GAMPJETT AGENDA

1
GAMP/JETT AGENDA

• GAMP Organization Bret Fisk
• GAMP 4 Whats Changed?
• Joint Equipment Transition Team
• (JETT, GAMP SIG)
• Development of a User Jim John
• Requirement Specification
• URS Development Experience Jim Cavanaugh
• Benefits of the GAMP/JETT Chris Roerig
• Methodology
• JETT Member Experience Jim John
• Questions Answers

2
GAMP Origin

• Produced By UK Pharmaceutical Industry Computer
  Validation Forum
• In conjunction with
• Association of the British Pharmaceutical
  Industry ( ABPI )
• Pharmaceutical Quality Group (PQG) of the
  Institute of Quality Assurance
• Version 1.0 Released March 1995
• Version 2.0 Released May 1996
• Version 3.0 Released March 1998
• Version 4.0 Released Dec 2001

3
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)

4
GAMP Organization
FDA
PDA
APV
Namur Group
Supplier Forum
GAMP Americas
GAMP Europe
MCA
5
Executive Summary of Good Automated Manufacturing
Practice (GAMP) Guide
6
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

7
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.

8
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
9
User Responsibilities

• Validation (Master) Plan System Specific
  Validation Plan(s)
• Appendix M1
• Supplier Audit
• Appendix M2
• User Requirements Specification
• Appendix D1
• Supplier Education

10
New Edition GAMP 4
Strategic Framework
Quality Management Procedures
Practical Guidance (Good Practice)
Training/Materials Workshop
11
Plans for GAMP 4

• Official launch December 2001
• Next American Session 6/4-5 at
• Washington Conference
• Developed from GAMP 3 Guide
• Input from Special Interest Groups (SIGs)
• (e.g. 8 GAMP Americas SIGs)
• Wide review (industry regulators)
• Published by ISPE (www.ISPE.org)

12
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 (Released)
• Electronic Records and Signatures (Released, Part
  2 GAMP Interpretation of Part 11)
• IT Infrastructure Networks, Desktop,
• Harmonized Terminology

14
Additional Planned Guides

• Second Wave
• Control Systems including Stand-alone
  PLC/SCADA/DCS and Packaged Systems/Skid Mount
  Equipment
• Supplier Management
• Analytical Laboratory Equipment
• Global Systems ERP, MRPII, LIMS, EDMS

15
Additional Planned Guides

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

16
Training/Materials Workshop

UNDER DEVELOPMENT- Workshop training materials
from ISPE Seminars to facilitate hands-on
training examples dealing with real world issues
17
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

18
Joint Equipment Transition Team(www.JETTconsortiu
m.com)
19
Mission Statement

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

20
JETT MEMBERS

• USER Representatives
• Abbott Labs - Mike Quane
• Pharmacia - Dale Noteboom
• Eli Lilly - Bret Fisk
• Aventis John Dexter
• Perrigo Paul Coury
• SUPPLIER Representatives
• Paul Mueller - Russ Lindsey
• Bosch /TL Systems - Terry Petro
• Vector Corp - Don Rosendale
• Rockwell Bill McCarthy
• Millipore Ramon LeDoux

• CONSULTANT Reps
• BEK Engr Vince Miller
• Brock Solutions Jim John
• VAI Automation - Chris Roerig
• Performance Solns - Mike Filary
• Picard Tech - Michael Casey
• Frakes Engr Jim Cavanaugh
• Fluor Mike Humphries
• 15 Active Members
• 26 Assoc. Members Growing
• 30 Additional on Distribution list

21
JETT BASELINE EXAMPLE

• Available on JETT Website consists of
• User Requirement Specification
• Project Quality Plan
• Functional Design Specifications
• Acceptance Tests
• - Hardware - System
• - Software - Factory

22
JETT EQUIPMENT ACQUISITION MODEL
SUPPLIER


USER/(CONSULTANT if applicable)

Master Validation Plan
User Audit
Equipment Validation Plan
Engineering Feasibility Study and
Results

• Explanation to Supplier

P.O.
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

23
GAMP Issues

• User and Supplier Education
• GAMP Focus on Computer Systems
• Mechanical/Electrical not dealt with
• Difficult to relate to equipment in some
  sections
• Audits of Suppliers (PDA Audit Repository)
• GAMP usage of Validation vs Qualification
• Use of IEEE or home-grown terminology
• Cost of GAMP manual ( esp. CD Version)

24
JETT Efforts

• Clarifying GAMP Methodology
• Applying GAMP to Automated Equip.
• Communicating GAMP Approach
• Interphex 1997, 2000, 2001
• ISPE - Regional National Meetings
• Rockwell Automation Fair 2000
• Articles Published in
• Pharmaceutical Online
• Pharmaceutical Engineering
• Institute of Validation Technology
• Pharmaceutical Medical Packaging News
• Providing Input to GAMP Forum

25
JETT Efforts

• Developing URS Templates (14 out of 30)
• Pure Steam Generator - Fluid Bed Dryers
• Filling Machine - Dry Product Blender
• Freeze Dry Equipment - Tablet Coaters
• Multi Effect Still - Labeler
• Vial Washer - Bio Reactors
• Barrier Isolator HVAC System
• 16 additional equipment categories targeted.

