Review of GAMP Requirements for Validation

1
Review of GAMP Requirements for Validation

• Workshop M-8
• March 21, 2006
• 200 p.m. to 415 p.m.

Chris Roerig VAI Automation, Inc Ray LeDoux
Millipore Terry Petro Bosch Packaging Technology
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(No Transcript)
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GAMP/JETT AGENDA

• Introduction and GAMP Organization Chris
  Roerig
• Introduction to the JETT Consortium Chris Roerig
• GAMP Process Control Supplement Ray LeDoux
• Jett Risk Based Initiative Terry Petro
• Benefits of the GAMP/JETT Ray LeDoux
• Methodology
• Working Session ALL
• Questions Answers ALL

4
GAMP Forum Developments

• 12 Special Interest Groups (SIG's)
• GAMP Americas established Sept 2000
• 8 New Special Interest Groups established
• New groups incorporated into GAMP Forum
• North American JETT Consortium joined (2000)
• UK Suppliers Forum joined (2001)

5
GAMP Forum Organisation
APV
Namur Group
Supplier Forum
GAMP Americas
GAMP Europe
6
Executive Summary of Good Automated Manufacturing
Practice (GAMP) Guide
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GAMP Scope Automated Systems

• Consist of
• Hardware - Controlled Functions
• Software - Network Components
• Associated Documentation
• Applies to
• Automated Manufacturing Equipment
• Control Systems
• Automated Laboratory Systems
• Manufacturing Execution Systems
• Computers Running Manufacturing or Laboratory
  Databases

8
GAMP Purpose

• Help suppliers of automated systems to the
  pharmaceutical industry ensure that systems are
  developed following good practice and to provide
  proper documentary evidence that their systems
  meet the agreed specifications.

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GAMP Qualification Plan
A Basic Framework for Specification, Design and
Testing
USER REQUIREMENT
PERFORMANCE

Verifies
SPECIFICATION
QUALIFICATION

FUNCTIONAL
OPERATIONAL
SPECIFICATION
QUALIFICATION

Verifies

DESIGN
INSTALLATION
SPECIFICATION
QUALIFICATION
Verifies

SYSTEM
BUILD
GAMP 4.0 Figure 6.2
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Part 1 User Responsibilities

• Validation (Master) Plan System Specific
  Validation Plan(s)
• Appendix 6
• Supplier Audit
• Appendix 7
• User Requirements Specification
• Appendix 5
• Supplier Education

11
New Edition GAMP 4
Strategic Framework
Quality Management Procedures
Practical Guidance (Good Practice)
Training/Materials Workshop
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GAMP 4 Goals

• Software categories developed further
• Validation needs to be scaleable
• Global acceptance
• Examine the balance of work conducted by
  pharmaceutical manufacturers and their suppliers.
  
• Harmonization of terminology with other industry
  forums.

13
Best Practice Guides

• First Wave
• Calibration
• IT Infrastructure Networks, Desktop,
• Harmonized Terminology
• Electronic Records and Signatures

14
Additional Planned Guides

• Second Wave
• Validation of Process Control Systems (October
  2003)
• Supplier Management
• Analytical Laboratory Equipment
• Global Systems ERP, MRPII, LIMS, EDMS

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Additional Planned Guides

• Third Wave
• Legacy Systems
• Clinical Systems
• Medical Devices
• E-Applications Web-based software
• Manufacturing Execution Systems

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GAMP Summary

• International guideline
• Good starter system
• Continuing to evolve (GAMP4)
• Basis for Regulatory Agency Training and
  expectations
• Good common ground for CSV International
  Alignment

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Joint Equipment Transition Team(www.JETTconsortiu
m.com)
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Mission Statement

• Improve communications between Users and
  Suppliers to more effectively meet the
  validation requirements of the pharmaceutical
  industry.

