CONTRACT MANUFACTURING EVOLUTION -...

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1 CONTRACT MANUFACTURING EVOLUTION CONTRACT MANUFACTURING EVOLUTION CTP Tecnologie di Processo CTP Tecnologie di Processo è un’azienda certificata: CONTRACT MANUFACTURING EVOLUTION Schema relazione I. La motivazione II. L’analisi e le scelte III. Gli strumenti

Transcript of CONTRACT MANUFACTURING EVOLUTION -...

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CONTRACT MANUFACTURING EVOLUTIONCONTRACT MANUFACTURING EVOLUTION

CTP Tecnologie di Processo

CTP Tecnologie di Processo è un’azienda certificata:

CONTRACT MANUFACTURING EVOLUTIONSchema relazione

I. La motivazione

II. L’analisi e le scelte

III. Gli strumenti

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CONTRACT MANUFACTURING EVOLUTIONI. La motivazione

La situazione mondiale, le strategie del futuro

CONTRACT MANUFACTURING EVOLUTIONLa motivazione

RANKING BY ETHICAL DRUG SALES RANKING BY ETHICAL DRUG SALES -- 1981 Vs 20011981 Vs 2001

1981 2001

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CONTRACT MANUFACTURING EVOLUTIONLa motivazione

THE BLOCKBUSTER MODELTHE BLOCKBUSTER MODEL

CONTRACT MANUFACTURING EVOLUTIONLa motivazione

R&DR&D cost,cost, DevDev..times,times, NMENME outputoutput andand SalesSales worldworld growthgrowth fromfrom 19931993toto 20032003

140140

160160

180180

200200

exex

R&D ExpenditureR&D Expenditure Development timesDevelopment times NME outputNME output SalesSales

toto 003003

6060

8080

100100

120120

19941994 19951995 19961996 19971997 19981998 19991999 20002000 20012001 20022002 20032003 YearYear

Ind

Ind

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CONTRACT MANUFACTURING EVOLUTIONLa motivazione

Table 1: The leading pharmaceutical companies will lose between 14% and41% of their existing revenues as a result of patent expires

Company 2010 2011 2012Share of

Revenues (%)

AstraZenecaArimidex $2.2bn Seroquel $4.7bn Symbicort $3.7bn 38

BMSUS Plavix $4.8bn

Abilify $2.1bn 30Avapro $1.3bn

GSK Advair $3.8bn Avandia $2.5bn 23Eli Lill Z $4 8b 22Eli Lilly Zyprexa $4.8bn 22

MerckCozaar/Hyzaar

$3.2bn Singulair $4.5bn 22

Novartis Femara $1.1bn Diovan $6.0bn 14

Pfizer Aricept $800mLipitor $12.1bn Viagra $4.5bn

41Detrol $860mXalatan $1.6bn

Geodon $1.1bn

Sanofi-Aventis Taxotere $2bnUS Plavix $3.8bn

Lovenox $3.1bn 34Avapro $2.1bn

CONTRACT MANUFACTURING EVOLUTIONLa motivazione

•Innovation and product introductionno longe affo dable atD h

Globalizationno longer affordable atcountry/region level

•Leaders positioned in all keycountries with globally designedbusiness systems

Focus•All major pharmacos want to move

to a few attractive (high-volume,high-growth, high barriers to entry)Price pressure

from healthcare

Dry pharma pipelines

Increasing competition for in-licensing

therapeutic areas

Consolidation•Ongoing industry consolidation•Emergence of large global pharma

players with potential scaleadvantages in M&S, R&D, andOperations

from healthcare systems

Increasing shift from Rx to Gx

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CONTRACT MANUFACTURING EVOLUTIONLa motivazione

CAPACITY UTILIZATION*, 2002CAPACITY UTILIZATION*, 2002______________________ROUGH ESTIMATES BASEDROUGH ESTIMATES BASED

ON SITE VISITS**ON SITE VISITS**PercentUnused100%

-65% -73% -69%-56%

Unusedcapacity

Assuming

53%**There are significant

excess capacities

Solids formulation

Liquids formulation

Solids packaging

Liquids packaging

g5 x 2 shifts

* Defined as actual output divided by output of machine running at technical limit during full shift time

