Electronic Batch

Recording
Kevin Walls
Senior Solutions Consultant

The Canadian Market
Canada has the 4th largest concentration of pharmaceutical and
biotech companies in North America with over
100 bio tech firms;
112 manufacturing facilities;
21 research institutions;
large number of headquarter locations.

Account concentration is primarily in Ontario and Quebec.
Toronto, Mississauga, Kingston,Ottawa, London, and Guelph,
Montreal, Laval, Quebec City

Agenda
What is EBR ?
Making the Business case
Operational and Financial Benefits
Strategies
Best Practices-Implementation
How Electronic Batch Records aid in
Regulatory Compliance
What Comprises a World Class EBR Solution
Conclusion
"We Are Producing Two Things: Paper And Drugs"
Look familiar ?!
Research Clinical Trials
Full Production Small Batch
What is EBR ?
What is EBR ?
Electronic Batch Recording
Operator Instructions
Data Collection
Electronic Batch Record
Final electronic record of the Batch
Compilation in a single electronic record of all
Information
Data
Documents
Electronic Batch Record
Electronic Batch Record
Collection of Information required for reporting to
QA
Contract Customers
FDA
Provides for
Complete history of Batch
Identification of Material and Quality data of materials
Operator interactions
Electronic Signatures
Systems Data
LIMS
Automation
Historian
QA Reports
Quality due-diligence Information

What an Electronic Batch Record is Not

Your Old forms, reports scanned into a
system i.e. Paper Under Glass
An Electronic Document Management
Systems (EDMS)
Generally manages the creation of SOPs, forms,
memos, procedures
Electronic Records Management Systems
(ERMS).
Contains scanned or other electronic forms of
documents



Its Simple !
Implement an EBR System!!!!
Pull together
Product definition (master data management)
BOM
Work instructions
Production execution (electronic batch sheets)
Weigh and dispense operation reports
Primary Manufacturing
Formulation
Filling
Compression
Etc.
Secondary Manufacturing
Sub assembly
Finished goods
Production information (Automation batch records)
Capture processing formation directly
Automation layer information
Select Data Historian Data

Lessons Learned
Build a Business Case first
Analyze the Business
Process
Utilize previous work in
Standards
Vendor Systems
Implement in successful
phases
What makes sense for You
Change management People


Develop High Level Project Plan
Early phases
Education
Solve problems
Go for low hanging fruit
Later phases
Advance future strategy
Improve enterprise workflow (integrate)
Implement additional components of
the strategy
Information access gold mining
Process improvements
Analyze optimum production batches
Deviation analysis
Tool for improved decision making
Critical Issues
Failure to observe and understand current
processes that will be covered by EBR
Missing, erroneous, inadequate operator
Instructions
Incorrect sequencing of steps that will impact
enforcement of sequence
Lack of knowledge of source of the data
Missing, erroneous, inadequate equipment
information


Critical Issues
Lack of processing specifications that
become alarms
Current MBR is not aligned with process
validation
Understanding process to handle
documents not part of MBR
Willingness to modify the current SOPs
with new EBR system
80% of SOPs should be handled by the EBR
not in an SOP
Requirements on tracking items and
samples
Decisions on interfaces and other systems




Legal
The law does allow for records to be
retained either as original records or as true
copies such as photocopies, microfilm,
microfiche, or other accurate reproductions
of the original records.

To adopt such a system the standard
operating procedures (SOPs) must have a
consistent approach to scanning documents
and the SOPs must specify who is to
perform the scanning.


Despite the allowance for maintaining copies within the CFR, many
pharmaceutical companies are hesitant to implement this type of solution because
the electronic version of the document is not the original and they are reluctant to
make decisions that are not based on original documentation.
Canada Law
The Natural Health Products Regulations contain
requirements for manufacturing, packaging, labeling,
storing, importing, distributing and selling natural health
products. It is the sale of natural health products for the
purposes of manufacturing, packaging, labeling etc. that is
captured by these Regulations, not the sale of natural
health products by retailers.
These Regulations are intended to ensure that all
Canadians have ready access to natural health products
that are safe, effective and of high quality, while respecting
freedom of choice and philosophical and cultural diversity.
The Natural Health Products Regulations
Administered by the Natural Health Products Directorate
(NHPD), Health Products and Food Branch, Health Canada.
Published in the Canada Gazette, Part II on June 18, 2003.
The NHP Regulations will come into force on January 1, 2004,
with a transition period ranging:
Two years (for site licensing) to
Six years (for product licensing, for products already issued a
Drug Identification Number).

