Has someone used 500 ppb TOC as an acceptance criteria?
Can you share your experience with it?, how do you exposed it in an auditory?.
Thanks you so much
Yes, we do, and there was no question.
But currently, I’m not sure, altought I think it depends. If the problem is that you are no able to reach your limit because it’s under 500ppb, I think it would be right but you have to adjust your results to the values of your water the day you have taken the measure. It means: you have obtained a data of 300ppb of your cleaning and the wfi that day is on 40ppb, its obviously that you have more C than the water and it would be possible that you have to justify the difference.
If you have take that limit because it is not a direct contact equipment, I think it is ok.
If anyone responds you, he can help me too! So, thanks in advance!
I think criterion 500ppb TOC is an interim control prior to define acceptance limit for cleaning validation.
In FDA Inspector guideline, the arbitrary limit Inspectors would use is 10ppm.
We calculated the limit based on the risk-assessment from FMEA approach, considering the whole equipment exposed surface in our plant (worst-case). The results was 0.22 micrograms of C per cmq.
We collect samples from 10x10 cm surface and dilute the recovered material in 25 mL of low TOC water. The average TOC for water is about 20 ppb; we validated the method and calculated an average swab contribute to TOC of about 70 ppb. In this condition our theoretical limit of acceptance for TOC is 880 ppb.
Dear all I have a query
If toc limit increase in the wfi then what are the probable causes?
Plz help me out to know
500 ppb is only for WFI water. It has no relation to the toxicity of the molecule which is often >1 ppm TOC. Thus, imposing this limit has no scientific rationale!
We are a vaccine manufacturing facility, and currently use a 500ppb default acceptance criteria. The reason being that our “product” does not have a “toxicity” value. We correct / adjust for the TOC contributed by the WFI & swab by taking a negative control.
We have presented this several times to regulatory authorities with no negative feedback.
The 500pbb is overly restrictive in my opinion, and we are developing a rationale for a more approriate acceptance criteria based on historical data & the nature of our vaccine products.
The regulators will have no comment especially if you are too restrictive! If you are a vaccine manufacturer (ug protein/injection) go strictly by PDA technical report #49.
If you are a small molecule manufacturer you have to involve toxicity (ADE) in your carryover calculations. Biologicals are yet to be determined. But remember, Botox is an analog of Clostridium A Botulinum neurotoxin!