Radiation Sterilization - Sterilization Methods

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Chapter: Pharmaceutical Microbiology : Sterilization Procedures And Sterility Assurance

Several types of radiation find a sterilizing application in the manufacture of pharmaceutical and medical products, principal among which are accelerated electrons (particulate radiation), gamma rays and UV light (both electromagnetic radiations).



Several types of radiation find a sterilizing application in the manufacture of pharmaceutical and medical products, principal among which are accelerated electrons (particulate radiation), gamma rays and UV light (both electromagnetic radiations). The major target for these radiations is believed to be microbial DNA, with damage occurring as a consequence of ionization and free-radical production (gamma rays and electrons) or excitation (UV light). This latter process is less damaging and less lethal than ionization, and so UV irradiation is not as efficient a sterilization method as electron or gamma irradiation. Vegetative bacteria generally prove to be the most sensitive to irradiation (with notable exceptions, e.g. Deinococcus (Micrococcus) radiodurans), followed by moulds and yeasts, with bacterial spores and viruses as the most resistant (except in the case of UV light, where mould spores prove to be most resistant). The extent of DNA damage required to produce cell death can vary and this, together with the ability to carry out effective repair, probably determines the resistance of the organism to radiation. With ionizing radiations (gamma ray and accelerated electrons), microbial resistance decreases with the presence of moisture or dissolved oxygen (as a result of increased free-radical production) and also with elevated temperatures.


Radiation sterilization with high-energy gamma rays or accelerated electrons has proved to be a useful method for the industrial sterilization of heat-sensitive products. However, undesirable changes can occur in irradiated preparations, especially those in aqueous solution where radiolysis of water contributes to the damaging processes. In addition, certain glass or plastic (e.g. polypropylene, PTFE) materials used for packaging or for medical devices can also suffer damage. Thus, radiation sterilization is generally applied to articles in the dried state; these include surgical instruments, sutures, prostheses, unitdose ointments, plastic syringes and dry pharmaceutical products . With these radiations, destruction of a microbial population follows the classic survivor curves  and a D-value, given as a radiation dose, can be established for standard bacterial spores (e.g. B. pumilus) permitting a suitable sterilizing dose to be calculated. In the UK it is usual to apply a dose of 25 kGy (2.5 Mrad) for pharmaceutical and medical products, although lower doses are employed in the USA and Canada.


UV light, with its much lower energy, causes less damage to microbial DNA. This, coupled with its poor penetrability of normal packaging materials, renders UV light unsuitable for sterilization of pharmaceutical dosage forms. It does find applications, however, in the sterilization of air, for the surface sterilization of aseptic work areas, and for the treatment of manufacturing-grade water.


a)  Sterilizer Design And Operation


i)  Gamma ray sterilizers


Gamma rays for sterilization are usually derived from a cobalt-60 (60Co) source (caesium-137 may also be used), with a half-life of 5.25 years, which on disintegration emits radiation at two energy levels of 1.33 and 1.17 MeV. The isotope is held as pellets packed in metal rods, each rod carefully arranged within the source and containing up to 20 kCi (740 × 1012 Bq) of activity; these rods are replaced or rearranged as the activity of the source either drops or becomes unevenly distributed. A typical 60Co installation may contain up to 1 MCi (3.7 × 1016 Bq) of activity. For safety reasons, this source is housed within a reinforced concrete building with walls some 2 m thick, and it is raised from a sunken water-filled tank only when required for use. Control devices operate to ensure that the source is raised only when the chamber is locked and that it is immediately lowered if a malfunction occurs. Articles being sterilized are passed through the irradiation chamber on a conveyor belt or monorail system and move around the raised source, the rate of passage regulating the dose absorbed (Figure 21.9).



Radiation monitors are continually employed to detect any radiation leakage during operation or source storage, and to confirm a return to satisfactory background levels within the sterilization chamber following operation. The dose delivered is dependent upon source strength and exposure period, with dwell times typically up to 20 hours. The difference in radiation susceptibilities of microbial cells and humans may be gauged from the fact that a lethal human dose would be delivered by an exposure of seconds or minutes.


ii)                Electron accelerators


Two types of electron accelerator machine exist, the electrostatic accelerator and the microwave linear accelerator, producing electrons with maximum energies of 5 MeV and 10 MeV, respectively. Although higher energies would achieve better penetration into the product, there is a risk of induced radiation and so they are not used. In the first, a high-energy electron beam is generated by accelerating electrons from a hot filament down an evacuated tube under high potential difference, while in the second, additional energy is imparted to this beam in a pulsed manner by a synchronized travelling microwave. Articles for treatment are generally limited to small packs and are arranged on a horizontal conveyor belt, usually for irradiation from one side but sometimes from both. The sterilizing dose is delivered more rapidly in an electron accelerator than in a 60Co plant, with exposure times for sterilization usually amounting to only a few seconds or minutes. Varying extents of shielding, depending upon the size of the accelerator, are necessary to protect operators from X-rays generated by the bremsstrahlung effect.


iii)             Ultraviolet irradiation


The optimum wavelength for UV sterilization is around 260 nm. A suitable source for UV light in this region is a mercury lamp giving peak emission levels at 254 nm. These sources are generally wallor ceiling-mounted for air disinfection, or fixed to vessels for water treatment. Operators present in an irradiated room should wear appropriate protective clothing and eye shields.


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