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Efficiency ad Quality by DesignTo Reduce Cost of Compliance and

Efficiency ad Quality by DesignTo Reduce Cost of Compliance and

Dr. Valentijn de LeeuwDirector

ARC [email protected]

Efficiency ad Quality by DesignTo Reduce Cost of Compliance and Time to Market

Efficiency ad Quality by DesignTo Reduce Cost of Compliance and Time to Market

Dr. Valentijn de LeeuwDirector

Group France [email protected]

ContentsContentsCommon processes• Food, CPG, chemicals, biologicals and

Locating the challenges• Information hurdles • Clerical work, time losses and missed links• Paradigm shift in quality management and compliance• Future production methodologies

Implementing NPDI and quality management• Seamless information• Business process automation• Proactive, risk and science-based quality management• Implementing with a quality mindset

• Information, systems, people, processesExpected benefits• Personal workload and elapsed time, time to market, • Information and production quality, cost of quality and compliance

2© ARC Advisory Group

and pharma

Clerical work, time losses and missed linksuality management and compliance

Implementing NPDI and quality management

based quality managementImplementing with a quality mindset

Information, systems, people, processes

Personal workload and elapsed time, time to market, nformation and production quality, cost of quality and compliance

A PROCESS VIEWA PROCESS VIEW


A PROCESS VIEWA PROCESS VIEW

Proof of Concept Product and Process Definition

Strategic Marketing / BU

Claims development

Product life cycle (R&D plus Manufacturing and Supply Chain)

Product and Process Refinement,

Documentation

Product Development

RegulatoryCompliance

Process Development & Production

Marketing communications

& Sales

Supply Chain

Continuous and life-cycle dependent processesContinuous and life-cycle dependent processesStrategic planning

Portfolio management, Governance

Main recurring business processes

Operations

Asset Management


ApprovalProduction - Sales

Product life cycle (R&D plus Manufacturing and Supply Chain)

Product and Process Refinement,

Documentation

(Clinical) trials,Registration

Prepare production

cycle dependent processescycle dependent processesStrategic planning


Operations

Asset Management


Product lifecycleProduct lifecycleFood and Nutrition, CPG • Health Claims and Food safety can be minor for some products but important for others

Product Definition

Market testing andStrategy


(Health Claims)

Product life cycle (R&D plus Manufacturing and Supply Chain)Process definition

Documentation

Product Development

Regulatory &Compliance



& Sales

Supply Chain

ConceptRequirements

BenchmarkingPricing

Profitability

SpecificationInitial formulation

Shelf life

Stability testingFormulation

Long term stability

Formula

Efficacy testingSafety screening

(dose range)

Idem efficacyIdem safety

Efficacy testingSafety screeningEnvironmental

Dosage

Reg. requirementsInitial label Refined label Claims, Label

Trial ProductionProcess Technology Transfer

Prototype Production Process Development

(pilot scale) Pilot scale

Supplier screeningPackaging

Marketing message Awareness

Lab productionProcess Development

(lab scale)



Food safety can be minor for some products but important for others


Product life cycle (R&D plus Manufacturing and Supply Chain)Process definition

Documentation(Clinical trials), Registration

Prepare production

Profitability Profitability Market feedback,Profitability

Long term stability

Long termstability


Clinical trials I-III-efficacy-safety

Claims extension

Dose confirmation

NDA

Claims, Label Registration package

Claims confirmation

Approval

Trial ProductionProcess DevelopmentTechnology Transfer

Ramp up production Market feedback,Profitability

NPI


Clinical supplySecure full scale supply

Full supply chain

Awareness Art work, launch plan Launch, Brand image

Full scale

Proof of Concept Product and Process Definition


Claims development


Product life cycle (R&D plus Manufacturing and Supply Chain)Product and Process

Refinement, Documentation

Product Development

RegulatoryCompliance



& Sales

Supply Chain

ConceptRequirements Pricing Profitability

SynthesisInitial formulation

Analytical


Long term stability

Formula


(dose range)



PKDMEnvironmental Dosage

Reg. requirementsInitial label Refined label Claims, Label

Process Development(lab to pilot scale

Process screeningProcess Development

(lab scale)