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JETT MEMBERS

• USER Representatives
• Abbott Labs Pat Cashman
• Eli Lilly - Bret Fisk, Dave Kwilosz
• Aventis Pasteur Jeff ODonel
• Perrigo Paul Coury
• Medpoint Pharma Karl Boyvn
• SUPPLIER Representatives
• Bosch /TL Systems - Terry Petro
• Millipore Ramon LeDoux
• Vector Corp - Don Rosendale
• Rockwell Xieu Jiang

• CONSULTANT Reps
• VAI Automation - Chris Roerig
• Jim John CimQuest
• Jacobs Engrg Howard Bensel
• PV - Mike Filary
• Fluor-Daniel Mike Humphries
• BEK Engr Vince Miller
• 14 Active Members
• 45 Assoc. Members Growing

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JETT BASELINE EXAMPLE

• User Requirement Specification
• Project Planning
• Functional Design Specifications
• Acceptance Tests
• - Hardware - System
• - Software - Factory

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JETT EQUIPMENT ACQUISITION MODEL
SUPPLIER


USER/(CONSULTANT if applicable)

Master Validation Plan
User Audit
Equipment Validation Plan
Engineering Feasibility Study and
Results
P.O.

• Explanation to Supplier

RFQ
User Requirements Specification (Living Document)
Proposal

• Project Plan

• Quality Validation Plan

Proposal
P.O.
Proposal Analysis
Approval
Detailed Design Documentation (traceable to
Functional Specification)
Review Functional Specification
Approval
System Acceptance Test Specifications (IQ/OQ)
Review Detailed Design

• Hardware

• Software

Review System Acceptance Test Specifications
Approval
System Acceptance Testing and Results User
Witness Optional

Integrate with Validation Documentation as
appropriate

Maintenance Support Documentation

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JETT Efforts

• Applying GAMP to Automated Equipment
• Communicating GAMP Approach
• Interphex 1997, 2000, 2001, 2002, 2003, 2004,
  2005
• ISPE - Regional National Meetings
• Pharmaceutical Online Articles
• Pharmaceutical Engineering Articles
• Institute of Validation Technology Conferences
  and Articles
• Published in VPCS Supplement to GAMP 4

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JETT Efforts

• Provide Input to the GAMP Forum
• Develop Guidance Documents for Packaged,
  Automated Equipment
• URSs, Equipment Validation Plans, Functional and
  Design Specifications and IQ/OQs
• Work directly with OEMs, Users, Integrators,
  AEs, and Consultants.

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JETT Efforts

• Equipment Validation Plan Template
• URS Template
• Common equipment URS examples and templates
• Baseline example for Pure Steam Generator
• URS, FRS, HDS, SDS, FAT

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JETT Efforts

• Seventeen Released URS Documents, including

Vial Washer Glassware Washer Pure Steam
Generator Multi-effect WFI Still Saturated Steam
Autoclave Building Management System
Wide Range Filler Depyrogenation Tunnel Label
Rewinder Labeler Barrier Isolator Chromatography
Fluid Delivery Module
www.jettconsortium.com
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JETT Efforts

• Five URS Documents in Development
• Centrifuge
• Clean in Place System
• SCADA
• USP Water System
• Variable Data Inspection System
• Two Complete Document Packages
• Pure Steam Generator
• Wide Range Filler

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JETT Efforts

• Equipment Validation Plan Template
• URS Template and Procedures
• Common equipment URS examples
• Baseline Document examples including
• URS, FRS, HDS, SDS, FAT
• Risk Assessment Model

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GAMP Process Control Supplement

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GAMP Process Control Supplement - Purpose

• This Guide is intended is a supplement to
  the GAMP Guide, and provides a harmonized
  overview of the key elements involved in the
  lifecycle of process control systems, from
  inception to retirement. As such, the Guide
  complements the current Baseline Guide on
  Commissioning and Qualification from ISPE.

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GAMP Process Control Supplement - Scope

• Systems that control the manufacturing process,
  and have direct impact on product quality
  attributes at any stage in the life cycle.
  Product quality attributes include the identity,
  efficacy, strength, dosage, quality, disposition,
  safety, and purity of the product
• Systems that process, transfer, or store
  process information in electronic format

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GAMP Process Control Supplement - Benefits

• Application and adaptation of the general
  principles of GAMP 4 to process control systems
• A comprehensive overview of current best
  practice techniques for process control systems
• Reduction of the cost and time required to
  achieve compliant process control systems
• Application of good practice to the development
  and management of projects involving process
  control systems to meet regulatory expectations
• Harmonized approaches for embedded as well as
  standalone systems
• Detailed definition of engineering steps

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GAMP Process Control Supplement - Benefits

