1. Terry A. Ring Chemical Engineering University of Utah
AIChE Contest Week 2
Terry A. Ring
Chemical Engineering
University of Utah

2. Questions for the Week
The only reference I was unable to find was the following:
Jagschies, Gunter. “Flexible manufacturing: the new driver in monoclonal antibody process economics.” GE Healthcare Life Sciences Webinar 2009 Feb.
Can you help us find it?
Answer: I also cannot find this 2009 Webinar after a very good look around. Please use the article with a similar title posted in Canvas as a substitute reference, please see BPI_A_..... file.

3. Questions for Week What is loaded vs unloaded velocity?
I answered in error! – Column loaded with protein A would have a different velocity than without loading.
See Below: Velocity at load step can be different than non-load steps.
Load Step: Mab loading
Non-load steps may include: unloading Mab, flushing, regeneration, conditioning (pH adjustment and/or buffer) for Mab

4. Column Load Capacity
Similar to Ion Exchange which you have in your MT book.
Qd= load capacity of column (moles)/gm * column mass (gm)*Mw = [gm of loaded molecule] or
Qd= load capacity of column (moles)/mL * column volume (mL)*Mw = [gm of loaded molecule]
This load capacity can be done in terms of milli equivalents (meq) if more than one site is required for each loaded molecule. Note: that the number of sites per loaded molecule can change depending upon what is being loaded.
Co= loading concentration (gm of loading molecule/L)= Moles/L*Mw

5. Ethylene Diamine Tetra Acetic Acid (EDTA)
4 H+ ions Binding/EDTA =
1 Ca+2 binding/EDTA
1 Metal ion binding/EDTA
4 Na+ binding/EDTA

6. Column Loading Capacity
N = No. of column volumes (VC) for the non-load steps
Actually this needs to be in terms of the total volume of solution for the units to work out. ≈ VC*N
N needs to be the total Volume of all the non-load steps
To condition a column with H+ for example you need to run enough solution through the column so that all of the column load capacity, Qd, has been saturated with H+.
Qd = Volume1*Concentration (H+)[mole/L]*Mw, This is a minimum value! Usually 2x this to be sure.
2*Volume1 is what you would need for this non-load step.

7. CHO cell reactors Where do we get the kinetics of CHO cells?
Answer: See article put up in Canvas
- What are Mab simulation details in the example Mab production simulation we were given as a resource. This includes how to determine a mass stoichiometric equation for biological processes, their growth factor not appearing to be a design spec, and their method for determining the volumes of the reactors.
- What is the limiting condition on bioreactors that tells me when I should transport cells to the next step in the production (for example, is there a max cell concentration that I reach before moving the cells? or max product concentration?)
Answer: Please see the CHO cell kinetics paper that I have put up in canvas for you.  I believe it will answer most of your questions.

8. Follow-up Question
I did read through that article and there is some good information but they ran their experiments until the substrate was eliminated. Particularly for the production reactor this will not be the case as we are maintaining at least X g/L of substrate in the reactors.
Answer: These batch reactor experiments in the reference were used to determine the kinetics of CHO cells.  The data has been reduced into a rate expression with the rate constants given in the paper.  If you want to use this rate expression for a fed batch reactor or plug flow reactor you can do that by using the given kinetic expression and another reactor equation.

9. New Questions?