dr. d. marcozzi head of clinical and csv qa dept. of sigma-tau milano, 31 marzo, 2005 qual è il...
Post on 01-May-2015
220 Views
Preview:
TRANSCRIPT
Dr. D. MarcozziDr. D. MarcozziHead of Clinical and CSV QA dept. of SIGMA-TAUHead of Clinical and CSV QA dept. of SIGMA-TAU
Milano, 31 marzo, 2005
Qual è il Processo della Qual è il Processo della Computer System Validation?Computer System Validation?
Riunione Gruppo Riunione Gruppo GCPGCP
Parleremo di:Parleremo di:
FORNITORI
CONVALIDA
Nuova visione delle CONVALIDE
Analisi e Gestione del RISCHIO
Cos’è la CONVALIDA?Cos’è la CONVALIDA?
Si si …un bel Si si …un bel vestito….vestito….
Cos’è la CONVALIDA?Cos’è la CONVALIDA?
Cos’è la CONVALIDA?Cos’è la CONVALIDA?
Mi dicono Mi dicono che avrei che avrei fatto una fatto una
CONVALIDACONVALIDA????
Cos’è la CONVALIDA?Cos’è la CONVALIDA?
O meglio………….
Che cos’è la Computerized Che cos’è la Computerized System Validation (CSV)System Validation (CSV)
Primo: cos’è un Computerized Primo: cos’è un Computerized System?System?
Personnel
Software
Documentation
InstrumentHardware
Documentation
Control System
Operating Environment
Procedures
Infrastructure
Validation is….Validation is….
“Establishing documented evidence which provides a
high degree of assurance that a specific process
will consistently produce a product
meeting its pre-determined specifications
and quality attributes”
CurrentCurrent
Validation is the entire procedure of gathering
documented evidence that a computer-related process or
a system performs
according to its intended function
reliably and consistently throughout its life.
DocumentedDocumented
Process/systemProcess/system
Pre-DeterminedPre-Determined
Quality AttributesQuality Attributes
Entire ProcedureEntire Procedure
Reliably and Reliably and consistentlyconsistently
LifeLife
Le parole “CHIAVE”Le parole “CHIAVE”
The life cycle concept of The life cycle concept of Computer ValidationComputer Validation
Validation is a PROCESS, not an event
Validation activities span the entire System Life Cycle:
Planning Requirements Analysis Design Implementation Testing Acceptance On going Retirement
Requirements
System
Selection
Specify
&
Design
BuildSupplier
Testing
User
Qualification
Operation
Maintenance
Do
cu
me
nta
tio
n
Planning and ImplementationPlanning and ImplementationA Life cycle approachA Life cycle approach
URS
FS OQ
DS
PQ
IQ
System
Build
Planning and ImplementationPlanning and ImplementationA Life cycle approachA Life cycle approach
Planning
Specifications
Test Planning (IQ,OQ,PQ)
Review
Validation Plan
URS, FS, DS (required)
Doc. come testare il sistema
Validation Report
Testing Test e risultati
Planning and ImplementationPlanning and ImplementationA Life cycle approachA Life cycle approach
Validation activity and “life cycle”
PROJECT ACTIVITY
USER REQUIREMENTSFUNCTIONAL SPEC.
HW E SW DES. SPEC.SW MODULE DES. SPEC.
MECH. & ELECTRIC SPEC.
HW MANUF. & ASSEMBLYCODE SW MODULES
EQUIP. MANUF. & ASSEMBLY
HW TESTINGSW MOD.& INTEGR. TESTING
EQUIP TESTING
HW, SW, EQUIP. INSTALL.HW ACCEPTANCE TESTING
SYSTEM ACCEPTANCE TEST.
MAINTENANCECHANGE CONTROL
LIFE CYCLE PHASE
PLANNING & SPECIFICATION
DESIGN
CONSTRUCTION
TESTING
INSTALLATION
ACCEPTANCE TESTING
OPERATION
VALIDATION ACTIVITY
VALIDATION PLANSUPPLIER AUDITS
SPEC. REVIEW
DESIGN REVIEW
COSTRUCTION & CODE REVIEW
MONITOR SUPPLIER
IQ
OQPQ
VALIDATION REPORT
ONGOING OPERATION
Validation Scope and EffortValidation Scope and Effort
Validation Scope and Effort
should be commensurate with impact and value
of data, process, results. . .
size and complexity of the system and
how critical it is in
your routine and non-routine operations
Tanto più un sistema è critico e complesso tanto maggiore
sarà lo “sforzo” di convalida…quindi…
Sistemi Standard
Sistemi Customizzati
Sistemi Be-spoke
Basic Approach to ValidationBasic Approach to Validation
Validation is a process, not an event
Planning activity should be performed as a Team
Keep the validation process under control
Le finalità….da GCPLe finalità….da GCP
Qualora si avvalga di sistemi elettronici di
elaborazione dei dati e/o sistemi di inserimento a
distanza per la gestione dei dati relativi alla
sperimentazione, lo Sponsor….