• Detailed guidance on the generation of user
  requirements specifications
• Guidance on functionality and structures of
  process control systems as well as supplier
  services required
• Guidance on the supplier services required for
  regulated environments
• Avoids extensive and time-consuming
  retrospective validation of legacy process
  control systems, but provides for the application
  of a risk based approach, if required
• Clarifies the collaboration between user and
  supplier
• Guidance on incorporation of supplier
  documentation into the user validation
  documentation Modified and extended supplier
  audit to ensure compliance of the suppliers
  development processes and documentation

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GAMP Process Control Supplement - Release

• Introduction of the VPCS Guide
• ISPE Washington Conference - June 4,
  2003
• ISPE Zurich Conference - Sep 25, 2003
• Publication Availability - October 2003
• ISPE Training Session (Tampa) - Nov 12,
  2003
• ISPE Copenhagen Conference - Dec 5, 2003

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JETTs VPCS Contribution

• Equipment Acquisition Business Model
• - Business Process outlining how to work
  together
• Blank (Generic) URS Template
• Label Rewinder URS Template

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Risk Management for Unit Operations
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JETT Work on Risk

• Initiated by JETT Membership request 09/04
• Andre Powell, Abbott Laboratories recruited to
  
• lead effort 10/04
• Decision made to focus efforts on
• JETT Acquisition Model Revision
• Development of JETT Risk Management Process
• Document
• Use Documentation Set developed for Wide Range
  
• Filler for performing Risk Assessments

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JETT EQUIPMENT ACQUISITION MODEL- Version 1.0
SUPPLIER


USER/(CONSULTANT if applicable)

Master Validation Plan
User Audit
Equipment Validation Plan/ Risk
Assessment
Engineering Feasibility Study and
Results
P.O.

• Explanation to Supplier

RFQ
Proposal
User Requirements Specification (Living Document)

• Project Plan

• Quality Validation Plan

Proposal
P.O.
Proposal Analysis
Approval
Detailed Design Documentation (traceable to
Functional Specification)
Review Functional Specification
Approval
System Acceptance Test Specifications (IQ/OQ)
Review Detailed Design

• Hardware

• Software

Review System Acceptance Test Specifications
Approval
System Acceptance Testing and Results User
Witness Optional

Integrate with Validation Documentation as
appropriate

Maintenance Support Documentation

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JETT EQUIPMENT ACQUISITION MODEL Ver 2.0
SUPPLIER


USER/(CONSULTANT if applicable)

RFQ
RFQ
Proposal
Create Initial Traceability Matrix
PO
Spec
Approval
Living documents Input for Revisions
Detail Doc
Approval
FAT/SAT
Approval
Results

Manuals



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JETT Risk Management Model

• Scope
• Focus on product safety and efficacy
• Provides a disciplined environment for
• proactive decision making that involves
• Assessing (examination and evaluation)
• Controlling (avoidance, reduction or
  mitigation)
• Reviewing potential product risks

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JETT Risk Management Model
Overview The intent is to Document the process
of evaluating the risks to product SISPQ (Safety,
Identity, Strength, Purity and Quality) Using
Detailed understanding of the product or process
Resulting in Documentation of risk mitigation
controls (physical design, procedural,
qualification/commissioning testing or
automation) that are necessary to manage the
identified potential risks.
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JETT Risk Management Model

• Process
• Assignment of Team Members
• The System Owner should be assigned to lead the
  risk assessment process and assemble
• A cross-functional assessment team
• Standard Operating Procedures
• Applicable quality policies
• A Quality Assurance individual that did not
  participate in the risk assessment for the system
  should be assigned to review the assessments
• Document the Names, Titles, Department for each
  member of the Team in Section 1 of the Risk
  Assessment Report

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JETT Risk Management Model

• Process
• Assemble System Documentation
•          Process Specifications
•          Critical Process Parameters
•          Validation Documentation
•          Production Batch Records
•          SOPs
•          Screen Captures, System Reports
•          System Architecture

List all Documentation Used in Section 2 of the
Risk Assessment Report
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JETT Risk Management Model

• Process
• Assemble System Documentation
•          Process Specifications
•          Critical Process Parameters
•          Validation Documentation
•          Production Batch Records
•          SOPs
•          Screen Captures, System Reports
•          System Architecture
• List all Documentation Used in Section 2 of the
  Risk Assessment Report

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JETT Risk Management Model

• Process
• System Overview
• Identify the system to be assessed in Section 3
  of the Risk Assessment Report. Include a
  description of the function(s) of the system to
  be assessed.

