Overview of

Computerized Systems Compliance

Using the GAMP

5 Guide
J im J ohn
ProPharma Group, Inc.
(816) 682-2642
jim.john@propharmagroup.com
Who Cares About CSV?
Systems throughout the organization involved
in the development, production, storage and
distribution of pharmaceutical products or
medical devices have to be considered
Resources involved in any way with IT,
computer, or automated systems is affected:
Developers
Maintainers
Users
Purpose of This Presentation
To discuss and clarify key topics
Get to know the evolution of the GAMP
Methodology to the latest release
Consider where GAMP 5 concepts can
improve your existing methodology
GAMP Objectives
GAMP

guidance aims to achieve

computerized systems that are fit for
intended use and meet current regulatory
requirements, by building upon existing
industry good practice in an efficient and
effective manner.
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Guidance
It is not a prescriptive method or a standard,
but..
Pragmatic guidance
Approaches
Tools for the practitioner
Applied with expertise and good judgement
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Evolution of GAMP Guidance
5 4 3 2 1
Calibration Legacy Systems
Laboratory VPCS
ERES Testing
Data Archiving Global
Information Systems
IT Infrastructure
Drivers
Other Drivers
Avoid duplication
Leverage suppliers
Scale activities
Reflect today
Configurable packages
Development models
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Key Objectives
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patient safety
product quality
data integrity
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GAMP
Document
Structure
Main Body Overview
Key Concepts
Life Cycle
Quality Risk Management
Regulated Company Activities
Supplier Activities
Efficiency Improvements
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5 Key Concepts
Life Cycle Approach Within a QMS
ScaleableLife Cycle Activities
Process and Product Understanding
Science-Based Quality Risk Management
Leveraging Supplier Involvement
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User and Supplier Life Cycles
Product and Process Understanding
Basis of science- and risk-based decisions
Focus on critical aspects
Identify
Specify
Verify
CQAs / CPPs
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Life Cycle Approach Within a QMS
Suitable Life Cycle
Intrinsic to QMS
Continuous improvement
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Specif y
Plan
Verify
Confi gure
& Code
Report
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A Basic Framework For Achieving Compliance
and Fitness For Intended Use
Figure xx:
Figure 3.3: A General Approach for Achieving Compliance and Fitness for Intended Use
Source Figure 3.3, GAMP 5 A Risk Based Approach to Compliance GxP Computerized Systems Copyright ISPE 2008. All rights reserved.
GAMP V Model Transition
Verifies User Requirement
Specification
Functional
Specification
Design
Specification
System
Build
Installation
Qualification
Operational
Qualification
Performance
Qualification
Verifies
Verifies
ScaleableLife Cycle Activities
Risk
Complexity and Novelty
Supplier
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Science Based Quality Risk
Management
Focus on patient safety,
product quality,
and data integrity
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Assessment
Control
Communication
Review
Based on
ICH Q9
Leveraging Supplier Involvement
Assess:
Suitability
Accuracy
Completeness
Flexibility:
Format
Structure
Requirements
gathering
Risk assessments
Functional / other
specifications
Configuration
Testing
Support and
maintenance
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Life Cycle Phases
Compatibility with Other Standards
ASTM E2500 Standard Guide for
Specification, Design, and Verification of
Pharmaceutical and Biopharmaceutical
Manufacturing Systems and Equipment
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GAMP 5
Ongoing
Operations
GAMP 5
Reporting
and
Release
GAMP 5
Verification
GAMP 5
Specification
Configuration
Coding
GAMP 5
Planning
GAMP5 and ASTM E2500
Good Engineering Practice
Risk Management
Design Review
Change Management
Requirements Specification
and Design
Verification Acceptance
and
Release
Operations &
Continuous
Improvement
Product
Knowledge
Process
Knowledge
Regulatory
Requirements
Company
Quality Regs.
The Specification, Design, and Verification Process Diagram from ASTM E2500
Governance
Policies and procedures
Roles and responsibilities
Training
Supplier relationships
System inventory
Planning for compliance & validation
Continuous improvement
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Stages Within the Project Phase
Planning
Specification, configuration, and
coding
Verification
Reporting and release
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Planning
Activities
Responsibilities
Procedures
Timelines
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See Appendix M1
Specification, Configuration, &
Coding
Specifications allow
Development
Verification
Maintenance
Number and level of
detail varies
Defined process
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Verification
Testing
Reviews
Identify defects!