Natural Health Products Regulations
Module 10: Records
Among manufacturers, packagers, labelers, importers
and distributors of natural health products, who shall
maintain:
A. The master production document
B. The list of ingredients contained in each lot or batch
C. Records of any assessment conducted
D. A copy of the specifications
E. Records containing sufficient information to enable the
recall of every lot or batch of the natural health product that
has been made available for sale

US Law
Code of Federal Regulations, Title 21, Food and Drugs

http://www.access.gpo.gov/cgi-bin/cfrassemble.cgi

Part
11 Electronic records; electronic signatures 200 General
201 Labeling
GMP
210 Current good manufacturing practice in manufacturing,
processing, packing, or holding of drugs; general
211 Current good manufacturing practice for finished
pharmaceuticals

226 Current good manufacturing practice for Type A
medicated articles




Making the
Business Case
Factors for Consideration
Quick successes
Enroll
Show a return to your organization
Manage scope
Watch for scope creep
Map all decisions to the future strategy
Cost associated with each solution
Licenses
Services
Validation
Develop metrics for measuring success
1
st
time approval rate on batch records
Cycle time reduction
Reduction of batch related exceptions





User requirements specification
Basic design
Developing system
SW design / implementation
SW module test
System test
Pre-acceptance
HW installation
Integration
Integration test
Acceptance
Training
Maintenance /
support
Maintenance
Validation
Specify
Current As-Is Situation
Analyze current business
operation
Study current workflow/processes
Review audit reports
Internal
External (e.g. FDA)
Review deviation logs/reports
Analyze a cross section of
executed batch records
Identify real cycle time
Calculate impact of a MES
solution
Labor intensive process!
Requires a knowledgeable
individual
Interview key
individuals
Identify their pain
Solicit ideas
Assess existing
support systems
Look for redundancy
Identify functional gaps

Supply Chain
Visibility to plant floor
Electronic white board
Real time information
Lower Cost of operations
Cycle time reduction
Increase inventory turns
Reduce WIP
Improved customer delivery performance
Competitive tool


Design Future State Strategy (To-Be Model)
Summarize findings
Identify real pain to the organization
Myth-busting or paradigm shift


Develop a vision of the future
Review best practices
Describe the interaction of people and technology
Describe how strategy will solve existing problems
Outline a plan to attain that vision
Identify strategies to support organizational goals

Develop Benefits
Identify additional benefits to the organization
Provide metrics to measure success ($$)
2 Batches saved = $$$$$$$$$

Operational and
Financial
Benefits
Average Improvements with EBR
Reduced lead time 22 32%
Reduced cycle time 35 45%
Reduced data entry time 36 75%
Reduced WIP inventory 17 32%
Reduced defect rates 15 72%


Payback periods range from 3 to 25 months
MESA Survey (Averages)
Benefits
The advantages of an EBR system can be grouped into two
categories: operational efficiency and compliance
improvements.

Reduced cycle times reductions in the physical passing of
records between departments will lead to an overall reduction in the
time needed to produce and ship product.

Inventory Reductions reduction in WIP and held un-released
inventory

Improved accuracy and consistency of batch record the
structure provided by the electronic batch records will decrease
errors, which in turn will decrease the time spent by quality
assurance in the review of these records.
Benefits
Reduced costs of compliance automation of quality assurance
functions and reporting features in the software will decrease the
effort required to research product deviations.

Increased productivity electronic exchange of batch records
decreases the amount of time spent collecting the various
components of the batch record from different departments.

Cost avoidance batch records must be retained for at least one
year after the expiration of product. Use of electronic batch records
can eliminate the need to allocate resources to the storage and
retrieval of archived batch records.

Increased speed of product changes and product introductions
use of electronic batch records in the development process will lead
to greater efficiencies in a New Drug Application.

