GAMP5 - a lifecycle management framework for customized bioprocess solutions

Transcription

1 GE Healthcare Life Sciences GAMP5 - a lifecycle management framework for customized bioprocess solutions imagination at work

2 GE Healthcare s engineering department, Customized Bioprocess Solutions (CBS), has designed and produced customized bioprocess systems and columns for over two decades, mainly for customers in the biotechnology and biopharmaceutical industries. Over time, regulatory and validation requirements have demanded increased efficiency, and now focus on a risk-based validation approach. CBS has always been responsive to these changes, providing deliveries based on significant understanding of the customer s process and quality requirements. In this paper we summarize how CBS works to support equipment within a lifecycle approach based on ISPE baseline guide 5 and ASTM E-2500 guidelines, with valuable contributions from our customers, that go far beyond individual projects. CBS supports the current lifecycle management model tools, procedures, and workflows that allow CBS to focus on the significant GxP, process, and regulatory requirements throughout the entire design, production,, and post-delivery phases of a customized project. The aim of these activities is to increase customer control of the projects, leading to more efficient validation effort, reduced project time frames, and ultimately, enhanced quality. 2

3 Traditional vs. risk-based validation processes GE Healthcare equipment and software are developed and verified according to structured and documented procedures as required by Good Manufacturing Practice (GMP) standards, all defined within the internal quality management system (QMS) of GE Healthcare and based on the international standards EN ISO 9001 and ISO This allows for a consistent approach across all systems, enables leverage of validation activities, and results in a much faster and efficient commissioning and qualification (C&Q) phase, decreasing the start-up phase at the customer site (Fig 1). Furthermore, our comprehensive toolbox of Good Engineering Practice (GEP) and C&Q strategies, procedures, and templates, including standardized test methodologies and modular formats enable efficient, customerspecific validation lifecycle activities, such as change control verifications and requalifications performed over the equipment lifetime. Traditional validation method Specifications Design Construction Commissioning and Qualification GE Healthcare Validation Services approach Specifications Planning Design Construction Commissioning and Qualification Project time Fig 1. Traditional validation method vs the GE Healthcare Validation Services approach. The GE Healthcare approach uses a streamlined, risk-based approach to control costs and significantly reduce project time. Note that commissioning and qualification activities are now ideally performed throughout the validation period, with customer involvement. Historically, equipment qualification was considered a one-off activity necessary for using equipment in regulated environments. Regulations now require a validation lifecycle approach to demonstrate compliance throughout the equipment s working life. GAMP5 stresses a risk-based approach to validation, with increased emphasis on the control and documentation of processes that are critical to intended use and process understanding. Furthermore, the new risk-based approach in GAMP5 recognizes the value of supplier input, and leverages supplier involvement based on the five key concepts within GAMP5 (Fig 2). User Develop medicinal Produce medicinal Market and distribute medicinal Product and process understanding Life cycle approach within a QMS Scalable life cycle activities Science based quality risk management Leverage supplier involvement Supplier (of computerized systems and services Develop and services Deliver and services Maintain and support and services Fig 2. The risk-based approach to compliant GxP computerized systems under GAMP5. The five key risk-based concepts within GAMP5 are shown. 3

4 The primary objective of any program related to equipment and/or facility validation is to assure equipment and facility fitness for use. It is therefore important to have a deep understanding of the product and process in order to be able to make risk-based decisions. At CBS, our Subject Matter Experts (SMEs) help you to transform the Critical Process Parameters (CPPs) and Critical Quality Attributes (CQAs) into the Functional Specifications (FS), thereby saving time and costs during the system qualification. Figure 3 summarizes the responsibilities of customers and suppliers within the GAMP5 risk-based framework. Retirement Customer responsibility Operation Regulatory aspects Guideline compliance URS Master Validation plan Installation IQ OQ PQ Quality & Project Plan Design inputs: Functional and detailed Testing Hardware Software Full equipment Construction Hardware Software Package configuration Supplier responsibility Fig 3. Customer vs. supplier responsibilities within the GAMP5 risk-based validation approach. URS = User requirement specification. Validation and support policies for standard and customized GAMP defines the equipment lifecycle approach as including all phases from concept and implementation through to operation and retirement (Figure 3). Four major phases are defined for any computerized system project (Figs 4 and 6). GAMP recognizes that suppliers can be valuable in assisting companies in any or all phases of the lifecycle. Furthermore, GAMP differentiates between standard and customized systems. Table 1 and Figure 5 illustrate the main differences between GE Healthcare s standard and customized automated systems and software with respect to GAMP requirements and equipment examples. Good engineering practice Concept and design Project and build Implementation operation and verification Retirement DQ, System impact Release FTR, ITR, IQOQ, P11 DC Risk management, design and change management, knowledge management Fig 4. General project workflow within GAMP for computerized systems. DQ = Design qualification, FTR = Functional test records, ITR = Installation test records, IQOQ = Installation Qualification and Operational Qualification, P11 = 21 CFR part 11, DC = Decommissioning. 4

