg p

Improve productivity/faster analysisImprove productivity/faster analysis Lower cost of analysisLower cost of analysis Lower cost of analysisLower cost of analysis Improve results qualityImprove results quality Make scientific information more accessible across Make scientific information more accessible across

t it i

Eliminate duplicate effortEliminate duplicate effort

enterpriseenterprise

Eliminate duplicate effortEliminate duplicate effort Streamline regulatory submission Streamline regulatory submission

processesprocesses Defend intellectual propertyDefend intellectual property Defend intellectual propertyDefend intellectual property


Waters Informatics StrategyWaters Informatics Strategygygy

Open Design

InteroperabilityInteroperability

Integrations

Application Specific Solutions Application Specific Solutions


Case StudiesCase Studies

QC & Manufacturing Organization

R&D Global Analytics & Med Chem




The Case Study ChallengeThe Case Study Challengey gy g

Manage Analytical Data for a Global Pharmaceutical Organization by using a centralized data repository


Aims of the ProjectAims of the Projectjj

Single system for storing and retrieving all analytical dataSingle system for storing and retrieving all analytical data— All discovery sites world-wide (both internal & external)

— Integration with existing informatics tools

Single requesting tool for specialized analytical analyses

Replace existing in-house Oracle-base storage system— Integrated with in-house chemical structure systems


Project Design PlansProject Design Plansj gj g

Minimize data transfer around the world

No need for user training— No need to know where data was acquiredq

— Simple, intuitive user-interface

Allow multiple interfaces to the system Allow multiple interfaces to the system

Manage data retention policies— Automatically delete classes of data after a certain time

Integrate with CambridgeSoft eLNB



A Scientific Data Management A Scientific Data Management System SelectedSystem Selectedyy


Selection of SDMS over LIMSSelection of SDMS over LIMS

Analytical Request

Result Values

LIMS

Result Values


SDMS and LIMS are complimentary SDMS and LIMS are complimentary solutionssolutions

Data CentricSample CentricCompliant-ready Data Management (Printed Records & Instrument Data)

pSample Management

SchedulingResource Planning

Training & Certification

LIMS SDMS

gTest Specifications

LIMS SDMS

Instrument InterfacingWorksheets


WorksheetsELN

Calculations

The Solution ArchitectureThe Solution Architecture

C t HQ Remote Operations (n)Corporate HQ Remote Operations (n)

Data Center Laboratory

Database Catalog Managed Storage

Web Servers File Capture AgentsWeb Servers p g


Medicinal & Analytical Chemists

Meta Data

Raw Data

The Web InterfaceThe Web Interface


Integration with Integration with CambridgeSoftCambridgeSoft eLNBeLNBgg


Integration with Structure SearchesIntegration with Structure Searchesgg


Alignment with Project Plan?Alignment with Project Plan?g jg j

Minimize data transfer around the world

No need for user training— No need to know where data was acquiredq

— Simple, intuitive user-interface

Manage data retention policies Manage data retention policies— Automatically delete classes of data after a

certain time

Allow multiple interfaces to the system




The User Response?The User Response?pp

80% use it daily 80% use it daily

86% didn’t attend a training session

100% were able to use the system without help100% were able to use the system without help

100% agree that the system is easy to use

80% agree that the system aids their productivity80% agree that the system aids their productivity

96% are satisfied or very satisfied with the system


Case Study Exampley p

QC & Manufacturing OrganizationQC & Manufacturing Organization


Strategic Business NeedStrategic Business Needgg

VP of Operations:: Make a more Efficient Product Make a more Efficient Product Manufacturing Process.Manufacturing Process.


A Look at the Industry’s QC A Look at the Industry’s QC Cycle TimeCycle Timeyy


Reference: Raju, G.K., New Opportunities for Pharmaceutical Manufacturing, a 2001 presentation to FDA’s Science Board, www.pharmamanufacturing.com/whitepapers/2004/118.html

Identifying the BottleneckIdentifying the Bottlenecky gy g



Consequences of Delayed Certificate Consequences of Delayed Certificate of Analysisof Analysisyy

Limited shelf life Limited shelf life— A 15 day COA delay represents 17% of a 90 day shelf life for a

pharmaceutical product

Late/Non-shipment May translate into millions of dollars of lost revenue per batch— May translate into millions of dollars of lost revenue per batch

— May allow competitors to build market share with similar products


Industry Strategy for Improving Operational Industry Strategy for Improving Operational EfficiencyEfficiencyyy

Lean Waste Elimination

Waste Elimination

Workflow Improvement

Workflow Improvement

Cycle Time ReductionCycle Time Reduction


Quality Laboratory Environment at Quality Laboratory Environment at start of Project in 2006start of Project in 2006jj

Instrument Acquisition SystemsInstrument Acquisition Systems— No Standards (vendors, configuration, data (methods),

support)

— Unsecured data (poorly designed & managed infrastructure)— Unsecured data (poorly designed & managed infrastructure)

