I am from non-sterile API mfg industry.
My current methodology for CV is like this:
- Cleaning solvent is suggested by R&D.
- Cleaning quantities are defined based on experience ( X litres per square meter)
- Product changeover cleaning procedure is applied between batch to batch during validation batches.
- During these 3 runs of cleaning (after every PV batch), equipment are cleaned till result passes.
- Once all 3 runs are completed, cleaning procedure and quantities are fixed.
Is this approach acceptable for regulatory auditors?
There is no proof that the cleaning solvents and thus your cleaning procedure are effective. This must be science based. In fact some of them could proscribed residual solvents (OVIs). Check USP <624?>.
The cleaning acceptance criteria (carryover) MUST be based on the molecule’s toxicity or ADE (acceptable daily exposure).
Thanks for your response.
My concern is related to cleaning process confirmation, but not the limits. Limits are being established based on ADE only.
In general, Good! However, remember it is the ‘cleaning procedure’ and its effectiveness that is being evaluated and the analytical method is the yardstick. Be sure the cleaning procedure is effective and is science based. The only method to develop a cleaning procedure I have seen is:
- Dry, then weigh the tared weight of 3 stainless steel coupons.
- Spike the coupons with a known and accurate weight of formulation (~100 mg). Air dry.
- Dip the coupons into a solution of the cleaning solvents 50 times using a USP disintegration apparatus
- Gently rinse the coupons with distilled and deionized water.
- Dry, then weigh the coupons.
- Is there any formulation still left? It should be <1% of the original spiked mass.
- Be sure no Class I or II proscribed residual solvents are used. See USP section <467> for list. It does not make sense to contaminate your manufacturing process train.
I am not agree with your point no 4 & 5 because when you r validating cleaning method at a time of validation cleaning method shold be complete. Cleaned till result passes is not acceptable at all (which is described in ppint no 4).
Also described in point no. 5 that three runs are completed , cleaning quantities and runs are fixed is not acceptable because u are here validating pre-established cleaning method . Once you successfully validate it will be implemented at shop floor with scientific evidence that your cleaning method is efficient to remove contamination up to acceptable level. I suggest first prepare proper cleaning method , once you get confidence you start process validation &cleaning validation parallaly. Other points 1,2,3 are ok