Validation is Always Part of the Picture Ongoing Validation (DOE, IQ, OQ, PQ, PV)* Pre-IND Phase I Phase II Phase III Commercial Manufacturing * DOE = Design of Experiment IQ = Installation Qualificat OQ = Operational Qualificati PQ = Performance Qualificati PV = Process Validation Specification Development Final process validation Re-validation • The extent of IQ, OQ, PQ, validation, etc. depends on complexity of product • 6 sigma target
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Validation is Always Part of the Picture Ongoing Validation (DOE, IQ, OQ, PQ, PV)* Pre-INDPhase IPhase IIPhase III Commercial Manufacturing * DOE = Design.
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Validation is Always Part of the Picture
Ongoing Validation
(DOE, IQ, OQ, PQ, PV)*
Pre-IND Phase I Phase II Phase III Commercial Manufacturing
* DOE = Design of Experiment IQ = Installation Qualification OQ = Operational Qualification PQ = Performance Qualification PV = Process Validation
Specification DevelopmentFinal process validation
Re-validation
• The extent of IQ, OQ, PQ, validation, etc. depends on complexity of product
• 6 sigma target
GMPValidation of new premises
VALIDATIONVALIDATION
Clean areaPremises
ManufacturingProcesses
EquipmentManufacturing Support Syst.
UtilitySystems
AnalyticalMethods
PersonnelTraining
AsepticProcessing
In-ProcessControl
- HVAC System- LAF Units- Cold Storage- Env. Monitoring- Facility Cleaning- Transfer hatches- Verifi. of classific.
- Water systems- Plant Steam- Pure/Clean Steam- Process Gases
1.1 ToC of Module 1 or overall ToC,including Module 1
2.1 ToC of the CTD (Mod 2,3,4,5)
2.2 Introduction
2.3 Quality Overall Summary
2.4 Nonclinical Overview
2.5 Clinical Overview
2.7 Clinical Summary
2.6 Nonclinical Written and Tabulated Summaries
Module 1
Module 3 Module 4 Module 5
2.1
2.2
2.3
2.4 2.5
2.6 2.7
1.0
QualityNonclinical
Study ReportsClinical
Study Reports
Module 2
Paper CRF Process
Gather Data
Record on Source
Transcribe to CRF
File Copy of CRF
Monitor CRF
Updates to DM
Copy to DM
Data Processing
Issue Queries to Sites
Compare to Source
Answer Query
To DM
Is Response OK?
YES
NO
eCRF
Gather Data
Record on Source
Transcribe to e-CRF
Monitor e-CRF with Source
Generate electronic
Query
Answer on-line Queries
Approve e-CRF
e-CRF Printed for Site
Retention
Data Manager, Project Manager and Clinical Monitor Data (offline edit checks,
manual review)
Protocol Development
Protocol Concept
Stage Review/Approval
Investigator/IND HolderCooperative Group
Protocol DevelopmentDepartment Review
Institutional Scientific Review
IND HolderInstitutional Review Board
Food and Drug AdministrationProtocol Approval
Clinical Trial Monitoring
InvestigatorInstitutional Review Board
Data Safety and Monitoring BoardIND Holder
Food and Drug Administration
1-6 Months
Time Line
2-3 Months
2-3 months
2-6 years
THE R&D PROCESSDevelopment
Discovery Development
Approximately 10–15 years from idea to marketable drug
Preclinical studies Clinical studies
CHEMISTRY/ PHARMA-COLOGY
IND* PHASE I PHASE II PHASE III NDA** PHASE IV
Search for active
substances
Toxicology, efficacy
studies on various types of animals
Regulatory review
Efficacy studies on
healthy volunteers
Clinical studies on a limited scale
Comparative studies on a large number of patients
Regulatory review
Continued comparative studies*Investigational
New DrugApplication for permission to
administer a new drug to humans
50–150persons
100–200patients
500–5,000patients
Registration, market
introduction
**New Drug Application
Application for permission to market
a new drug
KNOWLEDGE
LEVEL
KNOWLEDGE
LEVEL
2–4 yrs. 2–6 months 3–6 yrs. 1–3 yrs.
TIME SPAN
Early Clinical 19
/04
/23
20
Drug Phases
Principle
Testing
Key Activities:• Submission• Single Ascending Dose study• Multi Ascending Dose study • Proof of Principle studies• Manufacture route identification• Dev. formulation for concept testing &
onwards• Dev. Patient Risk Management Plans
Achieved Objectives:• Safety• Effectiveness• Business Plan• Dose