26
GAMP/JETT AGENDA

• GAMP Organization Bret Fisk
• GAMP 4 Whats Changed?
• Joint Equipment Transition Team
• (JETT, GAMP SIG)
• Development of a User Jim John
• Requirement Specification
• URS Development Experience Jim Cavanaugh
• Benefits of the GAMP/JETT Chris Roerig
• Methodology
• JETT Member Experience Jim John
• Questions Answers

27
Design Qualification

• User Requirement Specification
• Functional Specification
• Design Specifications

28
User Requirements Spec (URS)

• Located in GAMP 4 Appendix D1
• Defines clearly and precisely, what the user
  wants the system to do
• Express requirements, not solutions
• Requirements should be testable
• Understandable by both user and supplier
• This is the user need list

29
User Requirements Spec (URS)

• Introduction
• Who produced the URS and under what authority
• Why the URS was produced
• The contractual status of the URS

30
User Requirements Spec (URS)

• Operational Requirements
• The overall system function, or purpose
• General description of system interfaces
• The environment that the system will operate in

31
URS - Differentiate Requirements

• GMP related requirements necessary for
  qualification of the system
• IQ/OQ/PQ testable requirements
• Contractual related requirements necessary to
  meet
• Internal corporate standards
• Local codes or standards such as NEC, UL, CE, ISA
  or ASTM
• Reviewed or tested in FAT

32
URS - Functions

• The system will fill vials without splashing or
  dripping
• The system will fully seat plug stoppers
• The system fill environment will meet Class A
  requirements
• The temperature distribution inside of the
  barrier/isolator will be /- 2deg C during H2O2
  sanitization

33
URS - Modes of Operation

• Start-up mode description
• Shut-down mode description
• Sanitization mode description
• Pressure Balance mode description
• Alarm mode description

34
URS - Performance

• System operation for the 5ml vial at 300 vials
  per minute net for a one hour continuous run
• Fill accuracy of /- 0.50 of target fill using
  Karo syrup as a placebo
• Greater than 99.8 fully seated stoppers
• Marred, scratched, broken or damaged product will
  not be counted as net product in the one hour
  test run

35
URS - Failure Mode

• The system will stop in a safe mode without
  damaging product
• Operator intervention is required to restart from
  a failure mode
• The reason for failure will be displayed to the
  operator

36
URS - Data Handling

• Definition of data ranges, parameters and limits
• Definition of critical data for 21CFR Part 11
• Definition of security levels of critical data
  for 21CFR Part 11
• Method and frequency of data archiving

37
URS - Interfaces

• The method of user interface is defined
• The interfaces to other equipment is defined
• Vial Washer
• Depyrogenation Tunnel
• Stopper Supply System
• Outfeed
• Air Handling

38
URS - Environment

• Definition of the environment that the system
  will operate within
• Physical layout of the plant and interfacing
  equipment
• Physical conditions of the environment
• Temperature range
• Humidity range
• Surrounding room classification

39
URS - Constraints

• Project schedule
• System availability for production
• Sanitation methods allowed
• Level of operator competency
• Maintenance requirements of the system
• Utilities available for the system

40
URS - Project Life Cycle

• Project management process
• Special requirements testing such as CE or
  Seismic
• Delivery and installation plans
• Documentation and archiving
• Special tools required
• Training of operators and maintenance personnel
• Supplier support

41
Design Qualification

• User Requirement Specification
• Functional Specification
• Design Specifications

42
Functional Specification (FS)

• Defines clearly and precisely what the supplier
  will supply in the system
• Express solutions to the requirements
• Understandable by both the user and supplier
• Include non-functional attributes
• This is the supplier can-do list
• Found in GAMP 4, Appendix D2

43
FS - Introduction

• Who produced the FS and under what authority
• Why the FS was produced
• The contractual status of the FS

44
FS - Overview

• Should provide a high level description of the
  system
• Main interfaces from the system to external
  sources and destinations
• Describe any assumptions that are made such as
• Standard Packages
• Operating System
• Specific hardware

45
Any divergence between the FS and the URS should
be noted in the FS and changes reflected in the
URS
46
FS - Functions

• The high level description should be broken down
  into individual functions
• The functions can mirror the functions in the URS
  if they are the same
• If the functions differ from the URS, the
  differences must be identified and described

