Stability studies calibration methods

Another aspect of traceability of the results is the linkage of data from the homogeneity study, the stability study, and the characterization study of the reference material. In order to establish this link, the coordinator must be in the position to demonstrate that the results of these three studies have a common reference. Such a reference can be a calibrant, reference material, or possibly some realization by means of a suitable method. If such a common reference is not available, it is impossible to link the data sets, and therefore it is impossible to translate the results from the homogeneity and stability studies to the characterization of the material. 

In addition to the direct absorbance methods, colorimetric methods are suited for relatively pure proteins as purification progresses. They are accurate if calibrated from a standard curve of the test protein reference sample and fast if automated. However, they are not as simple to perform as direct absorbance methods. Hence they are not as suitable for production as direct absorbance methods. The relative simplicity of colorimetric methods makes them more suited to automated formulation and stability studies and total-protein assays of complex mixtures. Microtiter plate versions of colorimetric assays allow for automation and consumption of relatively small sample sizes while requiring little specialized equipment or training. 

All stability studies on clinical trial materials must be carried out in full accordance with cGMPs, even if a research department carries out the studies. All studies must be carried out by adequately trained personnel under adequate work conditions. The personnel must use properly qualified and calibrated stability chambers, instruments, reagents, and standards. They must follow validated analytical methods and approved written procedures, and they must properly document all work. There must be proper sample and data traceability, change control, and go on. 

In summary, official German analytical methods for pesticide residues are always validated in several laboratories. These inter-laboratory studies avoid the acceptance of methods which cannot readily be reproduced in further laboratories and they do improve the ruggedness of analytical procedures applied. The recently introduced calibration with standards in matrix improves the trueness of the reported recovery data. Other aspects of validation (sample processing, analyte stability, extraction efficiency) are not considered. 

Residue study protocols typically either include quality specifications for analytical procedures or refer to a written analytical method that includes such specifications. The protocol for an LSMBS should also include analytical quality specifications, either directly or by reference to a method. Analytical specifications usually include minimum and maximum recovery of analyte from fortified control samples, minimum number of such fortifications per set of samples, minimum linearity in calibration, minimum stability of response to injection of calibration solutions, and limits of quantitation and of detection. 

The underlying calibration procedure of a newly developed analytical method has to be examined by basic validation studies to determine the reliability of the method and its efficiency in comparison with traditional methods. In order to ensure long-term stability, it is necessary to perform revalidations, which can be combined with the use of quality control charts, over meaningful time periods. 

Wang et al. studied the stability of nimodipine by HPLC, using beclomethazone dipropionate as an internal standard [33]. The method used a stainless steel column (25 cm x 4 mm) containing YWG C18H37, which was eluted at a flow rate of 1 mL/min) with methanol-water-ethyl ether (35 15 4). Detection was effected at 238 nm. The calibration graph... 

No final answer can be given to this question, for similar cases are also known in wet chemistry (for example, the Pack Analyzer ACA of DuPont de Nemours). Here, too, the apparatus or method is calibrated once for every batch and is rechecked daily or at regular intervals by means of the quality control sample. The system of dry chemistry can be viewed under the same aspect. The Ektachem system is known to be stable for more than 6 months, so that the apparatus or method need not be readjusted during this period but only supervised via quality control checks. The problem of calibration does not arise with Reflotron, since all the requisite data (calibration data) are stored on the reverse of the test slides. No data, however, are available on long-term studies of stability. The FDA has prescribed a 7-day or 30-day calibration rhythm for the Seralyzer system depending on the analyte to be analysed. 

The selection of reference materials is therefore critical in validating the performance of an analytical method (see Chapter 1). CRMs should be used at least in the initial evaluation studies and in establishing the acceptability of calibrators used in routine service. The specific characteristics of calibrators should be documented, along with the number of different concentrations of calibrating solutions and the frequency of their use. These latter choices depend on the characteristics of tlie analytical method, particularly the stability, reproducibility, and linearity. 

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