** Capacity utilization calculated as machine utilization time divided by maximum running time adapted to 5 x 2 shifts

CAPEX DEVELOPMENT FOR MAINTENANCECAPEX DEVELOPMENT FOR MAINTENANCE

CONTRACT MANUFACTURING EVOLUTIONLa motivazione

61

~ 88

EUR millions

Due to network andproduction fragmenta-tion, CapEx dedicated tonetwork maintenance

13% CAGR for CapEx maintenance versus

1% CAGR for productionvolume

~ 25 ~ 29 ~ 35 ~ 41

~ 61

1996 1998 20001994 2002 2004

has grown significantly

ProductionvolumePU, millions 626 717

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CONTRACT MANUFACTURING EVOLUTIONLa motivazione

2013: LA GRANDE GLACIAZIONE 2013: LA GRANDE GLACIAZIONE

Evoluzione fatturato Industria Farmaceutica Internazionale

2007 2008 2009 2010 2011 2012 2013 2014 2015

CONTRACT MANUFACTURING EVOLUTIONLa motivazione

ASPIRATIONS FOR NETWORKASPIRATIONS FOR NETWORKREORGANIZATIONREORGANIZATION

From To

• Fragmented network • Stable and flexible network g

• Complex product portfolio

• Underutilized capacities across sites and technologies

with strong launch capabilities

• Production of rewarded complexity only

• Appropriate capacity utilization of all technologies

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CONTRACT MANUFACTURING EVOLUTIONTYPES OF SITES IN FUTURE NETWORK

1 • Global/regional launch of products• G t th d t l hLaunch sites

Key market presence and

ongoing supply

• Guarantee smooth product launch• Preservation and further development of know-how and

expertise for key technologies (including new technologies)

2 • Focus on continuous, reliable low-cost supply• Production of mature products• Possible differentiation

–Large vs. small productsR /OTC N t l H lth

Competence centers for

specific technologies

–Rx/OTC vs. Natural Health

3• Global competence center for selected technologies• Product launch and ongoing supply combined on-site• Potential key technologies (es.)

–Respiratory drugs and devices–Sterile application forms

CONTRACT MANUFACTURING EVOLUTIONNETWORK STRATEGIES OF MAIN COMPANIES – EXAMPLES

• Network optimization BMS

AZ • Development of launch site

Abbott • Cost focus (improvement in individual plants, benchmarking)

• Aggressive plant network optimization and coherent supply chain setup to capture lowest possible COGS

– A few plants focused by forms and volumes

– Launch sites

Novartis

• Network optimization and regionalization of Ops responsibility

• Process excellence/lean manufacturing

J&J

GSK • Second round of network optimization

• Multiple productivity and quality improvements per plant

Novo-Nordisk • Application of lean manufacturing across all plants to free up capacity, limit investments, and reduce costs

• Cost focus (plant network, investments)

• Launch capabilities (to some extent forced by Xenical)

Roche

– Truly global Ops responsibility and stringent SCM processes

Pfizer • Focus plant distinctiveness (lean)

Warner-Lambert • Development of launch site

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CONTRACT MANUFACTURING EVOLUTIONII. L’analisi e le scelte

Scegliere la strategia, analizzare l’impatto e Scegliere la strategia, analizzare l’impatto e implementare i miglioramentiimplementare i miglioramentiimplementare i miglioramentiimplementare i miglioramenti

CONTRACT MANUFACTURING EVOLUTIONL’analisi e le scelte

IMPROVEMENT IN MANAGEMENT SYSTEMS AND BUSINESS PROCESSES

Business process excellenceEfficient and fully integrated

•Develop new processes for – Third‐party management–Global network coordination (product/volume allocation)

– Best practice transfer (benchmarking)

Business process excellenceEfficient and fully integrated management systems

•Consolidate and streamline management meeting landscape to two key meetings

•Consolidate current fragmented planning tools in one central fact base for key decisions ( g)

•Optimize existing processes– Annual discussion–Global asset management (corporate invest process)

– Personnel developmentCIVISOCIVISO

QbDQbD

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CONTRACT MANUFACTURING EVOLUTIONL’analisi e le scelte