47
FS - Functions

• The performance (response, accuracy, throughput)
  should be quantitative and unambiguous
• Safety and security of the system should be
  defined
• Configurable functions should be defined, along
  with ranges or limits

48
All requirements identified in the URS must be
traceable to the FS
49
FS - Data

• Operating parameters specific to the commodities
• Warning and alarm limits
• Product data developed from the system
• Retention of data developed from the system
• Security of data and parameters

50
FS - Interfaces

• Operator Interface
• Interface to SCADA, MES, etc.
• Interface to Washer/Tunnel
• Interface to product supply system
• Interface to stopper supply system
• Interface to Outfeed
• Interface to air handling
• Interface to sterilization system

51
FS - Attributes

• Definition of non-functional requirements
• Availability of the system
• Reliability of the system
• Redundancy plan for critical components
• Stand-by operation
• Maintainability of the system

52
FS - Review and Approval

• Upon completion of the functional specification,
  review is done, and proof of traceability of all
  requirements is made to the URS
• Review and approval by the user should take
  place before proceeding to the Design
  Specification

53
Proof of traceability of all requirements should
be provided in the Requirements Traceability
Matrix (RTM)
54
Requirements Traceability Matrix (RTM)

• List of all requirements in the URS
• Identifies location of requirement in the URS
• Identifies location that the requirement is
  addressed in the FS
• Identifies where the requirement is tested in the
  validation protocols

55
Design Qualification

• User Requirement Specification
• Functional Specification
• Design Specifications

56
Design Specifications (DS)

• The detailed specifications used to build the
  system
• Consists of machinery, control hardware, control
  software, interfaces and data processing
• Consists of both design specifications, and
  testing methods

57
DS - Machinery

• This part is not covered in the GAMP Guidelines
• Need to address in the same manner
• Define Materials, Finishes, Treatments
• Define methods of constructions
• Define any standards that need to be met

58
DS - Control Hardware

• Identify the approach of the controls
• Identify the layout of the controls
• Specify standard components
• Specify preferred manufacturers
• Identify environmental operational limits
• Define interface to other equipment

59
DS - Control Software

• Define the overall software boundaries
• Identify the software modules
• Define the interfaces between software modules
• Define the engineering parameters
• Identify data being generated
• Define the 21 CFR Part 11 plan

60
DS - Software Modules

• Write a DS for each module
• Define purpose and function of the module
• Define the interfaces between software modules
• Define the engineering parameters used in the
  module
• Identify data being generated from the module

61
DS - Interfaces

• List all of the interfaces, software and control
• Define data transferred
• Define communications protocols
• Washer, Tunnel, Stopper Supply, Outfeed, LAT,
  SCADA, etc.

62
DS - Data Processing

• List all data generated or used
• Engineering Parameters (recipes)
• Checkweigh Data
• HVAC environmental data
• Alarms and Faults
• Security Levels

63
Design Qualification

• Upon completion of the design phase of the
  project, review of all of the design
  specifications are done, and proof of
  traceability of all requirements is made to the
  FS and URS
• Approval by the user is required

64
Factory Acceptance Testing (FAT)

• Control Hardware FAT
• Software Module FAT
• Software FAT
• System FAT

65
Control Hardware FAT

• Verify that the control hardware is built
  according to the Control Hardware Design
  Specification
• Panels are manufactured as specified
• Components used are as specified
• System is wired as specified

66
Software Module FAT

• Verify that the Software Modules are programmed
  and function as specified in the Software Module
  Design Specification
• Module functions as specified
• Data is generated or received as specified
• Alarms and faults operate as specified
• Tested before installed in main program

67
Software FAT

• Verify that the overall PLC program operates as
  specified in the Software Design Specification
• All functions operate as specified
• Data is received, generated and transferred as
  specified, and complies with 21 CFR Part 11
  regulations
• All alarms and faults operate as specified
• Tested after installation into the system

68
System FAT

• Verify that the complete system operates as
  specified in the Design Specification
• Testing the overall function of the machine
• All systems function as specified
• The machine meets the contractual obligation to
  the User

69
Site Acceptance Testing (SAT)

• The complete system is installed and retested at
  the User site.
• All functions, alarms and data transfer is
  retested
• Interfaces to all peripheral equipment is tested
• All utilities are permanently installed and
  tested

70
Equipment Qualification

• Installation Qualification (IQ)
• Operational Qualification (OQ)
• Performance Qualification (PQ)
• Product Qualification

71
Installation Qualification (IQ)

• Verification that all machinery, control hardware
  and control software is identified, correct and
  installed per specifications

72
IQ - Machinery

• Verify scope of supply
• Verify format change parts
• Verify product contact parts
• Verify correct materials and finish
• Verify surface treatments

