Hi, im trying to validate a Tunnel sterilizer.
The heat distribution was passed, and the heat penetration should be performed.
When validating a tunnel sterilizer, i use 3 Kaye temperature loggers.
Here is the problem.
When i set temperature loggers, i should input, D-value, Z-value and targeting Fh value.
According to ‘Validation of Pharmaceutical Processes, Sterlie Products 2nd edition, page 504’,
i found Fh(250°C) with a Z-value of 46.4°C is 30.0
On page 504, D-value(250°C) is 4.99 but our sterilizer is set at 300°C for 10min (total running time is about 22min)
I think D-value will be lower than 4.99 but there are no references or data.
I know depyrogenation must be achieved 3-log reductions, so our endotoxin amples were turned out negative.
But i`d like to check the real Fh data by temperature loggers.
Please help me what is the D-value of Endotoxin unit at 300°C.
Or just verifying that Endotoxin was negative is satisfying with 3-log reduction? i don`t have to check real Fh data?
Hope anyone will answer me
thank you all.
I’m going to guess on a lot of things here, but this is how I understand the constants in the kill/lethality equation. The Fh value is the temperature at which you start to get 1 log reduction of kill every minute for that type of heat (wet or dry). The z value is the correction factor for anything above or below that Fh temperature (effective, corrected, actual kill rate). Now the D-value is specific to a lot of EIs, or BIs. Each lot of EIs or BIs will have a different D-value because, hey, all biological entities are different, some are tougher and some are weaker to kill.
The D-values posted represent (I expect) an average, common D-value for quite a few different lots of the BIs or EIs.
I also think if you look in that chapter, you’ll see a lot of references to PhD’s and Research Projects that are well documented and well defended. I always wondered why such defense of the sources information was given. I just assumed that if it was posted, then it must be accurate. I never thought to challenge it.
If you’d like to assume a different D-value, the D-value should be listed on the certifications you got with the EIs. I’m not sure, you might have to confirm this testing by sending out the BIs or the EIs to a lab to test the D-value (or you can do it yourself). But then you’ll have to continue to do this for every lot of BIs or EIs you get it (expensive).
In my experience, we used the “overkill” approach which assumes safety factors, and then just used the values published in the Agalloco book you referenced. Because we were using the overkill approach, any error introduced by the D-value, was small in comparison to the safety factor introduced by the overkill approach, and the sterilization cycle (depyrogenation cycle) was assumed to be effective.
Now I understood the D-value, then how can I prove the sterilizer was running by overkill approach?
Im trying to overkill the products, so I set the temperature at 300°C. Then the time is important. If the time is 30min, then it could be no problem, but I want to find the efficient time. Id like to have evidence that it was overkilled.
Is there any way to demonstrate the sterilization cycle was overkilld? Or just ‘LAL test’ is enough to demonstrate the EI was no more than 1/1000(3-log reduction) ?
You mentioned that the overkill values was published in the ‘Agalloco book’ and I found one on page 435.
However, I wonder it is only for 12-log reduction of BI, not for EI or only for ‘Autoclave steam sterilizer’.
I’m not sure about the comparison between the Endotoxin reduction and the BI redunction. That is a questions that I’ve had but haven’t been successful at hammering down.
Regarding trying to get an efficient time. The overkill method is not the most “efficient” method, but is generally assumed to be the most conservative. If you want the fastest cycle and still maintain proper sterilization, you might want to develop the cycle based on other “approaches”.
These include an enumeration approach test where you identify the present microbes, and determine their kill time (Z, Tbase, and D values) and design a cycle around these unique microbes where your process is. With this approach there is a lot of investment in understanding the microbes in the area, and then you have to maintain that knowledge with regular collection and identification of microbes.
There is another method called the half cycle approach, where during validation the cycle is reduced in half compared to the actual cycle.
A saw another cycle once, where the cycle was shortened by 5 minutes during validation. But I don’t have a reference to it.