we are doing bacteria culturing and get soluble product from its membrane at the end of culture, the production start from flask culture in 1L flask, then scale up to 10L flask, 200L fermentor and finally 3000L fermentor.
we’re going to use TOC as detection method in cleaning validation, if we adopt the 10ppm criteria, what will be the surface area used to calculate the limit of TOC mg/cm^2 or L? do you add up all flask and fermentor area or you do it flask by flask, fermentor by fermentor? I tried the latter one and get different limit, the bigger the vessel, the higher limit will be produced, but I feel the cleaning acceptance criteria should be the same for all product contact equipment, does anyone have the experience in similar situation?
Hello Hanks,
If you select 10 ppm criteria, then MACO = 10 x minimum batch size of the next product / 1,000,000
If your minimum batch size of next product is 500 L (equivalent to 500 kg), Then MACO = 10 x 500 kg/1000000 = 5g
If you are using all 4 flasks for your manufacturing process, you need to sum up the total surface area. Let us assume following values
Equipment - Surface area
1L flask - 300cm2
10L flask - 3000 cm2
200 L fermentor - 60,000 cm2
3000L fermentor - 9,00,000cm2 TOTAL - 9,63,300cm2
Then, your acceptable residue limit (ACR) would be 5g / 9,63,300cm2 = 5.2µg/cm2
I considered 1 mL of rinsing solvent for each 50cm2 of the surface area. Then (click on the following pic to get the calculations)