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

Gamma radiation. The use of ionizing radiation dates back to the discovery of X-rays by Roentgen in 1895, and gamma radiation has been an established sterilization method since the early 1970s (10). It has only been since the 21st century, however, that the use of gamma irradiation has increased within the biopharmaceutical industry, replacing more established and costly methods like ethylene oxide. This arises from the use of gamma radiation to sterilize consumables and single-use technologies used for aseptic filling operations (11). It is the recent impetus for new cleanroom technologies that is leading to an increased use of gamma radiation as the optimal sterilization method.

The process of gamma radiation is a form of ionization (i.e., electron disruption). Gamma radiation is one of the three types of natural radioactivity, the other two being alpha and beta radiation (12). Gamma radiation is in the form of electromagnetic rays, like X-rays or ultraviolet light, of a short (less than one-tenth of a nanometer), and thus energetic, wavelength. It provides a physical means of sterilization or decontamination as the rays pass through the product being sterilized (i.e., irradiated) (13). In doing so, the radiation kills bacteria, where there is sufficient energy, at the molecular level by breaking down bacterial DNA and inhibiting bacterial division (14).

The most common source of gamma rays for radiation processing comes from the radioactive isotope Cobalt 60, although other radionuclides can be used, such as Cesium 137. Each element decays at a specific rate and gives off energy in the form of gamma rays and other particles. Cobalt 60 is manufactured specifically for the gamma radiation process from non-radioactive Cobalt 59. The radioactive Cobalt 60 functions as the isotope source. High-energy photons are emitted from the Cobalt 60 to produce ionization (electron disruptions) throughout a product. The gamma process does not create residuals or impart radioactivity in processed products (15).

Gamma radiation is often referred to as a "cold process" for the temperature of the processed material that does not significantly increase (16). The sterilization process is not dependant on humidity, temperature, vacuum, or pressure, which means that the process is suitable for materials that cannot be subjected to high-temperature sterilization. The important variables for gamma radiation are the strength of the radiation dose (i.e., measurement of how much energy is absorbed when something is exposed to the radiation source) and the exposure time. The measurement of radiation is expressed in units called KiloGrays (KGy). One gray is the absorption of one joule of radiation energy by one kilogram of matter (17).

Standards. The regulatory requirements for gamma radiation are less defined than for sterilization by filtration, moist or dry heat, or by ethylene oxide. These methods of sterilization normally involve a direct biological challenge, as with biological indicators (preparations of a specific microorganism, with high resistance towards particular sterilization methods) for steam sterilization or a high population microbial challenge for filter validation. In the past Bacillus pumilus was used as a biological indicator to measure gamma irradiation. It was removed because the assessment of the product bioburden during validation was deemed to be a more accurate means of assessing potential resistance to the gamma radiation process. In contrast, with gamma radiation, the biological assessment is normally undertaken by an assessment of the product bioburden (i.e., the number of microorganisms on a certain amount of material prior to that material being sterilized) by assessing the total viable count (TVC) of the material, expressed as colony forming units (CFU).

For gamma radiation, the applicable standard is ISO 11137 "Sterilization of Health Care Products-Radiation" (18). The standard was developed in association with the Association for the Advancement of Medical Instrumentation (AAMI).

The standard is divided into three parts. The first part deals with validation and routine control methods. The second part deals with the establishment of radiation doses for items to be sterilized, and the third part relates to dosiometry. The standards function to determine how much radiation is permitted in order to achieve the desired level of sterilization when measured in terms of sterility assurance. The sterility assurance level is normally 106 (that is a theoretical concept where it is assumed that, in terms of probability, no more than one item sterilized out of one million would contain one or more microorganisms after the completion of the sterilization process) (19).

The official scope of the ISO 11137 standards is limited to medical devices. However, in the absence of any other applicable guidance, the standard is more often applied to other types of products and equipment.


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