Garantire e documentare che il sistema elettronico
per l’elaborazione dei dati sia conforme ai requisiti
di completezza, precisione, affidabilità stabiliti dallo
Sponsor e che questi siano conformi alle
caratteristiche prefissate (cioè Validazione)
Le finalitàLe finalità
Validating Data
Validating the
System handling
the Data
Nel 1999… l’FDANel 1999… l’FDA
Pubblica una nuova Guidance for Industry
“Computerized System Used in Clinical Trials”
Per essere accettabili, i dati debbono soddisfare certi elementi fondamentali di qualità se raccolti e
registrati elettronicamente o su carta
I dati debbono essere: ttribuibili (Source & Recorder are Known)
eggibili (Human readable) ontemporanei (Recorded when observed)
riginali (Honest data/not fraud)ccurati (Correct, repeatable results)
AL
CO
A
ALCOA
Ed ora… gli attori…Ed ora… gli attori…
CLIENTECLIENTE
FORNITOREFORNITORE
CLIENTECLIENTE
FORNITOREFORNITORE
USERUSER ITIT
QAQA
CLIENTECLIENTE
COMMERCIALECOMMERCIALE
e……e……
FORNITOREFORNITORE
QAQA
According to specific rules or guidelines defined for each environment
Il peso del QA….Il peso del QA….
ITQA
Il peso del QA….Il peso del QA….
Qualità della documentazione
Requisiti Regolatori
Requisiti di Processo
Requisiti Tecnici
Pianificazione e Testing
Qualifica dei fornitori
QA
IT
Il QA… ovunque nella Il QA… ovunque nella CSVCSV
Valutazione Fornitori
Risk Assessment
Definizione Requisiti Utente
Definizione delle politiche di convalida
Piani e test di convalida
Revisione ed Approvazione dei documenti di convalida
Il QA… ovunque nella Il QA… ovunque nella CSVCSV
Approvazione dei cambiamenti
Revisione ed Approvazione delle SOPs di convalida e CSV generali
Audit periodici
Punto di riferimento normative CSV
E le SOPs?E le SOPs? Training Vendor Evaluation Gestione Documentazione di Convalida Change Control Configuration Management Problem Reporting Security Back-up Restore Archiving Clinical Data Maintenance Disaster Recovery/Business Continuity Periodic Review
QAQA
COMMERCIALECOMMERCIALE
e……e……
FORNITOREFORNITORE
PQURS
FS OQ
DS IQ
System Build
Planning and ImplementationPlanning and ImplementationA Life cycle approachA Life cycle approach
Evaluation should preferably be derived from a
reliable audit of the software developer (supplier),
performed by the end user’s organization or a
trusted and competent third part.
Da GMP….. Da GMP…..
...Validation should be considered as part of the complete
life cycle of a computer system. This cycle includes the
stages
of planning, specification, programming, testing,
commissioning, documentation, operation, monitoring and
modifying… (by supplier!).
The software is a critical component of a computerized
system. The user of such software should take all reasonable
steps to ensure that it has been produced in accordance with
a System of Quality Assurance.
CS Validation CS Validation Documents Documents
Client responsibility Supplier responsibility
Planning
GAMP
Specifications
Testing
Validation Summary
On-Going
Test Plan
Design Spec.
Functional Spec.
Quality and Project Plan
Factory/Site Acceptance Test
Master Index
Validation Report.
Report IQR, OQR, PQR
Audit Report
Validation Plans
Validation Master Plan
User Requirement Specifications
SOPs
ProtocolliDQ, IQ, OQ, PQ
SOPs User Manuals
Why do we have to audit the Why do we have to audit the Suppliers?Suppliers?
The primary purpose of an audit is to The primary purpose of an audit is to assessassess the the
controlscontrols, , proceduresprocedures, and , and practicespractices which are in which are in
place for the place for the developmentdevelopment and and maintenancemaintenance of a of a
productproduct
Is a form of review that provides Is a form of review that provides confidenceconfidence
concerning the concerning the validityvalidity and and accuracyaccuracy of a of a productproduct or or
processprocess nownow and in the and in the futurefuture
Audits should be viewed as a Audits should be viewed as a learninglearning experienceexperience and and
should be conducted should be conducted asas a a cooperativecooperative efforteffort
SW Supplier EvaluationSW Supplier Evaluation
“To ensure that the supplier produces a quality
product, and to obtain information to plan
computer validation activities”
“Tools”
Collection of available information Request for Information (questionnaire) Audit Follow up
Intent
COSTS
RISKSEVALUATION
THROUGH REFERENCES
EVALUATION THROUGH
EXPERIENCES
REQUEST FOR INFORMATION
3RD PARTY AUDIT
SPECIFIC FIRM AUDIT
Supplier Evaluation ToolsSupplier Evaluation Tools
Supplier Qualification modelSupplier Qualification model
Information from other companies or from market
Request for Information (RFI)
Telephone Audit
Site Audit
SY
ST
EM
RIS
K C
AT
EG
OR
Y
EV
AL
UA
TIO
N C
OS
T
Check…Independence of SW Check…Independence of SW Validation Validation
Validation activities should be Validation activities should be conducted using the basic quality conducted using the basic quality
assurance precept of assurance precept of ““independenceindependence of of reviewreview”.”.