Product lifecycleProduct lifecyclePharmaceuticals, Biologicals and Chemicals




Product life cycle (R&D plus Manufacturing and Supply Chain)Product and Process

Refinement, Documentation

(Clinical) trials,Registration

Prepare production


Long term stability

Long termstability



Claims extensionPharmaco vigilance

Post approval research Dose confirmation

NDA

Claims, Label Registration package

Claims confirmation

Approval

Process Development(lab to pilot scale-up)

Process designTechnology Transfer

Market feedback,Profitability

Pilot scale

NPI



Full supply chain


and Chemicals

SEAMLESS INFORMATIONSEAMLESS INFORMATIONEfficiency by Design: from information hurdles to


SEAMLESS INFORMATIONSEAMLESS INFORMATIONEfficiency by Design: from information hurdles to

Opportunities for Seamless InformationOpportunities for Seamless InformationChallenges• Information is stored in isolated locations

but not generally accessible. Resulting risks:• Loosing and not using information• Incomplete view• Outdated, inaccurate information• Inconsistent methods and formats• Misunderstanding, conflicts• Searching available information or repeat work

Costs• Individual time load and elapsed time (Time• Additional effort• Increased financial and compliance risk• Increased cost of compliance


Opportunities for Seamless InformationOpportunities for Seamless Information

Information is stored in isolated locations – on PC’s or on paper but not generally accessible. Resulting risks:

Loosing and not using information

utdated, inaccurate informationInconsistent methods and formats

Searching available information or repeat work

Individual time load and elapsed time (Time-to-market)

Increased financial and compliance risk

Example 1: Innovation to ProfitabilityExample 1: Innovation to Profitability

Idea management, Innovation management, Opportunity assessment, • Business needs and innovations lead to initial specification. • The intent and targeted profitability is required for approval and

follow up by governance

Portfolio management, GovernancePortfolio management, Governance

Product Definition



Process definitionDocumentation

ConceptRequirements

BenchmarkingPricing

Profitability

Innovation, Idea, Specification and Portfolio


Example 1: Innovation to ProfitabilityExample 1: Innovation to Profitability

dea management, Innovation management, Opportunity assessment, Portfolio management

Business needs and innovations lead to initial specification. The intent and targeted profitability is required for approval and

Portfolio management, GovernancePortfolio management, Governance



(Clinical) trials, RegistrationPrepare production


`Innovation, Idea, Specification and Portfolio

Example 2: Specification to ComplianceExample 2: Specification to Compliance• Definition of a concept product:

• Define risk targets• Development: risk management and testing with respect to

specification• Risk management defines compliance testing requirements• Compliance testing proves compliance


Process Documentation

SpecificationRisk Targets

Regulatory Requirements

Testing, Risk Assessment

Validation, Compliance

Health Claims

Product Development

Regulatory &Compliance

Product Definition



Example 2: Specification to ComplianceExample 2: Specification to Complianceefinition of a concept product:

Development: risk management and testing with respect to

Risk management defines compliance testing requirementsCompliance testing proves compliance



(Clinical) trials, RegistrationPrepare production


Validation, Compliance


Success Factors for Seamless InformationSuccess Factors for Seamless InformationOther opportunities for seamless information:• Portfolio and project management• Recipe management throughout the development

cycle• Analytics, lab information and quality

management / production management• Product field tests (or clinical trials) with

profitability projections

Success Factors• Few common applications and data bases

• Few interfaces, bi-directional synchronization• Up to date shared information in contextual views• Consistent methods and appearance• Motivated and responsible users following …• … well-designed collaborative processes


Success Factors for Seamless InformationSuccess Factors for Seamless InformationOther opportunities for seamless information:

Portfolio and project managementRecipe management throughout the development

Analytics, lab information and quality management / production managementProduct field tests (or clinical trials) with

Few common applications and data basesdirectional synchronization

Up to date shared information in contextual viewsConsistent methods and appearanceMotivated and responsible users following …

designed collaborative processes

Complementary Data Models

Compatible Tools

Consistent Processes

Shared GoalsStrategy

People | Processes

Technology

Information

Design Operate Maintain

Benefits of Seamless InformationBenefits of Seamless InformationBenefits• Information:

