Sterilisation

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Validation in accordance with DIN EN ISO 11137, Part 2

Method 1

Method 1 of DIN EN ISO 11137- 2 describes the validity of the routine radiation sterilisation for a product and/or product group. The method is based on experimental confirmation, that the influence of radiation on the biocontamination (of the product) is greater than the standard resistance distribution of such a population of micro-organisms. Using Method 1, the sterilisation dose will be assigned according to the microbial contamination of the medical product. This relationship is specified in the tables of the DIN EN ISO 11137- 2 standard. It lists doses according to the mean bacterial status of the product (verification dose), which ensure a certain SAL (sterility assurance level) in the case of a standard resistance distribution in the bacterial population. The SAL describes the probability of the presence of a single viable micro-organism on a product after sterilisation. In the case of method 1, an SAL of 10-2 is selected for testing with the verification dose. This means that the validation can be accepted if no more than 2 out of 100 products are tested positive in the sterility test after irradiation of the products with the corresponding verification dose. In this case, the micro-organisms on the product are normally or less resistant to the irradiation process. Upon successful validation, the necessary dose for the routine irradiation to ensure an SAL of 10-6 is also tabulated in the standard.

GfPS-0016

The validation consists of:

1) Validation of bioburden method: Determination of the product-specific recovery rate (required once per product or product group respectively).

2) Determination of average bioburden over three independent production batches.

3) Determination of the verification dose based on the determined average bioburden of the product. The tables of EN ISO 11137-2 are used to determine the resistance status of the germ population (interim evaluation).

4) Irradiation of 100 samples from any batch with the verification dose.

5) Sterility tests of the 100 irradiated samples according to DIN EN ISO 11737-2.

6) Validation of the sterility test according to DIN EN ISO 11737-2: Test on unhindered microbial growth in the presence of product.

7) Final evaluation

Revalidation in accordance with DIN EN ISO 11137, Part 2

Method 1

Once the sterilisation dose has been established, periodic audits are required to reaffirm the sterilisation dose according to DIN EN ISO 11137-1. For products in regular production, audits shall be performed at set intervals of time.

According to DIN EN ISO 11137-1 generally an interval of time of three (3) months between the sterilisation dose audits is selected. An extension of the time period between the confirmatory verification dose experiments must be founded worked out and has to be documented. Therefore the aspects under point 12.1.3.1 of DIN EN ISO 11137-1 have to be considered.

Over periods of time, where the product is not manufactured, no sterilisation dose audits are required. According to DIN EN ISO 11137-2 a review of the data for controlling the environment and production-conditions together with the bioburden determinations should be carried out in conjunction with the sterilisation dose audits. An inspection of the data for guiding the environmental and manufacturing conditions should also follow together with the bioburden determinations.

The revalidation consists of:

1) Determination of the bioburden of samples from a production batch

2) Irradiation of 100 samples from the same batch with the verification dose determined in the validation.

3) Sterility tests of the 100 irradiated samples according to DIN EN ISO 11737-2.

4) Final evaluation

GfPS_2-0014

Validation in accordance with DIN EN ISO 11137, Part 2

VDmax method

The VDmax25 procedure in DIN EN ISO 11137- 2 describes the validity of the routine radiation sterilisation for a product or product group respectively. The method depends upon experimental verification that the microbial-load (bioburden) on the product is less resistant to the radiation than a microbial population with maximum resistance, when a SAL (sterility assurance level) of 10-6 is reached with the chosen sterilisation dosage. The SAL describes the probability of the presence of a single viable micro-organism on a product after sterilization. The validation is carried out using a SAL of 10-1 which is applied to 10 product units in the validation procedure with the verification dose. This means that the validation can be accepted if no more than 1 out of 10 products are tested positive in the sterility test after irradiation of the products with the corresponding verification dose. This SAL corresponding dosage (maximum verification dose, VDmax) is dependent on both the level of the microbial-load and the associated resistance characteristics of the load.

The method details a possibility of verifying that the 25 kGy dosage is the suitable sterilisation dosage for a SAL of 10-6 within the limits set by this method.

The VDmax method depends neither on the size of the production batch nor the frequency of production. The number of test samples required to ascertain the sterilisation dosage is 10 and remains always constant.

For using the VDmax25 method the mean microbial load (corrected average bioburden) per product must lie below 1000 colony forming units (cfu). Upon successful validation, 25 kGy are sufficient for the routine irradiation to ensure an SAL of 10-6

For using the VDmax15 method the microbial average bioburden of one product may not exceed the value of 1.5 cfu and an entire product unit must be used for bioburden-testing (SIP = sample item proportion = 1.0). Upon successful validation, 15 kGy are sufficient for the routine irradiation to ensure an SAL of 10-6

GfPS-0035

The validation consists of:

1) Validation of bioburden method: Determination of the product-specific recovery rate (required once per product or product group respectively).

2) Determination of average bioburden over three independent production batches.

3) Determination of the verification dose (VDmax) based on the determined average bioburden of the product. The tables of EN ISO 11137-2 are used to determine the resistance status of the germ population (interim evaluation).

4) Irradiation of 10 samples from any batch with the verification dose.

5) Sterility tests of the 10 irradiated samples according to DIN EN ISO 11737-2.

6) Validation of the sterility test according to DIN EN ISO 11737-2: Test on unhindered microbial growth in the presence of product.

7) Final evaluation

Revalidation in accordance with DIN EN ISO 11137, Part 2

VDmax25 method

Once the sterilisation dose has been established, periodic audits are required to reaffirm the sterilisation dose according to DIN EN ISO 11137-1. For products in regular production, audits shall be performed at set intervals of time.

According to DIN EN ISO 11137-1 generally an interval of time of three (3) months between the sterilisation dose audits is selected. An extension of the time period between the confirmatory verification dose experiments must be founded worked out and has to be documented. Therefore the aspects under point 12.1.3.1 of DIN EN ISO 11137-1 have to be considered.

Over periods of time, where the product is not manufactured, no sterilisation dose audits are required. According to DIN EN ISO 11137-2 a review of the data for controlling the environment and production-conditions together with the bioburden determinations should be carried out in conjunction with the sterilisation dose audits. An inspection of the data for guiding the environmental and manufacturing conditions should also follow together with the bioburden determinations.

The revalidation consists of:

1) Determination of the bioburden of samples from a production batch

2) Irradiation of 10 samples from the same batch with the verification dose determined in the validation (VDmax).

3) Sterility tests of the 10 irradiated samples according to DIN EN ISO 11737-2.

4) Final evaluation

 

Validation in accordance with DIN EN ISO 11137, Part 2

  • Method 1 for individual batches
  • VDmax15 method for individual batches
  • VDmax25 method for individual batches

Correspond to the aforementioned validation in terms of operational procedure. Revalidations are not carried out in these cases.

 

General processing time:

For validation, a processing time of approximately 5-8 weeks should be expected.

For revalidation, a processing time of approximately 4-6 weeks should be expected.

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