GAMP/JETT AGENDA GAMP Process Control Supplement Jim John Introduction and GAMP Organization Dale Noteboom GAMP Process Control Supplement Jim John Benefits of the GAMP/JETT Chris Roerig Methodology Working Session JETT Team Questions & Answers JETT Team

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 joining (2001)

GAMP Forum Organisation ISPE/GAMP JETT APV Namur Group Supplier Forum GAMP Americas GAMP Europe

Executive Summary of Good Automated Manufacturing Practice (GAMP) Guide 1

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 * GAMP’s definition of “Automated Systems” looks at the components that make up a system and applications. * The GAMP definition of Automated Systems is very broad and the practices it advocates may not be applicable to all systems. 2

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.” The purpose is drawn from the classic definition of validation with a focus on Suppliers employing these processes. 4

GAMP Qualification Plan A Basic Framework for Specification, Design and Testing USER REQUIREMENT PERFORMANCE SPECIFICATION Verifies QUALIFICATION FUNCTIONAL OPERATIONAL SPECIFICATION Verifies QUALIFICATION DESIGN INSTALLATION SPECIFICATION Verifies QUALIFICATION It describes a very timely and orderly flow of information. But in practice... SYSTEM BUILD GAMP 4.0 Figure 6.2

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 * The Validation Master Plan defines the “big picture” validation activities and is typically approved by management and QA. System Specific Validation Plan is a Validation Plan developed for the Suppliers that defines their responsibilities for specification and testing so that what they do can be utilized as part of the overall validation plan. You will not find the term (System Specific) used widely in GAMP. Its alluded to in the explanations of how documents and specifications should flow and therefore we’ve started using that term more commonly. * According to GAMP, each Supplier should be formally audited to ensure the quality of the services or equipment they supply. The audit should be done prior to seeking equipment/services from the Supplier. * The User is responsible for defining “WHAT” the equipment is suppose to do. It may be written by a third party but should be approved by the User. * The Users are responsible for Supplier education. 9

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

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.

Best Practice Guides First Wave Calibration IT Infrastructure: Networks, Desktop, Harmonized Terminology Electronic Records and Signatures

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

Additional Planned Guides Third Wave Legacy Systems Clinical Systems Medical Devices E-Applications: Web-based software Manufacturing Execution Systems

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 This introduction to GAMP has been very brief and fast-paced. It would take 1-2 days to do justice to GAMP and the tools it provides. As an International Guideline, GAMP provides a document that can be used with virtually all Suppliers and Manufacturers. The approaches advocated provide a good common sense approach and, as the JET team discovered, a “common ground” that meets the industry requirements. For a company that is ramping up its internal efforts or considering improving their existing practices, procedures or documentation, GAMP provides some well thought-out information. Finally, GAMP continues to evolve and improve its guidance to Suppliers and Users. JETT hopes to have input on the next revision of the document

Joint Equipment Transition Team (www.JETTconsortium.com)

Mission Statement Improve communications between Users and Suppliers to more effectively meet the “validation” requirements of the pharmaceutical industry.

JETT MEMBERS USER Representatives CONSULTANT Reps Abbott Labs – Tim Schuetter Pharmacia - Dale Noteboom Eli Lilly - Bret Fisk Aventis Behring – John Dexter Aventis Pasteur – Jeff O’Donel Perrigo – Paul Coury SUPPLIER Representatives Fisher-Rosemount – Jon Lustri Bosch /TL Systems - Terry Petro Vector Corp - Don Rosendale Rockwell – McCarthy, Jiang BOC Edwards – Mike Stella Millipore – Ramon LeDoux Invensys – Russell Regan CONSULTANT Reps VAI Automation - Chris Roerig Jacobs Engrg – Brokamp, Buede PV - Filary, Rivera, Lauderman PAC – Bruce Lauderman Fluor-Daniel – Mike Humphries BE&K Engr – Vince Miller Brock Solutions – John, Casey ~ 14 Active Members + 45 Assoc. Members & Growing

JETT BASELINE EXAMPLE User Requirement Specification Project Planning Functional & Design Specifications Acceptance Tests - Hardware - System - Software - Factory

