Automated Test Demonstration

The transducer qualification tests demonstrated that the sensors were highly sensitive, that they could withstand sharp temperature changes and that there was little change in sensitivity between 20 and 110°C. The sensors were used successfully to demonstrate that there were no cracks in the hangers. The inspection was performed to detect flaws at 1/20 of the thickness probed. The inspection required development of automated inspection facilities adapted to the characteristics of the different examined zones. 

As an initial (demonstration) application of the Icon/1000 control system, we automated two simultaneous acrylic lab polymerizations. In this application, heaters, agitators, and metering pumps are controlled. A batch proceeds automatically from state to state unless the operator intervenes through one of a series of color CRT touch screens allowing him to take complete manual control of the batch for as long as he desires. All important process variables are continually monitored and recorded. The entire control scheme was created, tested, and modified several times in the space of two months, without formal instruction, by a chemical engineer with little previous programming experience and no previous experience at all with this system. 

The final step of method development is validation of the HPLC method. Optimisation of chromatographic selectivity [110], performance verification testing of HPLC equipment [591], validation of computerised LC systems [592] and validation of analysis results using HPLC-PDA [34] were reported. The feasibility of automated validation of HPLC methods has been demonstrated [593]. Interlaboratory transfer of HPLC methods has been described [594]. 

Commercial application of the dendrimer-based reagent technology has been demonstrated by the successful development of The Stratus CS STAT fluorometric analyzer [5] marketed by Dade Behring Inc. This rapid automated point of care immunoassay system provides quantitative analysis of whole blood or preprocessed plasma samples via unit use assay test packs. Up to four test packs can be introduced for each sample. All reagents [5-9] required for specimen analyses are contained within the test packs. 

Validation of automated systems must demonstrate a lack of contamination or interference that might result from automated transfer, cleaning, or solution preparations procedures. Equivalency between the results generated from the manual method and the data generated from the automated system should be demonstrated. Since sensitivity to automated dissolution testing may be formulation related, qualification and validation of automated dissolution equipment needs to be established on a product-by-product basis (8,13) (see also Chapter 12 for a more detailed description of automation issues). 

Use of unusual automated methods of analysis, although desirable for control testing, may lead to delay in regulatory methods validation because the FDA laboratories must assemble and validate the system before running samples. To avoid this delay, applicants may demonstrate the equivalency of the automated procedure to that of a manual method based on the same chemistry. ... 

The USP 24 General Notices state that alternative methods may be used to determine that products comply with the pharmacopoeial standards for the advantages in accuracy, sensitivity, precision, selectivity, adaptability to automation or computerized data reduction, or any other special circumstances. Such alternative or automated methods shall be validated However, when disputed, the compendial method is conclusive as it is the official or referee test. In addition, USP Chapter (61) Microbial Limit Tests states that automated methods may be substituted provided they are validated and give equivalent or better results, whereas USP Chapter (71) Sterility Tests states that alternative procedures may be employed to demonstrate that an article is sterile, provided the results obtained are at least of equivalent reliability. 

Filters are sometimes derived from test cargo calibration runs to optimize the explosive detection. The PFNA detection algorithm can be totally automated but previous demonstrations (prior to the 2005 Ysleta Port of Entry testing) have used operator intervention to evaluate the basic scan alarm regions before a directed scan is made of the selected basic scan alarm regions. 

Robustness. Examples of typical possible sources of variation in automated methods are homogenization speed, homogenization time, age of sample, accuracy of solvent dispense, and temperature variation. If all studies described in the method development have been performed, the robustness of the sample preparation has been demonstrated and does not require additional testing. Parameters in relation to the measurement technique may need to be considered and are covered in the relevant chapter. 

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