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44 è m e Congrès International SFSTP – 6 et 7 juin 2012 LA LA

44 ème Congrès International SFSTP – 6 et 7 juin 2012

LALA CONNAISSANCECONNAISSANCE SCIENTIFIQUESCIENTIFIQUE AUAU SERVICESERVICE DEDE LALA QUALITEQUALITE PRODUITPRODUIT

ApportsApports dudu «« QualityQuality byby DesignDesign »» etet retoursretours ddexpexpéériencesriences

Nouvelle approche de validation Novo Nordisk

riences Nouvelle approche de validation Novo Nordisk 44 44 è è me me Congr Congr è
riences Nouvelle approche de validation Novo Nordisk 44 44 è è me me Congr Congr è
riences Nouvelle approche de validation Novo Nordisk 44 44 è è me me Congr Congr è

4444èèmeme CongrCongrèèss InternationalInternational SFSTPSFSTP 66--77 JuinJuin 20122012

44 44 è è me me Congr Congr è è s s International International SFSTP SFSTP
Validation and Quality Risk Management 44 44 è è me me Congr Congr è è
Validation and Quality Risk Management 44 44 è è me me Congr Congr è è
Validation and Quality Risk Management 44 44 è è me me Congr Congr è è

Validation and Quality Risk Management

4444èèmeme CongrCongrèèss InternationalInternational SFSTPSFSTP 66--77 JuinJuin 20122012

44 44 è è me me Congr Congr è è s s International International SFSTP SFSTP
Evolution réglementaire … Life to validation and Quality Risk Cycle Approach Management (Novo Nordisk New

Evolution réglementaire …

Life to validation and Quality Risk Cycle Approach Management (Novo Nordisk New Validation Concept) ICH:
Life
to validation and Quality Risk
Cycle Approach
Management
(Novo Nordisk
New Validation Concept)
ICH: Q8/9/10
(Pharma Dev, QRM, Quality Systems)
FDA:
ASTM:

E2500 (Standard for Specs, Design, & Verif.)

ISPE:

GAMP 5 (Automation & Comp.

Systems) & Baseline Guide

Volumes 5 &12 (C&Q, Verification)

Qual. Systems Approach to Pharma cGMP Regs

NOM – LABO
NOM – LABO

4444èèmeme CongrCongrèèss InternationalInternational SFSTPSFSTP 66--77 JuinJuin 20122012

LABO 44 44 è è me me Congr Congr è è s s International International SFSTP
New Validation Approach 44 44 è è me me Congr Congr è è s s
New Validation Approach 44 44 è è me me Congr Congr è è s s
New Validation Approach 44 44 è è me me Congr Congr è è s s

New Validation Approach

4444èèmeme CongrCongrèèss InternationalInternational SFSTPSFSTP 66--77 JuinJuin 20122012

44 44 è è me me Congr Congr è è s s International International SFSTP SFSTP
FDA Process validation overview Manufacturing Process Validation in NN NOM – LABO 44 44 è
FDA Process validation overview Manufacturing Process Validation in NN NOM – LABO 44 44 è

FDA Process validation overview

FDA Process validation overview Manufacturing Process Validation in NN NOM – LABO 44 44 è è
FDA Process validation overview Manufacturing Process Validation in NN NOM – LABO 44 44 è è

Manufacturing Process Validation in NN

validation overview Manufacturing Process Validation in NN NOM – LABO 44 44 è è me me
validation overview Manufacturing Process Validation in NN NOM – LABO 44 44 è è me me
validation overview Manufacturing Process Validation in NN NOM – LABO 44 44 è è me me
validation overview Manufacturing Process Validation in NN NOM – LABO 44 44 è è me me
validation overview Manufacturing Process Validation in NN NOM – LABO 44 44 è è me me
validation overview Manufacturing Process Validation in NN NOM – LABO 44 44 è è me me
NOM – LABO
NOM – LABO

4444èèmeme CongrCongrèèss InternationalInternational SFSTPSFSTP 66--77 JuinJuin 20122012

A Life Cycle Approach. Development Pilot Launch Production Process Process Qualification Qualification – –

A Life Cycle Approach.

