Siemens Process Automation End-user Summit- 2011€¦ · · 2011-09-21Siemens Process Automation End-user Summit- 2011 Experience. Technology. ... case & pallet of drug & then using

SPAES @ Goa 2011

Siemens Process Automation End-user Summit- 2011

Experience. Technology. Community

SPAES @ Goa 2011

Emerging Technologies in Pharma IndustryUse of Automation & IT for quality & manufacturing excellence..

SRAES @ Goa 2011Industry Sector2011-08-10/11

External Changes having direct impacts on the pharmaceutical manufacturing needs

Technology changeTechnology change

Industrial ITIndustrial IT

Advanced Advanced controlcontrol

IntegratedIntegratedsolutionsolution

Social changeSocial change

DemographicDemographic

Life styleLife style

PatientsPatients

Economical pressureEconomical pressure

Low pipe lineLow pipe line

ManufacturingManufacturing

Supply ChainSupply Chain

Market changeMarket change

New therapiesNew therapies

Delivery formDelivery form

PersonalizePersonalize

Pharmaceutical Pharmaceutical IndustryIndustry

driven by;Cost

Patient safety


Changes leading to new requirements / challenges

The situation for Pharma production changes Resulting requirements on

Technology changeTechnology change

Industrial ITIndustrial IT

Advanced Advanced controlcontrol

IntegratedIntegratedsolutionsolution

Social changeSocial change

DemographicDemographic

Life styleLife style

PatientsPatients

Economical pressureEconomical pressure

Low pipe lineLow pipe line

ManufacturingManufacturing

Supply ChainSupply Chain

Market changeMarket change

New therapiesNew therapies

Delivery formDelivery form

PersonalizePersonalize

Pharmaceutical Pharmaceutical IndustryIndustry

driven by;Cost

Patient safety

RegulationsRegulations

Manufacturing performanceFirst Time RightIncrease product throughputRecipe driven flexible manufacturing

Supply chainTracing & tracking / E-PedigreeDemand driven

Asset utilizationOverall Equipment Effectiveness / Efficiency (OEE)

Time to marketPaperless manufacturingProcess Analytical Technology (PAT)

EnvironmentEnergy managementWaste reductionHigh potent drugs

Integrated manufacturing based on Automation & IT is the key !


w

QbD (Quality by Design) using PAT


Large scope for improving quality / quality consistencyDrug makers can save significant cost by getting it right first time

Research driven companies 31%

Generic Manufacturers 51%

Contract Manufacturers 62%

Cost of manufacturing –Pharmaceutical Industry

Cost of Quality as % of cost of manufacturing, Pharma versus Semiconductor

How to reduce cost of

Quality?

‘Getting it right the first time’ is the key

Reduce existing inefficiencies in manufacturing

- Reduce re-work

- Reduce scrap / WIP (Work In Progress)

- Increase equipment efficiency / utilization


How to get the product ‘first time right’ ?Shift from traditional ‘Quality by Inspection’ to ‘QbD’ approach

Variable input Inconsistent qualityFrom Quality by

Control/Inspection& strict compliance

To Quality By Design, risk & science based

product development

Fixed process

Variable input Consistent qualityVariable process

PAT/QbDenabled

Traditional manufacturing

The key lies in understanding the CQPs of the product, understanding process parameters which determine CQPs & controlling such parameters in such a way that the product quality as well as process end point can be exactly predicted on line !

Process understanding is critical to achieving desired quality !


PAT ensures desired product quality without scrap / re-work (right first time) and also enables online product release !

Process feed

Hol

d /

rele

ase

LabProcess data (Temp,

Pressure, …)Closed loopClosed loopcontrolcontrol

Process output

LIMSLIMS

Sample

Classic control

Process Analyzer

monitoringmonitoringanalyzeranalyzer datadata

monitoringmonitoringproduct product qualityquality

PATPAT

mathematicalmathematicaltranslationtranslation

RealReal--timetimereleaserelease

Advanced Advanced ControlControl

Quality build in by design

Right first time

PAT (Process Analytical Technology) is the enabler for QbD


PAT = understanding + controlling mfg. process..better the understanding, lesser the risk..

PAT is a system for controlling manufacturing processes based on Online & timely measurements of critical Quality & performance attributes with the goal of ensuring final product Quality

Focus of PAT is process understanding, better the understanding, lesser the (quality related) risk

A process is well understood when:

- All critical sources of variability are identified & explained

- Such variability is managed by process control

- Product quality attributes can be accurately & reliably predicted

Process data collected during development phase helps in understanding process, hence development & manufacturing to be integrated from PAT perspective

Process Analyzer

DataMultivariate modeling

Information

1

2

3

4

Improved process understanding !

