| | | Finding #4: The raw material sampling and testing program is inadequate. Specifically:
a. ______________ supplied by (insert vendor here) has never been sampled and there is no assurance that the manufacturer can consistently provide material meeting specifications. The solution is ____________ from the vendor and is ___________ cell culture bioreactors. Deviations 18-081U and 18-163U were initiated due to contamination in the production bioreactors. In both cases, probable root causes included the _______ addition assembly _____bag, line, and valve). Testing of an unused _____ bag in inventory also resulted in a positive sample.
b. Product-contact ___________ and __________used during cell culture of the _________are not tested for bioburden.
My comments: that’s a lot of redaction. I will try to make sense of this but no guarantees I’m on target here. Here, the FDA is saying sampling and testing programs to ensure incoming materials are safe and at a level of cleanliness that’s required possibly as an input to downstream processes’ validations.
a. Something that an outside vendor provides to IMMU has never been sampled (tested) and there’s no assurance they can consistently provide material meeting specs. I’m guessing some kind of solution is provided by the vendor and is critical somehow to cell culture bioreactors. Seems like there were some deviations to some validations or product lots due to contamination in those bioreactors. I think the FDA goes on to claim that the containers that the vendor supplies their solution in are what they suspect the root cause of the contamination was. Yep, testing one of the bags in inventory resulted in a positive (read: contaminated) sample.
Ladies and gentlemen, this is not good. You always inspect incoming goods from a vendor because were you there when they made their product they’re delivering to you? NO. So do you know if it’s actually meeting your required specifications? NO. IMMU has made no effort to sample in the past according to the FDA and you know what? Turns out, the vendor’s products are dirty. IMMU was caught with its quality pants down.
To me, this shows that IMMU isn’t focusing on incoming quality of product and as you know: trash in, trash out. The FDA is concerned that trash is getting into IMMU’s bioreactors and creating product that could be dirty since IMMU’s other procedures are filled with gaps as to what to do when products are OUT OF SPEC (OOS). Honestly, the more I read the complaints, the more I put my FDA hat on and say “there’s no way I’m letting these guys sell intravenous (I assume) product.” It’s too risky! Sure, the first lots could be safe, but how long before we get our first IMMU-caused infection and death if we let these guys keep running the show the way they do? This stuff would never fly at my company. We have yet to see an FDA pre-approval denial.
b. Stuff that contacts product during cell culture are not tested for bioburden. Oh man, then how do you know if you’re not introducing bioburden during testing and inducing false alarms? Then you have to go and maybe wish to retest (see my previous post on finding 3 to understand this joke).
This shows carelessness on the part of the testing staff and procedure writers. Again, if I were the FDA and I find this in one place, who knows what other loose-y goose-y things they’re doing elsewhere that I just haven’t had time to find yet. All that to say, I’m less likely to approve.
As it stands right now, with 4 months away from PDUFA, FDA man has got to be having some serious doubts that a company can turn this around in 4 months. There are a lot of inefficiencies in getting stuff like this addressed fully. Think: writing new and GOOD procedure, validating and verifying the changes work through testing, approving the changes cross-functionally, training the staff, etc. It’s a lot of work. Mind you, after these changes are implemented, the FDA still needs to come back and verify. Do you think this got done in 4 months? Probably not.
In a way, I’m glad IMMU got hit with the CRL because if this is what they’re doing 4 months away from primetime, they’re not ready yet. They will come out from this experience a better, more professional company, but really…I think they either need to get some new quality consultants, ones that can really crack the whip and know what they’re doing, or they should sell and let a bigger Biopharm fix this mess with their experience. I don’t want to offend any of my consultant readers out there because I know you guys are the exception to my experience but just so you know...very few consultants have been “up to snuff” in my experience and they don’t really care about your outcome because they’re paid by the hour. Maybe IMMU got a bad batch that reported to Pehl and co. that everything was gravy. |
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