Application of quality by design to the development of analytical separation methods

Abstract

Recent pharmaceutical regulatory documents have stressed the critical importance of applying quality by design (QbD) principles for in-depth process understanding to ensure that product quality is built in by design. This article outlines the application of QbD concepts to the development of analytical separation methods, for example chromatography and capillary electrophoresis. QbD tools, for example risk assessment and design of experiments, enable enhanced quality to be integrated into the analytical method, enabling earlier understanding and identification of variables affecting method performance. A QbD guide is described, from identification of quality target product profile to definition of control strategy, emphasizing the main differences from the traditional quality by testing (QbT) approach. The different ways several authors have treated single QbD steps of method development are reviewed and compared. In a final section on outlook, attention is focused on general issues which have arisen from the surveyed literature, and on the need to change the researcher's mindset from the QbT to QbD approach as an important analytical trend for the near future.

Uncovering interaction by QbD in Optimization of Stability-indicating HPLC Method for Simultaneous Estimation of Low Dose Aspirin and Lansoprazole

“…6b. Battu and Pottabathini reported a new impurity, 7-(3-methyl-4-(2,2,2-trifluoroethoxy) pyridin-2-yl)-7H-benzo [4,5]imidazo [2,1b]benzo [4,5] imidazo [2,1-d]- [1,3,5]thiadiazine formed in harsh basic conditions [28] . DP-3(L), DP-4(A), DP-6(L) and DP-8(L), were formed in basic hydrolysis.…”

“…Even though International Conference on Harmonization (ICH Q8 R2) guidelines do not discuss analytical method development in correlation with design space, it is implicit that the concept can be utilized to analytical design space and continuous improvement in method understanding [1] . A number of excellent articles appeared in the literature [2][3][4][5][6][7][8] that described strategies for the application of QbD principles to chromatographic method development. The work presented in this article addressed key steps of AQbD with special focus on method optimization.…”

A quality by design (QbD) case study on enteric-coated pellets: Screening of critical variables and establishment of design space at laboratory scale

“…Once the DS is established, the validation becomes an exercise to demonstrate that the process will deliver a product of acceptable quality when operating within the DS [20]. No current regulatory document provides guidelines on how to estimate the DS level [19] and no new concept exists to implement a control strategy in the pharmaceutical industry [21]. Within our approach, basing on the initial risk assessment and DS, a CS created with all the eight factors was involved.…”

“…Thus, the validity of the model was established and the formulation variables and process parameters were robust within the control space. In QbD, robustness estimation is moved into method optimization for the definition of DS to ensure the CQAs values which were deduced from any working inside the DS are acceptable [19]. Once the DS is established, the validation becomes an exercise to demonstrate that the process will deliver a product of acceptable quality when operating within the DS [20].…”

Application of Design of Experiment and Simulation Methods in Liquid Chromatography Analysis of Topical HIV Microbicides Stampidine and HI443

“…The design of experiment is now getting much attention in analytical method development [1–4]. The US Food and Drug Administration (FDA) and the International Conference on Harmonization (ICH) guidelines (Q8, Q9 and Q10) recommend the use of the design of experiment approach in analytical methods development [5–8].…”