73
IQ - Utilities

• Verify that the utilities are as specified and
  connected correctly
• Electrical
• Pneumatic
• Vacuum
• Water
• Nitrogen
• Product

74
IQ Control Hardware

• Verify that the control hardware is as specified
• Components provided meet the specifications
• Components are marked according to the
  specifications
• Components are installed according to the
  manufacturer

75
IQ Control Software

• Verify that the control software is provided as
  specified
• Correct software is installed
• Correct version is provided

76
IQ Documentation

• Verify that all documentation is present
• Maintenance and operating manuals
• PID drawing
• Instrument list
• Hardware design drawings
• Electrical drawings
• Program printouts
• Calibration maintenance procedures

77
Equipment Qualification

• Installation Qualification (IQ)
• Operational Qualification (OQ)
• Performance Qualification (PQ)
• Product Qualification

78
Operational Qualification (OQ)

• Verification that all machinery, control hardware
  and control software functions are identified and
  operate correctly according to the specifications

79
OQ - Calibration

• All critical process instruments should be
  calibrated to NIST referenced standards prior to
  OQ testing
• Temperature
• Humidity
• Pressure
• Checkweigh Load Cells

80
OQ - Safety

• All safety features on the system should be
  tested prior to any further OQ tests
• Machinery Guarding
• Barrier Door Switches
• Glove Port Light Curtains
• Emergency Stop Switches
• Operator Maintenance Training
• Warning Labels

81
OQ - Machinery

• All functions of the machinery are tested to
  verify compliance to the URS
• Vial handling
• Filling
• Oxygen reduction
• Stoppering
• Checkweighing
• Vial eject
• Counter Accuracy
• Machine Interlocks Alarms

82
OQ - HVAC System

• All functions of the environmental control system
  are tested to verify compliance to the URS
• Air Pressure Balance
• Temperature Control
• Humidity Control
• Prescribed Air Flow
• Cleaning Sterilization Process

83
OQ - Performance of the System

• The overall function of the machine is tested
  including
• Product throughput
• Machine efficiency
• Interface to other equipment
• Product samples are tested for
• Fill accuracy
• Proper stopper placement
• Physical damage

84
OQ - Performance of the System

• The overall function of the Barrier/Isolator/HVAC
  is tested including
• Pressure balance throughout sequence
• Leak test integrity of system
• Adequate differential pressure at the mousehole
• Sterility of the Barrier/Isolator is tested for
• Viable particulates
• Non-viable particulates
• Residual hydrogen peroxide

85
Equipment Qualification

• Installation Qualification (IQ)
• Operational Qualification (OQ)
• Performance Qualification (PQ)
• Product Qualification

86
Performance Qualification (PQ)

• Verify that the entire system works correctly and
  consistently as defined in the URS.
• The complete operating environment is required to
  be functional using all procedures, equipment,
  utilities and raw materials.
• Strict change control must be followed at this
  point.

87
Performance Qualification (PQ)

• Complete sterilization process
• Demonstration of environmental transitions
• Product throughput of the system under pressure
  balance
• All products are tested under actual production
  conditions
• The entire range of production is tested

88
Product Qualification

• Testing with actual product
• Negative affect of product on equipment
• Corrosion in product path
• Residuals or build-up affecting performance
• Foaming or viscosity affecting fill rates
• Negative affect of equipment on product
• Leaching of product path materials into product
• Foaming, settling or shearing of product
• Viables or non-viables added to the product

89
Product Qualification

• Operators operating equipment
• SOPs
• Production Tickets/Batch Records Revised
• Cleaning of equipment between batches
• Three (or more) consecutive good batches

90
Preparation for Review with the FDA

• Organization of documentation
• Quality Report

91
Organization of Documentation

• The complete documentation set should be
  organized to allow quick and easy access to any
  information requested
• Organize the documentation in the sequence
  defined in GAMP
• Provide Table of Contents and indexes to define
  locations

92
Organization of Documentation

• Section 1User Documentation
• Master Validation Plan
• Equipment Validation Plan
• Supplier Audit
• User Requirement Specification
• Section 2Supplier Documentation
• Quality and Project Plan
• Supplier Qualification Documents

• Section 3Design Specifications
• Functional Specification
• Requirements Traceability Matrix
• Design Specifications
• Machinery Specification
• Control Hardware Spec.
• Software Specification
• Software Module Spec.

