Change about Chromatographic column

Chromatographic column
Good morning
Manufacturing Unit would implement a change about chromatographic column of purification production department. The change consists on adding resin (the same type of resine) to have more performance in terms of kilos of production of drug substance.
I must manage this change control as Quality Assurance, so I ask you to help me about all activities to do and to check; for example:
Type of change (major, minor)
Is it necessary re-qualification of column?..If it is yes, what are the technician parameters I must control?

I know that resin is one of the most important component of a chromatographic column, from which can depend trend of elution and consequently process production. Is it correct?
Do you think that it will be necessary a new validation of down stream process?

Thank you in advance to you

This question was answered by us many months back and it is in Biotechnology section.
You need to qualify the column incase if change
Hieght of column
Any change from normal columns to Radial columns
Normal coloumns to Pre frabricated or Disposable columns

You need to analyse the packing charecterestics and elution profiles.

Every thing should be qualified and this attracts a change control. After this you need to validate the whole process once again and put this procedure in manufacturing.


Thank you very much Durga
I read it in biotechnology section sometime ago but I didn’t remember it.
On the basis of you suggest me, I think that the change must be considered a majior change, because it has impact on process of manufacturing; moreover, if it is so, the change should be notified to the Agency of regulation (FDA … and AIFA for Italy).
I would like to know your opinion about this.

thank you in advance

It is really a big change. The reasons are listed below
-Elution profile might change
-Protein peaks might change (Peak = A+B–This change leads to tailing and that results in dilution)
-The cleaning process might change with RESIN change or Increase in Hieght of bed or even volume of bed.
-The over all loading changes and you need to have a repeatability of a proper loading of column and proper integrity test.

Normally if you keep the hieght constant the HETP (Hieght equavalent to Theoritical Plates) will remain constant and all parameters would be with in specified limits. But the fact remains how robust is that bed? And how big that change of either Bed volme Vs protein concentration and Bed volume Vs output protein peak volume?

That means during elution do you get same quality, quantity (in volume and in concentration when a peak is eluted) and how good or bad the extraneous-undesired -DNA/ GENETIC materials are removed from column and in over all how many volumes of wash.
Is this process economical in large volumes as we know buffer solution are very expensive to get prepared.
How good is the plug flow or Linear flow rate in relation with HETP? CM cube per hour. (Volumetric flow rates do not really sit in the stability of the column so Linear flow rates are to be considered).

Looking all these facts both FDA and AIFA (Wing of EMEA) will consider this as a Major change.


OK …thank you Durga
I think to understand … there are a few aspects I must consider, but I have the only last question.
Can this change to challenge into question the analytical methods (in process control and finished product - release of drug substance) validated for the current down stream process?

Thank you so much for your suggestions I believe always very usefuls.

Yes ofcourse.
If the quality of the particular Drug Product and or Drug substance (API) is dependent upon the parametric release by a praticular method of cHromatography in analytical scale, any change there of to the Software, Materials, Concentration, Buffers, Elution patterns or Binding materials need to be qualified by a change.
This change is also measured interms of risks.
All these changes must be controlled and validated.
This applies Downstream purification as well as a parametric release test.