— Poor design in response to regulatory requirements

Chromatography— Locally supported networked CDS

— Different vendor solutions

Laboratory Information Managementy g— A variety of LIMS solutions acquired through mergers &

acquisitions

— Little or no standardization in process, data and software


Little or no standardization in process, data and software

Business Project ObjectivesBusiness Project Objectivesj jj j

Develop an analytical environment with the following Develop an analytical environment with the following characteristics— Compliant

Standardized— Standardized

— Current

— Agile

— Cost effective


Identifying a Quality Laboratory Identifying a Quality Laboratory Standard ModelStandard Model

Adoption of the ISA S95 standard to structure a Global Manufacturing & Supply Operation


Informatics Implementation Steps used to Informatics Implementation Steps used to StreamStream--line Certificate of Analysis Processline Certificate of Analysis Processyy

1• Standardize Chromatography

Data System (CDS)

2• Standardize LIMS

2

d d3

• Standardize SDMS


Internal Review revealed several Internal Review revealed several varieties of CDS and LC Solutionsvarieties of CDS and LC Solutions


Standardize Testing Equipment on One Standardize Testing Equipment on One Chromatography Data SystemChromatography Data Systemg p y yg p y y


Continue to Leverage Capital Investments by using a Standardized Chromatography Data Systemy


Advantages of a Common Chromatography Data System Platformg p y y

Standardized Data formatStandardized Data format— Exchange of information easier— Reduced time for Review and sign-off

Reduced Training Effort

— Training required for only 1 software package

Improved Compliance

— Relational database provides better traceability

Promotes Collaboration

—Sharing methods easier—Data review from different geographies possible


g g p p

Standardized Chromatography Data System Standardized Chromatography Data System Streamlines Method ValidationStreamlines Method Validation


Next Step involved standardizing the Next Step involved standardizing the LIMS interfacesLIMS interfaces


Standardized LIMS Platform Standardized LIMS Platform streamlines ERP & CDS workflowstreamlines ERP & CDS workflow


Advantages of Implementing ERP Advantages of Implementing ERP and LIMS Solutionsand LIMS Solutions

Automates Testing RequestsAutomates Testing Requests— Issues QC test requests after receiving request from SAP

— Generates sample worklists

Single location to store testing results— QC Test Results stored within single LIMS from regional

Empower systems

— COA stored in LIMS


Automating the Workflow for Automating the Workflow for Remaining Testing Equipment?Remaining Testing Equipment?g g q pg g q p


Centrally Store Laboratory Data to Centrally Store Laboratory Data to Automate COA GenerationAutomate COA Generation


Feeding the LIMS Simplifies Feeding the LIMS Simplifies Laboratory WorkflowsLaboratory Workflowsyy


LIMS and SDMS are complimentary LIMS and SDMS are complimentary solutionssolutions

Data CentricSample CentricCompliant-ready Data Management (Printed Records & Instrument Data)

pSample Management

SchedulingResource Planning

Training & Certification

LIMS SDMS

gTest Specifications

LIMS SDMS

Instrument InterfacingWorksheets


WorksheetsELN

Calculations

2009 Warning Letters Raw Data2009 Warning Letters Raw Datagg

February 2009February 2009— no raw data used to support the verification of the software

used in … device.

— Failure to store and retain all raw data documentation — Failure to store and retain all raw data, documentation, protocols, final reports …generated as a result of nonclinical laboratory studies. (21 CFR §§ 58.190(a) and 58.195(b)].

March 2009 March 2009— The inspection revealed the absence of supporting data for

these products, including raw data for sensitivity studies; accelerated and real-time stability study data and protocols; accelerated and real-time stability study data and protocols; reproducibility data; and cut-off testing data, interference, pH and specific gravity data. Likewise, gas chromatography/mass spectrophotometry data and method comparison data for the


p p y pDrugs of Abuse Screening Tests was missing.

2009 2009 Warning Letters Warning Letters Raw DataRaw Datagg

May 2009May 2009— Raw data for definitive trial … were changed by the

study director without explanation.

August 2009 August 2009— a. Raw data (e.g., chromatograms, standard and sample

weights, calculations, standards, reagents, and instrument information) for And related substances method validation information) for …. And related substances, method validation were not available during the inspection.

©2010 Waters Corporation | COMPANY CONFIDENTIAL 41Injection Result

Advantages of a standardized Advantages of a standardized informatics solutioninformatics solution

SDMS captures laboratory data from different systems into a common data format

Data originating from different geographies — Captured and cataloged in a common formatCaptured and cataloged in a common format

Streamlined workflows and cycle-times— Reduced wasted efforts reduce operational costs

Management has better visibility to the big pictureManagement has better visibility to the big picture— Identify problems earlier

A t f d t


Acts as a feeder system — Electronic COA, eCTD submission process, LIMS, eNotebooks,

Next Step: Electronic WorksheetsNext Step: Electronic Worksheetspp


Significant Time Spent on QC Significant Time Spent on QC DocumentationDocumentation

