Validation operation control

The output of the FMEA analysis is paramount to the determination of the business risk (consequence of function failure) presented by a system. This risk is used to determine the level of rigor applied to the validation, operational control, maintenance, and documentation/information needed to verify and maintain system performance as indicated by Figure 31.5. It follows that the documentation/information supporting system functions is as critical to the pharmaceutical organization as the system function itself. 

Validation, operation, maintenance, security, change control, back-ip... 

Bioreactor operation and scale-up are not completely independent processes and should be assessed as different aspects of the same problem. Bioreactor operation must then consider process scale-up not only as the next step but also, as in the classic scale-down method, as a starting point. This means that bioreaction design should be done in scalable systems. A scalable system has to be inherently simple and reliable in operation and control, for easy validation and control in a production facility [56]. 

Air supply systems must be designed to avoid the introduction of contaminants into air flows or into manufacturing areas local environmental conditions and associated risk factors. Air supply systems must be validated, operated, monitored, and controlled to deliver the required air quality. 

I strongly believe that the facility s technical management and staff should read the procedures to ensure that particular needs are addressed with reference to operational control within the organization and individual countries regulatory requirements. It is, however, guaranteed to provide management with a tool to develop a set of validation SOPs in order to support the road map established for the on-time successful start-up of the facility operation in compliance with the GMP requirement. 

The first step toward validation is to establish a recordkeeping system that considers all aspects of the manufacturing process, including controls (or testing). A recordkeeping system must be established, if it does not exist already, to provide written records for the validation operations to be conducted. In order to duplicate a favorable result and prevent duplication of an unfavorable result, we must document the operations performed so that we have records that we can review, interpret, and pass judgment on. We cannot rely on memory and word of mouth. The system of recordkeeping has multiple facets. 

Computer systems that are identified as requiring validation must be included in the site validation master plan. A validation master plan is typically used as a high-level plan for the site or processes and systems that make up the facility GMP operations. The plan should outline the scope of the validation program, controls to be adopted, and how activities are to be conducted, documented, reviewed, approved, and reported. Target completion dates should be included for validation work in each area. 

The design, development, and system build phases need to deliver computer systems and services in a manner that facilitates effective and efficient system validation, operation, maintenance, modification, and upgrade. This applies to both stand-alone and embedded process control computer systems (see Sec. VI). 

Most firms today use a validation change control system, by which such documents as engineering work orders, revisions to standard operating procedures (SOPs), and proposed formulation order changes are reviewed by a committee of the same disciplines as those responsible for validation approvals. The objectives are to determine the potential impact on validation status before formally approving the change. This mechanism enables a firm to take immediate prospective action, obviating the need to revalidate the entire system. 

Systems should be in place to control changes and evaluate the extent of revalidation that the changes would necessitate. The extent of revalidation will depend upon the change s nature, scope, and potential impact on a validated system and established operating conditions. Changes that cause the system to operate outside of previously validated operating limits would be particularly significant. 

Premises Expression system defined Process scalability Primary definition of process No validation Refinement of operational control parameters Development of scale-down process models for validation Process out-of-limit definition Finalization of process control parameters Fixed and defined process and products Pivotal process validation and characterization studies Validated production process Well-characterized product Robust process ... 

How can validation and control of the blending operation be correlated to in-process testing of the dosage unit in production ... 

Tikhonov s theorem (Theorem 2.1) indicates a further requirement that must be fulfilled by the controllers in the fast time scale in order for the time-scale decomposition developed above to remain valid, these controllers must ensure the exponential stability of the fast dynamics. From a practical point of view, this is an intuitive requirement one cannot expect stability and control performance at the process level if the operation of the process units is not stable. 

Typically, colloidal suspensions are deposited on polycarbonate filters immediately following sampling to reduce post-collection precipitation or aggregation artifacts and mimic the operational procedures used to define dissolved and particulate sample components. Obviously, a well-dispersed dilute sample should be used to avoid artifactual particle overlap. Filter sections are then mounted on SEM stubs and carbon or metal coated (Au/Pd) for compositional analysis and micrographic imaging, respectively. The tedious nature of operator controlled analysis of particulate samples in the SEM and the TEM has often precluded the acquisition of statistically valid information regarding suspension composition. 

The object of loop testing is to ensure that all instmmentation components in a loop are in full operational order when connected together and are in a state ready for process commissioning and validation (Operational Qualification [OQ] and Performance Qnalification PA2])- Loop testing also encompasses the integration of instrumentation with any associated compnterized control systems. 

Until recentiy, infrastructure compliance was not a signihcant regulatory issue however recent inspections have indicated the importance of developing and maintaining a compliant Tf infrastructure. Regulatory observations of noncompliance to date are on the themes of validation and the role of QA, network documentation, and operational controls. 

All computerised systems used for the generation, measurement or assessment of data intended for regulatory submission should be developed, validated, operated and maintained in ways which are compliant with the GLP Principles. Appropriate controls for security and system integrity must also be adequately addressed during the whole life cycle of any computerised system. 

Instrumental and technical factors equipment within specification, working correctly, properly calibrated, procedures established for operational control and calibration, traceability of measurement to the criteria for test validity. 

Such operating lines exist for all multi-port PFRs. There is no requirement that idealized conditions, such as adiabatic or isothermal, be present during reactor operation. Therefore the data from a TS-PFR need not be gathered under idealized operating conditions in order to construct valid operating lines from which rates can be calculated. This greatly simplifies the temperature control requirements in TSR operation and makes the TS-PFR relatively simple to build. 

GP02-A5. 2006. Laboratory documents development and control, 5th ed. Approved guideline. GP19-A2. 2003. Laboratory instruments and data management systems Design of software user interfaces and end-user software systems validation, operation and monitoring, 2nd ed. Approved guideline. 

Sub-Contracting The execution by an independent person or organization, the contract acceptor, of an operations or verification for another person or organization, the contract giver. Validation Operations intended to demonstrate that every process, procedure and equipment used in the manufacturing, packaging or control of a product actually leads to the expected results. 

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