• Complete and accurate (up to date, correct)• Consistent and accessible

• Reduction of effort and cost• Individual work load,• Total work load • Compliance

• Reduction of time-to-market• Elapsed time

Gains• Reduced cost, risk and time to market

profitability• Improved collaboration -> social benefits

Currency

0


Benefits of Seamless InformationBenefits of Seamless Information

Complete and accurate (up to date, correct)

Reduced cost, risk and time to market -> increased product

> social benefits

Currency

Time

Investment period Return period

Payback period

Shorten time

Reduce cost

Sell earlier

Sell more

Sell longer

Reduce cost

BUSINESS PROCESS AUTOMATIONBUSINESS PROCESS AUTOMATION

Efficiency by Design: From waiting and missed links to


BUSINESS PROCESS BUSINESS PROCESS Efficiency by Design: From waiting and missed links to

Opportunities for Business Process AutomationOpportunities for Business Process AutomationChallenges and Opportunities in Research and Development• Lab automation

• Recurring activities• Automating data acquisition and calculations

• Specification, Formulation, Product development• ERP master data integration• Nutritional calculation and optimization

• Labels and packaging• Statements based on product composition

• Document review and release process• Access control, notification, versioning, signature• Design review and approval process

• Project Management• Budget and time tracking with respect to plan• Project plan schedules resources, sends reminders, triggers activities, …

• Recipe development (links with materials, conditions and equipment)• Reuse at different stages of scale-up• Hierarchy: Generic, master and control recipes


Opportunities for Business Process AutomationOpportunities for Business Process AutomationChallenges and Opportunities in Research and Development

Automating data acquisition and calculationsSpecification, Formulation, Product development

Nutritional calculation and optimization

Statements based on product composition

Access control, notification, versioning, signatureDesign review and approval process

Budget and time tracking with respect to planProject plan schedules resources, sends reminders, triggers activities, …

Recipe development (links with materials, conditions and equipment)up

Hierarchy: Generic, master and control recipes

Opportunities for Business Process AutomationOpportunities for Business Process AutomationChallenges and Opportunities in Production• Lab automation

• Increasing importance of at-line and in• Automate data acquisition and calculations

• Recipe management• Improvements and updates, homogeneous roll

• MES development• Inherits recipe, materials, quality management, equipment information

• MES production scheduling and management • Receives ERP orders• Reports actuals

• qualities, quantities consumed and produced, resources, genealogy, lot tracking• Performance management and continuous improvement

• Reuse MES information for real-time dashboards and historical data analysis


Opportunities for Business Process AutomationOpportunities for Business Process AutomationChallenges and Opportunities in Production

line and in-lineAutomate data acquisition and calculations

Improvements and updates, homogeneous roll-out

Inherits recipe, materials, quality management, equipment informationMES production scheduling and management

qualities, quantities consumed and produced, resources, genealogy, lot trackingPerformance management and continuous improvement

time dashboards and historical data analysis

Benefits of Business Process AutomationBenefits of Business Process AutomationBenefits• Definition of best practices

• Knowledge management• Community building

• Global roll out of best practices• Completeness, • Timeliness, • Consistency and • Quality

• Reduction of effort and cost• Automate clerical activities• Create availability for exception handling, thinking, design, ..

• Reduction of time-to-market• Elapsed time

Gains• Improved consistency of practices increases performance• Reduced cost, risk and time to market


Benefits of Business Process AutomationBenefits of Business Process Automation

Create availability for exception handling, thinking, design, ..