Cycle Time ComponentsSTEPS

Process/Unit OperationInterruption of the process

Cycle Time ComponentsIN QC/QAIN THE PROCESS/PLANT

p pSecuring of sample from processHolding of sample in plantDocumentation and verification of samplingTransferring of samples to QC LabBatching of samples in QCPreparation of test samplesActual test-separationActual test-measurementTest data collection and processingDocumentation and verification of testingTransferring of results for reviewTransferring of results for reviewDecision regarding impact on process

Process StepManual OperationInventory Hold


yTesting & Documentation


Combine SOP and Data Entry by Combine SOP and Data Entry by using Electronic SOP Formsusing Electronic SOP Formsgg

Stock No. 123456

34 Maple Street, Milford MA 01757Phone: 1-800-252-4752 Fax: 1-508-482-2004

Stock PreparationStep 1: Weigh the following into a clean dry 100 mL class "A" volumetric flask

SOPCompound Source Exp Desired (mg) Actual (mg)

a: Diphenhydramine VMR 22-Nov-07 40 23.13

b: Pseudoepherine HCL Bayer 11-Jan-08 600 6.72

c: Dextromethorphan HBr BASF 10-Feb-08 200 24.16

Table Continued. Batch No.

a: Diphenhydramine DIP-003

b: Pseudoepherine HCL PSD-02

c: Dextromethorphan HBr Dextromethorphan Hbr39398.8115751157

Compound Source Exp Desired (mL) Actual (mL)H2O-01 Waters 10-Feb-08 50 49.98

Step 2: Add 50 mL of purified WaterDextromethorphan HBr

volumetric flask.

Acceptable ( Conc (mg/mL) Total (mg)Std. A N 0.05 54.01

Balance ID No. Cal/Qual DateSrN-11679-B4 4-Nov-07

Confidential.

Step 3: Add purified Water to volumetric flask bringing solvent level to 100 mL.

Note: Swirl (sonicate if necessary) to dissolve completely.

Standard Details:

Balance Details:

Data Entry


Data Entry

An Electronic SOP Form can An Electronic SOP Form can integrate with ...integrate with ...gg


Direct interface with balances and pH Direct interface with balances and pH meters reduces transcription errorsmeters reduces transcription errorspp

<CR> 9.876 unit mg 09/08/2008 wli4345a tare y<CR><LF>mg

Stock No. 123456

9.876 mg

Compound Source Exp Desired (mg) Actual (mg)

a: Diphenhydramine VMR 22-Nov-07 40 23.13

b: Pseudoepherine HCL Bayer 11-Jan-08 600 6.72

c: Dextromethorphan HBr BASF 10-Feb-08 200 24.16

Table Continued. Batch No.

a: Diphenhydramine DIP-003

b: Pseudoepherine HCL PSD-02

c: Dextromethorphan HBr Dextromethorphan Hbr39398.8115751157

Compound Source Exp Desired (mL) Actual (mL)H2O-01 Waters 10-Feb-08 50 49.98

Step 2: Add 50 mL of purified WaterDextromethorphan HBr

34 Maple Street, Milford MA 01757Phone: 1-800-252-4752 Fax: 1-508-482-2004

Stock PreparationStep 1: Weigh the following into a clean dry 100 mL class "A" volumetric flask.

Note: Swirl (sonicate if necessary) to dissolve completely.

Acceptable ( Conc (mg/mL) Total (mg)Std. A N 0.05 54.01

Balance ID No. Cal/Qual DateSrN-11679-B4 4-Nov-07

Confidential.

Step 3: Add purified Water to volumetric flask bringing solvent level to 100 mL.

Standard Details:

Balance Details:


Example of an Intelligent SOP FormExample of an Intelligent SOP Formp gp g

Balance Interface

Chemical Inventory Interface

Auto Calculations

Fit for use Interface


Fit-for-use Interface

Error Proofing

Advantages of Intelligent Advantages of Intelligent WorksheetsWorksheets

Reduces Errors — Standardizes Data Input and Performs Error Proofing (~0%)p g ( )

— Reduces Transcription Errors by directly interfacing with other data sources (~ 0%)

Improves Data Review and Regulatory Compliance— Procedure documenting (up to ~80% faster)

— Easy Review of Centralized Results (~50% faster)

— Compliant-Ready SolutionCompliant Ready Solution

Improves Quality


— Management has immediate access to data

— Promotes collaboration between teams

ConclusionConclusion

Case studies Achieved a Standardized Data Management OperationBased on Standardization of CDS SDMS and LIMS (for QC)— Based on Standardization of CDS, SDMS, and LIMS (for QC)

A Centralized SDMS Provides Standardized Data Management — Improves laboratory productivity

— Centralizes all data into one location and improves compliance

— Acts as a data integrator and connector for all scientific information -certificate of analysis eCTD submissions and Electronic Laboratory certificate of analysis, eCTD submissions, and Electronic Laboratory Notebooks

A Standardized CDS Platform A Standardized CDS Platform — provides standardized data format, reduces training effort, improves

compliance and promotes collaboration



Documents

Data Management and Electronic Publication (SDMS/VP)...o Decrease document storage costs. ... — Electronic COA, eCTD submission process, LIMS, eNotebooks, Next Step: Electronic Worksheets