Benefits
Error reduction in documentation
Enforce data entry and sequencing
Provide immediate user feedback to adverse results
Eliminate calculation errors
Efficiency improvements
Eliminate redundant verifications
Materials checks
Weight verifications
Product Checks
Documentation requirements
Begin PAT indicatives
Time reduction in review cycle
Review by exception
Eliminate this step
Improve the demonstration of compliance!


TRUE ROI!
Strategies
Shareholder Value
Maximize Return on Equity
Financial Leverage Return on Assets
Asset Turnover
Total Assets
Minimize Inventory
Minimize
Inventory
Total Assets
Maximize Capital
Utilization
Improve Risk
Strategy
Total
Debt
/
Profit Margin
Sales
Revenue
Maximize Capital
Utilization
Max Sales
Revenue
Minimize Cost of
Sales
Longer use of
Assets
Maximize workplace
Efficiency
Net Earnings
/
/
+
Assets Materials Operations Finance
S
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P
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Improve Equipment Utilization
Extend Asset Life
Reduce Capital Expenditure
Reduce Cost of Ownership
Improve Asset Redeployment
Improve Recovery Process
Right Material at Right Time and Place
Reduce Product Information
Management
Reduce Inventory through :
Planning
Reduce Duplicate Information
Improved Handling
JIT - Eliminate False Stock-outs
Eliminate Obsolete Inventory
Maintenance Planning
Manage Parts and Equipment
Effectively
Improve Inventory Management
Reduce Inventory Handling

Strategic Sourcing
Reduce Purchasing Process Costs
Reduce Freight Costs
Contractual Compliance
Supplier Reduction and Partnering
Reduce Order to Cash Cycle Time
Improve Dispute Resolution
Improve Quality Management
Reduce Overtime Premium Costs
Reduce Lost Time
Reduce Outside Contractors
Decrease Downtime
Improve Scheduling
Deploy World Class Practices
Drive 6 Sigma Process Mgmt
Workforce Productivity
Reduce Lost Revenue
Increase Competitive Advantage
Increase Customer Loyalty
Increase Customer Satisfaction
Compliance
Reduced Transaction Costs
Reduction of Lost Revenue
Increase Customer Service Efficiency
5/5/2003
Bringing Shareholder
Value
SHAREHOLDER VALUE
=
Strategic to the MES
MES with an EBR component.
Many manufacturers have an MES; however, it lacks the ability to
capture all necessary data and summarize it in a format that is
useful as a batch record
The real value to be gained by the MES is that it can be integrated
with much of the equipment and systems used in the production
process. This has two key advantages over data collection
systems
The integrated MES will allow
Data to be captured in electronic form without the need to retain
certain printouts
Significantly reduces the amount of human interaction that must
occur in recording batch record information
Best Practices-
Implementation
4 Phase Approach
Phase 1 - Pre-Assessment Review ( MAP )
Definition of opportunity, Readiness and Scope
Time Required: 2-3 days
Phase 2 - Proof of Concepts (Select Recipes)
Initial Re-design
Documentation Guidelines
Pilot Testing, Change Control and Implementation
Time Required: 8-13 weeks
Phase 3 - Redesign & Harmonization
Re-design and harmonize remaining documents
Pilot Testing, Change Control and Implementation
Time Required: 13-16 weeks

Phase 4 - Additional opportunities
Add Manufacturing Execution System (MES) modules
Interface to business systems


4 Phase Approach Benefits
See results following a thorough assessment and
challenge of the current documentation
Simplification and elimination of all unnecessary,
superfluous and redundant content that was not
required for process control or cGMP reasons.

Document Reductions
Documents
Pages 30 - 50% reduction in pages
Entries 30 - 60% reduction in entries
Creation 25 - 40% reduction in document creation / revision time
Number 10 - 25% reduction in number of documents




0
50
100
150
200
250
Documents Pages
Paper
EBR
0
2000
4000
6000
8000
10000
12000
14000
Entries
Paper
EBR
Review Time Reductions

Review
Errors 50 - 80% reduction in documentation / procedural errors
Review 40 - 70% reduction in review cycle time

