Many sterilization methods are available for pharmaceuticals, healthcare devices, and labware, including steam, sterile-filtration,
ethylene oxide, vapor-phase hydrogen peroxide, electron-beam irradiation, and gamma irradiation. Each technique needs to be
evaluated before use based on various criteria. Most importantly, one must consider how the technique will affect the final
product characteristics and performance.
This article reviews the considerations for using gamma irradiation in pharmaceutical manufacturing. Specifically, the author
examines what gamma irradiation is, how it works, and what manufacturers need to consider when evaluating the method for terminal
sterilization of a product or component. The article, while not exhaustive, is intended to provoke consideration of this effective
sterilization method.
Background
Gamma irradiation is a fast, effective method for sterilization. The high-energy gamma rays (i.e., photons) from Cobalt 60
result in ionization events which can cause desirable effects (e.g., sterilization) as well as potential undesirable or unintentional
effects (e.g., change in the product's molecules or byproducts). Photons have no charge or mass, allowing them to penetrate
deeply into a material. The photons' penetration ability makes them ideally suited for sterilization of even relatively dense
products. The photons can cause electron displacement, free radical formation, and, ultimately, bond breakage, when they penetrate
a product. This mode of action can change the large biological molecules needed to support life such as DNA and enzymes, effectively
rendering any living organisms present nonviable and unable to reproduce (i.e., sterile).
This depth of penetration is one of the greatest advantages of gamma irradiation as a sterilization method. A pharmaceutical
or healthcare product in its final package (e.g., in its shipping carton) can, in most cases, be easily penetrated with gamma
irradiation. As outlined below, all sterilization methods have positive and negative characteristics that need to be evaluated
on a case-by-case basis as to the specific impact on the product and process. The author will review some of the common issues
related to pharmaceutical products.
Benefits of gamma irradiation include the following:
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Depth of photon penetration allows for sterilization of materials of various density levels
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Process does not require addition of heat or moisture
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Well documented for its effectiveness as a sterilization process
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Does not produce residuals as are of concern with Ethylene Oxide sterilization
- Simple methods are available for documenting a high sterility assurance level (SAL) such as 10-6
- Allows for terminal sterilization.
As with any process, one must also consider the potential negative aspects of its use. Because gamma irradiation produces
ionization events, it can lead to unintended or undesirable effects. Each product must be tested in its final form with irradiation
before a final decision to sterilize is made. A material's tolerance to gamma irradiation must be documented and its effects
known. The earlier in the development process that this is done, the more time and options will be available to adapt or modify
the product or processes needed to make the product successful. Early testing also means that all applicable data (e.g., safety,
efficacy, and potency) is produced for a product that also includes the effects of the sterilization process.
Pharmaceutical products cover a wide range of materials (e.g., containers, closures, excipients, and processes). The following
sections examine the effect of gamma irradiation as a sterilization process on these materials individually.
