Workshop on

Lean & 6 Sigma Principles for Labs in

Regulated Development & QC using
Informatics Case Studies

John Beary
Nordic User Training 2013

©2011 Waters Corporation 1

 Workshop Description

 In this workshop, the importance of Informatics solutions for

laboratory related Lean Six Sigma projects will be discussed

 We will explore how our Customers have leveraged Waters'

Laboratory Informatics solutions to support these initiatives by:
— Eliminating waste and defects
— Reducing variability
— Improving quality

©2011 Waters Corporation 2

 Pharma Continues to Embrace Operational
Excellence as Profitability is Pressured

©2011 Waters Corporation 3

 Roche - Area of Impact:
Laboratories

Champaneria, Nitin J., Lean Six Sigma and Operational Excellence at Roche, WCBF’s Lean & Six Sigma Summit – Chicago,
June 2009 http://www.sixsigmazone.com/presentations/lean-six-sigma-and-operational-excellance-at-roche
©2011 Waters Corporation 4
 Roche – List of Selected Projects

Champaneria, Nitin J., Lean Six Sigma and Operational Excellence at Roche, WCBF’s Lean & Six Sigma Summit – Chicago,
June 2009 http://www.sixsigmazone.com/presentations/lean-six-sigma-and-operational-excellance-at-roche
©2011 Waters Corporation 5
 Strategies to
Increase Efficiency and Quality

Lean
Increasing efficiency by eliminating unnecessary
steps within a process and reducing waste.

Six Sigma
Improve processes by eliminating
defects and reducing variability.

©2011 Waters Corporation 6

 Lean & Six Sigma

Lean Management
 Eliminate non-value added activities (waste)
 Reduce complexity
 Improve flow
Improve Speed

Six Sigma
 Reduce variation
 Reduce defects
 Reduce Cost of Poor Quality (COPQ)
Improve Quality

©2011 Waters Corporation 7

 Identifying Value and Non-Value
Added Activities

An Overview of Process Excellence and Lean Thinking at Johnson & Johnson, Edwin Nau, May 2007
http://www.ispe.org/galleries/midwest-files/ISPE-NauPresentatio98C9BA.pdf
©2011 Waters Corporation 8
 Business Demands

CEO CIO

You

Project
Scientists Managers

Laboratory Demands

©2011 Waters Corporation 9

 An Overview of Lean Six Sigma

Lean
Eliminate unnecessary, non-value added steps
within a process. Principles of “flow” and “pull”.
Makes sure we are working on the right
activities

Six Sigma
Improve processes by eliminating
defects and reducing variability

©2011 Waters Corporation 10

 Lean is the Elimination of Waste…

7 Kinds of Waste
Processing Motion
Inefficiency due Any movement that
to poor tool or does not added value
design

Defect/Rework Waiting
Not doing or making Waiting on parts,
it right first time or for a machine
to finish cycle

Inventory Transportation
Any more than the Any non-essential
minimum to get the Overproduction transport is waste
job done Producing too much,
or too soon

…waste elimination can be applied to any process

©2011 Waters Corporation 11
 Laboratory-Based
Workflows and Systems

 Harmonization & Standardization

 Centralization

 Reduce the Total Number of Software Applications

 Software Integration and Interoperability

 Improve Laboratory Efficiencies

 Lower Total Cost of Ownership

Removing WASTE, VARIABILITY, and RISK

©2011 Waters Corporation 12
 QC Workflow Analysis

From sampling instruction to

Sampling certificate of analysis creation,
where are the largest
Worklist
opportunities to minimize waste
Creation and variability?
Select SOP

Test
Execution

Complete SOP
Worksheet

Certificate of Analysis
Creation

©2011 Waters Corporation 13

 Situational Analysis: Identifying
Potential Areas of Improvement

©2011 Waters Corporation 14

 Situational Analysis: Identifying
Potential Areas of Improvement

©2011 Waters Corporation 15

 Situational Analysis: Identifying
Potential Areas of Improvement

©2011 Waters Corporation 16

 Potential Areas of Improvement:
Workflow Optimization

 Examples

— Analysis timelines

— Customized text and calculations

— Processing methods

— Asset utilization

©2011 Waters Corporation 17

 Analysis Timelines

 Use of e-signatures within Empower allows detailed analysis of

result workflow through the lab

 Metrics that can be calculated:

