GAMP Overview Presentation 04-03-2012 FINAL

Risk-Based Validation The
Benefits of the GAMP Approach

Kevin C. Martin
Chair, GAMP Americas
Sr. Vice President
Azzur Group LLC
April 10, 2012
ISPE CASA Technology Show
Agenda
20 Years of the GAMP Organization
GAMP Benefits
GAMP Contribution
Validation Productivity
Lean Validation
Current Technology Trends

Current Regulatory Activity
April 10, 2012
20 years of GAMP Development

Validation Productivity!
plus
April 10, 2012
April 10, 2012
GAMP Americas Leadership

Officers
Steering Committee
Chairman:
Kevin Martin, Azzur Group
Co-Chairman:
Michael Rutherford, Eli Lilly
Secretary:
Lorrie Schuessler, GSK
ISPE Staff PM
Scott Ludlum
Winnie Cappucci* , Retired- Bayer

Waunetka Clark, Abbott
Jim John, ProPharma Group
Paige Kane, Pfizer
Klaus Krause, Allergan
Eugene Longo , GAMP Puerto Rico
Randy Perez, Novartis
Judy Samardelis, Medimmune
Eric Staib, Covance
Robert Tollefsen, FDA
Bob Wherry, Sunovion
Blue indicates GAMP Council

*Denotes GAMP Council Chair
April 10, 2012
Active GAMP SIGs

GAMP Americas
GAMP Europe
Process Control Systems
Open Source Software
Laboratory Systems
Manufacturing Execution Systems

(co-chaired with Europe)
Risk Management
Joint Equipment Transition Team
(JETT)
Supplier Relationships
Outsourcing and Offshoring (with USA)
Calibration
GxP Controls Framework (proposed)
R&D / Clinical Systems (coordinated

D-A-CH
GAMP
with Europe)
Supplier Cooperation
Automated Testing (sub-set of
Testing SIG)
Testing (with USA)
Outsourcing and Offshoring (with

Europe)
GAMP Italia
IT Infrastructure Control &

Compliance (with Europe)
Metrics
April 10, 2012
Development Models and Methods

Equipment Qualification Workgroup
GAMP Nordic
Virtualization
Active GAMP SIGs - Brazil
GTG "Validation of IT Infrastructure and Processes

GTG " Validation of PLCs, Automated Systems, Shop-floor Systems, MES and BMS
GTG "Change Management for Computerized Systems and Maintenance of
Validated Status:
GTG Understanding e-records and e-signatures (ANVISA / EMA Annex 11 / 21CFR
Part 11 / GAMP)
GTG Validation Master Plan and Validation Plan for CSV
GTG Legacy Systems
GTG " Qualification and Suppliers Assessment
GTG "Testing GxP Systems (base GPG GAMP)
GTG "Organizational Structure for CSV
April 10, 2012
GAMP Good Practice Guides

1.
Validation of Process Controls Systems (Second Edition Feb 2011)
2.
Calibration Management (Second Edition Nov 2010)
3.
Manufacturing Execution Systems A Strategic and Program

Management Approach (Feb 2010)
4.
A Risk-Based Approach to Operation of GxP Computerized Systems - A

Companion Volume to GAMP 5 (Jan 2010)
5.
Electronic Data Archiving (Jul 2007)
6.
Testing of GxP Systems (Dec 2005)* (2nd Edition 3Q2012)
7.
Global Information Systems Control and Compliance (Nov 2005)
8.
IT Infrastructure Control and Compliance (Sep 2005)
9.
Validation of Laboratory Computerized Systems (Apr 2005) (2nd Edition

2Q2012)
10. Risk-Based Approach to Electronic Records and Signatures (Feb 2005)
11. Legacy Systems (Nov/ Dec 2003)*

* Available as a download at no cost to ISPE Members Only
April 10, 2012
GAMP 5
GAMP 5 Overview
Published: Feb 2008
April 10, 2012
GAMP 5 Continues to Address

Current regulatory initiatives
FDAs cGMPs for the 21st Century

PIC/S Guidance
Risk-based Part 11 Guidance
Global Standards
ICH Q8, Q9, Q10

ASTM E2500
Escalating cost pressures mandate efficiency
Facilitate a single company QMS

Need to take full advantage of supplier capability
Better compliance with less cost!
April 10, 2012
10
GAMP 5 Simplified V-model