5 Table 1. GAMP category relationships for standard and customized chromatography and filtration systems Definition Equipment examples Standard GE Healthcare plan and definition (concept phase) ÄKTAcrossflow ÄKTApilot ÄKTAprocess UniFlux Customized Customer plan and definition (concept phase) BioProcess chromatography systems BioProcess filtration systems GAMP software category 4 5 GAMP hardware category 1 2 GAMP validation requirements (GE Healthcare) GAMP validation requirements (customer) See Figure 5 See Figure 5 Validate only part of the system Validate complete system and verify operation vs requirements Approver of design documents GE Healthcare Customer Standard systems Customized systems Market requirement Performance User requirement Performance Functional System acceptance Functional System acceptance Software design Software module Software integration Software module Software design Software module Software integration Software module Build product Code modules Category 5 (custom) Custom Configuration Fig 5. Software module development milestones for standard (category 4; figure to the left) and customized (category 5; figure to the right) automated chromatography and filtration systems. The figure is modified from: GAMP Good Practice Guide: Testing of GxP Systems. ISPE, Tampa, Florida (2005). GE Healthcare Quality Management System An important factor ensuring the equipment s fitness for use is a stringent quality assurance and internal management system. GE Healthcare Life Sciences is strongly committed to the GMP key principles of a Quality Management System (QMS), in compliance with ISO international standards. The principles of the QMS include a commitment to customer satisfaction, compliance with laws and regulations, employee involvement, continual improvement, and a shared quality culture. GE Healthcare Life Sciences holds a global certificate for the ISO 9001 standard. The QMS is maintained to ensure that both customer and regulatory requirements are met. Furthermore, our QMS, which is used globally throughout Life Sciences, is continually assessed to maintain its suitability, adequacy, and effectiveness. All processes and systems are designed to enable continual improvement and thereby create better value for our customers. 5

6 Project management CBS project management is fully integrated within the GE Healthcare Life Sciences QMS for the manufacture of customized equipment. Figure 6 shows the representative milestones in a CBS project including delivery and support. Quotation phase Project planning Design Production and Verification Delivery and Support Installation and Validation Request for quotation Project kick off meeting Design review Functional acceptance test Support Training Service Technology review workflow Initial regulatory evaluation Extended Technology regulatory review evaluation Technology review closing Fig 6. A typical sequence of project phases employed at CBS for customized systems (GAMP category 5). The customer is normally involved in all phases of the project sequence. Quotation phase CBS can support the end-users and buyers in the User Requirements Specification (URS) process by using tools (e.g., URS templates, system configurator) to help define any type of system, and any kind of relevant requirements that the customer may need to include. Impact and Risk Assessments are important steps in the URS process, and CBS together with Life Sciences Validation Services can offer support in identifying boundaries of no impact, indirect impact, and direct impact systems. Design input Software configuration Define functions & develop models Design phase Each project is unique and a Quality and Project Plan (QPP) outlines any project specific requests customers may have and how these will be handled. A series of technology reviews, with input from CBS Subject Matter Experts (SMEs), ensures end-user technical requirements are fulfilled and included in the design, as well as assuring Quality by Design (QbD) customer inputs. Regulatory requirements are dealt with using a riskbased approach. Customers are highly involved in the design process through extensive formal design reviews together with the CBS project team. Before manufacturing commences, customer approval is required. During the entire project, change control procedures embedded in the QMS are used to secure any necessary changes after initiation of equipment manufacturing. Fail Test in simulated environment Pass Identify test for functional test plan Install software configuration on system computer Risk assessment input from technology review Software development work follows well-defined industry standards to allow for full auditing of development steps, thorough documentation, and quality management in accordance with ISO Our automated systems are normally controlled by GE Healthcare s widely used UNICORN control software, with process control strategies enabling effective Process Analytical Technology (PAT). Other control software (e.g., PLC) solutions are also available. Software development follows internal standard operating procedures (SOP) for the configuration of the system strategy (Fig 7). Fail Fail Functional test on system Pass FAT (If applicable) Production verification and release phases Equipment is installed at CBS test premises and subjected to a wide range of functional tests. Functional tests are executed in a test environment that resembles the production environment for the systems, with all media and utilities connected. Test results are collected step-by-step and compared with predetermined test results extracted from the acceptance criteria. Pass Release software configuration and create documentation Fig 7. The workflow followed when developing new UNICORN software modules. 6

