Gamma Sterilization of Pharmaceuticals

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Gamma Sterilization of Pharmaceuticals
May 2004
By Ruth Garcia, Betty Howard, Rose LaRue, Glenn Parton, and John WalkerSteris Isomedix Services (Mentor, OH)
Sterility is desirable not only for medical devices, but also to ensure the safety ofparenterals or injectable drugs. Various methods of reducing microbial loadin drugs and parenterals are available.
crucial step in pharmaceu-tical production is steril-ization. There are manysterilization methods tochoose from, such assteam, sterile filtration, ethylene oxidegas (EtO), electron beam (E-beam),and gamma radiation. Each techniquehas aspects that make it suitable orunsuitable for the sterilization of aparticular product.For example, EtO, while being ahighly effective method, leaves behindpotentially hazardous residuals and can-not reach products in airtight packages.E-beam, while being one of the fastestmethods of sterilization, cannot pene-trate well into dense product or bulkpackaging of some products. In addi-tion, the product complexities of hetero-geneous components often requireextensive product qualification. Gammaradiation can cause certain product andpackage materials to degrade.GAMMA BENEFITSGamma radiation does have somesignificant advantages over othermethods of producing sterile product.These benefits include: ? Better assurance of product sterilitythan filtration and aseptic processing.? No residue like EtO leaves behind.? More penetrating than E-beam.? Low-temperature process.? Simple validation process.The first aspect to consider whensterilizing with gamma is product tol-erance to the radiation. During use ofthis type of radiation, high-energyphotons bombard the product, caus-ing electron displacement within.These reactions, in turn, generatefree radicals, which aid in breakingchemical bonds. Disrupting microbialDNA renders any organisms that sur-vive the process nonviable or unableto reproduce.However, these high-energy reac-tions also have the potential to disruptbonds within the pharmaceutical for-mulation, to weaken the strength ofpackaging materials, and to causechanges in color or odor in somematerials. For these reasons, drugmanufacturers should perform pre-qualification Dmax (maximum dose)testing, whereby the drug and its pack-aging are subjected to a high dose ofgamma radiation and then evaluatedfor stability and functionality.Usually, the manufacturer will bethe party responsible for drug testing.Parameters to characterize typicallyinclude potency, efficacy, stability, bio-compatibility, and chemical accept-ability. Per guidelines under theInternational Conference on Harmo-nization (ICH), known as TechnicalRequirements for Registration ofPharmaceuticals for Human Use, it isrecommended to use high-performanceliquid chromatography (HPLC), massspectrometry, or gas chromatographyto characterize and compare differentanalytical aspects of irradiated prod-uct versus nonirradiated product. A qualified laboratory should per-form package testing. It is often recom-mended to have an aerosol challengeperformed on the product and pack-aging. This test entails placing thepackaged product inside an aerosolchamber and exposing it to high levelsof bacterial spores. The product isthen subjected to a sterility test, whichshows whether or not the packagingmaintains a sufficient barrier. In addition, at least one physicalchallenge should be performed on thepackaging, if applicable. These in-clude the peel test to determine theamount of pressure needed to openthe seal; the burst test to determine theamount of pressure needed to burstthe package and to locate areas ofweakness in the package; and the dyeStrategies forGamma Sterilization of Pharmaceuticalsby Ruth Garcia, Betty Howard, Rose LaRue, Glenn Parton, and John WalkerSteris Isomedix Services (Mentor, OH)Sterility is desirable not only for medical devices, but also to ensure the safety ofparenterals or injectable drugs. Various methods of reducing microbial loadin drugs and parenterals are available.
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