Possibili approcci al contract manufacturing

CONTRACT MANUFACTURING EVOLUTIONL’analisi e le scelte

CSOC t t S t O i tiContract Support Organization

+CMO

Contract Manufacturing Organization

Integrazione di un processo frammentato

CMSOContract Manufacturing and Support Organization

Single-source provider from manufacturing through commercial manufacture

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CONTRACT MANUFACTURING EVOLUTIONL’analisi e le scelte

CMSOContract Manufacturing and Support Organization

Formulation development

Analytical development and validation

Process developmentDossier writing

Industrial productions

Client ideaClient idea

Generic productGeneric product

Pilot batches

Production for clinical trials

Raw materialssourcing

Stability studies

Client productClient product

CONTRACT MANUFACTURING EVOLUTIONL’analisi e le scelte

Analytical development and validation

CMSO NEEDS CTP SUPPORT

Formulation development

and validation

Process developmentDossier writing

Industrial productions

CMSO LIFE CYCLECMSO LIFE CYCLE

CTP SYSTEM INTEGRATED COMPETENCES

Pilot batches

Production for clinical trials

Raw materialssourcing

Stability studies

INTEGRATED COMPETENCES

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CONTRACT MANUFACTURING EVOLUTIONL’analisi e le scelte

Passare da un concetto di PRODOTTO ad un concetto di SERVIZIO

Quello che per noi è normale attività per gli altri è un PROBLEMA

Ciò che per gli altri è un PROBLEMA per VOI deve essere un BUSINESS

Diventare partner STRATEGICI e non solo TATTICI

CLIENTI TARGET

Piccole e Medie Aziende prevalentemente commerciali magarisenza stabilimento produttivo

Grandi Aziende che vogliono delocalizzare produzioni mature o dinicchia

CLIENTI TARGET

CONTRACT MANUFACTURING EVOLUTIONL’analisi e le scelte

Excelvision, Unither, Pharma Stulln, Ursapharm, SIFI, Tubilux, Farmigea, COC, Moorfields, Vianex, Holopack,

Catalent, Montefarmaco, Nycomed, PharmaSter, Wockhardt, Patheon, Fareva, Haupt, Abbott, FDC-India,

Promed, Etc ……

Il mercato dei terzisti è un mercato altamente competitivoIl mercato dei terzisti è un mercato altamente competitivo

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CONTRACT MANUFACTURING EVOLUTIONL’analisi e le scelte

Il mercato dei terzisti è un mercato altamente competitivo

WHY MOVING PRODUCTS?WHY MOVING PRODUCTS?

GENERALMarket changesProduct life cyclesOptimizing production between locationsMergers & Acquisitions

ECONOMICInternational cost competitionTax advantagesSupply Chain rationalization

SEARCH FOR PRODUCTION EFFECTIVENESS

CONTRACT MANUFACTURING EVOLUTIONL’analisi e le scelte

IDENTIFIED IMPROVEMENT MEASURES

Dedicated process engineering function at launch site

Defined quality gates (acceptance criteria) for development process

1

2

ProcessProcess Development Transfer Life cycle optimization

IIMMPPRROOVVEEMMEE Defined quality gates (acceptance criteria) for development process

Own global standards for excipients, materials, and other elements

Cross-functional alignment and management

3

4

NNTT

MMEEAASSUURREESS

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CONTRACT MANUFACTURING EVOLUTIONIII. Gli strumenti

Vantaggi e criticità di alcune scelte.Vantaggi e criticità di alcune scelte.Quali sono e come usare gli strumenti di analisi.Quali sono e come usare gli strumenti di analisi.

CONTRACT MANUFACTURING EVOLUTIONGli strumenti

TERZIARIZZAZIONETERZIARIZZAZIONE DELLADELLA PRODUZIONEPRODUZIONE DELDEL FARMACOFARMACO NEINEIPAESIPAESI EXTRAEXTRA EE..UU..

Esclusione dei Paesi:Usa

Paesi Low CostPaesi Low Cost

UsaCanada

AustraliaIslanda

Giappone

Paesi consolidati:TurchiaIndiaCina

Paesi emergenti:Vietnam TunisiaMaroccoAlgeriaSud Corea

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CONTRACT MANUFACTURING EVOLUTIONGli strumenti

I. VERIFICA REGOLATORIAStato autorizzazioni, gap analysis,

integrazioni per importazioni

II. VERIFICA LOGISTICAII. VERIFICA LOGISTICASupply chain

III. VALUTAZIONE ECONOMICACosti fissi, addizionali e variabiliCosti fissi, addizionali e variabili

CONTRACT MANUFACTURING EVOLUTIONGli strumenti

VALUTAZIONE ECONOMICAVALUTAZIONE ECONOMICA

COSTI FISSI

• Costo A.P.I.

