Environment/Operation Life Cycle

All regulatory agencies adopt what amounts to a life cycle approach to developmental and operational control of computerized equipment, with emphasis on documentation of software development and quahty management especially in GLP environments. The life cycle for analytical instruments from the user s perspective includes the purchasing phase (including system/vendor qualification), the IQ, OQ and PQ phases of AIQ (Section 9.5.1a), the maintenance phase and, fmaEy, the retirement phase, which probably occurs more frequently with respect to computers and software than the analytical instruments... 

Life-cycle analysis, in principle, allows an objective and complete view of the impact of processes and products on the environment. For a manufacturer, life-cycle analysis requires an acceptance of responsibility for the impact of manufacturing in total. This means not just the manufacturers operations and the disposal of waste created by those operations but also those of raw materials suppliers and product users. 

Life Cycle Assessment - An Operational Guideline to the ISO Standards (2001) Ministry of Housing, Spatial Planning and the Environment and Centre of Environmental Science - Leiden University, The Netherlands. 

Article 3(37) of REACH defines exposure scenarios as the set of conditions, including operational conditions and risk management measures, that describe how the substance is manufactured or used during its life-cycle and how the manufacturer or importer controls, or recommends downstream users to control, exposures of humans and the environment [...] . 

ASSET PROTECTION. Shields intended for intentional detonation are to be designed to prevent damage to buildings, equipment, and other assets in the area. Damage prevention is considered adequate if normal operations are in no way interrupted or hindered as a result of any change to the operational environment from explosions in this type of shield, and the shield may be expected to remain operational throughout its designed life cycle. 

The terms instrument qualification and instrument validation are sometimes used indiscriminately. In this chapter, the term qualification refers to the site preparation and the testing employed to demonstrate that the instrument is properly installed in a suitable environment and the performance meets the predetermined specifications for its intended use. Qualification is a part of the whole validation life cycle. Validation refers to the process to provide assurance that the instrument is suitable for the intended application throughout the lifetime of the instrument. Installation qualification (IQ), operation qualification (OQ), and performance qualification (PQ) are performed to provide evidence that the user requirement specifications (URSs), functional requirement specifications (FRSs), and design qualification (DQs) have been met. The sequence of requirements setting and qualification events as well as the relationships between IQ, OQ, PQ and URS, FRS, and DQ are generally illustrated by the V diagram shown in Figure 2. Installation qualification demonstrates the fulfillment of the DQ. Similarly, OQ demonstrates the fulfillment of the functional requirements and PQ demonstrates the fulfillment of the user requirements. 

To maintain control of the computer system throughout its conception, implementation, and operational use in a GMP environment, it is required that the computer system application must be validated in a way that will establish auditable documented evidence that the computer system does what it is expected to do. As applicable, this needs to be carried out in conjunction with plant equipment to provide a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications and quality attributes. The methodology to achieve this is based on a recognized life-cycle mode. 

Description of process/environment Quality-related critical parameters Purpose and objectives of the system Major benefits of the system Special requirements Specific training needs System operating strategy Related GMP compliance/regulations Physical and logical boundaries System GMP risk assessment System validation rationale Life-cycle documentation Assumptions and prerequisites Limitations and exclusions Quality-related critical parameters/data Standard operating procedures System requirement specification Supplier and system history... 

Qualification is the process of establishing appropriately documented verifications and tests that provide a high level of assurance that a computer system will operate in accordance with predefined specifications. The specific approach to be used for each level of qualification should be outlined in the project validation plan and needs to focus on the critical parameters, data, and functionality of the computer system. While there are no absolute lines to be drawn between qualification testing of a computer system, it is recognized that the qualifications listed below provide the necessary control and continuity throughout the validation life cycle and must be approved for the system to be released for use in the GMP environment. 

As life-cycle qualification activities move to the in situ operating environment a methodical approach for the site calibration of control and monitoring instrumentation is needed to provide suitable calibration and any associated records for the loop instrumentation and regulating devices on critical parameter duty. 

PQ is intended to demonstrate that the process will function correctly in its normal operating environment. The demonstration may involve pilot lots, commercial-scale lots, or carefully designed simulations of either. In the case of drug substances, PQ protocols often involve individual modules (e.g., steps, unit operations) of a new process prior to pilot or commercial scale-up of the full process. When a given critical process parameter cannot be simulated at less than commercial scale, all other process parameters are often established first, to avoid potential interference with the first commercial batch that must involve the sensitive parameter. The three full-size lots required to authorize commercial distribution can, if desired, represent key PQ experiments however, there is no limit to the number of subsequent commercial lots that can also continue to be considered part of the PQ step in a validation life cycle. 

Computer Systems Validation (CSV) The formal assessment and reporting of quality and performance measures for all the life-cycle stages of software and system development, its implementation, qualification and acceptance, operation, modification, requalification, maintenance, and retirement, such that the user has a high level of confidence in the integrity of both the processes executed within the controlling computer system(s), and in those processes controlled by and/or linked to the computer system(s), within the prescribed operating environments) (MCA). 

The chemical safety assessment has to consider the manufacture or preparation of the substance as well as all identified uses. An identified use is a use of a substance or preparation containing it that is intended by a person involved in the supply chain or that is made known to him in writing by an immediate downstream user. The assessment shall consider all stages of the life cycle of the substance resulting from its manufacture and identified uses. The assessment has to be based on a comparison of the potential adverse effects of the substance with the known or reasonably foreseeable exposure of man or the environment, taking into account implemented and recommended risk management measures and operational conditions. 

Apart from the documentation of the life cycle for software, a QA System should be available for the IT system environment and operation. The IT-System environment comprises of the following ... 

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