Our Sterilization validation report (gamma irradiation at 25kGy) contains the average bioburden on the samples tested, upon which the dose was set.

During regular bioburden monitoring the level obviously fluctuates. I was wondering if there is a rule of thumb which says what range is acceptable and at what level an investigation into the bioburden/dose setting should be triggered?

eg If 10 x the average bioburben is measured during monitoring an investigation is required.

thanks
Simon

Did you have a look at ISO 11737-3 - Sterilization of Medical Devices - Microbiological methods, Part 3 - Guidance on evaluation and Interpretation of Bioburden Data ?

I dont have this standard but feel you could get some valuable info from this standard.

Also have a look at Bioburden Testing (http://http://www.wfhss.com/html/educ/lectures/efhss2004_bioburden_en.pdf) that I found very interesting.

Hi

I'm not aware of any specific guidelines, other than average bioburden being below 1000cfu when using VDmax25. Bioburden will be a factor of the nature of the product and the process complexity.

I have always taken this to be a case for doing SPC and using Xbar/R charts to set limits and to look for process changes.

Chris

Hi

I'm not aware of any specific guidelines, other than average bioburden being below 1000cfu when using VDmax25. Bioburden will be a factor of the nature of the product and the process complexity.

I have always taken this to be a case for doing SPC and using Xbar/R charts to set limits and to look for process changes.

Chris

Thats true Chris - even I have seen "average below 1000 cfu"

I was going through the GUIDE TO INSPECTIONS OF FOREIGN MEDICAL DEVICE MANUFACTURERS (http://http://www.fda.gov/ora/inspect_ref/igs/fordev.html) and found that the most important thing to be noted with regards to Bioburden is -

What is the bioburden on the device, and is the sterilization cycle able to destroy the bioburden to an appropriate SAL level.

Hi

I'm not aware of any specific guidelines, other than average bioburden being below 1000cfu when using VDmax25. Bioburden will be a factor of the nature of the product and the process complexity.

I have always taken this to be a case for doing SPC and using Xbar/R charts to set limits and to look for process changes.

Chris

Agree SPC is the way forward for setting your limits, some of our devices have upper limits of 25cfu where as others are around the 400cfu mark before prompting an investigation / root cause analysis etc.
I generally review each devices limits on an annual basis to see if we can lower the upper limits general rule for us is Average +3 standard deviations :2cents:

I believe you still have to perform dose audits on a regular basis (quarterly or semi-annually depending on rational developed by your company). If you are getting acceptable results this helps to prove that the fluctuations are not negatively impacting the product.

I would also suggest looking into additional testing for worst case scenario. If you have characterized the bioburden (what kind of bugs do you have?), you should determine an upper limit of bioburden, and then repeat verification dose level processing on products that have been innoculated with the 'worst case' level of bioburden.

In doing this, if you get good results, you have the proof, as long as bioburden stays under 'worst case scenario' that your product is sterile.

If you use a contract irradiator, they should have validation experts who should be happy to let you pick their brain...