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Supporting Processes
Risk Management
Change and Configuration Management
Design Review
Traceability
Document Management
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Design Review
Planned
Systematic
Identify Defects
Corrective Action
Scaleable
Rigor/Extent
Documentation
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See also Appendix M5
Traceability
Requirements
Specification
Design
Verification
Configure/Code
GAMP 5 Categories
Category
GAMP 4 GAMP 5
1
Operating system Infrastructure software
2
Firmware No longer used
3
Standard software packages Non-configured products
4
Configurable software
packages
Configured products
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Custom (bespoke) software Custom applications
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GAMP 5
Quality Risk Management
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Critical Processes are Those Which:
Generate, manipulate, or control data supporting
regulatory safety and efficacy submissions
Control critical parameters in preclinical, clinical,
development, and manufacturing
Control or provide information for product release
Control information required in case of product recall
Control adverse event or complaint recording or
reporting
Support pharmacovigilance (investigation of Adverse
risks)
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Definitions
Harm Damage to health, including the
damage that can occur from loss
of product quality or availability.
Hazard The potential source of harm.
Risk The combination of the
probability of occurrence of harm
and the severity of that harm.
Severity A measure of the possible
consequences of a hazard.
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Step 1 Initial Risk Assessment
Based on business processes, user requirements, regulatory
requirements and known functional areas
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Dont repeat unnecessarily!
Inputs Outputs
GxP or non-GxP
Major Risks
Considered
Overall Risk
User Requirements
GxP Regulations
Previous Assessments
Step 2 Identify Functions with GxP Impact
Functions with impact on patient safety, product quality, and
data integrity
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Specifications
System Architecture
Categorization of
Components
Inputs Outputs
List of Functions to
be further evaluated
Step 3 Perform Functional Risk Assessments
& Identify Controls
Functions from Step 2
SME Experience
Scenarios
Possible Hazards
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Breakdown of Risks
to Low, Medium and
High.
Detailed
Assessments and
Mitigation for High
Inputs Outputs
Functional Risk Assessment
Identify
Hazards and risk scenarios
Severity impact on safety quality or
other harm
Probability
Detectability
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GAMP Risk Assessment Tool
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Probability
S
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Low
Medium
High
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H
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Class 3
Class 2
Class 1
A simple two-step process:
Plot Severity vs. Probability to obtain Risk Class
GAMP Risk Assessment Tool
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Priority 1
Priority 3
Priority 2
3
2
1
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C
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Detectability
Plot Risk Classvs. Detectability to obtain Risk Priority
Step 3 (continued) Controlling the Risk
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Mitigation Strategies
Change the process
Change the design
Add new features
Apply external
procedures
Scenarios with
High Risk from
Functional
Analysis
Inputs
Outputs
Step 4 Implement & Verify Appropriate
Controls
Verification activity
should demonstrate
that the controls are
effective in performing
the required risk
reduction.
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Step 5 Review Risks Monitor Controls
Establish Periodic Review
of Control Effectiveness
Apply Risk Process in
Change Management
Activities
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Frequency and
extent of any
periodic review
should be based on
the level of risk
Risk-Based Decisions
What do they impact ?
Number and depth of design reviews
Need for, and extent of, source code review
Rigor of supplier evaluation
Depth and rigor of functional testing
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Operation Appendices
O1 Handover
O2 Establishing & Managing
Support Services
O3 Performance Monitoring
O4 Incident Management
O5 Corrective and
Preventive Action (CAPA)
Performance Monitoring
O6 Operational Change &
Configuration Management
O7 Repair Activity
O8 Periodic Review
O9 Backup and Restore
O10 Business Continuity
Management
O11 Security Management
O12 System Administration
O13 Archiving and Retrieval
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Summary
GAMP 5 provides more flexibility in the
number and types of validation lifecycle
products used.
Application of Risk and use of SME
Knowledge are keys to success
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