Development Pilot Launch Production Process Process Qualification Qualification – – Equipment Equipment &
Development
Pilot Launch
Production
Process Process Qualification Qualification – –
Equipment Equipment & & Facilities Facilities
(Stage (Stage 2.1) 2.1)
Process Process
Manufacturing Manufacturing
Continued Continued
Performance Performance
Process Process Design Design
Process Process Verification Verification
Qualification Qualification
(Stage (Stage 1) 1)
(Stage (Stage 3) 3)
(Stage (Stage 2.2) 2.2)
Control Strategy
Control Strategy
Quality Risk Management
Quality Risk Management
(Stage 2.2) 2.2) Control Strategy Quality Risk Management NOM – LABO 44 44 è è me
NOM – LABO
NOM – LABO

4444èèmeme CongrCongrèèss InternationalInternational SFSTPSFSTP 66--77 JuinJuin 20122012

LABO 44 44 è è me me Congr Congr è è s s International International SFSTP

ZANDILE SIGNORIA MZAYIFANI South Africa

ZANDILE SIGNORIA MZAYIFANI South Africa Zandile has type 2 diabetes Validation and Quality Risk Management New

Zandile has type 2 diabetes

Validation and Quality Risk Management

New Validation Approach

Manufacturing Process Design

Stage 1

New Validation Approach Manufacturing Process Design Stage 1 NOM – LABO 44 44 è è me
New Validation Approach Manufacturing Process Design Stage 1 NOM – LABO 44 44 è è me
NOM – LABO
NOM – LABO

4444èèmeme CongrCongrèèss InternationalInternational SFSTPSFSTP 66--77 JuinJuin 20122012

LABO 44 44 è è me me Congr Congr è è s s International International SFSTP
11 June 2012 Purpose of Process design – Stage 1 Le but de « process

11 June 2012

Purpose of Process design – Stage 1

11 June 2012 Purpose of Process design – Stage 1 Le but de « process justification
Le but de « process justification » est de démontrer que le procédé de production,
Le but de « process justification » est de démontrer
que le procédé de production, fonctionnant dans les
plages établies, fournira un produit répondant aux
spécifications.
fournira un produit répondant aux spécifications. NOM – LABO 44 44 è è me me Congr
NOM – LABO
NOM – LABO

4444èèmeme CongrCongrèèss InternationalInternational SFSTPSFSTP 66--77 JuinJuin 20122012

LABO 44 44 è è me me Congr Congr è è s s International International SFSTP
Quality in the product life cycle Production Critical Critical Control Quality Target Product profile (QTPP)

Quality in the product life cycle

Production Critical Critical Control Quality Target Product profile (QTPP) Equipment Process Quality Strategy
Production
Critical
Critical
Control
Quality Target
Product profile
(QTPP)
Equipment
Process
Quality
Strategy
(URS &
Parameters
Attributes
(CS)
DQ)
(CPP)
(CQA)

Les CQA et leur sévérité sont utilisés pour le QRM Un outil permettant de mettre en évidence les paramètres les plus importants S’ils ont un impact signifiant sur la qualité du produit , cela permettra de contrôler ceuxci et de diminuer le risque

de contrôler ceux ‐ ci et de diminuer le risque 44 44 è è me me
de contrôler ceux ‐ ci et de diminuer le risque 44 44 è è me me

4444èèmeme CongrCongrèèss InternationalInternational SFSTPSFSTP 66--77 JuinJuin 20122012

44 44 è è me me Congr Congr è è s s International International SFSTP SFSTP

ZANDILE SIGNORIA MZAYIFANI South Africa Zandile has type 2 diabetes

SIGNORIA MZAYIFANI South Africa Zandile has type 2 diabetes Validation and Quality Risk Management New Validation

