Auditing sterilization dose substantiated Vdmax 25

Edugar

Involved In Discussions
#1
Hi all,

I have a question about the ISO 11137 standard regarding the reason of doing the dose audit always with the Vdmax 25 originally obtained.

If the production to carry out the substantiation of 25 kGy dose is very clean (bioburden average 0,15) the Vdmax 25 is very low (0,9 kGy according table 9 ISO 11137-2). Then all the sterilization dose audits are carried out with an initial very low Vdmax 25 (0,9 kGy). In this situation there is a probable risk to get positives results in the sterility tests, if the bioburden increases (bioburden average 1,00), with inconvenient consequences.

In this case what do you do?
1. A documented factor of security to increase the initial bioburden average?
2. Modify the Vdmax 25 when you get a higher bioburden?

With these bioburden it does not make much sense, if some positives sterility tests are got, to carry out a confirmatory sterilization dose audit or to conclude that the sterilization dose of 25 kGy is not adequate.

What is your opinion?

Thanks in advance!!
 
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K

Kees Fremery

#2
Dear Edugar,

I understand your point. However we have to deal with facts. If you have an initial validation with a very low Bioburden, the verification dose is low also. That means a good environment in the production location.
The goal of the Dose audits is to maintain process effectiveness. If Bioburden increases during the year the change of failing a dose audit will increase also.
Therefore I always recommend frequent Bioburden monitoring so you can minimize the possibility of failing a dose audit.
Starting a validation with a "correction" for the Bioburden in order to get a higher verification dose looks attractive but in fact it is more manipulating to be honest.
If you go from low Bioburden to higher Bioburden it would be very rare that you will directly end up with 10 positive results in the verification experiment. If you find 1-4 positives you can augment the sterilization dose. 5 or more does indeed mean: STOP. Revalidate immediately.
This is exactly why I always emphasize the need for Bioburden monitoring. ISO 11137 states an interval of 3 months for VDmax25 but my recommendation is every batch or at least monthly and set up alert and action limits.

Kind regards,
Kees
 

Edugar

Involved In Discussions
#3
Dear Kees,

Thank you for your reply.

The facts are:
1. The initial bioburden average was 0,15. All microorganisms were aerobes.
2. The last bioburden average was 0,2. All microorganisms were aerobes.
3. The sterility test of the samples irradiated (from the same batch of the samples that the bioburden average was 0,2) two samples fails (both from moulds). Additionally please note that the sterility test (qualitative, liquid culture media, more culture time) is more sensitive than the bioburden test.
4. It would be possible that the confirmatory sterilization dose audit were some positive results.

It this case, has any sense to increase the sterilization dose (25 kGy) with these low bioburden?

Best regards.
 
K

Kees Fremery

#4
Dear Edugar,

To make sure: the Dose Audit failed?
Was during the initial vaildation (and the dose audit) the bioburden tested on Moulds and Yeasts? (Looks a silly question perhaps, but I know labs who only test for Aerobes)
If yes and they were not found, is looks very strange to me that in the test of sterility suddenly moulds appear. (TSB 14 days?)
This can not exclude a lab failure like contaminated instruments or test environment. I don't think of a technician failure because then you mostly deal with skin flora like staph aureus.
The only option according to ISO 11137 is indeed a confirmatory experiment with 0 failures. However if this this fails you need to do a Dose Augmentation.

My advise in this case would be to investigate the appearance of the moulds.
Looking at the Bioburden levels (again, I am curious about Mould and Yeast testing in the Bioburden) I even would not increase the dose at this stage and think of a rationale to make. Important also is the type of product we are talking about.

I always say: ISO 11137 is a very good guideline and added with common sense you can make it perfect.

I hope this helps you further, if you need more help I am willing to assist you in writing a rationale or something.

Kind regards,
Kees
 

Edugar

Involved In Discussions
#5
Dear Kees,

In reply to your questions:
1. Was during the initial validation (and the dose audit) the bioburden tested on Moulds and Yeasts? Yes. And the bioburden test was validated.
2. If yes and they were not found, is looks very strange to me that in the test of sterility suddenly moulds appear. (TSB 14 days? Yes, at 22ºC) In theory the sterility test (qualitative, liquid culture media, more culture time) is more sensitive than the bioburden test.
3. This can not exclude a lab failure like contaminated instruments or test environment. I don't think of a technician failure because then you mostly deal with skin flora like staph aureus. After the failed sterility test the lab carried out several checks to assure the results (environment, results of other sterility tests, ...)
The only option according to ISO 11137 is indeed a confirmatory experiment with 0 failures. However if this this fails you need to do a Dose Augmentation.

My advise in this case would be to investigate the appearance of the moulds. But according the results the bioburden looks under control.
Looking at the Bioburden levels (again, I am curious about Mould and Yeast testing in the Bioburden) I even would not increase the dose at this stage and think of a rationale to make. Important also is the type of product we are talking about.

I always say: ISO 11137 is a very good guideline and added with common sense you can make it perfect. Yes, common sense is very important.

Thank you again for your comments.
 
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