mes promotes operational excellence in pharmaceutical
TRANSCRIPT
MES promotes Operational Excellence in pharmaceutical production
Dr. Udo Ammerahl, Robin WUBayer Technology and Engineering (Shanghai) Co., Lt d.
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Pharmaceutical Industry: Production of Paper & Tabl ets
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Source: http://www.fda.gov
Case Study: FDA-Audit at Ranbaxy, India
Inspection by FDA revealed
� Inadequate recordkeeping
� Lack of 2nd person verification
� Failure of batch deviation investigations
� Failure of Quality Control Unit
Consequences
� Warning letters issued by FDA
� APIs and finished drug products are subject to refusal by U.S. market
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MES
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What’s a Manufacturing Execution System ( MES)?
A Manufacturing Execution System (MES) is a computerized system supporting the production management in all production related steps…
Leaving GoodsOrder PickingPackagingIncoming Goods Manufacturing
� Production planning
� Warehouse management
� Manufacturing
� Deviation management
� Material tracking
� Documentation
� Performance evaluation and optimization
� …
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Practical definition:A system comprised of hardware and software which helps control (and record) the decisions made by operators and equipment at the point of manufacture.
What’s a Manufacturing Execution System ( MES)?
MES = Manufacturing Excellence Strategy
� GMP-Compliance
� Product Quality
� Product Safety
This capability removes avoidable errors, delays and waste from their processes by “Right First Time ”.
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Operational Excellence in daily life
insert card
get money
take card
ATM
need more?
Yes!!!
No
enter pin
enter amount
leave
deviation
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Operational Excellence in daily life
ATM
insert card
take card
leave
need more?
No
enter pin
enter amount
Yes!!!
get money
Right first time
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Supervisor +
Scheduling
Office
QC - Lab
- Ground Floor -
Uhlmann
UPS 1070
Uhlmann
UPS 1070
Uhlmann
UPS 1030
Uhlmann
UPS 4
Uhlmann
BEC
Delivery
Packing
Bulk Pick-up
Control
Weighing
Mix 1
CW-
Delivery
CW Pick-
up
Mix 2
QA-Lab
Leisure
RoomToilet
Tool
Room
Granulating
2
Granulating
1
Tabletting 1
Tabletting 2
Tabletting 3
Coating 2
Coating 1
CW1
Weighing
CW2
CW3
IBC Wash
IBC Places
Canteen
Gatekeeper
Floor
Incoming
Goods
Sample
tab
Dangerous
Goods
Cooling
Warehouse
Batch
Warehouse
Leaving GoodsIncoming Goods
HBW with HBAS
Gate (Suppliers)
Gate
Silo 1
Silo 2
Pond
Conference
Room
MES supported production process
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Raw materials
WIP material
Finished goods
MES supported production process
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Electronic Documentation
Electronic workflows enforcing Quality Control Proc edures
AnalysisSampling
Print sample label Identify sample label
Sample labelDest.: Lab0815
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Raw materials
WIP material
Finished goods
MES supported production process
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Warehousing
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Raw materials
WIP material
Finished goods
MES supported production process
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Central Dispensing
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useridentification
selecting andstarting order
workroomidentification
GMP cleaninginstructions
selecting next itemposition in BOM
raw materialidentification
scaleidentification
weighing label printing
weighingprotocol
proportionedmaterialwarehouse
production
raw materialtransport
Weighing & Dispensing:Manufacturing Excellence by Best Practice Workflows
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Weighing & Dispensing
� Weighing & dispensing procedures according to GMP� Prevention of using wrong material� Reducing errors due to manual entries and ensuring
2nd person principle by integration of scales � Generation of compliant weighing reports
supports…
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Raw materials
WIP material
Finished goods
MES supported production process
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Product Quality and Safety by Material Flow Control
Material flow
� Definition of transports� Controlling of transports
Source: Granulation 01Dest.: Blending 99
1 2 3 4 5 6 7 8 9 0 1 2
Granulation
Print Label
Blending
Identify Label
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User Guidance by Electronic Work Instructions
Source: Novartis, NJ
Electronic work instructionsguide the operator through the manufacturing process
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Paper On Glass: all critical information in view
Manual data input
Deviation andevent overview
DCS recipeinformation
