For a look at studies that Amgen has done regarding the potential impact of e-beam radiation on protein products, click here. For a podcast interview with Skan COO Jim Spolyar on his company’s electron-beam work with GSK, Wyeth, and others, click here.
A clear advance in the world of pharmaceutical aseptic processing has been the popularization of low-energy electron beam technology for sterilization—the topic generated quite a bit of buzz at 2008’s ISPE annual meeting in Boca Raton, as well as at Pack Expo in Chicago. While high-energy electron beams have been used in a variety of industries for some time, low-energy e-beams have only come on the scene within the last decade.
ASTM’s Sixth International Workshop on Dosimetry for Radiation Processing
The topic of electron beam radiation for pharmaceutical processes will be one key area
One advantage of the technology is that the energy, while strong enough to eradicate surface contaminants of, say, a vial or syringe—or even a tub filled with syringes—does not penetrate either packaging material or product.
Another advantage of low e-beam technology is its high degree of efficiency, with the ability to reduce bioburden in milliseconds at room temperature, says Dave Icke, VP of Marketing for Advanced Electron Beam (Wilmington, Mass.). From inches away, the beam can break the chemical bonds of, and render inert, spores, viruses, molds and other potential contaminants.
AEB is one of the firms driving and capitalizing upon advances in low-energy electron beam technology. It manufactures electron beam emitters and has the backing of GE Energy Financial Services. AEB’s devices have found their way into processing equipment commercialized by companies such as Getinge Linac (Orsay, France), Metall+Plastic (Radolfzell-Stahringen, Germany) and Skan AG (Basel, Switzerland). (Getinge Linac is also developing in-line sterilization tunnels using medium-energy electron beams for sterilizing bulk-filled syringes.)
A low-voltage emitter can run between $50,000 and $125,000, Icke says, with a typical application requiring multiple units. An emitter filament tends to burn out after about 2,000 hours of use, requiring replacement on occasion. Yet there are clear cost benefits to be derived in the elimination of other sterilization process steps.
“The important distinction is that we are doing surface sterilization, not terminal sterilization,” says Icke. Whereas terminal sterilization by, for instance, gamma irradiation or ethylene oxide, is usually done offsite by a contractor, electron beams can sterilize product or packaging in-line and eliminate the need to go outside the sterile facility. Icke claims that this can reduce a typical sterilization cycle for vials or syringes from 21 days to less than 48 hours.
One company with a long history of electron beam usage (and the patents to prove it) is Baxter Healthcare. Pharmaceutical Manufacturing recently spoke with one of Baxter’s experts on the subject, John A. Williams, Manager of Baxter’s Sterility Assurance Research Center:
PhM: What first piqued your interest in electron beam technology for pharmaceutical applications? What possibilities did you envision, and what were the limitations at the time?
J.W.: Baxter has used electron beam technology for terminal sterilization since 1989. Electron beam technology is one of the “tools in our toolbox” with regard to sterilization options we consider for new and existing applications. One of the limitations of the technology was the availability of lower energy electron beam systems designed specifically for sterilization. Many of the initial electron beam system providers were concentrating on large, higher energy systems that were designed to sterilize products in their final cartons to compete directly against irradiation with gamma. Now you have electron beam equipment providers that recognize the unique sterilization applications that low-energy electron beam could be utilized for—that is, ones that are much more product specific.
PhM: Where is the technology today in terms of its development for pharma? Where is it on the adoption curve within the industry?
J.W.: Technology has advanced significantly in that the use of low-energy electron beams for the sterile transfer of materials into an isolator is becoming commonplace. The first system for this application was delivered in 2001 and now you have over 20 electron beam sterile transfer systems installed throughout the world.
PhM: Do you consider this to be a “breakthrough” technology, or is there another term you would use?
J.W.: The commercial availability of small, low-energy electron beam systems for sterilization is relatively recent (<10 years). I consider it an “enabling technology” as it enables manufacturers to economically and reliably sterilize the surface of a product. I remember several years ago asking a pharma company director why his company implemented electron beam technology and he indicated that by using radiation he eliminated many of the concerns and questions associated with assuring the sterility of those items transferred into his filling isolator. Quite simply, he stated that every regulator understands terminal sterilization with radiation.
PhM: What are the most obvious applications of low-voltage electron beam technologies in the pharma industry? How broad are these applications?
J.W.: The most obvious is the most widely used application: the use of low-energy electron beams to sterilize the surfaces of tubs of syringes prior to introduction into a filling isolator. What comes next? The sterilization of individual containers (vials, syringes, or bags) in line directly in front of the filling equipment and low-energy sterilization of surfaces prior to connection are potential applications.
PhM: What are the advantages of EB for sterilization as opposed to UV, or chemical or thermal means? Any disadvantages?
Installing an electron beam emitter into process equipment. Courtesy of Advanced Electron Beam.
J.W.: With UV, shadowing is an issue. Chemical sterilization has issues with residuals and many materials cannot handle the temperature rise associated with thermal sterilization. Electron beam has the distinct advantage of speed and, in my opinion, ease of validation. Disadvantage: Like any form of ionizing radiation, electrons ionize oxygen, producing ozone that must be properly exhausted. The initial capital cost has been mentioned as a disadvantage but that is offset with its throughput capabilities.
PhM: Are there concerns about low-voltage electron beams and product degradation or alteration? What about its impact upon packaging materials?
J.W.: The great appeal of electrons is, by controlling their energy, you control how deeply they penetrate into the material. By using low-energy electrons, they only penetrate a few microns (<50 microns) into the material being treated so the material effects are negligible.
PhM: For sterilization applications, how fast is the process? How does this data compare to other methods of sterilization?
J.W.: The low-energy electron beam systems for the sterile transfer of materials into an isolator are designed to handle six tubs of syringes a minute continuously. This is substantially faster than sterilization of the outside of the tubs with hydrogen peroxide, which is typically a batch process. The amount of literature available on the effectiveness and speed of radiation sterilization is quite large and comprehensive.
PhM: What are the limitations of the technology that need to be overcome before it becomes more widespread?
J.W.: I am actually of the opinion that, based upon the sheer number of systems being used for the sterile transfer of syringe tubs, the use of electron beams in pharma is widespread. Education is one limitation. Providing educational opportunities so pharma can have a better understanding of potential radiation sterilization options would increase the use of low-energy electrons as well as the potential for terminal sterilization of drugs with radiation. ASTM is sponsoring an international dosimetry workshop next year in Germany (Karlsruhe, October 4-8, 2009) that has a special topics session devoted to low-energy electron beam dosimetry.
About John A. Williams
John A. Williams is the Manager of the Corporate Sterility Assurance Research Center for Baxter Healthcare Corporation in Round Lake, IL. John has over twenty years of experience in the industrial applications of radiation for nondestructive testing, material modification, and sterilization.
Pharma Applications for Low-Energy E-Beams
Dave Icke, VP of Marketing for Advanced Electron Beam (AEB), sees three standard applications for low-energy electron beam technology in the pharmaceutical industry: