Can we use IR spectrometer for performing extractables test in sterilizing filtration?
Only as a screening method (maybe). It does not have the required sensitivity or ability to quantitate ppb.
If IR did not detect any new substance, that means that filter did not extract any substance to filtrate.Am I right?
No. It could also mean that the concentration is below your detection limit. Remember, weak radiation gives a weak response. IR is used at the expected concentration of 100’s of ppm or %.
For confirmation run a standard and a sample that has been spiked with the expected concentration.
I run sample before filtration and after filtration, according to PDA Technical Report #26.About detection limit: HPLC also has it detection limit and extractable can be below detection level of HPLC method.It is a circle with less and less detection limits.I think that if according to EP for identification of materials we used IR, it is enough sensitive.
Arzakan,
Perhaps, you have enough sensitivity, but it depends on your sample and the required detection limit.
HPLC has a sensitivity that depends on the detector. For instance PDA is about ppb, while MS is ppt or ppq.
Boomer_Chemist,
As our IR has enough sensitivity according to EP, it means that I can use it for exractable test.If the degree of compliance is 100% or 1,000 between before filtration and after filtration I have not any extracted substances in filtrate from filter.
OK. But why filter if it is interfering with the method? Try centrifugation in order to ‘clean-up’ the sample.
For aseptic filling of drugs according to USP 1229.4 and PDA Technical Report #26 companies have to perform validation of sterilizing filtration of liquids.
Damn! Now I see what you are trying to do. You are trying to duplicate the manufacturing process.
Your API could be filtered out because it is not dissolved (I assume you’re using a 0.22 um filter) OR the filter media collects the API. In the 1st case confirm that the API is dissolved (optical density at 650 nm). In the 2nd case, change the type of filter.
Be sure compounding tank is commissioned and qualified (IQ/OQ/PQ). I presume a ‘dye’ test has been performed in the OQ (operational qualification).
We performed all tests.Our FPs are water solutions and our API’s are dissolved.We use 0.22 um filters for sterilizing filtration.
You may have to reformulate. Most of our parenterals (my former life) were formulated in dilute acetic acid.
Our’s in water for injection.
We used USP water for injection too. But we also acidified all the API’s sidegroups so they could not interact with the filter media. To ensure sterility we also Tyndallized (a form of thermal sterilization) the vials too.
So you are using a sterilizing filter to prepare your solution for sterile filling, and you are using WFI water as the diluent. This is pretty common. Your question is about how to perform the extractibles test to ensure the filter itself does not interact with your product. Is that correct?
Yes, you understand my question.Can I do it with IR spectrometer.
I feel a little underqualified to answer this question, but here are a few thoughts.
Extractibles and leechables testing is most applicable to materials which are in contact with the product for a long period of time (think primary containers). If the product does not touch the product for very long, is there as high of a risk? I just did some reading, and the FDA does focus their discussion on packaging/labeling, but there is some discussion among other groups about extractibles and leechables for other components.
Here is a good article about the extractibles of componenets including sterilizing filters. The last few pages discuss analytical methods. IR spectrometer is not listed unfortunately. So it might still be possible, just not listed here.
I know I didn’t conclusively answer your question, but hopefully the article helps somewhat.
http://www.biophorum.com/user_uploads/extractables-protocol.pdf
1 Like
Thanks
One last thought. I believe (I’m not sure though) that we had the filter manufacturer do extractibles testing for us (in a past job). You might want to just pay the filter manufacturer to do the testing, if they do that sort of thing. They might have the methods developed already.
If you sign a CDA (confidentiality disclosure agreement) you might be able to get a list of the extractables and leachables from the filter manufacturer. The actual concentrations in your case you may have to contract out to lab that is capable (QA audited…).