Verifies
Validationmodel better illustrates scalability
Validation
This
options for phases
Plan
Report
Validation
Activities
Blended specifications (e.g.
URS/FS,
FS/DS, even URS/FS/DS)
Design review as opposed to formal DQ
Blending
User of classical qualification
Acceptance of
Verifies(e.g. IOQ, OQ/PQ, melding
Requirements
testing
computer
validation
with
equipment
C&Q)
(URS)
(PQ)
Plan
Functional
Specification
(FS)
Development
Activities
Design
Specify
Specification
Risk
Management
throughout the
Verifies
process
(DS)
GAMP 5 stresses that

this model does not imply
aSystem
waterfallBuild
development
methodology
Activities
April 10, 2012
Report
Functional
testing
(OQ)
Verifies
Installation
Verify
Verification
Activities
(IQ)
This can be applied to nonlinear approaches like spiral or

or
SystemBuild
Build Developer
testsiterative methodologies, agile
(Structural, unit, &
(including
Configure
integration) software development, etc.
developer tests)
11
GAMP 5 Life Cycle Concept

Features:
Simplified V-
Repetitive V Activities Within the Life Cycle
migration
Model
URS
Release
Changes
GxP Assessment
Concept
Project
Operation
Retirement
Supplier
Involvement*
* This could be a complex supply chain

Supplier may provide knowledge, experience, documentation & services throughout lifecycle
April 10, 2012
12
Plan
Specify
Build
Verify
Report
Risk mgmt
throughout
process
Repetition of Vactivities for

changes
Incorporates
end-of-life
activities
Risk Management Goals

Systematic process for identifying, assessing, mitigating,
controlling, and communicating risk, based on
Good science
Process and product understanding
Recognize that zero risk is impractical and unattainable
Aim is for acceptable risk
Consistent with risk-based approach based on ISO

14971 (and ERES GPG) as well as other contemporary
risk based tools
April 10, 2012
13
5-Step Quality Risk Management Process

Step 1
Perform initial risk assessment & determine system impact
Step 2
Identify functions impacting patient safety, quality, and data integrity
Step 3
Perform functional risk assessments & identify controls
Step 4
Implement & verify appropriate controls
Step 5
Review Risks and monitor controls
April 10, 2012
14
The Desired State

Historical State
Desired State
High
Medium
Low
Risk Based Approach
Focus Validation Effort
Focus Validation Effort
1990s Validation Approach
High
Medium
Low
April 10, 2012
15
Stakeholders the GAMP Benefits

All stakeholders depend on reliable
systems
Performing as expected
from the beginning
continuously
with minimal attention
A proven roadmap when going from

manual to automated systems
We have a great responsibility!

April 10, 2012
16
GAMP 5 Enables Increased

Validation Productivity
Focussed on efficient and effective
validation
Making validation productive
OED: producing abundantly
Webster's: Yielding results, benefit or
profit
Eliminate the Waste!!!
April 10, 2012
17
Universal Approach
GAMP methodology applies to all
types of systems
Large database systems
Process control systems
Spreadsheets etc.
Needs tailoring to each project for
maximum efficiency
April 10, 2012
Consider all the elements of the

validation process
18
Uniform Approach
The V model is almost universally
applicable
It is capable of considerable flexibility
Many dialects exist
Fundamentals remain
Document
Handover
Design Review
Plan >Check > Do > Record

Planning
Specifications
April 10, 2012
Protocols
Change management
19
QMS* for Systems Validation

The Validation Process is well-documented
Based on QMS principles
Widely understood
Adopts standard elements of QMS
Planning
Specifications
Risk-based approach
Verification
Documentation
Change management
Continuous improvement
*QMS = Quality Management System

April 10, 2012
20
Knowledge of Systems
To validate effectively we need to know our
systems;
Why we want them

What they do
How they do it
Where the risks lie
How the risks are controlled
Follow a System Life Cycle - Use GAMP5 as a

tool
Payback is immediate increased efficiency of
operation
April 10, 2012
21
Benchmarking for Continuous

Improvement
12 Good Validation Practices
Policies and
Procedures
Good Project
Management Practices
Validation Planning
Validation Strategy
Specifications and
Design Review
Protocols
Documentation
Change Management
Practices
Training
Handover
Maintaining Control in
Operation
Post-project reviews
Acknowledgment: David Selby, NSF-DBA

April 10, 2012
22
Benchmark Assessment
Highest scores highlighted Green
Next lowest highlighted Yellow
Lowest Scores highlighted Red
Absolute numbers not meaningful
Averages are more reliable
Look at the concentration of colour

