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

Abstract

he 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 end-users 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. IMAGE: A cobalt-60 source rack in the storage pool of a gamma irradiation facility.

Gamma Irradiation of Animal Serum: General Regulatory Environment and Process Controls

“…Product and irradiation process specifications should be developed from information generated during process definition (i.e., establishing minimum required and maximum acceptable radiation doses for the serum product) [21] and performance qualification (PQ) dose map studies. [25] Process specifications should also clearly define all requirements, including those for maintaining the cold chain. [26] Figure 1 demonstrates the complexity of the serum irradiation process.…”

“…Process controls during routine irradiation have been detailed previously. [25] The dose delivered to the serum product is monitored using a dosimetry system which has been calibrated for the conditions of use and is traceable to national or international standards. Upon completion of the irradiation process, the processing history records must be reviewed and approved by designated contract irradiator personnel.…”

“…It must be noted that narrow dose ranges are substantially more difficult to achieve and hence, more costly. [25] A well-informed supplier working with a skilled contract irradiator will be able to resolve many of the issues that have been highlighted in this review of serum irradiation. The end-user must also be educated in the irradiation process and understand that their suppliers must rely on a number of vendors to deliver their irradiated serum.…”

Gamma Irradiation of Animal Serum: Maintaining the Cold Chain Throughout the Process

“…They have the necessary expertise and have conducted dose-mapping studies to assure that intended gamma radiation fluencies (absorbed doses) will be achieved routinely during the irradiation process. [8] Serum to be gamma irradiated must therefore be shipped under appropriate conditions from the supplier to the irradiation facility and then back to the supplier following irradiation.…”

“…Typically, the serum will be in the irradiator for several hours during which it will convey multiple times beside the unshielded source of radiation. [8] In addition, consideration has to be given to handling time before and after irradiation as serum batches typically represent large process loads (typically 2000 L). The time and temperature associated with the processing of a given serum load is also influenced by the geographic location of the irradiation facility and seasonality (esp., winter vs. summer), as these determine the fluctuations in external ambient temperature.…”