Validation Hardware

There were no written standard operating procedures for, but not limited to, system validation, hardware and software change control, revalidation,... [FDA Warning Letter]... 

Test rim of the equipment (+ documentation) i=> Computer validation (hardware/software) if the analytical equipment is electronically controlled => Training of suitable operators (h- documentation)... 

Step (6) can be broken down as given in Table 2.7. If the hardware and its operation is under control, and some experience with similar problems is available, experiments need only be carried out late in the selection process to prove/disprove the viability of a tentative protocol. Laboratory work will earnestly begin with the optimization of instrumental parameters, and will continue with validation. In following such a simulation procedure, days and weeks of costly lab work can be replaced by hours or days of desk work. 

Validations fall into two types prospective and retrospective. In prospective validation (see flow chart in Figure 2) the validation is done in a sequential manner, involving installation qualification and operational qualification (IQ/OQ) of equipment (e.g., chromatography instrumentation or column hardware). Appropriate calibrations accompany the IQ/OQ. Process qualification, or PQ, involves formal review and approval of a PQ protocol, execution of this protocol, and issuance of a formal PQ report which includes data analysis and recommendations (i.e., approval/certification of the process). If the process is not approved, the report may recommend a redesign or redoing of the validation protocol and, in some cases, a return of the process to process development for further optimization. 

The computerized systems, both hardware and software, that form part of the GLP study should comply with the requirements of the principles of GLP. This relates to the development, validation, operation and maintenance of the system. Validation means that tests have been carried out to demonstrate that the system is fit for its intended purpose. Like any other validation, this will be the use of objective evidence to confirm that the pre-set requirements for the system have been met. There will be a number of different types of computer system, ranging from personal computers and programmable analytical instruments to a laboratory information management system (LIMS). The extent of validation depends on the impact the system has on product quality, safety and record integrity. A risk-based approach can be used to assess the extent of validation required, focusing effort on critical areas. A computerized analytical system in a QC laboratory requires full validation (equipment qualification) with clear boundaries set on its range of operation because this has a high... 

For incompressible flow in a horizontal pipe of constant diameter and without fittings or valves show that the pressure is a linear function of pipe length. What other assumptions are required for this result Is this result valid for nonhorizontal pipes How will the presence of fittings, valves, and other hardware affect this result ... 

For the application of biomolecular NMR in the process of hit identification and hit validation, four important components have to be optimized (i) supply of the target molecule, (ii) selection of ligands, (iii) hardware for automated sample preparation and high-sensitivity measurements, and (iv) software tools for automated data evaluation. 

For the first time in the history of chemical sciences, theoretical predictions have achieved the level of reliability that allows them to rival experimental measurements in accuracy on a routine basis. Only a decade ago, such a statement would be valid only with severe qualifications as high-level quantum-chemical calculations were feasible only for molecules composed of a few atoms. Improvements in both hardware performance and the level of sophistication of electronic structure methods have contributed equally to this impressive progress that has taken place only recently. 

The change control SOP warrants particular attention. This procedure should clearly spell out how any deviations in instrument operation/per-formance, and hardware/firmware/software updates are to be handled and documented. It should also make clear what distinguishes routine maintenance, minor vs. major changes and what the procedural differences should be. The change control procedure may be a specific SOP, as part of an HPLC system s validation plan, or as part of the corporate validation master plan (VMP) that is established within each company. 

Note As is often the case, the HPLC system will be under computer control, which is likely to be part of a data-handling system. Since the data generated from the OQ hardware tests typically require chromatographic data handling, the data-handling software should be validated beforehand. The data-handlingfLC control software installation and IQ/OQ implementation, which are not addressed in this chapter, may take a considerable amount of time. This is often the case since this process typically involves an initial client/server implementation. 

The LC control software, either stand-alone or as part of an overall data-handling system, should be tested by means of a separate OQ protocol. This protocol only needs to address the communica-tions/control integrity of the hardware (e.g., setting up a run/sequence with the proper instrument parameters, the ability to start and stop the pump, etc.). It should cover all the required instrument control functions listed as part of the protocol s functional specifications. It does not need to include specific hardware performance testing, such as linearity or flow rate. The latter tests are performed separately, as part of the individual hardware validation described below. 

This chapter will address the validation of the hardware and will not specifically address the validation of the data-handling software as this is beyond the intended scope. 

For the purposes of presentation, the velocity held is usually presented at regular intervals. This new scheme is very efficient and incorporates a vector validation procedure, making it independent of operator intervention. The time it takes to compute a vector field depends on the computer hardware and it ranges from 350 mesh points per second on a PC 150 MHz Pentium to 1400 mesh points per second on a 200-megahertz dual Pro. 

System Suitability System suitability refers to the validation of all components of an analysis system taken as a unit, a "system." For example, the analysis of an environmental water for pesticide residue involves a "method," which includes sampling (must represent the water in question), sample handling (e.g., what container is appropriate), sample preparation (perhaps an extraction process that includes the glassware, technique, timing, etc.), standards preparation (pipets, flasks, technique, etc.), injection technique, the instrument, and data handling (computer hardware and soft-... 

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