Looking for guidance on approach for container closure integrity testing for a new device. The device stores HCT at -80c. I don't currently have access to Biological SME's in cryopreservation, but it seems through cursory research that microbial pathogen hazards are present within low temperature freezers or Liquid Nitrogen freezers.
USP<1207> states that deterministic test methods should be used to assess CCI. Given the intended use environment, Laser Headspace analysis would be the ideal method of analysis. With this said, Laser Headspace and other deterministic methods are going to identify leaks below 10um. This is a very very high bar which I'm nervous about from a practical perspective.
It seems that other devices have used combinations of Dye Ingress, bubble, and Microbial Challenge as a validation method. However, these are both probabilistic test methods and don't really challenge down to the leak sizes noted in USP (although Microbial Challenge would).
For those that may have more practical experience here, does FDA still consider probabilistic methods valid? If a combination of these methods can illustrate sterility under extremely hazardous conditions would it be fair to assume this validation technique would be accepted?
USP<1207> states that deterministic test methods should be used to assess CCI. Given the intended use environment, Laser Headspace analysis would be the ideal method of analysis. With this said, Laser Headspace and other deterministic methods are going to identify leaks below 10um. This is a very very high bar which I'm nervous about from a practical perspective.
It seems that other devices have used combinations of Dye Ingress, bubble, and Microbial Challenge as a validation method. However, these are both probabilistic test methods and don't really challenge down to the leak sizes noted in USP (although Microbial Challenge would).
For those that may have more practical experience here, does FDA still consider probabilistic methods valid? If a combination of these methods can illustrate sterility under extremely hazardous conditions would it be fair to assume this validation technique would be accepted?
