Stability testing attributes evaluated

Specifications set for each test attribute should be evaluated at each test point. Specifications can be set for release of the product and for shelf life as discussed in ICH guidelines Q6A and Q6B. The shelf life of the product is determined by all available stability information. Justifiable differences between shelf life and release acceptance criteria are appropriate. 

Test attributes procedures and acceptance criteria selection of batches testing frequency storage containers, conditions, and period, as well as data evaluation are discussed in great detail. Data evaluation considers out-of-specification results. Documentation covers protocols and protocol amendments, deviation reports, out-of-specification reports, test results and raw data, and stability reports. 

A flow diagram on how to analyze and evaluate longterm stability data for appropriate quantitative test attributes from a study with a multifactor full or reduced design is provided in Appendix A. The statistical method used for data analysis should consider the stability study design to provide a valid statistical inference for the estimated retest period or shelf fife. 

Where such reprocessing occurs, written process change procedures should be approved by the quality control unit that clearly specify the conditions and limitations of repeating chemical reactions. In addition, the procedures should establish how this type of reprocessing will be evaluated, and what additional tests will be conducted on the reprocessed material to show that the resulting material is of a purity and quality comparable to that normally produced by the process. These tests should include, as appropriate, purity, impurity profiles, stability testing on initial reprocessed tots, and testing for physical attributes. 

Physical testing encompasses a wide range of techniques, from visual examination to spectroscopy. It is often the physical attributes which the patient or practitioner can evaluate prior to administration. For example, a particle found in a parenteral formulation can foretell the presence of a new chemical degradant found during stability studies. Many of the procedures in this chapter are performed routinely as part of release or stability testing of API or pharmaceutical products. 

We note that the calculation of At/ will depend primarily on local information about solute-solvent interactions i.c., the magnitude of A U is of molecular order. An accurate determination of this partition function is therefore possible based on the molecular details of the solution in the vicinity of the solute. The success of the test-particle method can be attributed to this property. A second feature of these relations, apparent in Eq. (4), is the evaluation of solute conformational stability in solution by separately calculating the equilibrium distribution of solute conformations for an isolated molecule and the solvent response to this distribution. This evaluation will likewise depend on primarily local interactions between the solute and solvent. For macromolecular solutes, simple physical approximations involving only partially hydrated solutes might be sufficient. 

Various dry powder attributes are assessed at release and on stability. These include physieal eharaeteristies sueh as appearance, content uniformity, delivered dose uniformity, and partiele size distribution. Chemieal attributes that may be assessed include drug eontent, purity, and identity, as well as the water content. Dry powders may also undergo mieroseopie evaluation for foreign particulate matter, unusual agglomeration, and partiele size. Mierobial limits should also be examined, including the total aerobie, yeast, and mold eounts. The presence of specific pathogens should be ruled out. The dry powders may be dissolved to test for pH. 

A systematic approach should be adopted in the presentation and evaluation of the stability information, incorporating, as appropriate, results from the physical, chemical, biological, and microbiological tests, including particular attributes of the dosage form (e.g., dissolution rate for solid oral dosage forms). 

Stability data (not only assay but also degradation products and other attributes as appropriate) should be evaluated using generally accepted statistical methods. The time at which the 95% one-sided confidence limit intersects the acceptable specification limit is usually determined. If statistical tests on the slopes of the regression lines and the zero-time intercepts for the individual batches show that batch-to-batch variability is small (e.g., p values for the level of significance of rejection are more than 0.25), data may be combined into one overall estimate. If the data show very little degradation and variability and it is apparent from visual inspection that the proposed expiration dating eriod will be met, formal statistical analysis may not be necessary. 

Characterization, as it applies to catalyst science, is usually used to describe both the performance characteristics (evaluation) and the physical attributes (analyses) of the materials under investigation. Personnel involved in catalyst evaluation utilize custom designed equipment to determine the performance of a catalyst in a particular process. The design of the equipment typically follows that of the process, but on a much smaller laboratory scale. These simulations attempt to "mimic" the process, or parts of the process, and as such the data generated are relative not only to the process but to the test equipment and conditions (see Dartzenburg). Conversion, activity, stability, abrasion resistance, crush strength, etc. are terms often encountered in evaluation. Analysis, on the other hand, describes or measures the physical quantities of size or mat-... 

The primary objective of method validation is to provide a high degree of assurance that the specified method consistently provides accurate test results that evaluate a product against its defined specification and quality attributes (Chapter 12). The regulations require that validation data be available to establish that the analytical procedures used in testing meet proper standards of accuracy and reliability. All analytical procedures require some form of validation, regardless of whether the method is used for stability, in-process analysis, release, or acceptance. Most of the discussions focus on the validation of HPLC methods using assay and purity determinations nevertheless, fundamentals of the approach can be applied to most method validation activities. 

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