Bioburden 0 cfu for Dose Setting using the VDmax25

Kees Fremerij

Starting to get Involved
#1
When using the VDmax25 and all Bioburden levels are below the detection limit (eg < 2 cfu, not a single colony on the plates) you should use the zero counts for the verification dose and not the actual detection limit of 2. This is correct? This leads to 0 kGy for verification. Or should you make use of the Harry Potter like approach with calculating based on the Poisson Distribution. It looks like magic that with no colonies at all, you end up with a theoretical number for Bioburden of something below 1 cfu. This will give you a verification dose. I look very straight: no colonies, no verification dose and straight to sterility testing.
Am I correct in this or should magic help in this situation...
Thanks in advance!
 
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NicoleinFlorida

Inactive Registered Visitor
#3
Hello Kees,
Do you mean you have< 2 CFU before sterilization? I am not an expert in this area, but here are a few questions I think about when come to this situation.

How is your manufacturing condition? Are you using the correct method to remove the microorganisms? Have you tried all the medias for different microogansims (Table A.1 in ISO 11737-1)?
 

Kees Fremerij

Starting to get Involved
#4
Hi Nicolein,

After packaging, prior to sterilization indeed. Bioburden is historical very low (prior to packaging a heat step of 900 °C. Then the question is, no colonies found, detection limit due to dilution is 2 so final result of Bioburden is <2
Which value to use for verification dose setting. I say 0.
The number of 2 will give 5,2 kGy and I think this is not correct.

Thanks for reply!
 

Ronen E

Problem Solver
Staff member
Moderator
#5
Hi Nicolein,

After packaging, prior to sterilization indeed. Bioburden is historical very low (prior to packaging a heat step of 900 °C. Then the question is, no colonies found, detection limit due to dilution is 2 so final result of Bioburden is <2
Which value to use for verification dose setting. I say 0.
The number of 2 will give 5,2 kGy and I think this is not correct.

Thanks for reply!
Hi,

I currently don't have time to review this issue properly, but please bear in mind that 5.2kGy is a very low dose (some would say almost equivalent to 0 in terms of lethality).

Cheers,
Ronen.
 

planB

Trusted Information Resource
#6
Kees Fremerij,

unfortunately, the applicable standard is not very clear what to do in your case. I have seen cases where for bioburden "< xy CFU" a verification dose for "=xy CFU" has been chosen.

Howewer, ISO 11137-2, section 9.3.4.2, NOTE 2 says:

When no colonies are observed in the determination of bioburden, this is sometimes expressed as being below the limit of detection. Use of the limit of detection as a bioburden value in calculating average bioburden could lead to an overestimation. Overestimation could affect the validity of the verification dose experiment.
So the safest way to go would be to really set your verification dose to zero - which should not be too much of a process validation failure risk considering that your products have seen a 900°C heat process.

HTH,
 
#7
Hello Kees,

I am facing the same issue right now, no colonies on plates before irradiation of products, How to decide dose kGy for verification?

In our process, products get cleaned with pressurized steam followed by pressurized air before packaging.

I am stuck on deciding the radiation dose for verification.

Your help will be appreciated.

Thank you in advance!
Karishma
 

planB

Trusted Information Resource
#8
Karishma,

please refer to my posting above yours.

Other options:

  • Is pooling of samples an option in your case (Clause 7.2.3.2 of ISO 11137-2)?
  • statistical estimation is suggested in this article:

    Estimation of Average Bioburden Values for Low-Bioburden Products

    The authors include John Kowalski and Gregg Mosley, two heavy-weights in the field of sterilisation.

    Have a look at at Figure 3 in this article: based on the chosen distribution, an average bioburden of 0.3 CFU is estimated for no re-covered bioburden on 10 samples.

HTH,

Gerhard
 

Kees Fremerij

Starting to get Involved
#10
Karishma,

please refer to my posting above yours.

Other options:

  • Is pooling of samples an option in your case (Clause 7.2.3.2 of ISO 11137-2)?
  • statistical estimation is suggested in this article:

    Estimation of Average Bioburden Values for Low-Bioburden Products

    The authors include John Kowalski and Gregg Mosley, two heavy-weights in the field of sterilisation.

    Have a look at at Figure 3 in this article: based on the chosen distribution, an average bioburden of 0.3 CFU is estimated for no re-covered bioburden on 10 samples.

HTH,

Gerhard
I completely agree Gerhard, thanks for your reply.
Statistically you should not use "zero" at all and I hope the next revision of ISO 11137 will change this.
ISO 11737-1 already refers to this Possoin distribution.

Best regards,
Kees
 
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