93
Organization of Documentation

• Section 4Test Specifications
• System Test
• Approved Protocol(s)
• Approved Report(s)
• Control Hardware Test
• Approved Protocol(s)
• Approved Report(s)
• Software Test
• Approved Protocol(s)
• Approved Report(s)
• Software Module Tests
• Approved Protocol(s)
• Approved Report(s)

• Section 5Equipment Qualification
• IQ Protocols
• Approved Protocol(s)
• Approved Report(s)
• OQ Protocols
• Approved Protocol(s)
• Approved Report(s)
• PQ Protocols
• Approved Protocol(s)
• Approved Report(s)
• Product Qualification Protocols
• Approved Protocol(s)
• Approved Report(s)

94
Organization of Documentation

• Section 6 Quality Report
• Summary of Overall Testing Efforts
• Identify areas of non-compliance (Deviations)
• Correction plan
• Corrective actions
• Repeat testing and results
• Review and approval from responsible Management

95
GAMP/JETT AGENDA

• GAMP Organization Bret Fisk
• GAMP 4 Whats Changed?
• Joint Equipment Transition Team
• (JETT, GAMP SIG)
• Development of a User Jim John
• Requirement Specification
• URS Development Experience Jim Cavanaugh
• Benefits of the GAMP/JETT Chris Roerig
• Methodology
• JETT Member Experience Jim John
• Questions Answers

96
Remember this Classic?
97
And we askDo you think the customer had a good
URS?
98
Creating URSs Practical Experience / Lessons
Learned

• Intro
• Its only the Requirements Mon!
• Tips for getting Equipment Specific Information
• Looking at the Entire Process
• Putting it all together
• Lessons Learned

99
Intro

• Only about 1 ½ years in the Pharmaceutical
  Industry
• Learn by Doing
• This is my experiences of trying to put all the
  pieces together
• Manufacturing Engineer with Lots of Hands On
  Experience
• Specified and purchased a lot of Equipment in the
  past
• We were The Heavier the Spec the Better
• Frustrated Manufacturing Grunt, that is always
  looking for a Better Way
• Like many things, Start with the End in Mind
• Like the cartoon, how many times have you
  received something short of what you wanted?

URSs are the way!
100
The Hierarchy of Validation

• FDA develops the Codes (CFRs)
• GAMP defines a methodology for producing the
  documentation to prove a system is validated
• Recommendations
• Best Practices
• Limited Examples
• JETT has created numerous URS templates for skid
  mounted equipment
• If you get the requirements right, you have a
  chance at a validated system, per GAMP
  Methodology

JETT is continually asked How do you create a
URS?
101
Its only the Requirements Mon!
102
Where does the idea of Requirements come from?

• GAMP follows a very similar path as Software
  Development.
• The GAMP V Model is used to model S.D. It all
  starts with the Requirements
• IEEE 830 - Recommended practice for Software
  Requirement Specification
• As a control systems integrator, many customers
  are not familiar with Requirements Definition
  or the URS. Many Controls Engineers arent
  also!!

Requirements are nothing new...We must
Educate!!!
103
Why use Requirements?

• As a Systems Integrator, we only have two
  problems
• 1) Getting the Customer to START making up their
  Mind
• 2) Getting the Customer to STOP Making up their
  Mind

• They create the happy medium between
• The specs being written on the back of an
  envelope while the salesman and the engineer are
  out at the bar
• Having a foot high stack of papers telling the
  vendor all the specifications they must adhere to

• Requirements are a perfect way to
• Accurately define the project scope
• Prevent Scope Creep

104
Defining Requirements is Like Project Management

• Many people do not want to spend the upfront time
  planning and gathering data, they want to get
  into the fun stuff of the project right away.
• But on the other hand, people do not want to (in
  most cases) plan 1 year for a 6 month project

But in most cases, Poor Requirements Definition
result in overly optimistic delivery dates
overly optimistic cost estimates
105
How often do we not have time to spend up-front,
during the planning phase. But we have to make
the time to do it over.
106
Which Requirements are we talking about?

• There are Requirements for
• Overall Project
• Process Requirements (Mechanical)
• Computer System (GAMP)
• Skid Mounted Unit Processes

JETT is focused on the Latter
107
Tips for getting Equipment Specific Information
108
Where does one Start?

• We will go back to the basics
• Well assume a summer intern is doing the project
• The World Wide Web (WWW) is a beautiful thing
• Search for (I like Google)
• Basics (ie Basics of Lyophilization)
• 101 (ie Lyphilization 101)
• Fundamentals (ie Fundamenbtals of
  Lyophilization)
• Search the above with other words such as Freeze
  Drying
• Go to www.jettconsortium.com to see if URS
  template is available

Get enough info to be able to converse with The
Experts
109
Find out who the Manufacturers are

• Contact your (the usrers) Operations Personnel
  - see whos equipment you are using
• Go to web sites like www.devicelink.com to find
  other manufacturers.
• Go to manufacturers web sites, find out the
  local vendor representative or sales rep. for the
  equipment
• Contact the vendors, get brochures on their
  systems
• Inquire from the vendor if they have Quote
  Forms, Equipment Data Sheet, or Functional
  Specification Document that can be sent out

Continue the Quest for Knowledge!
110
Seek out your Company Expert

• Describe the process and the equipment in as much
  detail as you can
• Describe the finished product requirements in the
  same details
• Schedule a walk through on a piece of equipment
  with the company expert
• At this point, your knowledge will allow you
  converse like an expert
• Ask about
• Major Components
• Major Functions
• Critical Process Parameters
• Any gotchas that have been problems in the
  past
• Ask for Guide Form Specifications that might
  still be available
• Ask if a URS has recently been written, seek it
  out!!!