Validation and Quality Risk Management

New Validation Approach

Manufacturing Process Qualification – Equipment & Facilities

-

Stage 2.1

Qualification – Equipment & Facilities - Stage 2.1 NOM – LABO 44 44 è è me
Qualification – Equipment & Facilities - Stage 2.1 NOM – LABO 44 44 è è me
Qualification – Equipment & Facilities - Stage 2.1 NOM – LABO 44 44 è è me
NOM – LABO
NOM – LABO

4444èèmeme CongrCongrèèss InternationalInternational SFSTPSFSTP 66--77 JuinJuin 20122012

LABO 44 44 è è me me Congr Congr è è s s International International SFSTP
Process qualification – Equipment and facility – Stage 2.1 Application au projet « FLACONS »

Process qualification – Equipment and facility – Stage 2.1

Application au projet « FLACONS » site NN Chartres
Application au projet « FLACONS »
site NN Chartres
2.1 Application au projet « FLACONS » site NN Chartres NOM – LABO 44 44 è
NOM – LABO
NOM – LABO

4444èèmeme CongrCongrèèss InternationalInternational SFSTPSFSTP 66--77 JuinJuin 20122012

LABO 44 44 è è me me Congr Congr è è s s International International SFSTP
Quality project strategy / Risk management IQ OQ PQ FAT SAT FAT SAT IQ OQ

Quality project strategy / Risk management

IQ OQ PQ
IQ
OQ
PQ
FAT SAT FAT SAT IQ OQ
FAT
SAT
FAT
SAT
IQ
OQ
URS
URS
risk assessment
risk
assessment
IQ OQ PQ FAT SAT FAT SAT IQ OQ URS risk assessment procurement Redondance des activités

procurement

Redondance des activités Beaucoup de documents générés Analyse de criticité simpliste Planning long Coûts supérieurs

CRITICAL STEP

risk URS assessment
risk
URS
assessment

supplier

involment

CRITICAL STEP risk URS assessment supplier involment procurement PQ inspection follow Accroitre le management de

procurement

PQ

inspection follow

Accroitre le management de la qualité en amont des phases projet Mise en place d’une équipe et d’un planning Qualité très tôt dans le projet

teams with experts of all départements Multi compétences

up during

construction

départements Multi compétences up during construction NOM – LABO 44 44 è è me me Congr
NOM – LABO
NOM – LABO
Multi compétences up during construction NOM – LABO 44 44 è è me me Congr Congr

4444èèmeme CongrCongrèèss InternationalInternational SFSTPSFSTP 66--77 JuinJuin 20122012

Quality project strategy ‐ Benefices QUALITY Meilleure compréhension des procédés Meilleure maitrise des

Quality project strategy Benefices

QUALITY Meilleure compréhension des procédés Meilleure maitrise des risques Esprit Qualité totale Implication de
QUALITY
Meilleure compréhension des procédés
Meilleure maitrise des risques
Esprit Qualité totale
Implication de tous les experts (…. fournisseur ….)
HUMAN RESSOURCES
Management du risque
Esprit d’équipe
Meilleures connaissances des procédés
BUSINESS
Pas de redondance des activités
Temps de qualification réduit
Coûts réduits , maitrisés
Temps de qualification réduit Coûts réduits , maitrisés NOM – LABO 44 44 è è me
NOM – LABO
NOM – LABO

4444èèmeme CongrCongrèèss InternationalInternational SFSTPSFSTP 66--77 JuinJuin 20122012

LABO 44 44 è è me me Congr Congr è è s s International International SFSTP
SPECIFICATIONS DESIGN AND MANUFACTURE PHASE PHASE Risk analysis Risk Risk reduction Identification safety risk
SPECIFICATIONS DESIGN AND MANUFACTURE PHASE PHASE Risk analysis Risk Risk reduction Identification safety risk
SPECIFICATIONS
DESIGN AND MANUFACTURE PHASE
PHASE
Risk analysis
Risk
Risk
reduction
Identification
safety risk
safety risk
analysis
identification
(impact)
Identification
Action
of critical
plan for
GxP risk
GxP risk
functions and
risk
analysis
identification
elements per
reduction
(impact)
system
business risk
business
identification
risk
analysis
(impact)

