GAMP Overview Presentation 04-03-2012 FINAL

April 10, 2012 ISPE CASA Technology Show
Risk-Based Validation The

Benefits of the GAMP
Approach
Kevin C. Martin
Chair, GAMP
Americas
Sr. Vice President
Azzur Group LLC
2
Agenda
20 Years of the GAMP
Organization
GAMP Benefits
GAMP Contribution
Validation Productivity
Lean Validation
Current Technology Trends
Current Regulatory Activity
20 years of GAMP Development
Validation Productivity!
plus
3
4
GAMP
Americas Leadership
Officers
Chairman:
Kevin Martin, Azzur Group
Co-Chairman:
Michael Rutherford, Eli Lilly
Secretary:
Lorrie Schuessler, GSK

ISPE Staff PM
Scott Ludlum
Steering Committee
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
5
Active GAMP
SIGs
GAMP
Americas
Laboratory Systems
Manufacturing Execution Systems
(co-chaired with Europe)
Risk Management
Joint Equipment Transition Team
(JETT)
R&D / Clinical Systems (coordinated
with Europe)
Automated Testing (sub-set of
Testing SIG)
Outsourcing and Offshoring (with
Europe)
IT Infrastructure Control &
Compliance (with Europe)
Metrics

GAMP
Europe
Process Control Systems
Testing (with USA)
Supplier Relationships
Outsourcing and Offshoring (with USA)
Calibration
GxP Controls Framework (proposed)
GAMP
D-A-CH
Supplier Cooperation
Open Source Software
Development Models and Methods
GAMP
Italia
Equipment Qualification Workgroup
GAMP
Nordic
Virtualization

6
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

7
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)* (2
nd
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) (2
nd
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
8
GAMP
5
GAMP
5 Overview

Published: Feb 2008
9
GAMP
5 Continues to Address
Current regulatory initiatives
FDAs cGMPs for the 21
st
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!
10

Risk
Management
throughout the
process

Specify
Build or
Configure
Verify
Report Plan
GAMP
5 stresses that
this model does not imply
a waterfall development
methodology
GAMP
5 Simplified V-model
This can be applied to non-
linear approaches like spiral or
iterative methodologies, agile
software development, etc.
This model better illustrates scalability options for phases
Blended specifications (e.g. URS/FS, FS/DS, even URS/FS/DS)
Design review as opposed to formal DQ
Blending of classical qualification (e.g. IOQ, OQ/PQ, melding of
computer validation with equipment C&Q)
User
Requirements
(URS)
Validation
Plan
Functional
Specification
(FS)
Design
Specification
(DS)

System Build
(including
developer tests)

Developer tests
(Structural, unit, &
integration)
Functional
testing
(OQ)
Acceptance
testing
(PQ)
Validation
Report
Installation
(IQ)
Verifies
Verifies
Verifies
Verifies
Development
Activities
Verification
Activities
System Build
Activities
Validation Activities
11
GAMP
5 Life Cycle Concept

Features:
Simplified V-
Model
Plan
Specify
Build
Verify
Report
Risk mgmt
throughout
process
Repetition of V-
activities for
changes
Incorporates
end-of-life
activities
Changes
Repetitive V Activities Within the Life Cycle
URS
migration
Release
GxP Assessment
* This could be a complex supply chain
Supplier may provide knowledge, experience, documentation & services throughout lifecycle
Supplier
Involvement*
Concept Project Operation Retirement
12
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
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
14
High
Medium Low
Low
Risk Based Approach 1990s Validation Approach
F
o
c
u
s

V
a
l
i
d
a
t
i
o
n

E
f
f
o
r
t

F
o
c
u
s

V
a
l
i
d
a
t
i
o
n

E
f
f
o
r
t

Historical State
Desired State
The Desired State
High
Medium
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!
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!!!

