Problems in setting Limits for Cleaning Validation

Hi all, I would like to ask advice in regards to setting limits for Cleaning Validation.

The cleanliness limits I will be taking into consideration is that “the amount of residue in the equipment after cleaning will be less than 20ppm of the following batch”.

In this case would it be possible to take 20ppm for each equipment and hence have a total ppm value for all the installations[i.e. the whole line] ?

This way when calculating the swab limits I was planning on using the total ppm value and the toal surface area for the whole line. i.e.

Swab Limit = Total MACOppm/ Total Installation surface area.

Any suggestions or advice would be much appreciated. Thanks :slight_smile:

what type of equipment are you cleaning?

Hey, so the site mainly deals with Non-sterile production of Penicillin APIs. The equipment im working with a mostly reacotrs, silos, hoppers, dryers etc etc all 316L Stainless steel. The cleaning agents applied are Process water and 20% Sodium Hydroxide solution.

Here’s how I developed a cleaning process for a manufacturing filling line.

  1. Establish procedures for the cleaning/washing process. Procedures included washing for 5 minutes, purging the line, and restarting another cycle. My main consideration was minimizing concentrations of quaternary ammonium compounds (QAC) throughout the equipment.

  2. Determine sampling points on the filling line. I sampled from each of the filling heads and the tanks that feed in to the filler.

  3. I conducted FIVE 5 minute wash cycles and collected samples after each cycle. I observed QAC concentrations to determine where the concentrations leveled off (i.e. stopped decreasing or decreased past the sensitivity of my measurement system). Take pH, osmolality, and conductivity measurements and see if there are statistically significant correlations that can characterize “clean”.

  4. Established the number of wash cycles based on results of step 3). Wash cycles required = 4.

  5. Conduct Cleaning Process Validation. After manufacturing filled a worst-case product (highest QAC conc.) conduct sample collection for 4 wash cycles. Since results of cleaning processes are mostly homogeneous I claim to establish ABSOLUTE confidence in the capability of the cleaning process after 3 successful wash cycles.

There is one caveat. The QAC measuring method must pass a Measurement System Analysis in order to claim the 3 wash cycle conclusion.

I hope this helps.

Hey Imperium,

Thanks for all the pointers, they will definitely help me out when Im setting up my Validation protocols. Would have liked some more infor on Swabbing limits and calculations though, but im sure ill stumble on something in the document you posted. Cheers