JETT EQUIPMENT ACQUISITION MODEL USER/(CONSULTANT if applicable) SUPPLIER 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 Proposal Quality & Validation Plan Functional Specification (traceable to URS) P.O. Proposal Analysis Approval Detailed Design Documentation (traceable to Functional Specification) Review Functional Specification Approval Review Detailed Design System Acceptance Test Specifications (IQ/OQ) 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

JETT Efforts Applying GAMP to Automated Equipment Communicating GAMP Approach Interphex 1997, 2000, & 2001 ISPE - Regional & National Meetings Pharmaceutical Online Articles Pharmaceutical Engineering Articles Institute of Validation Technology – Conferences and Articles Published in VPCS Supplement to GAMP 4

JETT Efforts Providing Input to GAMP Forum Developing Guidance for Equipment URS’s, Equipment Validation Plans, Functional and Design Specifications and IQ/OQ’s Working directly with Industry OEM’s

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

JETT Efforts Released URS Documents Glassware Washers Vial Washer Saturated Steam Autoclave Label Rewinder Labeler Multiple-Effect Still Vial Washer Barrier Isolator & HVAC System Chromatography Pure Steam Generator

JETT Efforts URS Documents in development Granulators Tablet Press Variable Data Inspection BioReactors Building Management Systems Centrifuge CIP Systems Fluid Bed Dryer Freeze Dryer Tablet Coater Purified Water System Wide Range Filler Tangential Flow Filtration System SCADA System Cappers Blender Depyrogenation Tunnel

GAMP Process Control Supplement

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.”

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

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

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 supplier’s development processes and documentation

GAMP Process Control Supplement - Release Global Introduction of the VPCS Guide ISPE Washington Continuing Advancement Conference – June 4 Arlington, VA

JETT Benefits Analysis Chris Roerig

Benefits of JETT Approach Provides Standards/Guidelines for Project Lifecycle Deliverables Documentation Approvals Industry Consistency One of the challenges I talked about was a lack of consistency among suppliers. What GAMP does extremely well is to set standards for what’s expected in the User/Supplier relationship. If GAMP is being followed, both sides know what the steps in the project will be… what deliverables and documentation are expected on both sides… and when it’s time to nail down decisions about requirements, design, and function.

Benefits of JETT Approach "Speed to Market" Smoother Procurement Process Smoother Validation Process Shorter Project Schedule Reduced Project Costs Integration Services Validation Re-work 9

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

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

Savings Analysis % of Purchase Price Consultant 3 - 4 % savings Gains: Functional, Design, & Test Spec Development FAT Losses Integrator Audits Time savings 3-10 weeks

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

two equivalent sterile filling lines 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)

Pre-GAMP Project Engineering Performance 7 days 5 weeks Requirements Specification Minimal 0 <30% 100 Efficiency (Day 1) Design Qualification Pre-Delivery Inspection Installation Qualification Operational Qualification Software Review Not done 0 60% 100 7 days Now Availability (for production) Wastage Maintainability Retrospective Validation 0 70% 100 5 weeks 0 8-12% 100 Not done Poor Misc. Controls Validation Total Man days (approx.) Not done Significant Documentation 0 100 Adequate 30 days

(+ several consultations) Post-GAMP Project Engineering Performance Comprehensive - 2 weeks (+ several consultations) Requirements Specification 0 75% 100 Efficiency (Day 1) Significant Design Qualification Pre-Delivery Inspection Installation Qualification Operational Qualification Software Review 0 90%100 7 days Now Availability (for production) Wastage Maintainability Retrospective Validation 0 100 5 weeks 0 1% 100 4 days Good Misc. Controls Validation Total Man days (approx.) Unnecessary 2 weeks Documentation 0 100 Good 90 days

To derive benefit when validating automated systems :- Summary To derive benefit when validating automated systems :- post GAMP 0 75% 0 90% adopt “good engineering practices” adopt the common approach (GAMP) manage the benefits through measure them 0 1% 100%

How Do I Get Started? JETT Web Site GAMP 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

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

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

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

URS Content Checklist Safety and security Data Interfaces Environment Archive Capacity Speed Definition of data and valid ranges Interfaces Environment

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

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

URS Lifecycle Tools Training Support from vendor after: Engineering Operations Maintenance Support from vendor after: FAT Validation complete