Most people will cooperate if one shows a sincere
interest in learning
111
Create Short List of Suppliers

• Work with suppliers that can provide Value Add
• Work to understand the
• Operational Requirements
• Performance Specifications
• Functional Requirements
• Commodity Requirements
• Utilities
• Any Constraints (size of room, headroom, specific
  PLC, etc.)
• Remember the vendor is the EQUIPMENT Expert
• Make sure the PROCESS is also well understood

Use the expertise of the Supplier
112
Looking at the Entire Process
113
Once you have become an expert.

• Use an approach I used many years ago to make
  sure you have thought the entire process through
  - Your Process Model
• The Mass-Flow Analogy for you MEs
• Kirchoffs Current Law for you EEs
• Four Port Parameter again for you EEs
• The Material Energy Balance for you ChemEs
• The Black Box approach for you Aujo-magicEs
• (Automation)

What goes in.. must come out
114
Basics Equipment Model
115
Discrete Equipment Model
Examples Packaging Equipment Cappers Blister
Packers Washers Fillers Freeze Dryer Loader

• Utilities - In
• Air HVAC Power Etc.
• Water Steam Refrigeration
• Describe available service constraints
• Describe special product environmental
  requirements.

• Scrap / Trimmings
• Anything that must be removed?
• Empty rolls from label Stock
• Edge trimmings from Blister Pack

Equipment Process What is equipment supposed to
do? What Analytical Methods are used to Verify
correct Process Operation

• Raw Product Input
• How is it brought to machine
• Conveyor interface to other equipment
• Height, orientation, location of inlet
• Orientation of raw product
• How much run-time w/o intervention

• Finished Product Output
• How is it removed from machine
• Conveyor Interface to other equipment
• Height, Orientation, Location of Outlet
• Orientation of Finished Product

• Secondary Input
• Packaging, Bottles, Caps, etc.?
• Commodities
• How do they get to machine
• How much run-time w/o intervention
• Special Orientation

• Utilities - Out
• Air HVAC Power Sewage
• Water Refrigeration Steam/Condensate
• Describe by-products that must be handled

• Controls
• Operator Interface
• Specific manufacturer(s)
• Specific screen layouts

Process Data Control Schemes
Recipes
LAN

• Product Families to Run on Equipment
• How many unique products to be run?
• How many unique geometry's
• How many unique chemistry's
• How many unique labels required on finished
  product

• Process Rate
• How much Finished Product is required?
• How Much (qty/hour, qty/shift, qty/day)
• How Fast
• Overall Run Time (hrs/day, days/week)
• How much run-time w/o intervention

• Product Identification
• Any ID on Product or Container required?
• Date / Lot
• Batch
• Time Stamp

116
Batch Equipment Model

• Utilities - In
• Air HVAC Power Etc.
• Water Steam Refrigeration
• Describe available service constraints
• Describe special product environmental
  requirements.

Examples Bio Reactors Fluid Bed
Dryer Granulators Freeze Dryer Blenders Autoclav
e Centrifuges Tablet Coater Sterilizers
Autoclaves Chromatography

• Vessel Cleaning Methods
• How will vessels be cleaned between Batches
• External CIP / SIP
• Internal CIP / SIP

Equipment Process What is equipment supposed to
do? What Analytical Methods are used to Verify
correct Process Operation Size of Vessel
Raw Product Input How is it brought to machine?

Finished Product Output How is it removed from
machine?

• Utilities - Out
• Air HVAC Power Sewage
• Water Refrigeration Steam/Condensate
• Describe by-products that must be handled

Secondary Input Reactants, Catalysts, Water, etc.?
Process Data Electronic Batch Records
Control Schemes Recipes
LAN

• Batch Identification
• Any ID on Batch?
• Control Recipe Record
• Batch
• Time Stamp
• Electronic or Manual Batch Records

• Product Families to Run on Equipment
• How many unique products to be run?
• Unique Chemistries
• Minimum / Maximum Batch Time

• Process Rate
• How much Finished Product is required?
• Batch Size (qty/hour, qty/shift, qty/day)
• Overall Run Time (hrs/day, days/week)
• How much run-time w/o intervention

117
Continuous Process Equipment Model
Examples Water Purifier Pure Steam
Generator Water Systems Multi-Effect
Still Isolator Environmental System Depyro
Tunnel

• Utilities - In
• Air HVAC Power Etc.
• Water Steam Refrigeration
• Describe available service constraints
• Describe special product environmental
  requirements.