OPERATION PHASE

Risk acceptance

risk analysis (impact) OPERATION PHASE Risk acceptance Evaluation acceptance of residual risk Risk
Evaluation acceptance of residual risk Risk management/control control system training plans documentation /
Evaluation acceptance of
residual risk
Risk management/control
control system
training plans
documentation /
instructions
disaster recovery plan
periodical evaluation
/ validation
maintenance
calibration plans

USER

NOM – LABO
NOM – LABO

4444èèmeme CongrCongrèèss InternationalInternational SFSTPSFSTP 66--77 JuinJuin 20122012

User/supplier cooperation approach BASIC DESIGN DETAILED DESIGN Purchasing package URS + Tech doc + Q

User/supplier cooperation approach

BASIC DESIGN DETAILED DESIGN Purchasing package URS + Tech doc + Q strategy Technical and
BASIC DESIGN
DETAILED
DESIGN
Purchasing package
URS + Tech doc + Q
strategy
Technical and
Quality
alignment
CONTRACT
Quality
assessment
by Q PM

CONSTRUCTION

PHASE

follow up on shop floor by engineering and technical experts

COMMISSIONNIG PHASE QUALIFICATION PHASE Mid project End project evaluation evaluation Quality Status by Q PM
COMMISSIONNIG
PHASE
QUALIFICATION
PHASE
Mid project
End project
evaluation
evaluation
Quality
Status by Q
PM
NOM – LABO
NOM – LABO

4444èèmeme CongrCongrèèss InternationalInternational SFSTPSFSTP 66--77 JuinJuin 20122012

LABO 44 44 è è me me Congr Congr è è s s International International SFSTP
DESIGN AND MANUFACTURE PHASE CONSTRUCTION COMMISSIONNIG PHASE PHASE QUALIFICATION PHASE Inspections follow up be
DESIGN AND MANUFACTURE PHASE CONSTRUCTION COMMISSIONNIG PHASE PHASE QUALIFICATION PHASE Inspections follow up be
DESIGN AND MANUFACTURE
PHASE
CONSTRUCTION
COMMISSIONNIG PHASE
PHASE
QUALIFICATION PHASE
Inspections
follow up
be on shop
floor
DOCUMENTATION (PROCEDURES, INSTRUCTIONS, MAINTENANCE
PLAN, CALIBRATION PLAN, VALIDATION PERIODICITY…….)
IQ
OQ
PQ
PPQ
pre tests
FACTORY
FACTORY
ACCEPTANCE
pre tests
ACCEPTANCE
TESTS
TESTS
TRAINING
TRAINING
SPECIFICATIONS PHASE BASIC DETAILED DESIGN DESIGN VMP URS FS
SPECIFICATIONS
PHASE
BASIC
DETAILED
DESIGN
DESIGN
VMP
URS
FS

Risk

assessment

criticality

impact

(RAR,

RCL/FMEA….)

DESIGN

REVIEW

NOM – LABO
NOM – LABO

4444èèmeme CongrCongrèèss InternationalInternational SFSTPSFSTP 66--77 JuinJuin 20122012

OPERATION

PHASE

HANDOVER

User supplier User + supplier
User
supplier
User + supplier
International SFSTP SFSTP 6 6 - - 7 7 Juin Juin 2012 2012 OPERATION PHASE HANDOVER
NOM – LABO 44 44 è è me me Congr Congr è è s s
NOM – LABO 44 44 è è me me Congr Congr è è s s
NOM – LABO
NOM – LABO

4444èèmeme CongrCongrèèss InternationalInternational SFSTPSFSTP 66--77 JuinJuin 20122012

LABO 44 44 è è me me Congr Congr è è s s International International SFSTP
New Validation Approach Process performance qualification - Stage 2.1 NOM – LABO 44 44 è

New Validation Approach

Process performance qualification

- Stage 2.1

Approach Process performance qualification - Stage 2.1 NOM – LABO 44 44 è è me me
Approach Process performance qualification - Stage 2.1 NOM – LABO 44 44 è è me me
NOM – LABO
NOM – LABO