Improved consistency of practices increases performanceReduced cost, risk and time to market -> increased product profitability

PROACTIVE, RISKAND SCIENCE-QUALITY MANAGEMENT

PROACTIVE, RISKAND SCIENCE-QUALITY MANAGEMENT

Quality by Design: From pure “QC” to


PROACTIVE, RISK-BASED -BASED

QUALITY MANAGEMENT

PROACTIVE, RISK-BASED -BASED

QUALITY MANAGEMENT

Quality by Design: From pure “QC” to

Trends in Quality ManagementTrends in Quality ManagementTraditional approach (favored by FDA in the past)• Controlling process conditions tightly• Keeping the process as is

• Any changes would require new validation• QC by lab analysis after production

• Batches wait until quality confirmedRecent trend (stimulated since recently by FDA)• More pro-active QM by controlling materials and conditions

• Conditions can be adjusted to meet end quality• Harmonization and guidance by ICH

• US (FDA), Europa (EMA) and Japan• Targets human pharmaceuticals but guidance has general value


Trends in Quality ManagementTrends in Quality ManagementTraditional approach (favored by FDA in the past)

Controlling process conditions tightly

Any changes would require new validationQC by lab analysis after production

Batches wait until quality confirmedRecent trend (stimulated since recently by FDA)

active QM by controlling materials and conditionsConditions can be adjusted to meet end quality

Harmonization and guidance by ICHUS (FDA), Europa (EMA) and JapanTargets human pharmaceuticals but guidance has general value

Paradigm Shift and GuidelinesParadigm Shift and GuidelinesA new paradigm for quality1. Quality must be mainly built in and it will not only improve by

additional testing and inspection2. Better utilization of modern science throughout product lifecycle3. QRM is a key enabler throughout product lifecycle4. Robust PQS, with appropriate knowledge management, assures quality

throughout product life cycle5. An integrated approach to development, manufacturing and quality for

both industry and regulatorsICH have published guidelines for• Quality by Design (Q8)• Quality Risk Management (Q9)• Production Quality System (Q10

Recognized and adopted by US, European and Japanese regulators• Consistent with science-based and risk• FDA has published simple and insightful examples of how to use Q8, Q9

and Q10 19© ARC Advisory Group

Paradigm Shift and GuidelinesParadigm Shift and Guidelines

Quality must be mainly built in and it will not only improve by

Better utilization of modern science throughout product lifecycleQRM is a key enabler throughout product lifecycleRobust PQS, with appropriate knowledge management, assures quality

An integrated approach to development, manufacturing and quality for

ICH have published guidelines for

Recognized and adopted by US, European and Japanese

based and risk-based approach by regulatorsFDA has published simple and insightful examples of how to use Q8, Q9

Quality by Design Quality by Design Let’s boil an egg• Ingredient: 1 egg• Duration: about 10 minutes• Result: often good, sometimes soft, sometimes hard, rarely

rotten• QC: test hardness, test freshness

How can we guarantee the hardness?• Hardness = f (time, weight)• Experiments:

• measure hardness as f (time, weight), determine optimum• Control strategy: calculate and control boiling time• Result: hardness by design, rarely rotten• QC: test freshness


Result: often good, sometimes soft, sometimes hard, rarely

QC: test hardness, test freshness

How can we guarantee the hardness?

measure hardness as f (time, weight), determine optimumControl strategy: calculate and control boiling timeResult: hardness by design, rarely rotten

Quality by Design Quality by Design How can we guarantee the freshness?• A) Qualify supplier, supplier process control and QC• B) Quality by Design

• Freshness = f (time, density)• Experiments to determine threshold density• Control strategy: determine also volume, calculate density, discard

or keep depending on value• Result: freshness and hardness proven a priori

You get the picture?


How can we guarantee the freshness?A) Qualify supplier, supplier process control and QC

Experiments to determine threshold densityControl strategy: determine also volume, calculate density, discard

freshness and hardness proven a priori

TerminologyTerminologyQuality Target Product Profile (QTPP)• RequirementsCritical Material Attribute (CMA)• Test or calculate CMA is within Critical Process Parameter (CPP)• Control the process to guarantee CPP is within range• Prove the control is reliableIn Process Control (IPC)• Parameters measured during the processCritical Quality Attribute (CQA)• Quality of product needs to be within this range

• for efficacy, safety or other criteria


Quality Target Product Profile (QTPP)

Material Attribute (CMA)Test or calculate CMA is within range

Parameter (CPP)Control the process to guarantee CPP is within range

Parameters measured during the processAttribute (CQA)

