Hold time studies in cleaning validation

GOOD VALIDATION PRACTICE (cGVP) CLEANING VALIDATION
1

Hello there,

I am performing hold time study for filter bag of fluid bed dryer. In the previous study, my ex-colleagues concluded that the clean hold time is 15 days. I am new to cleaning validation and this makes me confused:

  • What is the strategy for conducting the clean hold time study? I mean which day(s) should be selected to sampling? I see some companies choose days 1st, 3rd, 7th and 15th, but I really don’t know what is the basic of these selection.
  • What if the test results show the presence of microorganism in the day 7th and their absence in the day 15th? If we conclude that the clean hold time is 15 days, then we manufacture drugs in the day 10th, how can we assure that our products will not be contaminated?

Thank you for take the time to look into my matter.

Best regards,

Tri

2

I see you have stepped on a ‘landmine’ in cleaning validation!

  1. There is no general answer to your question. It depends on the stability of the molecule, effectiveness of your cleaning procedure… Generally, I use 4 days or a long weekend when production is terminated when the equipment is not totally cleaned.

  2. The answer depends on your drug product! It may have or not a microbial specification. Some microbes cannot tolerate exposure to air for a long time (they are called facultative anaerobes), some are spores and only germinate or become vegetative under ideal conditions, some die but generate toxic endotoxins (thus the LAL test).

  3. There is no 100% assurance that your drug products are not contaminated. Thus, the purpose of validation (it comes close).