0
100
200
300
400
500
600
Errors
Paper
EBR
0
50
100
150
200
250
300
350
400
450
Review Hours
Paper
EBR
Cycle Time Reductions
Cycle Time
Release 30 - 60% reduction in product release
Manufacturing 15 - 20% reduction in manufacturing
Investigations 20 - 30% reduction in investigation time
New Recipe 10 45% reduction in Prep Time
Training 20 - 30% reduction in training time



0
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4
6
8
10
12
14
16
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C
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Paper
EBR
World Class Solution
Meets all 21 CFR 11 Requirements
passwords, access, audit trails and Archiving
Creates new documents
in 10 to 20 percent of the time it normally takes
Makes simultaneous changes to multiple documents
quickly and easily
Document Library
Documents are built using a library of work instructions (building
blocks) that contains variable parameter fields for process or
product specific information
Ensures documentation content
consistency through the use of building blocks and process
templates
Archives all master documents

Equipment
Isolated dispensing system
Weighing
protocol
Equipment
data
SCADA
Operators
Manual
documentation
and signature
Environment (e.g. sterile rooms)
Alarm lists and
sensor curves
BATCH
PROTOCOL
Head
Text
Head
Text
Head
Text
Head
Text
Phase 1
Analyze and Re-engineer the Paper Batch Record
Equipment
Integrated dispensing system
Weighing
protocol
Equipment
data
SCADA
Operators
Manual
documentation
and signatures
Environment (e.g. sterile rooms)
Alarming lists and
sensor curves
BATCH
PROTOCOL
Head
Text
MASTER BATCH
DOCUMENT
Dispense
Historian
Phase 2
Uniform Style & Partial Automatic Data Acquisition
Equipment
Integrated dispensing system
Weighing
protocol
Equipment
data
Operators
Online-documentation
and electronic signatures
Environment (e.g. sterile rooms)
Alarming lists and
sensor curves
BATCH
PROTOCOL
MASTER BATCH
DOCUMENT
?
SCADa
DISPENSE
Historian
EBR
Phase 3
Complete Electronic Data Acquisition
LIMS
Phase 4

Phase 4 - Additional opportunities
Add Manufacturing Execution System (MES) modules
Dispensing
Finite scheduling
Key performance monitoring
Training qualification
Interface to business systems
Enterprise resource planning system (e.g., SAP, etc.)
Documentation (e.g., Documentum etc)
Laboratory management
Learning management

How Electronic
Batch Records Aid
in Regulatory
Compliance
Even More Lessons Learned
Dont try to automate a disorganized paper system !
Validated
Database
Dynamic
download of
planned order
ERP data exchange
via LAN, WAN,
INTRANET

Finite
scheduling at
the electronic
planning board

Production-
control / data
management,
Reconciliation
of resources
Order data
Batch requirements
Material data


Electronic
order
processing
at the line
monitoring system
Automated
accounting of
consumptions

Trigger for material
deliveries
according to the
pull principle

Material
Functions
Master Data
Resources
Good Models to Understand
ERP
MES
Factory/Plant
Automation
Production
data
collection
Production
execution
Production
resource
management
Production
dispatching
Production
tracking
Production
performance
Detailed
production
scheduling
Production
schedule
Product
definition
management
Level 2 Control
(Batch, Discrete, Continuous)
Production
capability
Product
definition
Source: ISA SP95 Committee (modified)
Other













Production
Performance
analysis
Web
Marketplace
Enterprise
Systems
Manufacturing
Execution
Automation
Platforms
Automation
Components
Plant Floor
S
e
a
m
l
e
s
s


C
o
n
n
e
c
t
i
v
i
t
y

Vertically Integrated Solutions
Bulk
Intermediate
PMX
Time to Market, Financial Performance, Quality
Primary
Commercial
Production
Secondary
Commercial
Production
ERP
What Comprises a World
Class EBR Solution



What makes a Good Solution ?
Browser Based
Forward and Backward
Visibility
Full Data Integration
ERP
Weigh and Dispense
LIMS
eDMS
Machine Devices
Process Control
Data Historian
MSDS
Material Certifications
SOPs

Web based procedures
View and select orders
Execute electronic procedures
See forward and backward
Full security
Access SOPs and other
supporting documents
Import Outside image and
Documents
Electronic batch record review