— First injection to first result processing
— First result processing to last result generation
— Last result generation to first sign off (level 1)
— First sign off to second sign off (level 2 review)
— Total time
— All metrics measured in days

©2011 Waters Corporation 18

 Discovering Waste and Variability
in Analysis Timelines

Project 1
Project 2
Project 3
Project 4
Project 5
Project 6
Project 7
Project 8
Project 9
Project 10

Project 1

Project 2

Project 3
Project 4

Project 5
Project 6

Project 7
Project 8

Project 9

Project 10

©2011 Waters Corporation 19

 Custom Text and Calculations

 Text fields (enumerated custom fields)

— Provide consistent format and searchability using drop-down lists

 Calculated fields
— Perform custom calculations
such as percent purity without relying
on external calculations or specialized
software programs

©2011 Waters Corporation 20

 Optimize Use of Custom Fields

Project A

Project B

Project C

Project D

Project E

Project F

Project G

Project H

Project I

Project J

Project K

Project L

Project M

Project N

Project P

©2011 Waters Corporation 21

 Processing Method Optimization

 Automated processing preferred versus manual integration

— Saves time
— Provides better result integrity
 Review number of results per channel
 Review percentage of results requiring manual integration

©2011 Waters Corporation 22

 Asset Management

 Asset utilization within the laboratory

— Specifically those assets controlled by Empower 3
o HPLC
o GC
— Is asset use optimized to the workload?
— Can asset servicing be conducted without impacting lab
productivity?

©2011 Waters Corporation 23

 Opportunities with Asset Utilization

©2011 Waters Corporation 24

 Minimizing Waste
with Asset Utilization

©2011 Waters Corporation 25

 Instrument/User ‘Flexibility’

©2011 Waters Corporation 26

 Lean is the Elimination of Waste…

7 Kinds of Waste
Processing
Information sent automatically Motion
even when not required, Looking for data and
printing documents before information, re-entering
they are required, spreadsheet data, filing hardcopies,
data calculations document archiving

Defect/Rework Waiting
Incorrect data entry, Waiting for the next step,
manual re-integration, system downtime,
incorrect calculations, hardcopy retrieval, audit
outdated SOP’s, delays, review delays,
regenerating data approval delays

Inventory Transportation
Files and documents Movement of files and
awaiting to be Overproduction documents from one
processed, material Too much paperwork, location to another,
queued for release, excessive lead time from storage of intermediaries
documents awaiting approval delays waiting for approvals
signature

…Waters Informatics can impact these

©2011 Waters Corporation 27
 Case Study Example

QC & Manufacturing Organization

©2011 Waters Corporation 28

 Consequences of
Delayed Certificate of Analysis

 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 allow competitors to build market share with similar products

©2011 Waters Corporation 29

 Strategic Need: Making the
Manufacturing Process More Efficient

VP of Operations:: Make a More Efficient Product

Manufacturing Process

©2011 Waters Corporation 30

 Strategy for Improving
Operational Efficiency

Lean Waste
Elimination
Workflow
Improvement
Cycle Time
Reduction

©2011 Waters Corporation 31

 Informatics Implementation Steps Used to
Streamline Certificate of Analysis Process

• Standardize Chromatography Data

System (CDS)
1

• Standardize Data Management

2
• Implement Electronic SOP
Documentation and Workflow
3 System

©2011 Waters Corporation 32

 Standardize Testing Equipment on
One Chromatography Data System

©2011 Waters Corporation 33

 Operational Excellence:
Advantages of a Common CDS Platform

 Standardizes data format

— Exchange of information easier
— Reduces time for review and sign-off

 Reduces training effort

— Training required for only 1 software package

 Improves compliance
— Relational database provides better traceability

 Promotes collaboration
— Easier sharing of methods
— Data review from different geographies possible

©2011 Waters Corporation 34

 Empower Enables CDS Standardization by
Supporting Multi-Instrument Vendor Control