Quality of product needs to be within this rangefor efficacy, safety or other criteria

Quality Risk ManagementQuality Risk ManagementRisk Assessment • Product (impact of CMA variability on CQA

• Hardness: risk low• Freshness: risk low• …

• Process (impact of CPP variability on CQA)• Water contaminated• …

Control Strategies• Hardness and Freshness see above• ...• Water turbidity measurement, refresh depends on value (IPC)

Batch release strategy• What would be the proof based on control strategies that CQA

are guaranteed “A Priori”23

© ARC Advisory Group

Quality Risk ManagementQuality Risk Management

(impact of CMA variability on CQA)

Process (impact of CPP variability on CQA)

Hardness and Freshness see above

Water turbidity measurement, refresh depends on value (IPC)

What would be the proof based on control strategies that CQA

Example: Overall Risk Assessment for ProcessExample: Overall Risk Assessment for Process

Process stepsvisual inspection

weighing den

CQAshell integrityhardnessfreshnesscleanness

no impact to CQAknown or potential impact. Control mitigates know or potential impact to CQA. Study and im


Example: Overall Risk Assessment for ProcessExample: Overall Risk Assessment for Process

sity boiling cooling packaging

riskmprovemen required

Production Quality System (not exhaustive)Production Quality System (not exhaustive)Standard Operating Procedures• Electronic Work Instructions• Process Monitoring and Analysis

Process control and operations Management• Recipe management (design, master, control)• Automated recipe execution

Compliance testing and QC• QC to prove adequacy of RT compliance• QC sampling strategy

Real-time compliance and release testing• In-line, at-line• Hard PAT (instruments, sensors, • Soft PAT (hard PAT plus calculations) of IPC

Recording and ReportingContinual Improvement


Production Quality System (not exhaustive)Production Quality System (not exhaustive)Standard Operating Procedures

Process Monitoring and AnalysisProcess control and operations Management

Recipe management (design, master, control)

QC to prove adequacy of RT compliance

time compliance and release testing

Hard PAT (instruments, sensors, analysers) of IPCSoft PAT (hard PAT plus calculations) of IPC

Implementing Quality ManagementImplementing Quality ManagementAll sectors (with varying emphases)

Product Definition


Product and Quality life cyclesProcess definition

Documentation

ConceptRequirements

BenchmarkingPricing

Profitability

SpecificationInitial formulation

Shelf life


Long term stability

Formula


(dose range)


Efficacy testingSafety screeningEnvironmental

Dosage

Reg. requirementsInitial label Refined label Profitability

Process DevelopmentTechnology Transfer

Process Development(pilot scale)

Pilot scale



Lab productionProcess Development

(lab scale)

QTPPCharacterizationScreening DOE

Excipient compatibility

DOE process parametersCPP rangesDesign IPC

Control strategy

Verify CPP ranges,Refine control strategy

CMA, CQA rangesRA eff. & safety

RA FormulationRA Process (1)

FMEA CMA, CQA, CPPRA Process (2)

KM Define Batch recordsIdentify Suppliers (CMA)

Improve understanding from scale

Basic Control Strategy

QbD

QRM

PQS


Implementing Quality ManagementImplementing Quality Management


Product and Quality life cyclesProcess definition

Documentation(Clinical) trials, Registration

Prepare production


Long term stability

Long termstability



Claims extension

Dose confirmation

Profitability Claims, labelRegistration package

Claims confirmation

Process DevelopmentTechnology Transfer

Ramp up production Market feedback,Profitability



Full supply chain


Full scale

Continuous ImprovementSPC, MVDA

Verify CPP ranges,Refine control strategy

Define QCSOP, EWI, MESDocumentation

Continual RAFMEA CMA, CQA, CPPRA Process (2)

Implement CAPA’sCheck PQS

Automated ControlMonitoring & Analysis

RT release and QCReporting

Improve understanding from scale-up

Basic Control Strategy

Process performanceImplement IPC

Enhance controlCompliance testing

Benefits of Proactive Quality ManagementBenefits of Proactive Quality Management

Improved process understandingImproved quality• Reduced number of off-spec batches• Increased capacity

