In a lot of bioreactor contamination investigations, the root cause is never found, that is: the cause of bioreactor contamination is not conclusively determined.
This is quite disappointing in a cGMP environment because the way problems get fixed is that you find the root cause, the technical folk propose a solution, you write it up in a CAPA and push it through the "change implementation team" and you never have to deal with that problem again.
But if root cause is never found, there is no corrective action; there certainly is no preventative action and the chain reaction of cGMP improvement never takes place.
One reason the true the proverbial smoking gun is never found is because there are too many other "smoldering guns" at the crime scene. As they say of a theory that cannot be confirmed, but also cannot be denied on Discovery Channel's show Mythbusters, "It's plausible."
One reason these plausible sterility risks exist was because you didn't know about them. (if so, call me).
Another reason these plausible sterility risks exist was because they weren't worth fixing because the system wasn't "broke." You had bigger fish to fry and it's hard justifying that precious budget dollars should be spent on a system that was "working" fine.
That reasoning works until you get back-to-back contaminations and your biotech manufacturing plant is perceived to be out-of-control.
Now, you're staring down a laundry list of potential causes, all of which are plausible, many of the solvable, none of which you can cross off your list as the true root cause.
Which gets me to the point of this missive. You're not going to be mired in contamination for your entire career. You're going to have periods of success. All the sterility risks you can address during that time will ensure that your periods of failure in the future are short-lived.
This is quite disappointing in a cGMP environment because the way problems get fixed is that you find the root cause, the technical folk propose a solution, you write it up in a CAPA and push it through the "change implementation team" and you never have to deal with that problem again.
But if root cause is never found, there is no corrective action; there certainly is no preventative action and the chain reaction of cGMP improvement never takes place.
One reason the true the proverbial smoking gun is never found is because there are too many other "smoldering guns" at the crime scene. As they say of a theory that cannot be confirmed, but also cannot be denied on Discovery Channel's show Mythbusters, "It's plausible."- It is plausible to tilt your system to be more susceptible to contamination after you've sent thousands of liters of untreated, un-decontaminated cell culture down the drain.
- It is plausible that floor drains with no air-breaks are the source of your microbial contaminations.
- It is plausible that after several dozen pure cultures that the status-quo valve sequence on your feed-delivery line was pulling a vacuum and that sucks non-sterile fluid into your bioreactor.
- It is plausible that misaligned or misfit elastomers was the sterility breach that failed to keep out microbial contaminants.
- It is plausible that you were using the wrong type of steam for sterilization.
One reason these plausible sterility risks exist was because you didn't know about them. (if so, call me).
Another reason these plausible sterility risks exist was because they weren't worth fixing because the system wasn't "broke." You had bigger fish to fry and it's hard justifying that precious budget dollars should be spent on a system that was "working" fine.
That reasoning works until you get back-to-back contaminations and your biotech manufacturing plant is perceived to be out-of-control.
Now, you're staring down a laundry list of potential causes, all of which are plausible, many of the solvable, none of which you can cross off your list as the true root cause.
Which gets me to the point of this missive. You're not going to be mired in contamination for your entire career. You're going to have periods of success. All the sterility risks you can address during that time will ensure that your periods of failure in the future are short-lived.
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