7 The same functional tests serve as a template for the Factory Acceptance Test (FAT), and together with customer specific tests, they comprise the FAT protocol. Deviations are documented on fault log sheets, and if changes need to be implemented they are handled via change control. All test results have to be approved by the customer before product release. After product release, the equipment is packed and delivered to the customer. GE Healthcare Life Sciences Validation Services In line with the new approach favored in GAMP5, GE Healthcare has adopted a broader, long-term approach to its equipment service offerings. This lifecycle management approach includes a new range of programs aimed at simplifying the maintenance, service, and upgrading of equipment. GE Healthcare Life Sciences Validation Services provide a comprehensive suite of streamlined validation services to support the equipment through its entire lifecycle. Benefits of engaging GE Healthcare Life Sciences Validation Services: Significant reduction in time for equipment qualification Consistent verification support throughout product lifecycles Proven history of GxP compliant equipment and satisfied customers, including the world s leading pharmaceutical and biotech companies Global network of field support and cgmp trained service staff Predictable costs and timelines Validation include Installation and Operational Qualifications, 21 CFR part 11 and EU Annex 11 verifications, Change Control Protocols (CCP), Requalifications (RQ), Standard Operating Procedures (SOP), and Decommissioning. These activities can be transformed into a full modular approach, in accordance with the new trends within C&Q, and are available either as single items, or as components of a larger periodic or lifetime service agreement with GE Healthcare (Brochure: GE Healthcare Validation Services, GE Healthcare, Edition AA, 2009). After-sales support GE Healthcare Life Sciences Service agreements are tailored to your needs, ensuring that your system is maintained optimally and your total cost of ownership is predictable during its lifecycle. A Service Agreement extends the life of your system through planned maintenance of critical components, and insures your investment against unexpected breakdown costs. The added-value of the knowledge and expertise of our highly trained field service engineers ensures that you can rely on expert service and first-class application support, giving you the peace of mind you need to keep your research moving. Service Agreements provide: Confidence in your results through regular Preventive Maintenance visits and part replacements Predictable ownership costs, as rates are guaranteed for the duration of the contract Minimized disruptions with priority response from our trained Service Engineers Preventative Maintenance (PM) forms the core of our service offering and keeps your system running in peak condition and assists in meeting regulatory compliance. The PM forms the core of our service offering. PM maximizes performance and minimizes downtime by preventing problems before they occur. Preventative Maintenance: Ensures the quality of your results through replacement of critical components and extensive Extends the life of your system Enables traceability via visit records Replacement of all components subject to wear 7

8 GE Healthcare Life Sciences - your partner for the future With an emphasis on quality and lifecycle management, CBS has delivered more than 2000 systems and 8000 columns worldwide to a wide range of biotechnology and biopharmaceutical companies for a wide range of applications. In addition, GE Healthcare Life Sciences Validation Services has supplied validation documentation to more than 4500 of these projects. Manufacturing sites that have used CBS equipment and validated them with the support of GE Healthcare Life Sciences Validation Services, have been audited numerous times by the FDA and other inspection agencies. We can ensure efficient C&Q and ongoing verifications of your equipment to fulfill current regulations, interpretations of regulations, and compliance, with documentation support throughout the entire lifecycle. Our focus is on supplying our customers with high quality equipment, controlled project management, and lifecycle management, all based on customer needs and in line with current regulatory requirements. Strong customer relationships have always been central to our work and are the main impetus for our focused project teams here at CBS. We develop new solutions together with our customers and GAMP guidance visualizes the need for strong customer collaboration in the future. For local office contact information, visit GE Healthcare Bio-Sciences AB Björkgatan Uppsala Sweden imagination at work GE, imagination at work, and GE monogram are trademark of General Electric Company. ÄKTA, ÄKTAcrossflow, ÄKTApilot, ÄKTAprocess, AxiChrom, BioProcess, UNICORN, and UniFlux are trademarks of GE Healthcare companies. All third party trademarks are the property of their respective owners General Electric Company All rights reserved First published Feb All goods and services are sold subject to the terms and conditions of sale of the company within GE Healthcare which supplies them. A copy of these terms and conditions is available on request. Contact your local GE Healthcare representative for the most current information. GE Healthcare UK Limited, Amersham Place, Little Chalfont, Buckinghamshire, HP7 9NA UK GE Healthcare Europe, GmbH Munzinger Strasse 5, D Freiburg Germany GE Healthcare Bio-Sciences Corp. 800 Centennial Avenue, P.O. Box 1327, Piscataway, NJ USA GE Healthcare Japan Corp. Sanken Bldg., , Hyakunincho, Shinjuku-ku, Tokyo Japan AA 02/2011