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JETT Risk Management Model

• Process
• Risk Assessment Scope
• The risk assessment may be performed on the
  entire system or only on specific functions,
  depending upon the relationship of these
  functions to critical attributes of the product
  or process and extent of the proposed changes or
  additions.
•  
• Define the scope of the assessment in Section 4
  of the Risk Assessment Report.

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JETT Risk Management Model

• Process
• Risk Assessment Parameters
• Examples of how these parameters may directly or
  indirectly impact the products performance
  include
• Safety of patients and consumers
• Non-sterile product
• Sub or super potent material
• Product not meeting performance requirements
• Mix-up involving samples

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JETT Risk Management Model

• Process
• Risk Assessment Parameters (Continued)
• Quality or efficacy of finished product
• Specification not met
• Incorrect composition
• Raw materials errors
• Packaging or packaging materials errors
• Failure of environmental or storage conditions
• Lot traceability
• Labeling errors

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JETT Risk Management Model

• Process
• Risk Assessment Parameters (Continued)
• Incorrect data for support of product release
  or
• regulatory submissions
• Integrity of laboratory or inspection results
• Statistical evaluations
• Calculations of results

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JETT Risk Management Model

• Process
• Risk Assessment Parameters (Continued)
• Generally, the parameters to be considered for
  the risk assessment include controlled or
  monitored variables associated with
•          Critical Process Parameters
•          Product Release (included in the batch
  or
• device history record)
•          Product Acceptance/Rejection Decisions
• Document the appropriate parameters in Section 5
  of the Risk Assessment.

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JETT Risk Management Model

• Process
• Controlled/Monitored Functions
• Identify the controlled/monitored function(s)
  that could have a potential effect on the risk
  assessment parameters. These functions can
  include the following
• - Security - HMI
• - Alarms/Messages - Trending
• - Numerical calculations - Reports
• - Process/Sequential Control - Recipe
  Management
• - External system interfaces - Interlocks
       
• - Data archiving and restoration
• Document the Controlled/Monitored Functions in
  the
• Risk Assessment Table.

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JETT Risk Management Model

• Process
• Risk Assessment Parameters
• For each function the assessment team should
  evaluate all risk assessment parameters
  identified in section 5 that could be affected..
•  Risk Scenarios
• The risk assessment team should identify possible
  risk scenarios for all identified functions with
  associated Risk Assessment Parameters.

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JETT Risk Management Model

• Process
• Effects
• The assessment team must document the likely
  effect or effects (note that each risk scenario
  may have more than one effect) for each of the
  identified Risk Scenarios.
• Document the Risk Scenario(s) and Effect(s) in
  the Risk Scenario and Effect columns of the Risk
  Assessment Table.

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JETT Risk Management Model

• Process
• Evaluate and Rate Risks
• Each risk parameter/function and risk scenario
  must be evaluated and rated based upon the
  impact, likelihood, probability of detection, and
  priority assessment
• Document the ratings for each on the Risk
  Assessment Table.

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JETT Risk Management Model
Process Impact Rating Table Description De
finition Low Expected to have a minor negative
impact. The damage would not be expected to
have a long-term detrimental effect. Medium E
xpected to have moderate impact. The impact
could be expected to have short to
medium-term detrimental effects. High Expect
ed to have a very significant negative impact.
The impact could be expected to have
significant long-term effects and potentially
catastrophic short-term effects.
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JETT Risk Management Model
Process Likelihood Rating Table Description
Definition Low Unlikely to occur during the
life of the system Medium Likely to occur
sometime during the life of the
system High Will occur several times during
the life of the system
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JETT Risk Management Model
Process Detection Rating Table Description
Definition Low Detection of the fault
condition is perceived to be unlikely (e.g.
less than one event in three occurrences) Medium
Detection of the fault condition is perceived to
be reasonably likely (e.g. one event in every
two occurrences) High Detection of the
fault condition is perceived to be highly
likely (e.g. one event in every one occurrences)
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Application

• Starting Risk Assessment using URS and resultant
  RTM for Wide Range Filler
• Initial Focus
• Identify Critical Parameters
• Identify Critical Functions
• Stay Tuned to JETT Website for updates through
  Meeting Minutes and Document Postings