• Vessel Cleaning Methods
• How will vessels be cleaned between Batches
• External CIP / SIP
• Internal CIP / SIP

Equipment Process What is equipment supposed to
do? What Analytical Methods are used to Verify
correct Process Operation Throughput of Process
Finished Product Output How is it removed from
machine?
Raw Product Input How is it brought to machine?

• Utilities - Out
• Air HVAC Power Sewage
• Water Refrigeration Steam/Condensate
• Describe by-products that must be handled

Secondary Input Reactants, Catalysts, Water, etc.?

• Controls
• Operator Interface
• Specific manufacturer(s)
• Specific screen layouts

Process Data Control Schemes
Recipes
LAN

• Product Identification
• Any Time Stamping of Data from Instruments?
• Temperature, pH, DO Levels
• Conductivity, etc.

• Product Families to Run on Equipment
• How many unique products to be produced?
• How many unique chemistries
• How many destinations

• Process Rate
• How much Finished Product is required?
• How Much (qty/hour, qty/shift, qty/day)
• How Fast
• Overall Run Time (hrs/day, days/week)
• How much run-time w/o intervention

118
Putting it all together

• Use JETTs Blank URS Template, or
• Borrow an existing internal format that has been
  Approved
• Follow GAMP Guidelines for URS Structure -
  Appendix D1
• Functions (Security is the BIG one now)
• Data
• Interfaces
• Environment
• Constraints
• Review with Internal Expert
• Review with Vendor(s)

Formatting takes a little time..but,It is
essential to have the right information
119
Lessons Learned

• Settle on Alarms (Informational Messages) up
  front
• Get QC on Board early
• Do not try to design the equipment or process
• Experience is the best teacher, do your best and
  learn from it
• If it makes sense, it is probably the right thing
  to do
• Insure that requirements are Testable, and
  specific
• Define Requirements with traceability in mind
• During the Project, countless references are made
  back to the Requirements, make sure they are
  right!!!!
• Recognize that it is a Journey, continually seek
  to improve the process
• Communicate, Communicate, Communicate

120
GAMP Manual Page 1
It is vital for quality to be built into new
computer systems during their development and
commissioning once a system is installed and
operating, the opportunity to improve quality
cost effectively is gone.
Validation has to be part of the development
process
121
FDA Opinion

• In the eyes of the FDA.
• If you cant produce the documentation, then it
  has not been done Period!

122
GAMP/JETT AGENDA

• GAMP Organization Bret Fisk
• GAMP 4 Whats Changed?
• Joint Equipment Transition Team
• (JETT, GAMP SIG)
• Development of a User Jim John
• Requirement Specification
• URS Development Experience Jim Cavanaugh
• Benefits of the GAMP/JETT Chris Roerig
• Methodology
• JETT Member Experience Jim John
• Questions Answers

123
JETT Benefits AnalysisChris Roerig
124
Benefits of JETT Approach

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

125
Benefits of JETT Approach

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

126
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

127
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

128
Savings Analysis of Purchase Price

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

129
Real World Example
Courtesy of Dr. David Selby, David Begg
Associates, Kirkbymoorside, N. Yorks, UK YO6 6AX
130
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)

131
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
132
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
133
Summary
To derive benefit when validating automated
systems -
post GAMP
134
GAMP/JETT AGENDA

• GAMP Organization Bret Fisk
• GAMP 4 Whats Changed?
• Joint Equipment Transition Team
• (JETT, GAMP SIG)
• Development of a User Jim John
• Requirement Specification
• URS Development Experience Jim Cavanaugh
• Benefits of the GAMP/JETT Chris Roerig
• Methodology
• JETT Member Experience Jim John
• Questions Answers

135
Recent Experiences Using a User Requirement
Specification for Equipment Acquisition Jim John
136
Getting Started

• Review the GAMP philosophy with the Project Team
  and Supplier. (Set expectations)
• Begin with the end in mind. Stephen Covey.
• Very early in project, develop the project team
  vision
• Final installation and operation.
• Validation.
• What will be tested.
• Acceptance criteria.
• How it will be tested.
• When it will be tested.
• Requirements and specifications development.