Order /batch header
Material datainformation
LIMSdata
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Batch Review focus on Exceptions
� Focus on deviations and non-conformities� Follow pre-defined approval workflow
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Key functionality: Electronic Batch Recording
� Secure user guidance� Deviation and event handling
� Traffic light functions for process monitoring� Electronic workflow for processing deviations� Electronic signatures to comment and approve deviations
� Generation of reliable reports and documentation
supports…
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Raw materials
WIP material
Finished goods
MES supported production process
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Equipment Management ensuring GMP-Compliance
� Point-of-use identification � Status verification and enforcing cleaning rules� Electronic equipment logbook � Managing equipment calibration
1 2 3 4 5 6 7 8 9 0 1 2 8
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Status verification
Allocated
Not clean
In Cleaning
Cleaned
Paper-basedstatus change
Start cleaning
Confirmcleaning
Allocateto order
Release
Allocated
Not clean
In Cleaning
Cleaned
Start cleaning
Confirmcleaning
Allocateto order
Release
MES-basedstatus change
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Raw materials
WIP material
Finished goods
MES supported production process
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Product Quality and Safety by Facility Control
Identifying and verifying workroom and readingits status from the system
Source: Novartis, NJ
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Raw materials
WIP material
Finished goods
MES supported production process
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Packaging
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Key Requirements of 21 CFR Part 11
(1) Inspection: Accurate reports and copies of ER 11.10 (b)
(2) Protection: Retrieval of electronic records 11.10 (c)
(3) Access and authority check 11.10 (d+g)
(4) Audit trail 11.10 (e)
(5) Operational checks: Sequencing of steps 11.10 (f)
(6) Control access and use of system operation docs 11.10 (ki+kii)
(7) Display signature and meaning 11.50 (a, aiii)
(8) Signature integrity 11.70
(9) Unique signature, non-biometric signature 11.100(a).200(a1)
(10) Maintain uniqueness of signature 11.300a
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Benefits from Manufacturing Excellence Strategy
Safe and high quality pharmaceutical products by� Best-practice workflows and GMP-compliant procedures
� Barcode identification of material and equipment
� Guidance for operators during all production and logistic related activities
� Online deviation management
� Right-First-Time approach
� Transparent and complete documentation
Efficient pharmaceutical production by
� Review by exception
� Electronic workflow for review and approval
� Paperless production
� Integration of different data sources: SCADA, LIMS, ERP etc.
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� PAS-X from WERUM is standard for MES in pharmaceutical industry: 14 of top 20 using PAS-X
� Global roll-out contracts with e.g.
� PAS-X is multilingual, where the Chinese HMI is a unique feature in the local market!
� BTES exclusively represent PAS-X in China
What’s PAS-X?
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Werum AG, Headquarters, Lueneburg, Germany
Werum America Inc., Headquarters, Parsippany, NJ, U SA
� Best-in-class MES product for Pharma & Biotech
� Professional services� Customer satisfaction & long term partnerships
Werum at a Glance
� Founded 1969� 400+ employees� Constant growth:
25+% per year overall� Strong financials
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Werum’s History in MES
Eight global contracts for Top20First MES project in Asia
First global MES contract
First large US implementationFirst PAS-X Biotech customer
No. 1 in MES for Pharma & Bio (ARC)Company of the year (Frost & Sullivan)
1993199319931993 2009200920092009
First big international PAS-X customer
First complete PAS-X version
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More than 500 MES installations,
customers in 30+ countries
Werum’s Business Today
Revenue by industry Revenue by region
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Key Customers
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What’s PAS-X?
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“Typical installation”
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� Reduction of defects (product quality) by 15%
� Reduction of manufacturing cycle time by 45%
� Reduction of data entry time by 75%
� Reduction of batch deviations by 90%
� Reduction of WIP “Work In Process” by 20%
� Reduction of paperwork between shifts by 55%
� Elimination of lost paperwork by 60%
Benefits identified by MESA organisationMESA = Manufacturing Enterprise Systems Association
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Why need for MES ?