Shortened time to batch releaseUpfront effort, with downstream benefits• Increased effort in design and risk management• Reduced effort in QC

Not only applicable to “Big • “Simple changes can lead to big wins”


Benefits of Proactive Quality ManagementBenefits of Proactive Quality Management

Improved process understanding

spec batches

Shortened time to batch releaseUpfront effort, with downstream benefits

Increased effort in design and risk management

Not only applicable to “Big Pharma”“Simple changes can lead to big wins”

FUTURE PRODUCTION TECHNOLOGYFUTURE PRODUCTION TECHNOLOGY

Quality by Design: From Batch to Continuous


FUTURE PRODUCTION FUTURE PRODUCTION Quality by Design: From Batch to Continuous

Other Industry ChallengesOther Industry Challenges

Duration and effort of proof of food, chemical pharmaceutical safety (clinical and field trials)Introducing gradual improvements in product and processTime to marketPrice pressuresSustainability and Energy efficiencyResponding flexibly to market demands• Patient and customer needs: product changes• Demand variability: production rate changes


Other Industry ChallengesOther Industry Challenges

Duration and effort of proof of food, chemical pharmaceutical safety (clinical and field trials)Introducing gradual improvements in product and

Sustainability and Energy efficiencyResponding flexibly to market demands

Patient and customer needs: product changesDemand variability: production rate changes

Emerging Trends In Production TechnologyEmerging Trends In Production TechnologyModular production will become increasingly important• Cheaper and faster to design and build

• Adding small scale production modules rather than equipment

• Standard equipment from catalog• Equipment can be modularized itself

• Intensification and sustainability• Less steel, less energy consumption

• Continuous production• Mobile production

• Production units can travel to optimum location

More information: e.g. EU F3 FAct


n Production Technologyn Production TechnologyModular production will become increasingly important

Cheaper and faster to design and buildAdding small scale production modules rather than upscaling

Standard equipment from catalogEquipment can be modularized itself

Intensification and sustainabilityLess steel, less energy consumption

Production units can travel to optimum location

FAct

TAKE AWAYTAKE AWAYEfficiency and Quality By Design: Conclusions and


Efficiency and Quality By Design: Conclusions and

Implementing QM With QualityImplementing QM With QualityInformation Requirements – Quality and Efficiency by Design• Complete and consistent• Accurate – Information reflects the “actual” situation • Timely – Information properly reflects the “current” • Accessible – easy to use, quick response• Secure • Available – systems and data: time gains

Systems Requirements – Efficiency by Design• As few systems and interfaces as possible

maintenance• Trades and regions can collaborate in real• Central data repository (with limited replication) • Risk and analysis tools built-in – no transfers, errors, or time lost

Processes and people – Quality by Design• Determine best practices first, then business process automation• Everyone should use the system(s) or its added value will decrease

• Change management, training and coaching required• Implement recommendations for QbD, QRM and PQS• Make business case for organizational, process and methodology changes


Implementing QM With QualityImplementing QM With QualityQuality and Efficiency by Design

Information reflects the “actual” situation – less reworkInformation properly reflects the “current” situation – less time losses

easy to use, quick response

systems and data: time gainsEfficiency by Design

As few systems and interfaces as possible – reduce implementation and

Trades and regions can collaborate in real-time – no double workCentral data repository (with limited replication) – no erroneous data

no transfers, errors, or time lostQuality by Design

Determine best practices first, then business process automationEveryone should use the system(s) or its added value will decrease

Change management, training and coaching required, QRM and PQS

Make business case for organizational, process and methodology changes

Expected BenefitsExpected Benefits

Reducing cost of documentation and complianceShorten time to market Profitability increase and financial risk decrease• Reducing time to operational readiness• Operational and maintenance cost

Reduced quality and safety risksImproved quality and throughput• Shortened time to batch release• Reduced off-spec


Reducing cost of documentation and compliance

Profitability increase and financial risk decreaseReducing time to operational readinessOperational and maintenance cost