5


US FDA has taken initiatives to facilitate application of new technologies like PAT for Pharma manufacturing

US FDA has released guidance for PAT in Sep’04, & various other white papers on application of PAT for Pharma manufacturing & new risk based approach, with an objective to:

- Improve manufacturing quality

- Accelerate drug development

- Reduce regulatory burden

US FDA’s future focus #:

- Integration of R&D and manufacturing

- Development of ‘quality surrogates’ for clinical performance (link CPAs to clinical outcome)

- Rigorous, mechanistically based & statistically controlled processes

(# Keynote address at IFPAC February 2007, by FDA's Chief Medical Officer, Dr. Janet Woodcock)

By US FDA in September 2004


Analyzers (for gathering data) and PAT software (for processing data) are THE key components of PAT solution..


Raw Material

Dryer

Granulator Tablet press

Blender

Qualitycheck

Coating

Delay Delay Delay Delay

High inventory including “work in progress”, long changeovers, disconnected processes, high process losses off line analysis, low asset utilization, …

1 to 2 months to

release

Blender

PAT has the potential to ‘change the clock speed of drug manufacturing’

Raw Material

Dryer

Granulator Tablet press

Blender

Qualitycheck

SIPATSIPAT

Coating

In/At line check

Cycle time can come down from typical 1-2 months to 2 days !

Right First Time

Real time release


Business drivers for PAT go much beyond quality..

Company Image

Reduced risk via technology platform, anti-counterfeitingImproved product trackingReverse poor imageImproved quality system throught auditsReduced risk fo recall, warning letter, consent decree

Validation Optimization

Validation needs understandinIntegral part of projectBuilt validation into process

Improve Existing Process

Gain new process understandingProcess optimizationReduced cost of qualityRaw material specificationsKnow product availability + yieldReal Time Release

New Product Development

Real Time Release (RTR)Fast time to marketFast scale-upClinical batchesProcess optimizationReduced cost of quality

End of life-cycle

Transferability of processScale down

Site to Site transfer

Accelerate transferReduce validation effortReduce project timeMitigate transfer riskMove manufacturing to mosteffective site

PAT/QbD


Siemens plays key role in developing concepts & solutions for continuous manufacturing based on PAT

The project ‘SPRINT’ (Secondary Processes INTensification)

- project launched in UK by technology strategy board (backed by UK Govt.)

- objective is to provide proof of feasibility for continuous manufacturing using PAT

Partners: from all fields of expertise

- GlaxoSmithKline as End User

- GEA as supplier for process technology and machinery

- Siemens as solution provider for process automation & information technology

Results are encouraging !

PoF completed in record 4 month time

Approval from regulatory authorities underway

To be followed by implementation in production unit!


Expected results of ‘SPRINT’ project answer our question !

Expected results after implementing the concept for a production unit:

85% reduction in waste / scrap

60% lower capital cost

65% less building volume

60% less manpower

Reduction in WIP,

Increased equipment efficiency

Reduced cost of Quality!

By increased process understanding & control

through PAT !


w

Ensuring drug quality beyond manufacturing


Counterfeit medicines – a growing global concern....has serious implications on society & drug manufacturers

European commission observed sharp increase in seized counterfeit drugs in 2007, +51% wrt 2006

Counterfeits account for 10% of medicines worldwide, (up to 50% in some countries) as per WHO

India and China accounted for 64% counterfeitproducts seized in year 2009

The result is twofold:

- Deaths of thousands of people (more compared to car accident deaths!)

- Loss of revenue due to counterfeiting (est. €35 billion in 2007) & due to non traceability related write offs (€ 2 to 6 billion) (est.)


Counterfeit medicines – a growing global concernThe evidence is chilling


Mass serialization & e-PedigreePermanent solution to counterfeits !

Mass serialization involves assigning unique identification number to each package, case & pallet of drug & then using that number to record all transactions involving the product, thus giving information about drug pedigree

As defined by US FDA, a drug pedigree is a statement of origin that identifies each prior sale, purchase or trade of a drug including dates of those transactions & the names & addresses of the parties involved in them..

e-Pedigree (electronic pedigree) for medicines is simply capturing & recording drug pedigree data in an electronic format, enabling use of IT

Manufacturer Before W/S Wholesale Pharmacy Patient

Global pedigree Database


The world has taken serious note of the issue,Guidelines are being put in place..

In March 2010, US FDA released a guidance for standardized numeric identifier (code)

Most of the states in US have already law in place (red) / law being drafted (green) for drug pedigree & tracking

e.g. Californian law mandates e-Pedigree for drug makers by Jan 2015 & for drug wholesalers & retailers July 2016..

