Hi all.
I have a rationale for the establishment of the swab limit, and I quote from the protocol;
"… currently manufactures … for which normal therapeutic dose is 400 mg per day. According to the FDA guideline1 acceptance criteria for chemical limit test is 1/1000 of daily dose and it is estimated to be 0.04 mg per swab. In order to account for recovery of API from swabs and unavoidable variability in swab sampling; (…)has determined that the acceptance criteria for chemical limit test for all equipment parts is 0.01 mg per swab.
1Validation of Cleaning Processes (7/93): Guide to Inspections Validation of Cleaning Process, FDA"
I am having a hard time finding a correlation between the 400 mg therapeutic dose, the thousandth of the therapeutic dose, and the 0.04mg per swab (without accounting for the “variability in swab sampling”).
Can anyone help?
Take the risk! What’s your opinion? Thanks in advance.
The EMA and FDA are expecting companies to use toxicological and pharmacological data to determine a health-based limit. They are not accepting the 10 ppm or or some fraction of the low clinical dose as a limiting setting method. .EMA just published a draft guidance (the comment period just closed) where they clearly state that 10 ppm and 1/100th of a low clinical dose are not acceptable and toxicological and pharmacological data must be used to set a threshold value. Here is the link
http://www.ema.europa.eu/docs/en_GB/...C500137091.pdf
Until the guidance is issued by the EMA I suggest that you apply the 1/1000th of the daily dose using the following approach - to derive the limit per swab you need to take into account the worst case next product batch size and maximum daily intake; you will also need to take into account the total shared surface area of the equipment parts to give you the limit per cm2 and the limit per swab will be based on the area that you swab.
Limit (per cm2) = (1/1000 x Min Daily Dose of Product A x Batch Size of Product B) / (Max Daily Intake of Product B x Total Surface Area)
Limit per swab = Limit x swab area
Thank you SAWILKINS that is a very informative paper, and the approach is more thorough that the regular MACO evaluation by 1/1000 of the therapeutic dose.
BillyBoy, I had the point of view as you, but I want it a confirmation.
Now, how does FDA takes the regulations of EMA? Is it ok to use an European guideline? Maybe you have some experience with this kind of things.
Thank you SAWILKINS that is a very informative paper, and the approach is more thorough that the regular MACO evaluation by 1/1000 of the therapeutic dose.
BillyBoy, I had the point of view as you, but I want it a confirmation.
Now, how does FDA takes the regulations of EMA? Is it ok to use an European guideline? Maybe you have some experience with this kind of things.