• Costo service

COSTI ADDIZIONALI

• Costo convalida interna produttiva/analitica

• Costo di convalida analitica per il rilascio del prodotto

COSTI VARIABILI

• Costo adattamento prodotto requisiti nazionali

• Costo per risk l i d• Costo service

• Costo Materie Prime

• Costo materiali di confezionamento

• Costo trasporto

• Costo di release

del prodotto• Costo stabilità on-going

e PQR• Costo mantenimento

certificazione EU• Costo qualifica interna

supply chain• Costo di adattamento

impianti (eventuali)

analysis prodotto

• Costo mantenimento progetto

• Costo derivante dalla riserva di sicurezza del prodotto

• Costo derivante dalle fluttuazioni monetarie

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CONTRACT MANUFACTURING EVOLUTIONGli strumenti

PRODUCT TECHNOLOGY TRANSFERPRODUCT TECHNOLOGY TRANSFER

Come dare un servizio, fare business ed Come dare un servizio, fare business ed evitare ritardi nello start up produttivoevitare ritardi nello start up produttivo

CONTRACT MANUFACTURING EVOLUTIONGli strumenti

THE MAJOR OBSTACLESTHE MAJOR OBSTACLESN t f t f / j t• No management of transfer / no project manager

• No consistent transfer team• Regulatory requirements unclear• Priority for production in the plant• Ineffective communications between functions • Poor definition of the target• Industrial strategy unclear• Process not transferable• Vague definition of the tasks• Cultural misunderstanding• Unavailability of people• Unrealistic timelines and lack of cost evaluation• No integration of the receiving site expectations• Lack of training• …..

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CONTRACT MANUFACTURING EVOLUTIONGli strumenti

PRODUCT TRANSFER MATERIALPRODUCT TRANSFER MATERIAL

STANDARD

GUIDELINES

•Transfer Standard

•Product transfer between manufacturing sites•Analytical technology transfers between sites

STANDARD DOCUMENTS

SUPPORT DOCUMENTS

•Pre-evaluation document•Project Definition Document (PDD)•Transfer Activity Monitoring Document (TAMD)•Monthly report

•Training material

CONTRACT MANUFACTURING EVOLUTIONGli strumenti

GENERAL PROCESS FLOWCHARTGENERAL PROCESS FLOWCHART

PRE-EVALUATIONPHASE

FEASIBILITYPHASE

PREPARATORY

Data collectionfor a first

appraisal

Preliminaryevaluation

Document preparation Detailed

evaluation Regulatory

ProjectDefinitionDocument

PREPARATORYPHASE

OPERATIONALPHASE

PROJECTCOMPLETION

ProtocolsMaterialsDocumentation Trial batches

and Process qualification Submission

Agency review Market approval(s)

Validation activities

CTP support

Regulatory Support

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CONTRACT MANUFACTURING EVOLUTIONGli strumenti

TRANSFER TEAM ORGANISATIONTRANSFER TEAM ORGANISATION

Analytical Dev.Analytical Dev.

Donor siteDonor site

QualityAssurance

QualityAssurance Equipment

& FacilitiesEquipment& Facilities

&Quality control

&Quality controlFinanceFinance

Manufacturing

IndustrialTechnologyIndustrial

TechnologyRegulatory

AffairsRegulatory

AffairsSupply chainSupply chain

ManufacturingPackaging& Artwork

CONTRACT MANUFACTURING EVOLUTIONGli strumenti

THE PROJECT LEADERTHE PROJECT LEADER

• Expert named from CTP Team

• Leads a group of individuals from different functional areas(within receiving site but also from external) to develop andexecute a strategy that delivers the business benefit

PlanningProjectLeader

PlanningLeading

OrganizingControlling

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CONTRACT MANUFACTURING EVOLUTIONGli strumenti

