Designated laboratories acceptable performance

Within CEN TC 275, a distinct protocol for the conduct of inter-laboratory method validation trials is not selected or required, but it is recommended to apply ISO 5725 or the ISO/International Union for Pure and Applied Chemistry (lUPAC) harmonized protocol. " In the past, results of several national and international interlaboratory trials had been accepted. Nevertheless, the following fundamental aspects of the harmonized protocol for the design of method-performance studies should be fulfilled ... 

The procedure must provide adequate detail so that a designated laboratory can reproduce the method without deviation. The validation report includes the experimental design and the data that justify the conclusion that the analytical method performs as intended. Minimum acceptable performance criteria must also be defined in the report. 

Recalling that at its First Session the Conference of the States Parties adopted the Criteria for the designation of laboratories by the OPCW (C-I/DEC.61), the Criteria for acceptable performance of laboratories in proficiency testing (C-I/DEC.62), and the Criteria for the conduct of OPCW/PTS proficiency testing (C-I/DEC.65, all dated 22 May 1997) ... 

DQ is performed by the supplier of the equipment or system at the supplier s factory as part of the factory acceptance test (FAT). IQ (based on site acceptance test—SAT), OQ, and PQ are performed on-site at the GMP facility. For a GMP manufacturing facility, the validation activities include the facility design, FTVAC system, environment control, laboratory and production equipment, water system, gases and utilities, cleaning, and analytical methods. Validation protocols (IQ, QQ, and PQ) are prepared for each item, listing all critical steps and acceptance criteria. Deviations are reviewed and resolved before the validation activity proceeds to the next phase. 

Although petroleum refiners are not unfamiliar with questions of thermal stability of petroleum products, jet fuel stability requirements (stable in the range 400—500°F) presented a new set of problems. One of the first things to be done was to define limits of acceptable stability. Such limits naturally would depend upon individual engine design and the environment to which the fuel is exposed. Fuels meeting one set of conditions could conceivably fail to meet another set. The solution devise some sort of laboratory test that would correlate with actual engine performance... 

The information in this chapter applies specifically to the first element sample preparation. The sample preparation steps are usually the most tedious and labor-intensive part of an analysis. By automating the sample preparation, a significant improvement in efficiency can be achieved. It is important to make sure that (1) suitable instrument qualification has been concluded successfully before initiation of automated sample preparation validation [2], (2) the operational reliability of the automated workstation is acceptable, (3) the analyte measurement procedure has been optimized (e.g., LC run conditions), and (4) appropriate training in use of the instrument has been provided to the operator(s). The equipment used to perform automated sample preparation can be purchased as off-the-shelf units that are precustomized, or it can be built by the laboratory in conjunction with a vendor (custom-designed system). Off-the-shelf workstations for fully automated dissolution testing, automated assay, and content uniformity testing are available from a variety of suppliers, such as Zymark (www.zymark.com) and Sotax (www.sotax.com). These workstations are very well represented in the pharmaceutical industry and are all based on the same functional requirements and basic principles. 

For a computer system in an analytical laboratory, OQ can mean, for example, verifying correct communication between the computer and other hardware. As part of the product documentation, vendors should provide operating procedures for the tests, limits for acceptance criteria, and recommendations in case these criteria cannot be met. The documentation should also include algorithms for critical calculations and procedures on how to verify the algorithms in a user s environment. If the user finds the tests recommended by the vendor inappropriate or insufficient, the user can design and perform other or additional tests. 

In order to more easily design and ultimately interpret the results of a validation study, it is important to define two factors that define the reliability of an alternative method before the study starts. These factors are reproducibility and predictive capability of the alternative method. It is of critical importance that these performance factors are clearly stated before a validation study starts. When these performance characteristics are defined beforehand, they provide critical information needed to design the study so that it includes the appropriate number of laboratories, an acceptable set of test substances, and the appropriate range of toxicity. They also provide benchmarks that can be used to set the criteria that an alternative method must meet in order to be considered reliable. If the data obtained from the study meet or exceed these predefined performance criteria, then it confirms that the alternative method performs as described by its developers. If the method fails to perform at a level equivalent to the criteria set at the start of the study, then its performance cannot be confirmed. 

Unmanned satellite laboratories are a possible alternative to a central laboratory facility. To demonstrate the practicality of such an approach, investigators at the University of Virginia have developed remote automated laboratory systems- (RALS) designed to automate POCT in hospital intensive care units. The results from the analytical instruments in each RALS are sent to a central monitoring workstation several floors away from the satellite laboratory by a network interface, where results are viewed and either accepted or rejected by a trained medical technologist before being released for clinical use. Error codes built into the analytical instruments are also passed to the main laboratory by the computer netw ork. Technologists in the control center can also shut down the satellite laboratory when necessary, as in the case of instrument failure. Patient information is downloaded from the hospital information system in real time so that users can select their patients and the tests to perform from a fist presented on the computer touchscreen. 

---