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
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
Plan >Check > Do > Record
Planning
Specifications
Design Review
Protocols
Change management
Document
Handover
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
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
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
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
23
Benchmarking Results - Typical
8 9 7 6 7 6 7 6 5 4 5 1
7 9 9 8 6 6 8 6 3 5 7 6
6 7 7 5 5 6 8 8 8 4 5 6
8 8 10 6 5 8 7 8 10 8 5 3
7 8 9 8 7 7 9 8 6 4 5 7
6 6 5 4 5 7 7 8 8 4 3 2
7 8 9 4 6 7 6 8 6 5 2 5
4 5 5 6 5 6 7 7 4 4 4 3
7 8 5 4 6 6 8 9 7 3 6 5
7 5 7 6 7 8 8 9 3 4 3 1
6 7 6 5 3 8 9 8 6 3 6 4
4 4 6 7 6 8 7 6 4 2 2 0
7 6 5 5 5 7 7 7 5 4 4 1
8 4 3 8 6 7 7 7 4 4 3 1
7 4 5 5 6 8 6 8 4 5 3 5
6 6 8 7 5 7 7 6 3 5 5 3
3 2 4 5 3 6 8 7 2 3 4 3
7 5 4 5 5 8 9 6 6 4 5 3
7 5 7 7 6 7 8 6 6 5 6 6
8 7 4 6 6 7 8 9 8 7 8 5
8 7 5 6 6 8 8 8 7 5 6 5
7 7 3 3 4 6 6 7 6 5 4 4
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
Protocols,
Documentation
Change
Management
Handover
Control in Operation
Post-project Reviews
Project
Management
Planning
Strategy
Training
Policies and
Procedures
Specifications and
Design Review
Example 1: Ampoule Filling Line
Pre-GAMP
Specification
Development
5 days
Protocol Development
1 week
FAT Testing
3 days
Initial efficiency
35%
Final Efficiency
65%
Post-GAMP2
Specification
Development
5 weeks
Protocol Development
4 weeks
FAT Testing
2 weeks
Initial efficiency
75%
Final Efficiency
95%
Mid 90s
Comparison of validation of
two liquid injection filling lines
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
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
27
Example 3: Re-engineering the Verification Process
Validation Waste
Waiting Motion Defects
Transportation
Over-production
Extra Processing
Inventory
WASTE
Inactive
players
Long lead
times for
meetings
Slow project
initiation
Priority
conflicts
Sequential
activities
Staff
turnover
Late
detection
Effort to
re-work
High training
requirement
Physical
document
circulation
Implementation of
optional features
Unclear
purpose
Multiple
planners
Multiple
forms
Too many
signatures
Too many
people
Too many
documents
Wrong
skills mix
Acknowledgment: Guy Wingate, GSK
28
Example 3: Re-engineering the Verification Process
Savings identified:
Adopting good practices ~5%
Adopting standardized practices ~30+%
Focussing of GMP activities ~20%
Scaled approach ~10%
Leverage supplier expertise
Rigorously applied risk-based approach
Average Cost of Validation
Acknowledgment: Guy Wingate, GSK
29
Example 3: Re-engineering the Validation Process
Upgrade Projects Cost Savings*
1 50%
2 58%
3 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
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 non-
serious 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.
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.
Training management for non-
production staff.
Corrupt electronic signature on
audit report.
...Think carefully here...
Acknowledgment: Ellis Daw, GSK
31
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
Positive and negative testing (as appropriate)
-evidence required (e.g., critical screen shots, report(s), witness signatures
- QA and 2
nd
person review required

Standard
Positive testing, including multiple/alternative path testing
-standard evidence required (outcome, tester initials, date)
- 2
nd
person review required (QA review not required)

Minimal
Minimal testing
-Vendor or leveraged documentation
- verification may be required to test requirement
- 2
nd
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
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.
33
Example 6: Business Benefits
Pre GAMP
Business processes not
defined
Requirements
unclear/incomplete
Projects over-ran
User expectations not met
Acknowledgment: Winnie Cappucci (formerly Bayer)
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
34
What is Lean Validation?
Lean Validation is defined as the
delivery of validation services with as
little waste as possible.
35
History of the Problem
36
Problem Statement
COST OF VALIDATION
~ 25% of the total capital
TIME
Inadequate cycle times
Effort takes too long
Inability to support timelines based on
business needs
37
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
What have we typically seen?
38
Major cause of contract breaks
schedule
cost
Work environment
stress
anxiety
morale
What is the impact?
39
IQ
OQ
PQ
rework
churn
rework
Current Qualification Practice
40
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
Lets Re-design the Process
41
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!!!
Re-design Tools
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
43
Some Other Cost Savings
Measures
44
Document Approvers

Typical approval cycle is five
validation documents approvers
Lean Approach: Should be two
document approvers
System Owner
Quality

45
Benefits (of reduced approvers)

Reduced cycle times
Faster turnaround of verification
documents
Cost efficient
Reduced numbers of EDM users
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

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

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

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:
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

51
Validation Productivity Priorities
Upgrade the validation system
Focus on the
the front end (validation planning,
strategy and specification development)
the back end (handover and maintaining
control in operation)
6.6 6.2 6.0 5.7 5.5 7.0 7.5 7.4 5.5 4.4 4.6 3.6
52
Standardize the approach across the
organization
Focus on
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
Low Medium High
54
Spend project time
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
56
Continuous Improvement
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
58
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
Thank You!

59

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April 10, 2012 ISPE CASA Technology Show

Risk-Based Validation The

5 Life Cycle Concept

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