Abstract

In this era of competition quality has been given prime magnitude; failure to meet such quality allied goals produces massive shift of company in share of market. In this context pharmaceutical industry is utmost regulated industry as it is governed by authoritative regulatory bodies. “Quality could be planned and most of quality deficit arises in the way process is planned and developed”, this thought of well known quality expert Joseph Moses Juran gives foundation to the concept of quality by design (QbD). USFDA launched a pilot programme in 2005 to permit participating firms a prospect to submit chemistry, manufacturing, and controls (CMC) of NDA information representing application of QbD. Now USFDA is accelerating QbD drive by making warning to generic manufacturers from January 2013. QbD has its perspectives to contribute the drug design, development, and manufacture of high-quality drug products. In the present review basic consideration of the QbD approach, its historical background, and regulatory needs are discussed. In detail explanation of elements of QbD i.e. method intent, design of experiment, and risk assessment is given. Application of QbD to pharmaceutical and biopharmaceutical processes, development and unit operation associated with it are briefly mentioned. Detail account of QbD to analytical technique is explained thoroughly by referencing examples. Commerially available chromatography optimization software, DryLab was used to perform computer simulations.

Highlights:

• New trends in chromatographic method development.
• Recent developments in chromatographic screening, modeling and knowledge management.
• Evolution of strategies for pharmaceutical method development in SFC and HPLC.
• DryLab was the first software for the modeling and simulation of reversed phase HPLC separations.
• The future outlook for improved method development algorithms and intelligent systems.

A platform analytical quality by design approach for methods development is presented in this paper. This approach is not limited just to method development following the same logical Analytical quality by design (AQbD) process, it is also exploited across a range of applications in method development with commonality in equipment and procedures. As demonstrated by the development process of 3 methods, the systematic approach strategy offers a thorough understanding of the method scientific strength. The knowledge gained from the UHPLC-UV peptide mapping method can be easily transferred to the UHPLC–MS oxidation method and the UHPLC-UV C-terminal heterogeneity methods of the same protein.

Using the DryLab simulation, the cost saving was tremendous. It shortened the method development time from the typical 1-3 months to about 1 week. Importantly, the unknown factors in chromatography became more predictable. The direct cost saving involved labor, consumable, and instrument time. Even more significant were the lateral benefits, as the productivity of scientists could be increased by multiple factors.