Application of Sterilization by Gamma Radiation for Single-Use Disposable Technologies in the Biopharmaceutical Sector - Pharmaceutical Technology

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Application of Sterilization by Gamma Radiation for Single-Use Disposable Technologies in the Biopharmaceutical Sector
This paper examines the process of gamma irradiation of plastic materials used as part of single-use disposable systems in the pharmaceutical and biotechnology sectors, with a focus on validation requirements.

Pharmaceutical Technology
Volume 36, Issue 5, pp. s20-s30

Packaging and dose determination. Although gamma radiation is commonly used to sterilize plastics, not all types of plastics can be treated at a sufficient dose to achieve sterilization without degrading the plastic (20). The assessment of degradation is on-going and should be undertaken throughout the shelf life of the material (the application of ionizing radiation causes the excitation of polymer molecules, where, over time, the adsorbed dose can result in changes to the physical or chemical properties of the polymers). The plastic material to be irradiated is normally referred to as the "product." Most products are placed into an outer packaging in order to protect the irradiated product and to keep the product sterile once sterilized. The product remains sterile provided that the outer packaging remains intact. Occasionally, large or complex products cannot be tested in their entirety and a staged sterilization process is required. In such circumstances, thought should be given to the conditions under which final assembly will take place in order to avoid contamination from the environment or from personnel.

Given the range of different types of single-use sterilized disposable products being developed, and the range of different packaging configurations, the required gamma radiation dose to achieve sterilization or to protect the product from degradation will vary considerably. There is also considerable variation with types of plastic. For example, a relatively low dose of radiation is required to sterilize polypropylene when compared with polystyrene. Furthermore, the assessment of the dose is more straightforward for small items, such as a plastic container, and more complex for single-use systems. Single-use systems have variables including tubing length, different numbers and types of filters, and differences in the design of containers, bags, and valves, which make the determination of the irradiation dose more complicated. Considering these factors, a common radiation dose used for plastics is in the range 15–25 kGy (21).

For the process of sterilization, the wrapped product is normally packed into a special container, typically manufactured from aluminum, called a tote. A tote has fixed internal dimensions and is designed to transport product through the radiation process. The weight and dimensions of the tote must be accounted for when establishing the radiation dose.

The dose determination is the key validation step when using gamma radiation. The dose is the amount of gamma radiation absorbed by an item undergoing sterilization. This is normally set as a range, where a minimum and maximum dose is established. The minimum dose is established as the point where sterilization occurs, and the maximum dose is the point beyond which the product is no longer compatible with the sterilization process. In general, the higher the dose rate, the lower the adverse effects upon polymer products. This is mainly due to the diffusion of oxygen during the irradiation process.

Validation steps

To validate a load, there are three aspects to consider: establishing the dose range, measuring the effectiveness of the sterilization, and dose mapping.

Irradiation validation. Irradiation validation is designed to set the dose range. The primary focus is to determine if the irradiation process damages the packaging material or the product to be sterilized. Damage is assessed by calculating the maximum dose. This assessment is examined through stability trials, whereby samples are held at under defined storage conditions (i.e., temperature and relative humidity) and examined at periodic intervals for discoloration, brittleness, and other damage.

Ionizing radiation generates free radicals in plastic polymers leading to degradation from chain scission (i.e., changes in molecular weight) or alterations to cross-linking. Potential radiation effects on some materials include embrittlement (i.e., change to material hardness), discoloration (i.e., often yellowing caused by surface oxidation), unpleasant odor (i.e., from volatile material formed by reactions from within the polymers), or lack of functionality due to a compromised physical trait, such as tensile strength (22).


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