April 10, 2012
23
Benchmarking Results - Typical

8
10
Protocols,
6
8
6
Documentation
6
8
8
Change
8
7
8
Management
10
6
Training
Policies and
4
Procedures7
3
7
7
8
4
6
Specifications
and
5
6
5
Design
Review
9
Project
2
4
Management
5
4
Planning
5
7
Strategy
7
4
Handover
4
4
3
Control in Operation
3
6
5
Post-project Reviews
145
137
133
126
120
154
165
162
121
97
101
79
6.6
6.2
6.0
5.7
5.5
7.0
7.5
7.4
5.5
4.4
4.6
3.6
Example 1: Ampoule Filling Line

Mid 90s
Comparison of validation of
two liquid injection filling lines
Pre-GAMP
Post-GAMP2
Specification
Development
5 days
Specification
Development
5 weeks
Protocol Development
1 week
Protocol Development
4 weeks
FAT Testing
3 days
FAT Testing
2 weeks
Initial efficiency
35%
Initial efficiency
75%
Final Efficiency
65%
Final Efficiency
95%
April 10, 2012
25
Cost Effective Approach

How much does Validation Cost?
Some figures (% of total project cost):
Current industry average 20 25%

Major pharma company (top 10) 16%
GSK 4%*
Pfizer 4%*
Best in class ~ 1.2%
* Figures published in 2008

April 10, 2012
26
Example 2: SAP Financials

GAMP methodology applied to global
implementation of SAP Financials
Scenario:
Lead site
Decision to use validation rigor (GAMP Methodology) for
all modules
Lead by QA validation expert
Tough to get Finance to understand what that meant
IT Project manager: This guy has no idea how to
implement a finance system.
Testing went like a dream!
Project on time and on budget
Weve never had a test phase that went so smoothly with
so few problems
Acknowledgment: Randy Perez, Novartis

April 10, 2012
27
Example 3: Re-engineering the Verification Process
Validation Waste
Waiting
Motion
Slow project
initiation
Inactive
players
Physical
document
circulation
Sequential
activities
Priority
conflicts
Long lead
times for
meetings
High training
requirement
Defects
Late
detection
Staff
turnover
Wrong
skills mix
Effort to
re-work
WASTE
Implementation of
optional features
Unclear
purpose
Multiple
planners
Multiple
forms
Too many
signatures
Over-production
Transportation
Too many
documents
Too many
people
Inventory
Extra Processing
Acknowledgment: Guy Wingate, GSK

April 10, 2012
28
Example 3: Re-engineering the Verification Process
Savings identified:
Adopting good practices
~5%
Adopting standardized practices

Focussing of GMP activities
~30+%
~20%
Scaled approach
~10%
Leverage supplier expertise
Rigorously applied risk-based approach
Average Cost of Validation

Acknowledgment: Guy Wingate, GSK
April 10, 2012
29
Example 3: Re-engineering the Validation Process
Upgrade Projects
Cost Savings*
50%
58%
72%
Total Savings
>$1.5m
Cost savings comparing V model alone (GAMP 4)

vs.
V model + E 2500 (GAMP 5)
Acknowledgment: Lily Mo, Pfizer Global Quality Operations

April 10, 2012
30
Example 4: Application of Risk Management (Scaleability)

High
Medium
Low
Definition
Severe potential harm to

patients, (e.g. death,
hospitalization, long term
effects).
Risk has potential for nonserious impact on patient safety

and/or product quality.
Risk has little or no potential

impact on patient safety and/or
product quality.
Criteria
Product is unusable or
ineffective such that harm is
likely.
Loss or corruption of records
has potential for severe harm to
patients.
....and so on for your
organisation.
Impacts product quality but with

no or negligible impact on
patient safety (e.g. cosmetic
defect).
would have non-serious impact
on patient safety or product
quality.
..... and so on for your
organisation.
Regulatory requirement with

little or no impact on product
quality and/or patient safety.
would violate regulatory
requirements but have no impact
on patient safety or product
quality
...and so on for your
organisation.
...Think carefully here...

Possible
Examples
Training management for staff

operating in aseptic area.
Dispensing of active ingredients
for production, sterilization hold
times.
Incomplete break line on OTC

tablet.
Checkweigher detection of
incompletely filled blister packs.
Acknowledgment: Ellis Daw, GSK

April 10, 2012
31
Training management for nonproduction staff.

