Cleaning Validation for Solvents used in the manufacturing process

Hi all,

Should we assess for the solvents used in the manufacturing process, eg Toluene. Should limits be calculated using maco - or how should I go about setting limits for Solvent Levels.

Dear dancetoes,

in my opinion you should assess for the solvents used in the manufacturing process, especially less volatile solvents like Toluene. A good starting point to set acceptance levels would be ICH Q3C and USP <467>.

Best regards


I think u should use cleaning solvent which is already used in the process or select solvent which have low toxicity value and your product is highly soluble. This would b helping to control solvent traces from product

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Avoid class I and II residual solvents as defined in USP <467>. Carryover acceptance limits are calculated using the ADE (acceptable daily exposure). This applies to solvents that are used as cleaning agents, since residues may be present in the drug product.

The best cleaning solution is made up of your process stream (if possible) without cleaning agents.
Next best is process fluid with cleaning agents
Worst is using a cleaning solution which is different than normal process fluid (it sounds like this is the process you have).

That being said, there is a calculation using LD50 to determine allowable caryover limit (mACO) to test for cleaning agents which are not part of your normal process…

Google LD50 Cleaning Validation, and you’ll get a bunch of hits.