PPLLOOCC ACTIVITES AND DELIVERIESACTIVITES AND DELIVERIES

Define products to be transferred (formulations, packs, markets,volumes)

Audit receiving site

Establish current status for regulatory and quality issues

Define process in receiving site

Define regulatory strategy

Define capital and revenue costs of implementationDefine analytical methods transfer strategy

Identify supply chain issuesEstablish project schedule

Confirm project profitability

Prepare documentation, SOPs, methods, equipment, …

CONTRACT MANUFACTURING EVOLUTIONGli strumenti

Assicurazione di Qualità

L’Assicurazione di QualitàL Assicurazione di Qualitànella scelta e nella gestione delle attività in outsourcing

Il processo di scelta di un possibile partner a cui affidare attività in outsourcingè un processo multifunzionale che deve essere gestito in accordo al Sistema diQualità sia del Committente sia del Fabbricante.

• Customer Service e Production Service LevelCustomer Service e Production Service Level• Scouting e auditing a fornitori• Implementazione file o software per calcolo costi per offerte e verifica aconsuntivo della redditività

• Implementazione Sistema QA per servizio al cliente (info su change,deviazioni, non conformità, ecc.)

• Adattamento del Regolatorio per supportare il cliente nelle attivitàregolatorie per il trasferimento della produzione e delle analisi relative

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CONTRACT MANUFACTURING EVOLUTIONGli strumenti

Assicurazione di Qualità

In ambito farmaceutico, il processo di selezione di un partner perp p pattività in outsourcing non solo deve tenere conto delle esigenzelogistiche, economiche e/o di fornitura, ma deve anche ottemperareai requisiti regolatori e GMP.

Capitolo 7 “Contract Manufacture andAnalysis” EU GMPAnalysis” – EU GMPCapitolo 6 “Quality Control” – EU GMPAnnex 16 “Certification by a Qualified

Person and Batch Release”

Sviluppo o adattamento di struttura per contrattualistica ecapitolati tecnici

CONTRACT MANUFACTURING EVOLUTIONGli strumenti

Ruolo QA

TechnicalTechnical AgreementAgreement

La sottoscrizione di un Technical Agreement tra le parti:

Sancisce la conclusione del processo di selezione del partner esterno;

E’ un elemento essenziale ed irrinunciabile per ottemperare agli obblighinormativi;

E’ il documento essenziale e di riferimento per la gestione delle attività neltempo;

Deve essere redatto e sottoscritto tra le parti in modo da definirechiaramente, concordare e controllare le attività affidate a terzi;

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Deve essere redatto in modo da definire chiaramente le responsabilitàdelle parti:

• Acquisto materiali (reagenti, colonne, standard)• Modalità di campionamento• Modalità di campionamento• Invio e conservazione dei campioni di analisi• Analisi (redazione ed approvazione metodiche e specifiche)• Conservazione dei campioni d’archivio• Conservazione dei dati analitici• Rilascio (modalità di certificazione e rilascio)• Modalità di gestione di OOS, deviazioni e change• Modalità di gestione di difettosità e/o reclami

Deve chiaramente indicare le modalità seguite nel rilascio dei lotti dallaQP

Deve essere redatto da personale tecnicamente competente per quantoconcerne gli aspetti tecnici sia tecnologici, sia analitici, sia GMP, sialegali

Il contesto normativo

Technical AgreementTechnical Agreement

Codice civile

Decreto legislativo 14.04.06 n. 219 – codice deimedicinali

Legge 18.06.98 n. 192 – subfornitura

Decreto legislativo 6.09.2005 n. 2006 – codice delconsumo

CTP TECHNICAL AND LEGAL SUPPORT

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CONTRACT MANUFACTURING EVOLUTIONGli strumenti

“Quality by Design” “Quality by Design” per migliorare il servizio al cliente e ridurre i costiper migliorare il servizio al cliente e ridurre i costiper migliorare il servizio al cliente e ridurre i costiper migliorare il servizio al cliente e ridurre i costi

Quality by Design

Quality Risk ManagementQuality Risk ManagementTrack & Trending

DOCUMENT MANAGEMENT SYSTEM

CONTRACT MANUFACTURING EVOLUTIONGli strumenti

Quality by DesignScopeScope

The main problem is variabilityPharmaceutical Products are of good quality. Quality itself is not the issue, butpharmaceutical development and manufacturing could be improved because:Uncontrolled variability in e.g. properties of the starting materials or themanufacturing process affects the quality of the medicinal product.