4444èèmeme CongrCongrèèss InternationalInternational SFSTPSFSTP 66--77 JuinJuin 20122012

LABO 44 44 è è me me Congr Congr è è s s International International SFSTP
Number of PPQ batches Process performance qualification Old Term New Term Process Validation (PV) Process

Number of PPQ batches

Process performance qualification

Old Term

New Term

Process Validation (PV)

Process Performance Qualification (PPQ)

• 3 lots: ce n’est plus un nombre magique ! • Cependant, dans la plupart
• 3 lots: ce n’est plus un nombre magique !
• Cependant, dans la plupart des cas, 3 lots seront exécutés mais avec un
rationnel.
• Un rationnel sera aussi nécessaire pour le nombre de lots choisis
• Le nombre de lots doit être suffisant pour démontrer la reproductibilité
• les données de laboratoire et d'études préliminaires ainsi que les données
issues des études cliniques peuvent être employées pour le rationnel
• Le PPQ doit avoir un nombre important de prélèvements et définir quelles
données doivent être collectées et évaluées
• La reproductibilité doit être démontrée : comparaison d’un lot à l’autre et variation
dans un même lot

4444èèmeme CongrCongrèèss InternationalInternational SFSTPSFSTP 66--77 JuinJuin 20122012

lot 44 44 è è me me Congr Congr è è s s International International SFSTP
lot 44 44 è è me me Congr Congr è è s s International International SFSTP
Validation and Quality Risk Management GERALD JOHN GARWOOD South Africa Gerald has type 2 diabetes

Validation and Quality Risk Management

GERALD JOHN GARWOOD South Africa Gerald has type 2 diabetes

New Validation Approach

Continued Process Verification

Stage 3

Validation Approach Continued Process Verification Stage 3 NOM – LABO 44 44 è è me me
Validation Approach Continued Process Verification Stage 3 NOM – LABO 44 44 è è me me
NOM – LABO
NOM – LABO

4444èèmeme CongrCongrèèss InternationalInternational SFSTPSFSTP 66--77 JuinJuin 20122012

LABO 44 44 è è me me Congr Congr è è s s International International SFSTP
Continued Process Verification • L’assurance en continu que le processus demeure sous contrôle pendant la

Continued Process Verification

• L’assurance en continu que le processus demeure sous contrôle pendant la fabrication

• Les données devraient être statistiquement analysées et passées en revue par un personnel qualifié.

• Des contrôles de tendances réguliers doivent donner l’assurance que les attributs de qualité sont sous contrôle

que les attributs de qualité sont sous contrôle 44 44 è è me me Congr Congr
que les attributs de qualité sont sous contrôle 44 44 è è me me Congr Congr

4444èèmeme CongrCongrèèss InternationalInternational SFSTPSFSTP 66--77 JuinJuin 20122012

44 44 è è me me Congr Congr è è s s International International SFSTP SFSTP
44 44 è è me me Congr Congr è è s s International International SFSTP SFSTP
44 44 è è me me Congr Congr è è s s International International SFSTP SFSTP
Continued Process Verification Review Long term Annual Product Review (APR) Periodic System evaluation (PSE) Risk

Continued Process Verification

Review

Long term
Long
term
Annual Product Review (APR) Periodic System evaluation (PSE) Risk Review
Annual Product Review (APR)
Periodic System evaluation (PSE)
Risk Review
Short term
Short
term
Environmental monitoring Control Chart Script (CCS)
Environmental monitoring
Control Chart Script (CCS)
term Environmental monitoring Control Chart Script (CCS) NOM – LABO 44 44 è è me me
NOM – LABO
NOM – LABO

4444èèmeme CongrCongrèèss InternationalInternational SFSTPSFSTP 66--77 JuinJuin 20122012

LABO 44 44 è è me me Congr Congr è è s s International International SFSTP
Short term review process = Review of trends in control charts To be reviewed at

Short term review process = Review of trends in control charts

To be reviewed at least every second week Take Take Start Start trend trend improvement
To be reviewed
at least every second
week
Take Take
Start Start trend trend
improvement improvement
investigation investigation
On-going data
collection and
generation of
control charts
from CQA
action action
Evaluation Evaluation
meeting meeting
No No action action
needed needed
NOM – LABO
NOM – LABO