Most of the countries have adopted some standard for serialization & coding of drugs (though not uniform)

EFPIA (European Federation of Pharmaceutical Industries & Associations) is running a project to standardize the same

France (by December 2010) Belgium & Italy are mandating serial number for each saleable pack

Brazil announced law no. 11903 on 14th Jan 2009 making tracking of all drugs mandatory within 3 years

Korea to mandate tracking of drugs by 2012, China contemplating on similar lines


Serialization & tracking – Global architecture

Man

ufac

ture

r inf

rast

ruct

ure Track & Trace

Databases

Tracing and Object Data

Verify, Update Status information

Verify, Update Status, Store tracing information


7 8 9



Verify, Update Status information

Receiving Delivery Receiving Delivery Receiving Sell

Distributor WholesalerDrugManufacturer

Rea

l Wor

ld Packaging DeliveryDrug

Production

ERPLocal

AutoIDService

Initiate production / packaging

Confirm Serial#

3

5

Provide serial #’s to suppliers

Initiate serial# generation to packaging supplier

12 Confirm serial#

4

Confirm Serial#6 Generate

Point-of-Sale

Legend: Manufacturer – Serialization LogisticPoint-Of-Sales Track & Trace Databases

CentralSerialization

Service

Track & TraceDatabases


Serialization & e-pedigreeApplication as per Brazilian law

Brazil

China

Blank labels From Brazilian1

Serialization & aggregation on packaging line

Serialized, aggregated products with: GTIN, IUM, Medicine Registration #, Product Lot # , Expiration Date

2

Electronic notification of item IUM Numbers to the Brazilian

National Tracking System3

Law no. 11903 on 14th Jan 2009 making tracking of all drugs to be sold in Brazil mandatory within 3 years: Drug makers to start serializing items in 1st year, data to be integrated to public database in 2nd year, retail stores to be integrated in 3rd year (2012)

Every saleable unit will carry a 2D Data Matrix printed on security label, provided & distributed by Brazilian authority (label size 19mmx25mm, DM code size 9mmx9mm)

The label to contain information like GTIN (product identifier), IUM (medical Unique Identifier as per GS1 standard for serialization), medicine registration no., batch number and expiry date


Automation & IT is THE backbone for any serialization / tracing tracking & e-Pedigree solution

Global Logistic

chain

Leve

l 4Le

vel 5

ERP

Leve

l 3Le

vel 2

Leve

l 1

Site Manager

Control- / Acquisition

level

Device level

Enterprise-wide connection for Event dataAuthentication Services

Auto ID Devices like DMC Printer, Cameras, RFID Reader/Writer, Barcode Scanner

Device-ManagementData acquisitionProcess support at the packaging line

Track&Trace Enterprise database

Serial number handlingAcquisition/Reports/Monitoring/Alarm messagesAcquisition and summary of EventsBatch & User management


Siemens plays key role in developing concepts & solutions for e-Pedigree – in IT as well as Automation

EFPIA has launched a pilot project for feasibility study of e-Pedigree solution

Siemens to provide IT solution along with SAP & HP

25 pharmacies in Sweden with 180 dispensing points selected

Involves tracking 25 products with 110,000 packs from 14 companies

Solution based on Siemens-SAP architecture

To be recommended as standard solution by EFPIA after success

Data Matrix Code identification mandatory by Dec’10 in France

Germany based ‘pester pack’ chose Siemens as partner for automation & IT for implementing serialization solution for its end of the line packaging machines

Coding unit including controls integrated in packaging line, code via manual input from HMI or via MES / ERP

Machines now fully compliant with French coding requirement


PAT & e-Pedigree ensure & enhance for end to end quality in Pharmaceutical Industry !

Summary PAT Summary e-Pedigree

The need for ensuring drug pedigree is well understood by all agencies & is beyond question

Concepts / policies & laws are currently being put in place to ensure drug pedigree

Need for harmony / standardization between various existing concepts / standards

PAT has the potential to transform quality as well as manufacturing scenario for Pharmaceutical Industry

US FDA has already released guidance for PAT and made PAT as part of its long term strategy

Need for stakeholders (analyzer, automation & IT vendors & users) to work together (PAT is a solution)

Automation & IT is the key for ‘end to end’ quality for Pharmaceutical Industry !