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CONTRACT MANUFACTURING EVOLUTIONGli strumenti

Quality by DesignScopeScope

How can variability be reduced?By obtaining increased process and product understanding in order toidentify and appropriately manage critical sources of variability and henceachieve “right first time” performance.Need for a shift in paradigm:From compliance

To enhanced product and process understanding

CONTRACT MANUFACTURING EVOLUTIONGli strumenti

D i d t t

Quality by DesignScope

Desired state:• Product quality and performance achieved and assured by design of effective and

efficient manufacturing processes• Product specifications based on mechanistic understanding of how formulation and

process factors impact product performance• Continuous "real time" quality assurance

How to deliver the desired state?Invest in Pharmaceutical DevelopmentpIdentify critical material and process parameters affecting product quality (usingprior knowledge, risk management tools, DOE, MVA)Understand and if possible express mathematically their relationship with the criticalquality attributesDesign a process measurement system to allow on-line or at-line monitoring ofcritical quality attributesDesign a control system that will allow adjustment of critical quality attributesImplement a quality system that allows continuous improvement

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CONTRACT MANUFACTURING EVOLUTIONGli strumenti

Quality by DesignKey AspectsKey Aspects

ICH Q8: Pharmaceutical DevelopmentICH Q8: Pharmaceutical Development“Quality cannot be tested into products; quality should be

built in by design”

CONTRACT MANUFACTURING EVOLUTIONGli strumenti

Quality by DesignApplications

Pharmaceutical Development- Systematic, establishment of design spaceManufacturing process- Not set, but adjustable within design space- Lifecycle approach to validation: continuous process verification,

alternative strategies to the conventional 3 batches approachP t lProcess controls- PAT tools used with feed forward and feedback controlsProduct specifications- Based on desired product performance with relevant supportive dataControl strategy- Quality controls shifted upstream. Possibility of real-time release or

reduced end-product testing

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CONTRACT MANUFACTURING EVOLUTIONGli strumenti

Quality by DesignToolsTools

Regulatory tools to support the Desired state

Q lit Ri k M tQuality Risk ManagementTrack & Trending

DOCUMENT MANAGEMENT SYSTEM

CONTRACT MANUFACTURING EVOLUTIONGli strumenti

Quality Risk ManagementProcess flow

Risk Assessment

What can go wrong?

What is the likelihood (probability) it would go wrong?

What are the consequences?

Risk analysis is a systematic use of information to identify specificsources of harm (hazards) and to estimate the risk.

Risk evaluation compares the estimated risk against given riskcriteria using a quantitative or qualitative scale to determine thesignificance of the risk.

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CONTRACT MANUFACTURING EVOLUTIONGli strumenti

Quality Risk ManagementApplicationsApplications

1. Development (e.g. Specification Setting, Test Method Selection and processdevelopment).

2. Regulatory scrutiny during pre and post approval.3. As a component of Quality systems (e.g. Auditing, Deviations/Discrepancies,

Complaints & Recall Management, Change management)4. Facility systems management (e.g. Design, Hygiene, Qualification, environmental

control, Preventative maintenance and Computerized systems)control, Preventative maintenance and Computerized systems)5. Materials Management (e.g. Supply chain, Assessment and evaluation of suppliers

and contract manufacturers, procurement and release of material)6. Production (e.g. PAT, Validation, in-process sampling, testing, reporting and

trending)7. Laboratory controls (e.g. validation, testing, methods development, stability).8. Packaging and labeling (e.g. Selection of container closure system and label

controls).9. Regulatory Authority Activities

CONTRACT MANUFACTURING EVOLUTIONGli strumenti

Track & TrendingScope

Reference guideline: ICH Q10

To use effective monitoring systems for process performance andproduct quality providing assurance of continued capability ofprocesses.

Identification and implementation of necessary product qualityimprovements, process improvements, variability reduction,innovations, and quality system tools, thereby increasing theability to consistently fulfil quality and financial requirements.Risk Management techniques may be used to identify necessaryareas for improvement.

