Tuesday, May 7, 2013

Play-by-play of Microbial Contamination Response

As indicated in a previous post, the classic sign of contamination observed in your dissolved oxygen (dO2) trends.

But how does this play out in real-life?

In my experience, the front-lines are the ones detecting contamination.  Your operator is typically the first person to see alarms on the HMI.

For cell cultures, they're going to see that the dissolved oxygen (dO2) is at 0%.  That pH has also "crashed" to a low number.

In response to these signals, the dO2 controller is max'ed out at 100%, and the pH controller has the peristaltic pump for sodium carbonate (alkali solution) spinning.

The operator (probably on a walkie-talkie) calls out to the front-line technical support group, such as manufacturing sciences campaign support group, to verify; at which point, they'll pull up a trend on PI and see something like this on the dO2 trend:
dissolved oxygen contamination

If the trends look like a contamination, he can recommend that the bioreactor contamination response SOP be executed.


Hemocytometer
courtesy of Jacopo Werther
The bioreactor contamination response starts with pulling a sample and verifying under a hemocytometer as well as sending the sample to QC.

Most quality control have a microbiology department with guys who run the validated tests for detecting contamination or bioburden.

If foreign microbes are confirmed in the samples, the bioreactor decontamination response is executed to inactivate the microbes and send them to the waste-kill pit.

The contamination response SOP also mobilizes all the relevant departments: Production, QA, Manufacturing Sciences, QC, Facilities.  All for one of those politically-savvy contamination meetings.

No one likes having to go to one because these meetings are a huge bummer.  The company just produced scrap.  A bioreactor is out of commission.  And your workload just increased for this "non-routine" item.

From here, you pick your favorite root-cause analysis tool and run through the system.

Our experience is that this tends to work if your contaminations aren't back-to-back.   Biotech firms can endure the sporadic contaminations, but if you start getting back-to-back contaminations, faith in the existing contamination response goes out the window and people start looking for 3rd-party consultants.

You call your network,  you search the internet,  and you end up reading blog posts by some company that's trying to sell their contamination consulting services.  You might check LinkedIn to see if you have any connections in common.

You might download a microbial contamination case study and see if they've solved some tough problems.

Then, you might want to call them, but when you do, you can't say too much until you get a non-disclosure agreement going.

After that, you're free to send them information while they prepare a quote for services.

They come in, see things you haven't seen, write up a report, and boo-yah, life is good again.  At least that's how it goes if the third-party consultant is Zymergi.



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