Baseline Validation

FIGURE 2.12 Typical validation DSC baseline data obtained from ambient to 300°C at 5°C/min. Empty general pans were placed in both the sample and reference positions. Nitrogen purge gas at 25 ml/min. Heat flow and derivative sample temperature (heating rate) plotted against temperature. 

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The FDA also requires evidence revalidation whenever a change is made to the software to determine the extent and impact of the change on the entire software system. Baseline validation will be allowed for low-risk devices. 

Section 3.3 Requirements Baseline Validation. Includes the approach and methods to validate that the requirements baseline established from requirements analysis is both upward and downward traceable to customer expectations, project and enterprise constraints, and external constraints. 

This baseline should include the incremental cost for production created by catastrophic machine failures and other parameters. If they are available or can be obtained, they will help greatly in establishing a valid baseline. 

During the implementation stage of a predictive maintenance program, all classes of machinery should be monitored to establish a valid baseline data set. Full vibration... 

Of all the requirements that have to be fulfilled by a manufacturer, starting with responsibilities and reporting relationships, warehousing practices, service contract policies, airhandUng equipment, etc., only a few of those will be touched upon here that directly relate to the analytical laboratory. Key phrases are underlined or are in italics Acceptance Criteria, Accuracy, Baseline, Calibration, Concentration range. Control samples. Data Clean-Up, Deviation, Error propagation. Error recovery. Interference, Linearity, Noise, Numerical artifact. Precision, Recovery, Reliability, Repeatability, Reproducibility, Ruggedness, Selectivity, Specifications, System Suitability, Validation. 

IF LAB VALUE IS WITHIN 5 DAYS OF DOSING, RETAIN IT AS A VALID BASELINE VALUE. ... 

If the cholesterol measurement is non-missing and was taken within the five days prior to drug dosing, then the cholesterol values are valid values for baseline. Note that because the cholesterol data are sorted chronologically (as mentioned in note 1), the last non-missing value within the five-day window is carried forward in time as... 

The major problem in data reduction is to select the relevant range of data from a chromatogram such as the one shown in Figure 5. We do not limit our data collection process to the data that will actually be used to calculate the distribution parameters because we find that values outside of the range used in data reduction help to characterize baseline drift and provide indications of the validity of the results. 

Ponceau 4R, E-124 and Erythrosine, E-127) using a buffered mobile phase. Separation of dyes was performed in an ODS column (150 X 3.9 mm i.d. particle size 3 pm). Components of the mobile phase were methanol (eluent A) and 0.1 M NaH2P04/Na2HP04 buffer (pH = 7). The gradient elution started with 20 per cent A and reached 100 per cent in 2 min, final hold 4 min. The flow rate was 2 ml/min and dyes were detected at 520 nm. The baseline separation of dyes in 6 min is illustrated in Fig. 3.34. Commercial samples were diluted and injected into the analytical column without any pretreatment. The amounts of dyes found in the samples are compiled in Table 3.20. It was concluded from the good validation parameters that the technique is specific, sensitive, accurate and rapid. Consequently, its application for the determination of these synthetic dyes in drinks was proposed [112],... 

An MEKC method for the determination of ibuprofen, codeine phosphate hemihydrate, their nine potential degradation products, and impurities in a commercial tablet formulation was developed, optimized, and fully validated according to ICH guidelines and submitted to the regulatory authorities. The optimized system containing ACN as organic modifier allowed baseline separation of ibuprofen, codeine, and nine related substances within 12 min. 

Baseline separation of the cephalosporin antibiotic cephradine, its main impurity cephalexin, and other related impurities was achieved by MEKC. The method was validated in compliance with the USP XXII analytical performance parameters and the results were comparable with a validated LC method, depicting CE to be a valuable alternative technique to LC in pharmaceutical quality control. In most cases, the amount of impurities relative to the main compound measured by MEKC is similar to that obtained by LC. However, some reports reveal that there are differences in number and amount of impurities between MEKC and LC analysis. MEKC permitted the determination of seven known and three unknown impurities in cefotaxime and the results were in good agreement with those of LC. ° MEKC yielded a higher amount of the cefotaxime dimer but a lower amount of an unidentified impurity with respect to LC. The differences may be due to the easier formation of the dimer in the aqueous sample solvent used in MEKC compared to the hydroorganic... 

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