4444èèmeme CongrCongrèèss InternationalInternational SFSTPSFSTP 66--77 JuinJuin 20122012

LABO 44 44 è è me me Congr Congr è è s s International International SFSTP
Examples of Control Charts Scrips Control charts make s it possible to: Overview and underst

Examples of Control Charts Scrips

Examples of Control Charts Scrips Control charts make s it possible to: Overview and underst and

Control charts makes it possible to:

Overview and understand the process. React timely if a process is out of trend.

the process. React timely if a proce ss is out of trend. UCL and LCL =

UCL and LCL = Control chart limits

USL and LSL = Specification limits

NOM – LABO
NOM – LABO

4444èèmeme CongrCongrèèss InternationalInternational SFSTPSFSTP 66--77 JuinJuin 20122012

LABO 44 44 è è me me Congr Congr è è s s International International SFSTP

GERALD JOHN GARWOOD South Africa

GERALD JOHN GARWOOD South Africa Validation and Quality Risk Management Gerald has type 2 diabetes New

Validation and Quality Risk Management

Gerald has type 2 diabetes

New Validation Approach

Control Strategy

has type 2 diabetes New Validation Approach Control Strategy NOM – LABO 44 44 è è
has type 2 diabetes New Validation Approach Control Strategy NOM – LABO 44 44 è è
NOM – LABO
NOM – LABO

4444èèmeme CongrCongrèèss InternationalInternational SFSTPSFSTP 66--77 JuinJuin 20122012

LABO 44 44 è è me me Congr Congr è è s s International International SFSTP
Validation and control strategy Context The elements in the Control Strategy Materials DS, DP, raw

Validation and control strategy Context The elements in the Control Strategy

Materials DS, DP, raw materials and components Quality Equipment Attributes Facility and equipment operating
Materials
DS, DP, raw materials and
components
Quality
Equipment
Attributes
Facility and
equipment operating
conditions
Attributes Facility and equipment operating conditions Environment Room classification and monitoring Control
Attributes Facility and equipment operating conditions Environment Room classification and monitoring Control

Environment Room classification and monitoring

Control strategy report
Control strategy report

Process steps and parameters

People Training and right competences

Measurements

In-process controls, finished product specifications and associated methods

NOM – LABO
NOM – LABO

4444èèmeme CongrCongrèèss InternationalInternational SFSTPSFSTP 66--77 JuinJuin 20122012

LABO 44 44 è è me me Congr Congr è è s s International International SFSTP
Validation and control strategy Context Stage 3 Facility FMECA CSR PQ PSE URS review OQ

Validation and control strategy Context

Stage 3 Facility FMECA CSR PQ PSE URS review OQ Design IQ DQ Test Changes
Stage 3
Facility FMECA
CSR
PQ
PSE
URS
review
OQ
Design
IQ
DQ
Test
Changes and incidents
Stage 2.1
Stage 1
Stage 2.2
Short term review
Process FMECA
Control
Process
parameters
Critical PP
Impact
Process
Process
Monitor
Assessment
Performance
Manufacture
APR
justification
Qualification (PPQ)
Non critical PP
Process steps
Control strategy
defined
Control strategy
Control strategy
verified
implemented
NOM – LABO
NOM – LABO

4444èèmeme CongrCongrèèss InternationalInternational SFSTPSFSTP 66--77 JuinJuin 20122012

LABO 44 44 è è me me Congr Congr è è s s International International SFSTP
MERCI MERCI ! ! NOM – LABO 44 44 è è me me Congr Congr

MERCIMERCI !!

NOM – LABO
NOM – LABO
MERCI MERCI ! ! NOM – LABO 44 44 è è me me Congr Congr è

4444èèmeme CongrCongrèèss InternationalInternational SFSTPSFSTP 66--77 JuinJuin 20122012

LABO 44 44 è è me me Congr Congr è è s s International International SFSTP