137
Involve Key Parties Early

• Operations Representative(s)
• Technical Manager
• Floor Operations
• Process/Equipment Engineering
• Automation Engineering
• SCADA Systems Engineering
• Reliability Maintenance Engineering
• Environmental Health Safety
• Industrial Engineering
• Regulatory

• Quality Assurance
• Product QA
• Microbiological QA
• Validation
• Qualified Utilities Engineering
• Non-Qualified Utilities Engineering
• Qualified HVAC Engineering
• Non-Qualified HVAC Engineering
• Computer Validation Specialist
• Product Introductory Professional

138
Lessons Learned

• Developing and maintaining URS.
• Brainstorm with Team.
• Review at key times.
• Initial release.
• During acquisition process.
• After learning more about equipment and process.
• Update, Update, Update (Using revision control.)
• Make sure specifications in URS are testable.
• Not all items in the URS are tested at PQ.
• Not all items in URS are related to validation.

139
Lessons Learned

• Presentation of requirements format is flexible.
• Text
• Tables
• Drawings

140
Typical Text Specification
 
 
1.1.1.1.              The system shall have
provisions for a minimum of initially AA
(quantity) different specific operating cycles.
The following parameters represent the minimum
and the supplier can provide greater ranges and
smaller increments of adjustment for these recipe
selectable parameters            Number of
Pre-Vacuum cycles (0-BB)          Sterilization
Temperature Set point (CCC-DDD?C, 0.E?C
increments)          Jacket Temperature Set
point (FFF-GGG?C, 0.H?C increments)         
Exposure Time (0-III minutes, K minute
increments)          Steam Flush Duration (0-LL
minutes, M minute increments)          Slow
Exhaust Duration (By rate, To Be Determined from
submittals)          Post Vacuum Duration (By
rate, To Be Determined from submittals)         
Jacket Temp. Set point during Post Vacuum
(ambient-NNN?C, 0.P?C increments)         
Condensate Cooler (QQC minimum, 0.RC
increments)  
 
 
1.1.1.2.              The system shall have an
automated Daily Air Removal Test (DART) cycle.
The DART cycle shall have the same air removal
phase (pressure and vacuum set points) and charge
phase as the production forced air removal cycle.
The exposure phase shall be set to SS (quantity)
minutes dwell time at a sterilization temperature
of TTToC. Exhaust shall be fast vacuum
drying shall be U minute at or below V.V psia.
(Reference EN-XXX, Section Y.Y.Y.Y and
Z.Z.Z.Z.)  
141
Typical Table Requirements
ELECTRICAL
142
(No Transcript)
143
Lessons Learned

• URS level of detail depends on complexity of
  equipment.
• Autoclave
• Portable Sterile Product Tanks
• Somebody has to carry the torch!
• Capture updates, clarifications, etc. they
  happen in many different meetings and
  interactions.
• Keep URS current.

144
Lessons LearnedCommunicate, Communicate,
Communicate!

• Supplier-User communications critical.
• Audit and understand Suppliers capabilities.
• Regular communications during the project a must!
• Issue resolution.
• Progress reporting.
• Budget in the estimate for face-to-face meetings.
• Phone and e-mail have limitations.
• Get management support. ()
• Line-by-line review of URS with selected Supplier
  prior to placing PO.
• Review design and construction at intermediate
  states.

145
Lessons LearnedURS alone doesnt guarantee
success!

• Establish and get agreement on documentation
  Deliverables
• Timing
• How differences of opinion will be handled.
• Submittal reviews must catch detail design
  issues.
• May require spoon feeding information to
  critical User review parties.
• Summarize information.
• Provide one-on-one tutorials of material.
• If information isnt forthcoming from Supplier
• Assess risk.
• Determine actions to take.
• Intermediate checks and inspections are
  invaluable.

146
Recent Project Experience Feedback from the
Supplier

• Did the URS improve the overall procurement
  process?
• It was a good start for the project because the
  requirements were clearly defined.
• Yes, it provided a good overview of what was
  required.
• Any specific areas the URS helped?
• Process and software engineering were helped
  because requirements for control system
  parameters, alarms etc. were clearly defined in
  the very beginning of the project.
• The performance data sheet and utility data was
  helpful because it summarized the key points in a
  quick manner.

147
Recent Project Experience Feedback from the
Supplier

• What improvements would you recommend?
• As a general point from the Suppliers point of
  view, the fewer revisions are issued after
  manufacturing of the unit has begun, the more
  cost-effective for both Supplier and Customer.
• its good to state items only once and in one
  area as much as possible. Some of these
  documents I get state the same item in five
  different places.
• Would you recommend this approach to others to be
  used on future projects?
• Yes, we definitely feel developing a URS is a
  good approach. Any exceptions to Suppliers
  standard specification can and must be agreed in
  the beginning of the project and from the
  Suppliers perspective URS is a good tool for
  that.
• Yes, I definitely recommend this concise
  approach. I like the fact that the document was
  more generic to specific construction
  requirements and instrumentation requirements.
  As stated earlier it is always more cost
  effective to use the vendor standard where
  possible .

148
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