Corrupt electronic signature on
audit report.
Example 4: Application of Risk Management (Scaleability)

Probability of Failure (Development Classification)
Severity
1 (Customised)
2 (Configurable)
3 (Non-Configurable)
High (H)
Intensive
Standard
Minimal
Medium (M)
Intensive
Standard
Minimal
Low (L)
Standard
Minimal
Minimal
Rigor of Verification
Intensive
Standard
Minimal
Positive and negative testing (as appropriate)

-evidence required (e.g., critical screen shots, report(s), witness signatures
- QA and 2nd person review required
Positive testing, including multiple/alternative path testing
-standard evidence required (outcome, tester initials, date)
- 2nd person review required (QA review not required)
Minimal testing
-Vendor or leveraged documentation
- verification may be required to test requirement
- 2nd person review required (QA review not required)
High: functions impacting product release, process control, batch records, complaints, recall,
regulatory filings, adverse event recording etc.
Medium: functions impacting support processes driven by GMP regulations, critical business processes
Low: functions impacting supporting processes NOT driven by regulation
Acknowledgment: Lily Mo, Pfizer Global Quality Operations
April 10, 2012
32
Example 5: Leveraging Supplier Testing
System
Business Workflow Mapping Tool
Limited configuration required to
implement at customers site
Approach
Extended audit to verify Supplier
Functional Risk Assessment and Testing
Additional effort, 4 days to conduct the
review of Functional Risk Assessment
and Supplier Testing
Outcome
Regulated company testing more spot
checks of high impact functions (3 days)
Original regulated company test plan
allowed for 6 man weeks testing
Acknowledgment: Chris Reid, Integrity Solutions Ltd.
April 10, 2012
33
Example 6: Business Benefits
Pre GAMP
Business processes not

defined
Requirements
unclear/incomplete
Projects over-ran
User expectations not met
Post GAMP
Adoption of lifecycle approach
Brought discipline (painfully!)
Users understood business
processes
Users understood business
needs
Requirements and quality
attributes traceable to business
process
Requirements prioritised
Compliance to timelines and
costs (mostly)
System understood by users
Systems accepted by users
Traceability made maintenance
easy
Acknowledgment: Winnie Cappucci (formerly Bayer)

April 10, 2012
34
What is Lean Validation?

Lean Validation is defined as the
delivery of validation services with as
little waste as possible.
April 10, 2012
35
History of the Problem
April 10, 2012
36
Problem Statement
COST OF VALIDATION
~ 25% of the total capital
TIME
April 10, 2012
Inadequate cycle times

Effort takes too long
Inability to support timelines based on
business needs
37
What have we typically seen?
No uniform practice
Unclear expectations
Unclear roles and responsibilities
Duplication of effort and rework
Significant resource commitment
Inconsistencies
Functionally siloed activities
Re-interpretation of requirements leading to
re-drafting of protocols
Multiple reviews / approvals for each protocol
April 10, 2012
38
What is the impact?

Major cause of contract breaks
schedule
cost
Work environment
April 10, 2012
stress
anxiety
morale
39
Current Qualification Practice

rework
IQ
churn
OQ
PQ
rework
April 10, 2012
40
Lets Re-design the Process

Integration and alignment of Qualification &
Capital execution
Application of Front-End Loading (FEL)
principles
Early cross-functional involvement,
understanding, consensus and commitment
Conformance to regulatory and cGMP
expectations from the start
April 10, 2012
41
Re-design Tools
Defined, integrated work flow process
Identification of key milestones
identified interdependencies between
construction & qualification activities
Responsibilities Matrix
Defined roles and responsibilities
Standard Qualification templates
Process & Packaging Equipment
Laboratory Systems
Any Automation!!!
April 10, 2012
42
Cost Savings
Reduced cost to less than 20% of
capital expenses
Achieved a cost profile of 10% or less
of capital expenses
Eliminating or reducing non-value
added work
April 10, 2012
43
Some Other Cost Savings

Measures
April 10, 2012
44
Document Approvers
Typical approval cycle is five
validation documents approvers
Lean Approach: Should be two
document approvers
April 10, 2012
System Owner
Quality
45
Benefits (of reduced approvers)

Reduced cycle times
Faster turnaround of verification
documents
Cost efficient
Reduced numbers of EDM users
April 10, 2012
Lower license cost for reduced number

of document approvers
46
Verification Forms
Implementation of verification forms instead
of protocols
Driven by SOP
Individual Forms are pre-approved
Installation & Functional Verification forms
Forms can be created by leveraging existing
protocols
April 10, 2012
47
Verification Forms (cont.)

Forms can be created from requirements and
design documents
Forms can be used for the validation of
changes to existing systems
Examples of verification forms
Security verification
Recipe verification
Audit trail verification
Parameter verification
P&ID verification
Loop check verification
April 10, 2012
48
Benefits of implementing verification

forms
Cycle time reduction

Faster turnaround time
Only one approval cycle
Cost reduction: ~ $ 750 per form vs
$ 5,000 per protocol
April 10, 2012
49
Productive Validation its Very Important!