Reduced quality and safety risksImproved quality and throughput

Shortened time to batch release

Q&AQ&A


AcronymsAcronymsCAPA Corrective and Preventive ActionCPP Critical Process Parameter. Its variability has impact on a CQA. Should be monitored and

controlled to ensure desired qualityCQA Critical quality attribute (should be within a limited range)DOE Design of experimentsEWI Electronic work instructionsFMEA Failure Mode and Effect AnalysisIPC In Process Control: monitoring and control to adjust the process and ensure the API conforms to

its CQA’sIPT In Process Tests: tests during manufacture rather than QA after the factKM Knowledge managementMES Manufacturing Execution SystemMOM Manufacturing Operations ManagementMVDA Multivariate data analysisPAT Process Analytical TechnologyPQS Pharmaceutical or Production Quality SystemQA Quality AssuranceQC Quality ControlQRA Quality Risk AssessmentQRM Quality risk managementQTPP Quality Target Product ProfileRA Risk assessmentRTRT Real time release testingSOP Standard operating procedureSPC Statistical process control


rocess Parameter. Its variability has impact on a CQA. Should be monitored and

ritical quality attribute (should be within a limited range)

In Process Control: monitoring and control to adjust the process and ensure the API conforms to

In Process Tests: tests during manufacture rather than QA after the fact

Manufacturing Operations Management

Pharmaceutical or Production Quality System

ReferencesReferencesFDA, “Guidance for Industry, Q8, Q9 and Q10, Questions http://www.fda.gov/downloads/Drugs/Guidances/UCM210822.Q8/Q9/Q10 Training Page ICH, http://www.ich.org/products/guidelines/quality/trainingq8q9q10.htmlFDA, “Quality By Design for ANDA’s, an example for ImmediateDosage forms” (detailed example of using http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/AbbreviatedNewDrugApplicationANDAGenerics/UCM304305.EU F3 Factory project http://www.f3factory.com/scripts/pages/en/Novartis MIT center for continuous manufacturing mit.mit.eduARC on Modular engineering and modular production, including translation of Tauchnitz paper on efficient engineering and engineering systems http://www.automation.siemens.com/mcms/plantsoftware/en/comos-industry-solution/pharma/Documents/ARC%20White%20Paper%20Comos%20For%20Life%20Sciences.pdf


FDA, “Guidance for Industry, Q8, Q9 and Q10, Questions and Answers”, http://www.fda.gov/downloads/Drugs/Guidances/UCM210822.pdf

http://www.ich.org/products/guidelines/quality/training-programme-for-

FDA, “Quality By Design for ANDA’s, an example for Immediate-Release Dosage forms” (detailed example of using QbD) http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/AbbreviatedNewDrugApplicationANDAGenerics/UCM304305.pdf

http://www.f3factory.com/scripts/pages/en/home.phpcontinuous manufacturing http://novartis-

ARC on Modular engineering and modular production, including translation paper on efficient engineering and engineering systems

://www.automation.siemens.com/mcms/plant-engineering-

solution/pharma/Documents/ARC%20White%20Paper%20Comos%20For

MES? ERP? MES? ERP?

ISA 95 terms: Business Planning and Operations Management are defined as domains

Level 4

Level 3

Business Planning & Logistics

Plant Production Scheduling,Operational Management, etc

Manufacturing Operations Management

Dispatching Production, Detailed ProductionScheduling, Reliability Assurance, ...


ISA 95 terms: Business Planning and Operations Management are defined as domains

3

Ti

4

Ti

Operations Management (OM) or MES?Operations Management (OM) or MES?

Operations Management is the official syntax• Manufacturing Execution System (MES) is more often used

BP (and OM) applications overlap BP and OM domainsISA-95 functions are distributed over BP and OM applicationsARC studies how companies set the boundaries

OM App

EAM app ERP app


Operations Management (OM) or MES?Operations Management (OM) or MES?

Operations Management is the official syntaxManufacturing Execution System (MES) is more often used(and OM) applications overlap BP and OM domains95 functions are distributed over BP and OM

ARC studies how companies set the boundaries

LIMS P&S appBP Domain

OM Domain