w

Improving OEE with Integrated manufacturing


Typical ‘liquids’ process consists of four broad steps

- Weighing- Dispensing- Assembly

- Active ingredients- Non active ingredients

- Weighing & dispensing- Balance verification

Preparation

In process testing & SamplingClean room monitoring

Formulation

- Dose WFI- Solution prep- Mixing- Filtration

-Utilities: WFI, PW, ...- Filters

- Adding Raw Material- Dosing- Sampling

Finishing

- Wash/sterilize- Filling/stopping- Lyo-philization- Capping- Inspection

- Vials- Bottles- Capsules- Caps- Stoppers

- Line clearance- Sampling- Reconciliation

Packaging

- Primary packaging- Endpackaging- Labeling

- Inserts- Cartons- Labels

- Line clearance- Reconciliation

Ass

embl

y/Ve

hicl

e

Sem

i fin

ishe

d go

ods

Fini

shed

goo

ds

Clean room


Using high voltage, pressure, vacuum, laser, camera etc.

7. Leak testing

Put into trays for intermediate storage

8. Traying

Typical steps / equipments used in ‘finishing’ of liquids

Containers washed with WFI

1. Washing

Containers sterilized with dry heat @ 300 °C

2. Sterilizing tunnel

Around 400-600 containers per minute

3. Filling

Frozen to powder at -70 °C to increase shelf life

4. Freeze drying

Apply aluminum caps to guarantee sterility

5. Capping

Manual or camera, particles, cosmetic / functional defects

6. Inspection


In today’s scenario, there are ‘automation islands’throughout the manufacturing line..

A AA

CCC

A A

B BBB

????M1 M3M2

MES / ERP


..making integration almost impossible if not impossible

DataInterface 2

Machine 1 from OEM x Machine 2 from OEM y Machine n from OEM z

PLCHMI

I/O I/O

Drives

Motors

LV Sensors

Net

wor

k

Net

wor

kMotionControl

PLCHMI

I/O

Drives

Motors

LV LV Sensors

PLC PLC

I/O

Motors

Drives

LV Sensors

DataInterface n

Line Overview HMI

MIS/MES

????????

No DataInterface

Diversity

Complexity

Difficult integration

Difficult Diagnosis

High Asset Costs

Many plants are currently made up of different products, systems and interfaces from different suppliers thus creating high diversity & complexityMissing standardized network structure and machine data interfacespreventing simple integration of the Machines and higher level systems


‘Initial investment cost’ governs decision for machine automation, leading to high lifecycle costs

Initial investment

Spares MaintenanceService

Downtimes

UpgradesTraining

Invest

Capital

Energy

Personal

Space

Support

Extension

Additional operating costoccurred by:

poor integration

complex service

increased spare part purchase / storage

elevated training costs

non-optimized energy consumption


Option 1: Easy integration with ‘cba’ approach (component based automation)

Same open communication standardDefined machine interfacesNo additional programming for Intercommunication

Machine – Machine, Line ControlLine Monitoring, Data acquisition

Ethernet TCP/IP

ERP

verticalIntegration

horizontal Integration

Cleaning Conveyor Filling Conveyor Packaging

Cleaning(Vendor A)

Conveyor 2(Vendor B)

Filling(Vendor C)

Packaging(Vendor D)

Conveyor 1(Vendor B)

Fieldbus X Fieldbus Y Parallel Wiring Fieldbus Y Fieldbus Z

MES


cbA - Each machine is represented as a software component

Mechanicalcomponents

Controlsoftware

Intelligent field device

HMI block

ResultComponents withdefined Data interface

The machine interface contains all data for the intercommunication, visualization and data acquisition

Filling product 1reset operatesenable finishedstop enable

faultstart


Creating the component

The manufacturer/vendor of the machinePrograms the machine control as he is used to, application specificDefines and maps the relevant machine data to a bi-directional interface from a technological viewEncapsulates the functionality of the machine control and interface description in a SW componentautomatically generated by programming tool

Vendor BFilling Filling product 1

reset operatesenable finishedstop enable

faultstart


faultstart


faultstart

XML


Easy integration at site with ‘cbA’ enabled machines

Maschine 1ON STARTINGSTART READYSTOP

Lifestate

RUNNINGHELD


Lifestate

RUNNINGHELD


Lifestate

RUNNINGHELD


Lifestate

RUNNINGHELD

3rd Step

SIMATICWinCC

Plant Owner

2nd Step

SIMATICiMap

Integrator

STEP7shadow projectand download

1st Step

Machine A

Machine AMachine B

Machine AMachine C

OEMs

XML-file interface definition


Option 2: Project specific standardization in close collaboration with OEMs & automation supplier