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CONTRACT MANUFACTURING EVOLUTIONGli strumenti

Track & TrendingApplicationsApplications

Quality and financial toolsAnnual Product Review1. QA – QC Data Monitoring2. Process data Monitoring3. Engineering Data Monitoring5. Change Managing System6. CAPA Managing System7. KPIs System8. Toll Manufacturing Price Evaluation9. “Control panel”

Stream: Stock Reporting and ManagementMonFor: Supplier Performance MonitorScheduler: Production Order CompilerOrdProd: Efficiency in Production

CONTRACT MANUFACTURING EVOLUTION

Track & TrendingApplications

5. KPIs systemName Definition

Quality service level (QSL)Rate of justified complaintsAccident frequency rateCapacity utilization

Capex maint./depr.wPCI*

wMCI*

Yield**

1 - (Rejected + reworked + reanalysed batches)/total batches(no. of total complaints)/(total PU produced)(no. of severe accidents)/(total labor hours)(Running time)/8,760 hours

(Capex for maintainance)/depreciationsDevelopment of production cost compared to base year, net of product mix changes

and inflation/devaluationDevelopment of material cost from 3rd parties compared to base year, net of product

mix changes(Value of employed material in endproduct)/(total value of employed material)

%ppmPpm%

%%

%

%

Qua-lity

Cost

Yield**Overall equipment

effectiveness (OEE)Turnover ratio forward (TRF)

Production service level (PSL)Intercompany service level

(ISL)Customer service level (CSL)

(Value of employed material in endproduct)/(total value of employed material) (Real running time)/(available capacity)

4 x (projected deliveries in month M+1, M+2 and M+3)/(total inventory at end of month M), deliveries/inventory valued at COG

Average of classified deviation in days for all items between requirement date and date of stock availability

(Number of correctly fulfilled intercompany order lines)/(total number of intercompany order lines)

(Number of correctly fulfilled customer order lines)/(total number of customer order lines)

%

%

%

%

Time

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CONTRACT MANUFACTURING EVOLUTIONGli strumenti

Track & TrendingFurther development

Problem AnalysisThe Track and Trending activities will lead to the highlighting of the mainproblems affecting quality level, costs, deviations and complaintsOnce highlighted the main problems (i.e. yields, market complaints, assayuncontrolled trends, analytical failure investigations, on hold products, etc.)is suggested to put in place a “Pareto” analysis in order to set up priorities inthe recovery plant e eco e y p a

Problem solvingOnce given priorities and put in place a recovery plan is suggested toevaluate possible causes for each problem highlightedOne possible approach is the “bone fish analysis”Is suggested to involve people of the department / s where the problem issupposed to come from

Track & TrendingFurther development

Quality Output Standardization

In every production plant, during normal production activities, could be highlighted someproducts with defects by automatic checkers or by production or analytical personnelproducts with defects by automatic checkers or by production or analytical personnel.Once highlighted these defects is very important to have in place common and approvedlists for defect evaluations in order to quickly give to the personnel a tool for checking andevaluating the problem and put in action a quick, shared and effective remediationactivity including resampling or reworking.This would lead to a common “Quality Behaviour” in every plant of a multinationalcompany, would reduce the on hold time and costs and would give to personnel a common“Quality Feeling”.

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Data Warehouse and Quality Compliance Assurance System

Track & TrendingFurther development

Q y p yUsually, in every company, there are software up and running; they areoften customized for each department’s needs (AS400, SAP, LIMS, POMS,etc.)

Very often these systems are not connected and lots of data in them haveto be put in at least twice or extracted manually and managed with excelor access files.

Is suggested to have aggsimple software that couldlink all the systems in placeand extract data in order tohave graphics, trends orhighlight quality “alarms”

Data Warehouse and Quality Compliance Assurance SystemEXAMPLE

Track & TrendingFurther development

The QA-Process module contains two separate but integratedapplications that can share data:QA Management ToolGMP Event Monitoring & Tracking of Identification , Recording andmonitoring of process eventsDeviation ManagementComplaint ManagementCAPA ManagementChange ManagementMBR e EBR, Master Batch Record and Electronic Batch RecordAPR & QPR Annual & Quality Product ReviewGMP Production Tool sManagement of Production , Materials and Service Level KPIs

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“Executive Summary Slide”“Executive Summary Slide”

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