Stability-indicating methods development

Case study 1 Stability-indicating method development for dual drug system... 

Further formulation changes, selection, and approvals occur during clinical testing with the intent of developing the proposed product for marketing. Each formulation must have new stability-indicating methods developed for assay and related compound measurement. Stability properties of all products developed for commercialization must be studied and reported in NDA (MAA) or supplemental submissions. 

In addition to online resources, other texts and references have discussed the process of validation for methods used in the pharmaceutical industry in relation to the regulatory guidance documents. These guides include discussions on method development in relation to method validation, the validation of non-chromatographic methods and stability indicating methods. 

To develop an HPLC stability-indicating method for Type I or II dissolution, the linearity must be wide enough, in combination with good sensitivity and minimal interference, to accommodate concentrations from low (possibly LOQ) to very high end, as the samples drawn represent the cumulative drug amount dissolved over time. As for an FiPLC method that is designed for Type VII dissolution, the linearity should accommodate the lower concentrations since it is a drug measurement of a controlled-release system. 

Obviously, the best way to develop a good method is to use all of the information that is available and not to rely solely on available impurities or partially degraded samples. For example, perhaps one or two impurities are available or are present in the drug substance. In this case the best strategy to develop a stability-indicating method is to use these impurities and to also generate partially degraded samples. 

A critical batch or run is one that provides primary support for label claims, indications, safety, efficacy, stability, or method development. 

Eventually, a stability-indicating method needs to be validated and to be included in the IND, IMPD, and NDA. These methods should be rugged and robust and meet all validation requirements at each particular stage of drug development. This method may be used also for content uniformity, and... 

All of the background information discussed in the addendum (Common Functional Groups) will help an analytical chemist with development of a stability-indicating method (SIM) that will assist in the development of an optimized formulation that will become a drug product in the marketplace. Remember, an analytical chemist must be able to provide knowledge, not just data. 

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