This is the sixth and last in a series of articles describing and demystifying the processes involved in the gamma irradiation of serum. This serum treatment is intended to mitigate the risk of introducing adventitious contaminants into cell cultures. In this article, we discuss the regulatory environment under which gamma irradiation of serum is performed, and provide additional details on best practices for documentation of the irradiation process, selection of the contract irradiator, evaluation of risk versus benefit needed to arrive at the radiation dose range to be used, as well as an understanding of the level of remaining risk following irradiation at that dose range. Gamma irradiation should not be viewed as a means of totally eliminating risk, but rather as a means of reducing the risk of introducing adventitious agents into cell cultures. A balance must be achieved between the desire to eliminate all adventitious contaminants, and the need to retain the desired performance characteristics of the serum, once irradiated…
Tag: <span>animal serum</span>
Gamma irradiation is a well-established process for reducing or eliminating the bacterial and viral load in medical devices, biologics, and other products such as animal sera. This process can lead to alterations in both the materials being treated and the product containers in use. High-energy radiation produces ionization and excitation in materials, generating energy-rich ions which undergo dissociation, abstraction, and additional reactions in a sequence that may lead to chemical alterations. The resulting chemical stabilization process, which occurs during, immediately following, and occasionally days after irradiation, often leads to physical and chemical cross-linking or chain scission. The physical changes to materials can include embrittlement, discoloration, odor generation, stiffening, softening, and enhancement or changes in chemical structure. This paper discusses how and why irradiated polymeric materials, including those of biological origin, may change their structure and effectiveness during and after exposure to gamma irradiation, and the potential impact of these changes on serum during irradiation…
This article examines two interrelated animal welfare topics: the transportation of pregnant cattle, and the collection of fetal bovine serum (FBS). The occurrence of pregnant cattle at slaughter is unavoidable because of health, management, and economic reasons, or because farmers may be unaware of their pregnancy status. Since cattle are often sold to slaughterhouses through intermediaries, the pregnancy status of the cow is usually unknown until after it has been slaughtered and the uterus exposed. In slaughterhouses where fetal blood is collected, technicians are responsible for the detection and proper handling of fetuses, making sure they remain inside the uterus until dead, or are immediately euthanized. The harvesting of fetal blood also provides a possible source of information, which upon request, may help farmers improve the management of their livestock operations. The serum industry endorses the animal welfare standards set forth by the World Organization for Animal Health (OIE), as well as all existing local and national standards relating to the transportation of pregnant cattle and the collection of fetal blood. This article concludes that there is nothing negative or unethical about collecting blood from a dead fetus. Rather it would be unethical not to utilize available fetal tissues obtained from the slaughter of pregnant cattle, especially since FBS, used as an ingredient in cell culture media, contributes greatly to the advancement of the life sciences industry, as well as the replacement and reduction of live animals used in research and testing…
This paper reviews the importance of maintaining low temperature storage and handling (i.e., cold chain) for animal serum through all stages of processing, from finished product to the actual end-user. This cold chain extends from serum manufacture through the irradiation process, during shipment back to the supplier post-irradiation, as well as storage at supplier, irradiation, and end-user facilities. Anecdotal experience and theoretical considerations emphasize the point that maintenance of the cold chain is necessary for preserving the performance of serum for cell culture and other applications…
The continued use of animal serum as an important component in biotechnology manufacturing processes has raised questions regarding both the reliability of geographic origin and possible adulteration of product. The International Serum Industry Association (ISIA) has implemented a traceability certification program designed to demonstrate traceability from slaughterhouse or abattoir to the end-user. This is based on an audit performed by an independent, approved third-party auditor according to an approved audit plan, using a detailed audit checklist. Recent advances have led to the development of a complementary testing program to determine geographic origin of material. The methodology described in this paper differentiates fetal bovine serum from newborn calf serum on the basis of biochemical composition…
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 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…