Page 36 - Assurance of Sterility for Sensitive Combination Products and Materials

24 Assurance of sterility for sensitive combination products and materials

moist heat. The most prevalent technologies—radiation and EO steriliza-
tion—comprehensively address the ideal characteristics of a sterilization
technology identified by Rutala [4]. The worldwide predominance of these
two modalities of terminal sterilization can be attributed to these character-
istics, along with readily available proven consensus standards and guidelines
[5,6] that were jointly developed by the industry and regulatory bodies
addressing every aspect of medical product sterilization [7].

3.1.1 History of radiation sterilization

In 1904, shortly after the discovery of X-rays by W.K. Roentgen (1895) and
the observation of radiation emitted by uranium by H. Becquerel (1896), the
application of radiation for food preservation was evaluated by S. C. Prescott
and W. L. Underwood [8–10]. Interest in the biocidal application of radia-
tion led to the issuance of a UK patent to Appleby and Banks in 1905 for
the application of ionizing radiation to kill bacteria in foods. A US patent
was later issued to D.C. Gillett in 1918 for an apparatus for preserving or-
ganic materials by the use of X-rays [8]. In 1929 preliminary investigational
work was published on logarithmic mortality rates of bacteria exposed to
radiation by M. Curie [11], F. Holweck [12], and M.A. Lacassagne [13] at
De L’Academe Des Sciences in Paris. By the late 1960s, gamma irradiation
was commonly used for large-scale terminal sterilization of medical devices
due to increased availability of radioactive sources [14, 15] and the higher
reliability of gamma irradiators with respect to electron beam accelerators
of/at that time.
Sources of radiation used for terminal radiation sterilization supply
electrons from electron beam accelerators or photons from either a radio-
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isotope (Co , Cs ) or accelerators (bremsstrahlung) to transfer energy to
the product. Source electrons or photons ionize molecules and atoms of the
product material initiating a cascade of scattered electrons throughout the
irradiated product. These scattered electrons damage nucleic acids, proteins,
and enzymes essential for a microorganism’s growth and proliferation [16].
The penetrating ability of these radiation sources facilitate the sterilization
of bulk medical products in their final packaging (terminal sterilization).
The amount of energy transferred and absorbed by a product is mea-
sured in units of absorbed dose called kilograys (kGy). The absorbed dose
is measured with a dosimeter and calibrated dosimetry system [17–19].
Sterility resulting from a validated radiation sterilization process is based
on a bioburden method [20] that directly correlates the minimum ab-
sorbed dose received by the product to a sterility assurance level (SAL).