Batch Recording Features
EBR is the mechanism to enforce Good Manufacturing
Practices and the ability to record the execution of GMP
Basic Instructions to Operator
SOP J ump to SOP or
HTML or PDF Link in
E-Document System
Commit but stay on
procedure
21CFR part11
E-Signature
And Comment
Graphics and
Instructions
Graphics and
Instructions
Clear
Instructions
Data without
Input
Clear - Clean - Consistent - Design
Canadian Forms Institute and
BFMA Standards
Edit Values
brought into the
EBR
Image of Data Collection that includes PLC and
Operator Input
File and Document
Uploads
Process
Start with
Signature
Bill of Parameters
or
Operator Input
Procedure step (recipe parameters)
Drive Down
Recipe
Parameters
Real Time Quality Control (Batch monitoring)
Models the evolution of representative good batches
Take all (incl. PAT) data and their correlation into
account
Use control charts for display, with limits computed
from traces of good batches
New batches monitored as they are evolving
Problems detected and interpreted on the fly
Culprit variables in problem batches clearly identified
Quality of the whole batches predicted as it is
evolving and at completion- possible 6 sigma control
Based on multidimensional informative data
measured during the batch evolution + multivariate
analysis
PAT and Regulatory Support
FDA is embracing PAT Technology
Lower Production Costs = Lower market product costs
Less Variants to monitor in production
Clear Data analysis once implemented
Not yet full supported by ICH, EAMA
Due to ICH Level 2 Nov 04
Possible Approval Spring 05
ICH = International Conference on Harmonization
From Raw PAT Data to EBR
Data Historian
Process Instrumentation
Multivariate Data
Analysis
Pull Data and Graphics Import
Server Storage and Process
Field Bus
Logic
Controller
Pull Select TAG Data
Push / Pull Tag parameters
EBR
Trend Data, Graphs
21CFRpart11 Signature
Multivariate Analysis Graph
View Historian data
Retrieve
Historian Data
Image of Variance Report Section
Optional Notes
by Operators
Review
Comments
Potential
Deviation Log
What makes a Good Solution ?
Provides
Cycle time reduction
Instant generation of batch protocol
Enforcing material flow
Product release review by exception
Clarity of information
Single style design of documents
Consistent history and repeatability of batches
Compliance
Improve demonstration of compliance
Meets 21CFR part11 and part 188, 210 etc
out of the box
Provides for information access
Process Improvement
Automatic calculations and alerts
Enforce sequencing and data entry
requirements
Reduce manual process checking and
recording
Real time focus of variations
Process Analytical Technologies (PAT)
Systems for analysis and control of manufacturing processes based
on timely measurements of critical quality parameters and
performance attributes of raw and in-process materials and
processes to assure acceptable end product quality at the completion
of the process
Electronic Batch Record (EBR)
Manufacturing Execution System (MES)
Private Trading Exchanges for Manufacturing (PTX-M)
AMR predicted market would reach $35 billion by 2005, but
Taggants & Related Detection Systems
Radiofrequency Identification applications (RFID)
Existing and Emerging Technology
Ref: Mark Lester, Consilient Capital / Compliance & Technology
Conclusion
Shareholder Value
Improve time to market
Asset Utilization

Improves/demonstrates regulatory compliance

Shop floor to top floor information portal

Cost effective

Remain competitive in the
life sciences industry!
Questions?
Kevin Walls, CFC
Solutions Consultant,
Propack Data - Rockwell Automation

Kwalls@ra.rockwell.com
For more information, contact:
Rockwell Automation
Toronto District
40 Bramtree Court
Brampton. Ontario

Danielle Lorimer
Industry Account Manager-Life Sciences
(905) 494-4284
dmlorimer@ra.rockwell.com

Thank You!
References
Selected text and data provided from reports by :

Health Products and Food Branch Inspectorate Doc 02-122102-681
Electronic Batch Records in the Pharmaceutical Industry Clarkson
Consulting
Concepts for Drug Lifecycle Management Rockwell Automation
EBR in a Regulatory Environment Rockwell Automation
US FDA Federal regulations 21CFR
Thomas Quinn, The Hollis Group Inc.
Charles Krumwiede, Brighton Associates, L.L.C.
Samedan Ltd Pharmaceutical Publishing