The average paper batch record contains:� 300 different steps (220 in MFG and 80 in PKG)� 500 signatures and initials, including QC review� 500 data points� 50 entries in log books (rooms and equipment)
Resulting in� Long throughput time� High probability of errors and deviations� The need for FTE to manage the paper processes and ensure compliance� No easy ways to review and analyse the collected data
Production Site in Suffern, NY
Case Study
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Benefits�Full MES functionality including EBR�These batches DO NOT have paper backup�Management of objects (equipment, material, resources) �Fast and easy access to information makes the difference �Pro-active process control prevents errors
Case Study
System environment: approx. 50 workplaces and 27 mobile units
“MES is in today's manufacturing environment an inevitable tool to manage the increase in Complexity and to close the last main manual
gap for being a Fully Integrated Supply Chain”
Richard Lemire, Exec. Director, Novartis Pharmaceut icals Corp. Suffern, NY.
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� Reduction of material scrap by 15%
� Reduction of defects by 25%
� Reduction of WIP “Work In Process” by 25%
� Reduction of manufacturing cycle time by 35%
� Reduction of data entry time by 80%
� Reduction of batch deviations by 80%
Using MES
Case Study
Project period of 2 yearsROI: 18 month
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“ genzyme Waterford Automation Program”
Vision:� To Implement Automation in the Waterford, Ireland f acility to achieve
Paperless Manufacturing supply, in � Warehouse, � Oral Dose, � Packaging, � Quality Control, � Fill Finish
Scope:� To implement a Manufacturing Execution System (MES) , Data
Historian System (DHS), Product Data Management Sys tem (LIMS) and appropriate system integration at the Waterford facility.
� Provide an integrated system which creates Electron ic Batch Records (EBR)
� Using bar-coding technology� MES to ERP integration� MES to LIMS integration
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Implemented PAS-X MES modules at Genzyme
� Weigh & Dispense
� Warehouse Management
� Electronic Batch Recording (EBR)
� Master batch records (MBR)
� Material tracking
� Deviation & Event Management
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Business drivers
� Significant change and growth was envisaged� Additional expansion with Oral Dose
� Introduction of multiple new products and technologies
� Significant increase in volume of existing Products
� Commercial Production in Fill Finish
� What did this mean Genzyme?� Challenges in the area of Volume, Complexity & Compliance
� Management of Costs and Competitive Advantage
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Operational risk (risk of batch failures, compliance issues, etc)
Scope of activities
Incr
ease
Headcount
Manufacturing volumeManufacturing complexity
RISK
2005 2010
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Benefits
� Manufacturing Process cycle times – 17% reduction
� Packaging Process Cycle times – 2% reduction
� Review Process cycle times – 46% reduction
� There was a significant positive impact on RFT trends.
� Paperless production
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Will it be a big investment??
No!� Off-the-shelf-solution with low validation and implementation effort� Incremental deployment strategy (Step by Step)
Benefits� Scalable investment effort� Solving the most urgent issues in a short time� Sustainable solution to convince inspectors� State of the art technology
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Off-the-shelf-solution includes…
Support for user requirement specification+ Functional specification+ Validation package+ Workshop to define VMP/ CSV+ Templates for risk analysis, IQ, OQ, PQ+ PAS-X Start Up Package+ Implementation+ Training
= “Ready for FDA”-package MESMES
Selection Phase
URSUser Requirement
Specification
Functional Specification Implementation Start up Validation
Acceptance�
3-6 monthsLow Risk Approach
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Closing remarks about PAS-X:
� Start small: After gaining experience with the system and recognizing the benefits, continue with incremental deployment according to actual requirements!
� PAS-X is standalone system: DCS, LIMS, ERP etc. not mandatory. However, benefits could even increase with comprehensive solution.
� Low hardware requirements to exploit benefits of PAS-X
� PAS-X increases Efficiency, Quality, Safety and Compliance by Right-First-Time approach
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� Master Data� Master Batch Records� Electronic Batch Recording� Deviation Recording� Reporting, Analysis & Trends
� Automatic Execution� Process Data & Events
MES Layer
Process Layer
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Demonstratio
n System at BTES
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