CEX Chromatography and QbD

I was going through my previous posts on the media selection process last night while listening the to the Bruins game.  Those last two minutes were heartbreaking. Anyways, using the augmenting process to build up a body of knowledge for the model led to a different conclusion than that proposed by the authors despite using the same data set.  Which is more correct?  What's the best way to process a CCD data set?  I'm a big proponent of starting simple and then adding complexity.  With a CCD data set, I'll start with the full-factorial model to identify the statistically significant effects.  From there, the addition of center points allows a check for curvature.  If there's none, then the analysis is complete!  If the center points are in alignment with the full-factorial model, including the axial components becomes an important step in identifying what's driving higher order behavior.  Last, tying the results back to the underlying chemistry will become a vital link when writing up the work for archiving.  Being able to have traceability and sound scientific understanding of process behavior is SO important when the time comes from authoring the IND or, if you're lucky, the BLA.

The next article of merit is from Genor Biopharma in Shanghai.  The authors take an integrated approach to developing a cation exchange step using QbD principles.  One of their first steps is to define a fish-bone diagram of the factors affecting the process.  JMP allows you to do this quite easily as a quick sketch up of the process.

Start by making a two-column file in JMP (see below).  In this case, I've labeled them Parent and Child to make it easy to remember the order.  In every case, the child belongs to the parent and this would be repeated until you had all the children accounted for each parent in your process.

Setting up for a Fishbone diagram

In my version of JMP, I go to Graph and then diagram:

Next, put the categories into the appropriate placing within the GUI

and the result follows!

I like these diagrams throughout the design process.  They provide an easy reference for the preliminary FMEA that prioritizes the experiments and for documenting along the way which has the greatest impact on the process.

In the next posting, I'll take a deeper look at their QbD approach.