EO Batch Release Your Way to Full Validation

I have had several early-stage device company clients who are interested to get to “First In Man” (FIM) clinical use without breaking the bank. My job is to save the client enough money so they can pay my fee and have money left over for other things (like a great Christmas Party).

If device sterilization is a requirement, you do not need to perform a comprehensive (full) sterilization validation study before FIM. You can ensure adequate sterility assurance on a “batch release” basis, and save the time (and money) needed to perform a full validation.
For ethylene oxide (EO) sterilization of devices with a “nonpyrogenic” label claim, the following sequence of tests and batch releases can be performed to achieve full validation status per ISO 11135-1.
 0. Presterilization Bioburden Enumeration and Extraction Efficiency
1. Clinical Batch Release #1 (maximum load) – fractional cycle + full cycle
– inoculated device sterility testing for FIM-representative devices after fractional cycle
– candidate process challenge device (PCD) sterility testing after fractional cycle
– bioburden resistance testing for FIM-representative devices after fractional cycle
– PCD sterility testing after exposure to full cycle only
– EO residual testing for FIM-representative devices at 48 hours after end of full cycle aeration
– LAL endotoxin testing for FIM-representative devices after full cycle
– FIM human use devices exposed to fractional and full cycles
– Temperature and humidity probes monitor both cycles
Note: If all acceptance criteria are met, the FIM devices are acceptable for human use from a product sterility standpoint. Also, the PCD to be used for routine lot release going forward is selected.
2. Clinical Batch Release #2 (maximum load) – half cycle #1 + full cycle
– PCD sterility testing after exposure to half cycle only
– PCD sterility testing after exposure to full cycle only
– EO residual testing for FIM-representative devices at 24 hours after end of full cycle aeration
– LAL endotoxin testing for FIM-representative devices after full cycle
– FIM human use devices exposed to fractional and full cycles
– Temperature and humidity probes monitor both cycles
3. Clinical Batch Release #3 (maximum load) – half cycle #2 + full cycle
– PCD sterility testing after exposure to half cycle only
– PCD sterility testing after exposure to full cycle only
– EO residual testing for FIM-representative devices at 0 hours after end of full cycle aeration
– LAL endotoxin testing for FIM-representative devices after full cycle

– FIM human use devices exposed to fractional and full cycles
– Temperature and humidity probes monitor both cycles

 At this point EO residuals testing can be discontinued if a dissipation curve can be created from the 0, 24 and 48 hour results that demonstrates acceptable levels of residuals per ISO 10993-7.
4. Clinical Batch Release #4 (maximum load) – half cycle #3 + full cycle
– PCD sterility testing after exposure to half cycle only
– PCD sterility testing after exposure to full cycle only
 – LAL endotoxin testing for FIM-representative devices after full cycle

– FIM human use devices exposed to fractional and full cycles
– Temperature and humidity probes monitor both cycles
At this point, full validation status has been achieved for the maximum load!

Subsequent Batch Releases (maximum load) – full cycle only
– PCD sterility testing after exposure to full cycle only
– LAL endotoxin testing for FIM-representative devices after full cycle
– FIM human use devices exposed to full cycle

To validate a “minimum load”, another combined half cycle and full cycle is required with temperature and humidity probes. The acceptance criteria for the minimum load should be that the temperature and humidity profile should be equivalent or better than it was for the “maximum load”.  If the minimum load is judged to be a worse case (runs colder, larger ranges across the load, etc.) then 2 additional half/full cycle combinations must be performed before the minimum load cycle can be considered validated.