The third aspect of the validation is dose mapping. For this, the product, in its final packaging configuration, is profiled
in order to identify the high and low zones of absorbed dose in the product load. Dose mapping determines the loading configuration
that will be used during routine sterilization.
Understanding Gamma Sterilization, by Jerold Martin, Pall Life Sciences
The object of the validation is to set processing parameters and the product release specification. The validation parameters
are established through a performance qualification (dose mappings), which is typically run three times using the maximum
packaging size. The main steps for undertaking a performance qualification, for each product, are as follows:
- Evaluate product and process suitability
- Decide on the container presentation
- Undertake dose mapping
- Evaluate results
- Establish release specification
- Establish parameters for routine product sterilization.
The level of radiation is assessed using devices called dosimeters (i.e., a device, instrument, or system that measures the
exposure to radiation). It is important to assess the number of dosimeters required to assess the radiation dose. With a standard
tote, it is typical to use 15–20 dosimeters. This number is necessary in order to achieve an accurate assessment because the radiation dose applied to the
products packaged at the outer edge of the tote is often higher than the dose received by the material in the inner center
of the tote, as illustrated in Figure 1.
The key validation parameters are: product weight and volume, dimensions of packaging components and density, and the configuration
of the packaging components. With the dimensions, it is important that the product is evenly distributed because the radiation
dose is applied at the same level from both sides. With the issue of load configuration, this point is sometimes overlooked.
It is nonetheless important that the way that the components are packaged during validation be replicated for all successive
radiation runs. This is important because if the orientation alters, then this can cause changes to the density mix and thus
the effectiveness of the irradiation. Once the validation parameters are established, the parameters are used for routine
processing and no parameter should be permitted to vary significantly from the established parameter.
Once established, it is necessary that any future changes in product, its package, or the presentation of product for sterilization
are re-assessed for the effect on the appropriateness of the sterilization process. It is prudent to re-assess the validation
parameters at least on an annual basis and to assess the bioburden of the product quarterly, in order to determine that the
gamma radiation process remains effective (27). This assessment may include fractional studies. Here the product is irradiated
and tested at sublethal doses (i.e., at levels of gamma radiation below the minimum established in the validation study) to
check for continued dose efficacy. This is sometimes referred to as dose auditing.
Gamma radiation process
On completion of the validation, the standard manufactured batches of the product can be subjected to routine sterilization.
The sterilization process is based on the establishment of validation parameters.
To ensure good levels of quality control, it is recommended that the following steps be put in place:
- Product and packaging description
- Carrier loading configuration
- Minimum allowable dose
- Maximum allowable dose
- Location of the dosimeter in the load
- Specifications for temperature or humidity.
There are two methods of gamma radiation: continuous or batch. For both it is important that the distribution of gamma radiation
applied to the product is even. With the continuous method, an automated conveyance system functions to move the product past
a gamma source and back out on a continuous basis until the end of the cycle is achieved. With the batch methods, a set number
of totes are used at set positions within the irradiation chamber. Special chemical indicator labels should be fixed to each
item to indicate if irradiation has been successful. The radioisotope is then moved into an exposure position, and the product
is irradiated for a specified period of time. The method selected is dependent upon the method used during the validation.