Hello Everybody,
We use 99% IPA and 70 % IPA for cleaning our equipments. I was of he opinion that as IPA is a VOLATILE material we do not need to test for IPA residue after cleaning.
But now I have been advised to test for IPA residue. Can anyone advice whether how to test and sample for IPA residue and what should be our criteria?
Thank You.
i would think that would show up on a toc (total organic carbon)- are you able to do toc testing on your equipment?
IPA or 2-propanol is a known USP class III residual solvent. As will all residual solvents the amount that could be contained within a product must be monitored and maintained below acceptable levels. The previous post is correct you could perform a swab and get a TOC result, but that will not quantitate the known amount of IPA present. You may have to perform a GC assay on the residue of IPA to quantitate an amount to document that you are below permissible levels. For class III residual solvents the product cannot have more than 5000ppm or less the 0.5%. It is possible as IPA becomes a vapor it can be absorbed into your product.
Dear Mr. Karan Shah,
For your information even 99% IPA will leave some residue behind on equipment surfaces.
I have to agree with kingjw1, isopropyl alcohol is a Class 3 solvent. As per ICH Q3C Guideline – “Impurities: Guideline for Residual Solvents,” Class 3 solvents are considered as solvents with low toxic potential and such solvents have Permitted daily exposure (PDE) of 50 mg or more per day.
Before going into detail of how to test and sample IPA residues, first you need to develop an acceptance criterion (i.e. how much amount of IPA is considered acceptable to be carried over to next product). For which you may use the following formula:
CV acceptance criterion = (ADI x Batch size of next product x Swab area) / (Maximum daily dose of next product x Product contact surface area)
The above formula is the modification of formula used for Dose criterion, where (0.001*Minimum daily dose) is replaced by ADI (acceptable daily intake) value. The formula mentioned above is only for swab samples, you can modify it to derive limits for rinse samples. The ADI value for Isopropanol is 2.4 mg/kg bw/day (reference:
) i.e. 2.4 x 70 = 168 mg/person (70 kg is the body weight for a normal person you may change it as per your country’s regulations). Determine the acceptance criterion by using ADI = 168 mg/person in the formula mentioned earlier.
You may collect swab or rinse sample from the equipment surfaces and analyze the collected samples using Gas Chromatography to determine the content of IPA. Compare the results with the acceptance criteria to derive a conclusion.
Thanks.
Ovais
Thank You so much guys. That was very helpful…
Hello, we are currently using ethanol for disinfection at the end of the cleaning sequence! should we still need to develp acceptance criterion for this solvent and collect and analyse samples?
Thank you in advance for your reply.
Kind Regards,
Marina
Validation Scientist
If you are using ethanol to disinfect surfaces which have direct contact with product, you will have to follow route as mentioned, i.e. establish acceptance criterion, develop analytical method, collect and analyze samples.
Regards,