©2011 Waters Corporation 35

 Standardized Chromatography Data
System Streamlines Method Validation

©2011 Waters Corporation 36

 Standardized Chromatography Data
System Streamlines Method Validation

©2011 Waters Corporation 37

 Standardized Chromatography Data
System Streamlines Method Validation

©2011 Waters Corporation 38

 Business Intelligence for a
Standardized CDS

Empower Driven Services

©2011 Waters Corporation 39

 Add LIMS to Manage COA and
Use ERP to Manager Orders

©2011 Waters Corporation 40

 Add LIMS to Manage COA and
Use ERP to Manager Orders

©2011 Waters Corporation 41

 OpEx: Advantages of Integrating
ERP and LIMS Solutions

 Automates 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

©2011 Waters Corporation 42

 Centrally Store Laboratory Data to
Automate COA Generation

©2011 Waters Corporation 43

 Centrally Store Laboratory Data to
Automate COA Generation

©2011 Waters Corporation 44

 Centrally Store Laboratory Data to
Automate COA Generation

An Automated
Certificate of Analysis
Process
Standardized
Lab Data Management

Focus on
Science and Testing

©2011 Waters Corporation 45

 Centralized Data Storage Enables
the Use of Intelligent Forms

©2011 Waters Corporation 46

 Centralized Data Storage Enables
the Use of Intelligent Forms

©2011 Waters Corporation 47

 Combine SOP and Data Entry
by Using Electronic SOP Forms

Stock No. 123456

34 Maple Street, Milford MA 01757

Phone: 1-800-252-4752
Fax: 1-508-482-2004

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

SOP
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

Step 2: Add 50 mL of purified WaterDextromethorphan HBr

Compound Source Exp Desired (mL) Actual (mL)

H2O-01 Waters 10-Feb-08 50 49.98

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

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

to 100 mL.

Acceptable (Y/N)
Conc (mg/mL) Total (mg)
Standard Details:
Std. A N 0.05 54.01

Balance ID No. Cal/Qual Date

Balance Details:
SrN-11679-B4 4-Nov-07

Data Entry
Confidential.

©2011 Waters Corporation 48

 An Electronic SOP Form
Can Integrate with ...

©2011 Waters Corporation 49

 Direct Interface with Balances and pH
Meters Reduces Transcription Errors

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

Stock No. 123456

34 Maple Street, Milford MA 01757

Phone: 1-800-252-4752
Fax: 1-508-482-2004

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

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

9.876 mg
Table Continued. Batch No.
a: Diphenhydramine DIP-003
b: Pseudoepherine HCL PSD-02
c: Dextromethorphan HBr Dextromethorphan Hbr39398.8115751157

Step 2: Add 50 mL of purified WaterDextromethorphan HBr

Compound Source Exp Desired (mL) Actual (mL)

H2O-01 Waters 10-Feb-08 50 49.98

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

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

to 100 mL.

Acceptable (Y/N)
Conc (mg/mL) Total (mg)
Standard Details:
Std. A N 0.05 54.01

Balance ID No. Cal/Qual Date

Balance Details:
SrN-11679-B4 4-Nov-07

Confidential.

<CR> 9.876 uni

©2011 Waters Corporation 50

 Example of an Intelligent SOP Form

Balance Interface

Chemical Inventory Interface

Auto Calculations

Fit-for-use Interface

Error Proofing
©2011 Waters Corporation 51
 Operational Excellence:
Advantages of Intelligent Forms

 Reduces errors
— Standardizes Data Input and Performs Error Proofing (~0%)
— 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 Solution

 Improves quality
— Management has immediate access to data
— Promotes collaboration between teams

©2011 Waters Corporation 52

 Op Ex: Advantages of a Standardized,
Unified Informatics Solution

 Laboratory data from different systems captured into a common

data format using Waters NuGenesis SDMS

 Data originating from different geographies

— Captured and cataloged in a common format

 Streamlined workflows and cycle-times

— Reduced wasted efforts reduce operational costs

 Management has better visibility to the big picture

— Identify problems earlier

 Acts as a feeder system

— Electronic COA, eCTD submission process, LIMS, eNotebooks,

©2011 Waters Corporation 53

 Summary
 Science is science
— The rapid organized storage of information is critical to all
organizations—QC/QA, R&D, etc.
— The ability to find and reuse information is a necessity in today’s rapid
market evolution

 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
notebooks

 A standardized CDS platform

— Provides standardized data format, reduces training effort, improves
compliance and promotes collaboration

©2011 Waters Corporation 54