A quality by design approach to impurity method development for atomoxetine hydrochloride (LY139603)

Development of Quality-By-Design Analytical Methods

“…Similar generalized approaches to QbD analytical method development have been proposed and described. 13,16 …”

“…[8][9][10][11][12] The method goal concept can be illustrated using HPLC as an example. 8,13 The goal of an HPLC method for API is generally to separate and quantify the main compound and the critical quality attribute (CQA) impurities that may impact the quality of the drug product. This must be achieved while meeting method performance criteria based on regulatory requirements, such as specificity, linearity, accuracy, precision, sensitivity, robustness, and ruggedness.…”

“…For example, during robustness studies for an atomoxetine hydrochloride HPLC impurity profile method, it was found that resolution of the impurities of interest followed the same trend when method parameters such as n-propanol and temperature were varied. 13 As a result, an early eluting impurity pair was chosen for system suitability and became a convenient method control strategy because the two compounds involved were easily obtained. In certain cases, the system suitability test may need to be augmented with additional controls to properly manage risk.…”

“…7 The QbD concept can be extended to analytical methods. [8][9][10][11][12][13][14][15][16][17][18][19] This paper summarizes the current state of QbD as applied to the development of analytical methods small-molecule pharmaceutical process development, including synthesis of the active pharmaceutical ingredient (API) and formulation, and biopharmaceutical process development. In this section, we introduce the principles of QbD and briefly review the overall status of QbD in the pharmaceutical industry to illustrate the position that analytical QbD occupies in this paradigm.…”

Implementation of Quality by Design for the Development and Validation of Pioglitazone Hydrochloride by RP-UPLC with Application to Formulated Forms

“…It has become an important paradigm in the pharmaceutical industry since its introduction by the US Food and Drug Administration [3][4][5][6][7]. The QbD concept can be extended to analytical methods [8][9][10][11][12][13][14][15]. The analytical methods used for the analysis of active pharmaceutical ingredients (API) and drug products are an integral part of the QbD.…”