Thursday, July 18, 2013

The Peptone Is NOT Your Root Cause

Cell culture volumetric productivities are low and it's not looking like this campaign is going to make enough product. The Manufacturing Sciences team is on task and they suspect that the new peptone lot is root cause for the low titer but it's hard to say.

And it's hard to say because the one lot of peptone goes into many batches in varying amounts and given the multivariate nature of biological processes, there may be too many interactions to simplify this down to a single variable like peptone lots... but I digress.

Looking at peptone lots vs. cell culture performance is a waste of time unless you are willing to do more than just accept the peptone manufacturer's CofA here's why:

There are two outcomes of this analysis:

Outcome #1: Peptone lots do not correlate with cell culture performance. Which means the root cause of low volumetric productivity lies elsewhere.

Outcome #2: Peptone lots DO correlate with cell culture performance, but given the process is licensed with peptones and given that status-quo peptone vendors are already qualified, there's no obvious action to take (other than maintain the status-quo).

In programming, this logic would look something like:

if ( peptoneLotsImpactCellCulture ) {
} else {

See how the if-then statement is unnecessary? The same goes for analyzing whether or not peptone lots correlate with cell culture performance: the analysis is unnecessary.

Spending resources to solve a problem whose answer does not change what you are going to do is waste.

That said, what if peptone lots happen to diminish cell culture performance? That may be the case, but just because peptone lots diminish cell culture performance does not mean that peptone lots are the root cause. The true root cause in this case is the cell culture process' susceptibility to peptone lots,  or even the use of peptones in the first place. See blog post, "If Kryptonite is the Root Cause, What's the CAPA?"

Waste reduction and variability reduction are core objectives in manufacturing management. And waste reduction includes cutting out the wild-goose-chases for causes that are not in your control.


Anonymous said...

At company x we found that it was a combination of two undefined raw materials - peptone being one. We ended up pulling together a shake flask screening procedure. Because the impact was only to titer, we were able to do raw material screening in the MSAT lab - titers went back up.

OLY said...

Hey, thanks for commenting!

So you found the kryptonite and got rid of it... this time.