Companies need systems for:
operations to make much-needed products for patients
And to promote:
increased assurance of product quality

sustainability
Systems need validation

Validation needs to be efficient and effective by:
April 10, 2012
having an efficient validation process

applying effective governance
good in-depth training and expertise
continuous improvement
50
So what is left to do?

Improve our validation processes
theyre capable of much further

refinement
Standardize the approach

Judiciously apply risk management
and E 2500
Spend project time on the front end
of the system life cycle process
Look at the final steps around
handover
Get into the continuous
improvement mind-set
April 10, 2012
51
Validation Productivity Priorities

Upgrade the validation system
Focus on the
6.6
April 10, 2012
the front end (validation planning,

strategy and specification development)
the back end (handover and maintaining
control in operation)
6.2
6.0
5.7
5.5
7.0
7.5
7.4
5.5
4.4
52
4.6
3.6

Standardize the approach across the
organization
Focus on
April 10, 2012
Defining the deliverables

Scalability
Integration of E 2500 into the process
Involvement of SMEs and QA
Applying Globally
53

Focus on
Integrating risk management into the

entire process
Apply it ruthlessly
Spread it throughout the organization
once its right
High
April 10, 2012
Medium
Low
54

Spend project time
April 10, 2012
on planning
using risk management
using the expertise of SMEs
on design review
55

and dont forget
Handover
data accessibility for users
knowledge transfer
measured performance criteria
April 10, 2012
56

Continuous Improvement
April 10, 2012
Embrace new approaches

Learn from each project
Build the learning back into the
validation process
Spread the word
57
Validation Productivity The target?

Continuous improvement
cost effective validation projects

a few % of project cost
from
be part of the solution
April 10, 2012
58
Thank You!
Resources / More Information
Kevin C. Martin
GAMP Americas Chair
Azzur Group LLC
Sr. Vice President
+1.215.260.6327
kevin.martin@azzurgroup.com
Michael L. Rutherford
GAMP Americas Vice Chair
Consultant Business Systems Support
Development Center of Excellence
Eli Lilly and Company
317-276-1473
ml.rutherford@lilly.com
ISPE GAMP Community of Practice (COP) Website

http://www.ispe.org/gampcop
April 10, 2012
59

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Risk-Based Validation The

Benefits of the GAMP Approach

April 10, 2012

ISPE CASA Technology Show

Current Technology Trends

ISPE CASA Technology Show

20 years of GAMP Development

ISPE CASA Technology Show

April 10, 2012

ISPE CASA Technology Show

GAMP Americas Leadership

Winnie Cappucci* , Retired- Bayer

Blue indicates GAMP Council

ISPE CASA Technology Show

Active GAMP SIGs

Process Control Systems

Open Source Software

Manufacturing Execution Systems

GxP Controls Framework (proposed)

R&D / Clinical Systems (coordinated

Testing (with USA)

Outsourcing and Offshoring (with

IT Infrastructure Control &

April 10, 2012

Development Models and Methods

ISPE CASA Technology Show

Active GAMP SIGs - Brazil

GTG "Validation of IT Infrastructure and Processes

April 10, 2012

ISPE CASA Technology Show

GAMP Good Practice Guides

Validation of Process Controls Systems (Second Edition Feb 2011)

Calibration Management (Second Edition Nov 2010)

Manufacturing Execution Systems A Strategic and Program

A Risk-Based Approach to Operation of GxP Computerized Systems - A

Electronic Data Archiving (Jul 2007)

Testing of GxP Systems (Dec 2005)* (2nd Edition 3Q2012)

Global Information Systems Control and Compliance (Nov 2005)

IT Infrastructure Control and Compliance (Sep 2005)

Validation of Laboratory Computerized Systems (Apr 2005) (2nd Edition

10. Risk-Based Approach to Electronic Records and Signatures (Feb 2005)

11. Legacy Systems (Nov/ Dec 2003)*

ISPE CASA Technology Show

April 10, 2012

ISPE CASA Technology Show

GAMP 5 Continues to Address

FDAs cGMPs for the 21st Century

ICH Q8, Q9, Q10

Escalating cost pressures mandate efficiency

Facilitate a single company QMS

April 10, 2012

ISPE CASA Technology Show

GAMP 5 Simplified V-model

GAMP 5 stresses that

This can be applied to nonlinear approaches like spiral or

ISPE CASA Technology Show

GAMP 5 Life Cycle Concept

Repetitive V Activities Within the Life Cycle

* This could be a complex supply chain

April 10, 2012

ISPE CASA Technology Show

Repetition of Vactivities for

Risk Management Goals

Process and product understanding