Machine 1 from OEM x Machine 2 from OEM y Machine n from OEM z

Standard DataInterface

Net

wor

k

MotionControl

PLCHMI

I/O

Drives

Motors

LV

Standard DataInterface

Line Overview HMI

Standard Data Interface

Net

wor

k

HMI

I/O

Drives

Motors

LV

Net

wor

kPLCHMI

I/O

Drives

Motors

LV

MotionControl

MIS/MES

IntegrationLevel 5Overview visualizationCommunicationsDiagnosisBackUp&Recovery

Level 1:HardwareSoftware

Level 4:Data-Interfaces

Level 3:Architecture

Level 2:Specification

User & automation supplier define specificationsUser, automation supplier & OEM work closely to implement the laid down specifications, to achieve integration


Close collaboration is necessary among User, OEM & automation supplier, for integrated manufacturing line

ResponsibilitiesDelivers specific machine

to handle a specific production operation

Focus on machine specific optimization

ResponsibilitiesStandard & scalable platformEasy integrationGMP supporting functionsCost effective solutionsLong term worldwide Support (investment protection)Industry know How

ResponsibilitiesSpecify required machinery to fulfill

a specific production operationMachine must comply with the own

specific norms and standardsFocus on the optimized

functioning of the complete production line

Easy integration of the control level to the system structure

End-user

Supplier

OEM


Typical architecture of an integrated manufacturing line

Process network Ethernet

Production network Ethernet

Local HMI

Full local equipment controlLocal Equipment HMIObject orientedUniform look & feel by usingobject libraries

ERP

S7-315 PN/DP

SIMOTION DS7-414-2 +CP 443-1 Advanced

Panel PC MP 370 Inox

Central SCADAView Line statusVisualize Batch progressProduction Data Acquisitionfrom PU’sCritical alarms

MESProduct definitionProduction capabilityProd. scheduleProd. performance

WinCCflexible

Multi Panel

WinCCflexible RT

Equipment 2 Vendor BEquipment 1 Vendor A Equipment 3 Vendor C

WinCC ServerWinCC Clients

MP 277 Inox10“

WinCCflexible

MP


Integrated central recipe management



Local HMI

WinCC flexible + options:

AuditRecipes

Central SCADA

WinCC V6.0 + options:

SIMATIC LogonPM-CONTROL

WinCC Clients

WinCC server

Parameters EQ1Par1, Par2…..

Batch idProduct idQuantity…..



SIMATIC IT

Recipe xyz V2.1Batch idProduct idQuantity…..




ERP

ERP

SIMATIC IT

PDefMPOM

PM

HistorianProd SuiteOEE/DTM

DIS (B2MML)

SAP

MES

MP 370 Inox




Central archive depository & electronic batch records

SIMATIC IT



Local HMILocal EquipmentHMI WinCC flexibleAlarm & EventsEquipment RecipedownloadLocal data collection for EBRLocal archivesLocal audit trail

ERP

Machine 1 Machine 2

S7-315 PN/DP

SIMOTION D

S7-414-2 +CP 443-1 Advanced

Machine 3

Panel PC MP 370 Inox

Central SCADACentral archivedepository foralarms, audit trails& process dataData Mining

MESOverall EquipmentEfficiencyDowntime MngtBatch reporting

WinCC Clients

WinCC server

PDefM

POMPM

HistorianProdSuite

OEE/DTM

PM Open Import

SIMOTION D

MP 370 Inox


Line integration helps you achieve demands / needs due to new business drivers !

Manufacturing performance improvement

- Improved performance with flexible recipe driven manufacturing

Supply Chain optimization

- Tracing & tracking possible at central location / e-pedigree

Better asset utilization

- By downtime analysis & reduction

Reduced time to market

- By electronic batch records & paperless manufacturing


Siemens has all the necessary ingredients to deliver the solution

Know-how

Resources

SolutionPlatforms

Integration

Industry specific: regulations (validation, GMP, ...)Process specific (from molecule to production)Engineering specificSystem specific - Batch / DCS / PLC / IT

Products / SystemsSystem Add-On’s

Local & regional resourcesProject ManagementEngineering Validation / QA

Experience in integration technologiesOne-stop shopping

SPAES @ Goa 2011

We wish you a successful meeting!

Abhijit TambatProject Management, Engineering & CommissioningI IA AS DLS

Kalwa WorksThane Belapur RoadPhone: +91 (022) 2764-5707Fax: +91 (022) 2764-5627Cellular: +91 9820265282

E-Mail: [email protected]

Documents

Siemens Process Automation End-user Summit- 2011€¦ · · 2011-09-21Siemens Process Automation End-user Summit- 2011 Experience. Technology. ... case & pallet of drug & then using