Sterile Filtration for Viscous Liquid

GOOD VALIDATION PRACTICE (cGVP) PROCESS VALIDATION
1

Dear all,
Could we use larger pore size (0.45 um) to sterilize by filtration viscous liquid such as propylene glycol?
How do we perform filter integrity test: using water or propylene glycol?
Thanks in advance.

Regards,
Siswanto

2

You have special filters for such viscous products. Pleated filters will serve for these purposes. Such filters are often used to filter Hyaluronic acid which is having approx 144 cps viscosity. In pharma/biotech industries this is known to have highest viscosity as a drug substance. PEG, Anti body formulations and Propylene glycols come in a sequential order to have lesser viscosity.

You cannot filter thru 0.45 micron filter and say that the product is rendered sterile. You need to use a Sterilizing Grade membrane. I do not really bother what terminology manufacturers used to number them in 0.22 MICRONS or 0.1 MICRON.

All you have to ask the filter manufacturer if they have a suitable Sterilizing grade membrane.
When I worked as manufacturing chemist we manufactured Diclofenac sodium Injection using propylene glycol(Soluble base) between 45-50% we used to filter it thru a pleated filter cartridge. It took some time. But product was clean, clear and sterile.

3

yes. you can filter propylene glycol through sterilizing grade filter.
earlier we too used the 0.22 micron, hydrophillic capsule filter in one of our product, having propylene glycol & PEG 400 combination as base vehicle. it was some more time consuming process.
for integrity, if your vehicle is not aqueous based, need to do using propylene glycol.

regards,
Deepa

4

thanks for the info. USP mentioned in <1211> that the pore size should be 0.2 um or less.
which is the most suitable integrity test for viscous liquid?

5

0.2 MICRONS is suitable.It is Sterilizing Grade membrane.
If you go less than this micron size regulators think you have a micoplasma problem in your facility.
You need to justify why you went to 0.1 microns.
Avoid head aches.

6

of course I do not want to use less than 0.2 um pore size filter for this product… :smiley:
among typical use integrity tests: the bubble point test, the diffusive airflow test, the pressure hold test, and the forward flow test, which is the most suitable to be applied for viscous liquid sterile products?