58
JETT Benefits Analysis
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Benefits of JETT Approach

• Provides Standards/Guidelines for
• Project Lifecycle
• Deliverables
• Documentation
• Approvals
• Industry Consistency

60
Benefits of JETT Approach

• "Speed to Market"
• Smoother Procurement Process
• Smoother Validation Process
• Shorter Project Schedule
• Reduced Project Costs
• Integration Services
• Validation
• Re-work

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Savings Analysis of Purchase Price

• User 5-6 savings
• Gains
• Qualification Protocol development execution
• Life Cycle support (maintenance, upgrades)
• Losses
• Additional Auditing
• Validation Plan
• URS development
• Time Savings 3 - 14 weeks

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Savings Analysis of Purchase Price

• Supplier 3 - 6 savings
• Gains
• Functional, Design, Test spec development
• System production costs
• FAT
• Losses
• Supplier Audits
• Time Savings 6 - 8 weeks

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Savings Analysis of Purchase Price

• Consultant 3 - 4 savings
• Gains
• Functional, Design, Test Spec Development
• FAT
• Losses
• Integrator Audits
• Time savings 3-10 weeks

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Real World Example
Courtesy of Dr. David Selby, David Begg
Associates, Kirkbymoorside, N. Yorks, UK YO6 6AX
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Scenario

• two equivalent sterile filling lines
• 1991 - ampoules (pre GAMP)
• 1994 - vials (post GAMP)
• equivalent equipment train - tunnel
  steriliser - filler - automatic crack
  detection - automatic particulate inspection
• equivalent project cost (2m)

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Pre-GAMP Project
Engineering
Performance
Requirements Specification
Minimal
Efficiency (Day 1)
Not done
Design Qualification Pre-Delivery
Inspection Installation Qualification Operationa
l Qualification Software Review
0
7 days
Now Availability (for production) Wastage Maint
ainability Retrospective Validation
5 weeks
0
Not done
Poor
Misc. Controls Validation Total Man
days (approx.)
Not done
Significant
Documentation
0 100
Adequate
30 days
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Post-GAMP Project
Engineering
Performance
Comprehensive - 2 weeks ( several consultations)
Requirements Specification
Efficiency (Day 1)
Significant
Design Qualification Pre-Delivery
Inspection Installation Qualification Operationa
l Qualification Software Review
0
7 days
Now Availability (for production) Wastage Maint
ainability Retrospective Validation
4 days
Good
Misc. Controls Validation Total Man
days (approx.)
Unnecessary
Documentation
2 weeks
0 100
Good
90 days
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Summary
To derive benefit when validating automated
systems -
post GAMP
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How Do I Get Started?
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How Do I Get Started?

• JETT Web Site
• www.jettconsortium.com
• GAMP Web Site
• Contact JETT Members for Help
• Start with Baseline Piece of Equip.
• Promote with Users, QA, Suppliers
• Integrate in your Stds and Methods

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Working Session

• Break into functional groups
• QA/Validation
• Manufacturing/Operations
• Environmental/Safety/Utilities/Maintenance
• Engineering
• Select a piece of OEM equipment (simple)
• Develop portions of a URS
• Develop portions of project validation plan

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URS Guidelines

• Each statement
• Uniquely referenced
• Less than 250 words
• Express requirements, not design solution
• Each requirement should be testable
• URS should be understandable by user and supplier
• No ambiguity
• No contradictions
• Distinguish between mandatory and desirable
  items/requirements

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URS Content Checklist

• Functions required
• Product requirement
• Functional requirement
• Design requirement
• Modes of operation
• Performance and timing
• Failure actions
• Hardware
• Software

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URS Content Checklist

• Safety and security
• Data
• Archive
• Capacity
• Speed
• Definition of data and valid ranges
• Interfaces
• Environment

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URS Constraints

• Schedule
• Compatibility with existing networks, hardware,
  etc.
• Reliability requirements
• Legal issues, working methods, user skill levels,
  etc.
• Maintenance
• Ease of maintenance
• Expansion capability
• Expected lifetime
• Long-term support

76
URS Lifecycle

• Development e.g. project management/QA/mandatory
  design methods
• Testing
• Special testing under load conditions
• Test data
• Simulations
• Delivery
• Shipment directions
• Documents what supplier is expected to deliver

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URS Lifecycle

• Tools
• Training
• Engineering
• Operations
• Maintenance
• Support from vendor after
• FAT
• Validation complete