Regulatory Open Forum

Hi fellows,
I was given to understand that EtO residuals and biological indicators are tested for each lot. 1 unit for residuals and biological indicators as defined in the process.
The periodic tests are bio-burden and LAL, and they are usually done every quarter or after a certain number of manufactured LOTs. The sample size varies... I guess 5-10 units.

What is your experience with that, and is there a clear guidance regarding frequency and sample size for these types of tests?

Thanks,
Shimon

Hello Shimon,

The questions largely depend on the type of device, type of sterilisation performed, and the sterilisation validation process.  As you mention EtO (or EO) residuals, then assuming you are discussing Ethylene Oxide sterilisation.  For EtO residuals, this is usually performed during the sterilisation validation process because testing routinely during lot release would be time and cost prohibitive to companies.  However, depending on the product, i.e. a dense product, this might be part of the lot release.  Biological Indicators (BI) are tested for each sterilisation load, not necessarily a lot of product, because the sterilisation validation process accepts the use of BIs as the load release mechanism since testing sterility each and every time is reason validation is performed.  Bioburden and LAL testing also depend heavily on type of product, environmental monitoring, sterilisation validation, etc.  There are a number of standards which do explain this further such as ISO 10993-7, ISO 11135 for EtO, ISO 14644 series, ISO 11737 series, etc.

------------------------------
Richard Vincins RAC
Vice President Global Regulatory Affairs
------------------------------

Original Message:
Sent: 14-Jul-2021 09:01
From: Shimon Vaknin
Subject: Frequency and sample size for LOT release of EtO sterilized products

Hi fellows,
I was given to understand that EtO residuals and biological indicators are tested for each lot. 1 unit for residuals and biological indicators as defined in the process.
The periodic tests are bio-burden and LAL, and they are usually done every quarter or after a certain number of manufactured LOTs. The sample size varies... I guess 5-10 units.

What is your experience with that, and is there a clear guidance regarding frequency and sample size for these types of tests?

Thanks,
Shimon

Thank you Richard!
Original Message:
Sent: 15-Jul-2021 03:53
From: Richard Vincins
Subject: Frequency and sample size for LOT release of EtO sterilized products

Hello Shimon,

The questions largely depend on the type of device, type of sterilisation performed, and the sterilisation validation process.  As you mention EtO (or EO) residuals, then assuming you are discussing Ethylene Oxide sterilisation.  For EtO residuals, this is usually performed during the sterilisation validation process because testing routinely during lot release would be time and cost prohibitive to companies.  However, depending on the product, i.e. a dense product, this might be part of the lot release.  Biological Indicators (BI) are tested for each sterilisation load, not necessarily a lot of product, because the sterilisation validation process accepts the use of BIs as the load release mechanism since testing sterility each and every time is reason validation is performed.  Bioburden and LAL testing also depend heavily on type of product, environmental monitoring, sterilisation validation, etc.  There are a number of standards which do explain this further such as ISO 10993-7, ISO 11135 for EtO, ISO 14644 series, ISO 11737 series, etc.

------------------------------
Richard Vincins RAC
Vice President Global Regulatory Affairs

Original Message:
Sent: 14-Jul-2021 09:01
From: Shimon Vaknin
Subject: Frequency and sample size for LOT release of EtO sterilized products

Hi fellows,
I was given to understand that EtO residuals and biological indicators are tested for each lot. 1 unit for residuals and biological indicators as defined in the process.
The periodic tests are bio-burden and LAL, and they are usually done every quarter or after a certain number of manufactured LOTs. The sample size varies... I guess 5-10 units.

What is your experience with that, and is there a clear guidance regarding frequency and sample size for these types of tests?

Thanks,
Shimon

There are multiple guidance documents and standards supporting the sterilization process.  
AAMI ST72 supports USP requirements for Bacterial Endotoxin Testing and sample sizes.  ISO 11135 defines EO validation requirements and the ISO 10993 part 7 defines EO residual requirements.  Generally accepted practices for monitoring of controlled EO sterilization processes include LAL testing and BI testing for release.

Good Luck

------------------------------
Beverly Whitaker
Indigo Consulting Group, LLC
Beaufort SC
United States
------------------------------

Original Message:
Sent: 14-Jul-2021 09:01
From: Shimon Vaknin
Subject: Frequency and sample size for LOT release of EtO sterilized products

Hi fellows,
I was given to understand that EtO residuals and biological indicators are tested for each lot. 1 unit for residuals and biological indicators as defined in the process.
The periodic tests are bio-burden and LAL, and they are usually done every quarter or after a certain number of manufactured LOTs. The sample size varies... I guess 5-10 units.

What is your experience with that, and is there a clear guidance regarding frequency and sample size for these types of tests?

Thanks,
Shimon

Thank you Beverly!
Original Message:
Sent: 15-Jul-2021 07:40
From: Beverly Whitaker
Subject: Frequency and sample size for LOT release of EtO sterilized products

There are multiple guidance documents and standards supporting the sterilization process.
AAMI ST72 supports USP requirements for Bacterial Endotoxin Testing and sample sizes.  ISO 11135 defines EO validation requirements and the ISO 10993 part 7 defines EO residual requirements.  Generally accepted practices for monitoring of controlled EO sterilization processes include LAL testing and BI testing for release.

Good Luck

------------------------------
Beverly Whitaker
Indigo Consulting Group, LLC
Beaufort SC
United States

Original Message:
Sent: 14-Jul-2021 09:01
From: Shimon Vaknin
Subject: Frequency and sample size for LOT release of EtO sterilized products

Hi fellows,
I was given to understand that EtO residuals and biological indicators are tested for each lot. 1 unit for residuals and biological indicators as defined in the process.
The periodic tests are bio-burden and LAL, and they are usually done every quarter or after a certain number of manufactured LOTs. The sample size varies... I guess 5-10 units.

What is your experience with that, and is there a clear guidance regarding frequency and sample size for these types of tests?

Thanks,
Shimon