In the 1960s, at about the same time that exposure to gamma rays turned diffident physicist Dr. Bruce Banner into the Hulk, pharmaceutical companies began adopting gamma irradiation as a sterilization technique. Over time, new methods of radiation sterilization have emerged. Electron-beam sterilization, one of these new methods, is becoming increasingly popular among drugmakers.
Electron-beam, or e-beam, sterilization works much the same way that a tube television does. A device called an electron-beam accelerator produces electrons in a vacuum. Rather than being stopped by a TV screen, the electrons travel in a beam through an output window to the product. The radiation breaks down the DNA of the microbes with which it comes into contact, thus making them unable to replicate. A dose of about 25 kGy can yield a 7-log decrease in the amount of microorganisms on a surface (1).
Companies have installed e-beam sterilizers on line to treat products that travel along a conveyor belt. The technique aids the transfer of materials such as plastics and lightweight glass components into isolators, restricted-access barrier systems, or aseptic filling lines. Drugmakers previously did not have an effective way to introduce these materials into their aseptic environments. Instead, the industry either avoided them entirely or sanitized them. Operators used to wipe down glass-syringe tubs manually before transferring them into the aseptic fill room or isolator, a solution that many considered unsatisfactory. E-beam sterilization allows companies to use more plastics and to replace many sanitization applications.
Some manufacturers use e-beams for terminal sterilization, although the method is not common in this function. In the appropriate applications, e-beams also could replace other sterilization methods. For example, companies could use e-beams instead of gas to sterilize the exterior of any internally sterile packaged material, says Jim Agalloco, president of Agalloco and Associates, and a member of Pharmaceutical Technology’s editorial advisory board.
E-beam sterilization has many benefits for pharmaceutical companies. Unlike methods such as steam-in-place, e-beam sterilization requires no preparation and no poststerilization steps. The process is extremely rapid. “It’s literally like turning the TV on, exposing the item, and turning the TV off,” says Agalloco. E-beam sterilization is quick enough to enable production processes to run at a semicontinuous or continuous mode.
The technique has practical benefits at the plant level, too. Operators might appreciate the fact that e-beam accelerators incorporate a lot of shielding, are quite safe to use, and require little training. Plant managers might be pleased to know that e-beam sterilization can be considered a green technique because it does not require chemicals or water. The equipment uses little electricity and sometimes can cut utility costs by about 80% (2). In addition, e-beam accelerators can be fully integrated into a production process and are easy to validate.
Radiation-based sterilization has certain drawbacks, though, and e-beam sterilization is no exception. The technique damages particular materials such as plastics, but the degradation is not immediately apparent. It could take months for the material to break down, possibly because the free radicals that the process creates remain active during this time. Unfortunately, manufacturers cannot perform accelerated stability tests to determine whether e-beam sterilization is appropriate for a given substance.
E-beam sterilization can present its own challenges as well. Certain materials undergo a color change during the process. Although the change may not be clinically significant, it could raise aesthetic concerns or inspire doubt in patients’ minds. In addition, electrons sometimes strike oxygen molecules and create ozone within a container, which could pose problems for the drug product.
Manufacturers must keep in mind the limitations that e-beam sterilization imposes. For one, the technique requires a small target and is ineffective against large targets such as pallets. And because e-beams are not as powerful as gamma radiation, companies must restrict their use to materials that are easy to penetrate such as plastics and thin glass. Metals and powdered substances are harder to penetrate, and thus more difficult to sterilize effectively with e-beams, says Agalloco.
In recent years, e-beam sterilization has quickly gained favor in the pharmaceutical industry, despite its limitations. At first, radiation was considered the province of experts, and drugmakers shied away from the e-beam technique for a long time. It did not help that early e-beam systems were costly and could be a story and a half tall. As the technology evolved, the machines shrank, and the equipment became more affordable, e-beam sterilization became much more attractive to pharmaceutical companies, says Agalloco.
Even as the drug industry begins to embrace e-beam technology, observers have seen early signs that another form of radiation sterilization could have pharmaceutical applications. X-ray technology has been improving, and may now be at the point where e-beam was 15 years ago, says Agalloco. X-ray sterilization works by the same principle as e-beams, but uses more powerful radiation that penetrates materials better. Medical-device manufacturers now use X-rays to sterilize large targets such as pallets, and the process operates more quickly than the e-beam technique. On the other hand, X-rays potentially could cause more degradation and increase concerns about worker safety.
Although each method has its drawbacks, the pharmaceutical industry has discovered appropriate applications for several sterilization techniques. The newfound popularity of e-beams and the potential growth of X-rays show that technological developments continue to expand drugmakers’ options for radiation sterilization.
1. P. Fontcuberta, ISPE Washington Conference (Washington, D.C., 2009).
2. D. Icke, Pack Expo (Chicago, 2008).