We are going to start swab method validation for TOC analysis. Our QC lab has a TOC analyzer and it was validated in terms of IOQ and PQ, the low detection limit, linearity, accuracy, precision et al had been established, but all these test were based on water samples, no swab samples were tested.
My questions are:
Do we need to perform all these test again for swab sampling? my understanding is that the previous validation already tell us how reliable the TOC analyzer and the method is, so sample source shouldn’t be an issue.
Is it enough to just perform swab recovery test to demonstrate our current swab method can efficiently remove the residue from the equipment surface?
thanks in advance for any comments and explanations!
You are combining the two different topics, equipment qualification and cleaning validation.
You have already qualified your TOC analyzer. So, no need of further qualification with product.
You need to conduct the recovery studies to prove the effectiveness of your swab sampling
If your recovery is less than 70%, you may need to choose other sampling methods or need to compensate your test results with your recovery factor
Thanks to Veerraju for your comments, I am new in this field, my further question is, in the recovery test, do I only need to apply one concentrations of TOC sample (above the limit of quantitation) on the coupon surface? or I have to try several levels of TOC in the samples?
First, derive the “acceptable residue limit” based on dosage quantity / toxicity data / 10 ppm limit
Then, conduct the swab recovery with same concentration
As per FDA requirement, you need to justify the location of swabbing & solvent (used for extraction from medium) should be justified
our product is from microbial cultures and is water soluble, no data about dosage/toxicity right now. That is why we choose TOC as non-specific measurement, but we are not sure what conc. of TOC should be test. My assumption is like this:
If 10 ppm limit is chosen as acceptance criteria, the total allowable TOC left on the equipment can be calculated as 10 ppm x Max Vol of next batch,
the maximum allowable amount of TOC/area in the equipment is: Total TOC mg /total surface area cm2
so we can apply this amount of TOC to the equipment surface, drying, swab sampling, and analyze amount of TOC recovered.
Please correct me if it is wrong.
thanks a lot for helping.
You are almost right
Even though your product is in liquid form, it contains a solid key ingredient (Ex.: SCDM, Acacia etc)
Consider it as a main contaminant
So, Acceptable residue in Batch = Batch size x (10 mg / 10000000 mg) = A
Here batch size = Quantity of key ingredient in next batch, in milligrams
Then, Acceptable residue in swab area (for each cm2) = A / product contact surface area (cm2) = B
If you are swabbing 10 cm2 area, Then Swab limit = B / 10* volume of the solvent
Here solvent means, quantity of liquid used to extract the contaminant form swab
Thanks a lot for explanations, it helps a lot! It is nice to discuss with you.
Just want to clarify the concept of batch size, in the calculation of MAC, “batch size” means the processing capability of the equipment or the final amount of product from the equipment? For example, I have a 1000L bioreactor, the working volume is 700L, the final product is, let me put at 100g. If a 10 ppm is the acceptance limit after cleaning, does it mean the amount of contaminants should be less than 10 ppm in the next 700 L culture or in the next final product (different product with different harvest, 10g or 50g or unknown).
The total allowed carryover should be calculated on which: 10 ppm x 700 L or 10 ppm x 10g?
10 ppm in final harvest only
Even though you are processing 700 L batch, most of the water / solvent will be evaporated / discarded during the process
MACO is “into the next product”, but not “into the next process”
It is clear now, thank you very much, Veerraju!