Method transfer troubleshooting

Experience with CE method transfer in the biotech/pharmaceutical industry over the past 10—20 years has demonstrated that training is a key element that requires special attention for CE methods. A training video with troubleshooting examples can be very useful. Tips and hints should also be shared during the method transfer process. Other key elements for a successful transfer include selection of the proper testing strategy and assay acceptance criteria. 

A new topic is now included Chapter 20 about quahty assurance. Part of it could be found before in chapter 19 but now the subject is presented much broadly and independent of Analytical HPLC . Two chapters in the appendix were updated and expanded by Bruno E. Lendi, namely the ones about the instrument test (now chapter 25) and troubleshooting (now chapter 26). Some new sections were created 1.7, comparison of HPLC with capillary electrophoresis 2.11, how to obtain peak capacity 8.7, van Deemter curves and other coherences 11.3, hydrophilic interaction chromatography 17.2, method transfer 18.4, comprehensive two-dimensional HPLC 23.3, fast separations at 1000 bar 23.5, HPLC with superheated water. In addition, many details were improved and numerous references added. 

When issues arise with the performance of the method during the transfer, troubleshooting should be coordinated through both teams (sending and receiving labs). Troubleshooting guidelines are discussed subsequently. 

As part of the process of method transfer and troubleshooting methods, the production of some form of checklist or aide-memoire of historical issues should be... 

The level 3 method is used until synthetic routes and formulations have been finalized and forced degradation and preliminary stability studies have been conducted i.e., until the components that need to be separated in the final DS and in the final DP have been clearly determined. At this juncture, the focus shifts to the development of fast, robust and transferable final methods to be used for primary stability studies and post-approval analyses. Freqnently, separate methods are developed for DS and DP since the goals of each method are different (see Section I). Orthogonal methods continue to be of importance to troubleshoot any questions that may arise during the subsequent life cycle of the drug. 

As in any scientific document, one must provide a rationale for the parameters chosen and their effect on the overall success of the transfer. This includes an explanation for the system suitability parameters that have been established for the method. System suitability can be a powerful tool for troubleshooting method discrepancies in addition to being a test of the conformance of the system to a set of parameters before analysis. 

Method failures can, of course, occur at any stage in the progression from transfer to validation to sample testing. Therefore, the troubleshooting process discussed in this chapter applies to any of these stages. 

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