Gamma Irradiation of Frozen Animal Serum: Dose Mapping for Irradiation Process Validation

Abstract

The treatment of animal serum by gamma irradiation is performed to mitigate the risk of introducing undesired microorganisms (viruses, mollicutes, or other microbes) into a cell culture. Serum manufacturers and endusers utilize irradiation contractors to perform this process. The irradiation process must be validated, which involves establishing the: (A) minimum dose that achieves the required inactivation of the microorganisms of interest; (B) maximum acceptable dose at which the serum still maintains all of its required functional specifications; and (C) process used by the contract irradiator that allows treatment of the serum product within these defined limits. In the present article, we describe the best practices for qualifying the distribution and magnitude of absorbed dose (performance qualification [PQ] dose-mapping) when serum is gamma irradiated. PQ dose-mapping includes the following: (1) documentation of dose distribution characteristics in defined product load configurations for a specified pathway through the irradiator; (2) assessment of the process capability of the defined product load configurations and irradiation pathway for respecting the dose specification for the serum; and (3) development of a method for routine dose monitoring of the irradiation process with the defined product load configurations and the specified irradiation pathway. Introduction This article is one of a series of papers that are being authored under the sponsorship of the International Serum Industry Association (ISIA) with the purpose of establishing best practices for processes employed in the gamma irradiation of animal serum.[1] In the present article, we describe the best practices for qualifying the distribution and magnitude of absorbed dose (performance qualification [PQ] dose-mapping) when frozen animal serum is gamma irradiated. Routine irradiation of frozen animal serum is typically undertaken at contract irradiation facilities, and not by serum vendors or end-users themselves. The serum is usually irradiated in its final product container, where the containers are placed in specified quantities (with or without cardboard boxes that group several product containers together) at specified positions within a cryotainer, such as a lidded polystyrene box. The cryotainers can be specifically provided for the irradiation process by the operator of the gamma irradiation facility, or they can also be used for transport to and from the irradiation facility. Dry ice is used to ensure that the cold chain is maintained throughout the irradiation process. The importance of temperature control for preservation of serum performance has been stressed previously in a separate article in this series[2] and will be discussed in more detail in a future paper. Dry ice can be added in specified quantities to specific compartments of the cryotainer, or it can be added in bulk to fill up the entire cryotainer. The former can be done when the cryotainer is specifically designed for that purpose, with the intent to minimize the influence from the presence of dry ice on dose delivered to the serum product. The latter is the most common process, where the cryotainer is also used for transport to and from the irradiation facility. In this case, dry ice is added to the cryotainer in preparation for transport to the irradiation facility, and IMAGE: A cobalt-60 source rack in the storage pool of a gamma irradiation facility. (Courtesy of Sterigenics International, Leuven, Belgium.)