Self-validation is extremely difficult; Self-validation is extremely difficult; an an independentindependent reviewreview is always is always
better.better.
Computer system validation should be performed by persons other than those responsible for
building the system.
Check…Independence of SW Check…Independence of SW ValidationValidation
Validation: Client Validation: Client Responsibility ! Responsibility !
Manufacturer has flexibility in choosing how to apply the validation principles, but retains ultimate responsibility for demonstrating that the software has been validated.
NormativeGuidelines
PLANNING
Client Responsibility !Client Responsibility !
Client with regulatory responsibility
needs to assess the adequacy of the
software developer’s activities and
determine what additional efforts are
needed to establish that the software
is validated.
...but
Validation Responsibility is always on the Client’s side
Supplier selection (and supplier)is important
Validated Packages don’t Validated Packages don’t exist!!exist!!
SupplierSupplier maymay provideprovide a a
““ValidationValidation PackagePackage”, showing ”, showing
that the that the standardstandard versionversion of of
the product has been the product has been
validatedvalidated “in “in FactoryFactory””
ClientClient has to perform an “ has to perform an “on-on-SiteSite” Validation ” Validation
Quindi….Quindi….
La validazione è una nostra responsabilità
Si deve Validare nel nostro “ambiente” Non è una responsabilità del Fornitore
del sistema
I sistemi forniti (anche quelli più standard) sono validabili, da validare e non già
validati
Quanto più il fornitore è affidabile…di QUALITA’
Tanto meno sforzo di convalida dovremo
pianificare
Dopo e sempre Validare!!!
Prima Verificare!!!
Ora parliamo di Ora parliamo di
RISK MANAGEMENT….RISK MANAGEMENT….
RISK ANALYSIS…..RISK ANALYSIS…..
Solo un accenno…. Solo un accenno…. prendiamo spunto dalla prendiamo spunto dalla
realtà!realtà!
Da FDA….Da FDA….
Pharmaceutical Pharmaceutical CGMPs CGMPs for the 21for the 21st st centurycentury
A A RRisk-isk-BBased ased AApproach pproach FFinal inal RReport eport september 2004september 2004
In August 2002, FDA announced a significant new initiative, In August 2002, FDA announced a significant new initiative, Pharmaceutical Current Manufacturing Practices (CGMPs)Pharmaceutical Current Manufacturing Practices (CGMPs) for for the the 2121stst Century Century, to enhance and modernize the regulation of , to enhance and modernize the regulation of pharmaceutical manufacturing and product quality for pharmaceutical manufacturing and product quality for veterinary and human drugs…. veterinary and human drugs….
Objective:Objective:
Encourage implementation of risk-based approaches that Encourage implementation of risk-based approaches that focus both industry and Agency attention on critical areasfocus both industry and Agency attention on critical areas
Da FDA….Da FDA….
21 CFR Part 11 Guidance…21 CFR Part 11 Guidance…
Whit the issuance in 2003 of the guidance for Whit the issuance in 2003 of the guidance for industry industry part11, Electronic Records,part11, Electronic Records, ElectronicElectronic Signature-Signature- Scope and Application,Scope and Application, many barriers to many barriers to scientific and technological advances were removed, scientific and technological advances were removed, and the use of and the use of risk-based approachesrisk-based approaches to managing to managing computer systems is encouraged.computer systems is encouraged.
Risk AnalysisRisk Analysis//
Computer Validation Computer Validation
Protect against the risks to patient safety
Maximize the business benefits
Help to determine the extent of validation
Give a rationale to justify Validation approach in case of Inspection
Concentrate the validation effort
A Good StartA Good Start Perform AssessmentPerform Assessment
Dove siamo?
Dove vogliamo andare?
Da cosa cominciamo?
Risk Analysis: the ValueRisk Analysis: the Value
The more you know about your computer system
TestThe more you focus the validation
Better you will use your resources…. and Better you will use your resources…. and money!money!
Nuovo approccio alle Nuovo approccio alle Convalide….Convalide….
Nel 1990 GAMP…
Good Automated Manufacturing Practice
Scopo della linea-guida è quello di assistere le aziende farmaceutiche, biotecnologiche, medical devices nell’implementazione di sistemi
automatizati validati e compliant con i requisiti normativi
Nasce nell’ambient
e GMP
…nuove GAMP… 2001
Le nuove GAMP coprono tutti i requirements GMP, GCP, GLP e GDP
Si potrebbero chiamare GA “M-C-L-D” P
Più attenzione al Processo!
Nuovo approccio alle Nuovo approccio alle Convalide….Convalide….
Da…Da… PerformancePerformance
ProcessProcessA…..A…..
QUALIFICATION !QUALIFICATION !
FINE…..FINE…..
Grazie per la Grazie per la
PAZIENZA!!PAZIENZA!!
top related