WASHINGTON, D.C.A few pharmaceutical companies have jumped behind the proverbial wheel of barrier isolation technology, but many clean space-dependent industries continue to kick the tires.
Some contamination control industry observers say it comes down to cost and risk, while others say the market is hinged on the drafting of recommended practices. And one observer even sounds a bit like Henry Ford, suggesting that some day everyone will have an isolator along with his or her cleanrooms.
A Despatch UV chamber at Pharmacia and Upjohn shows the locally controlled environment at the entrance to the UV chamber. Photo courtesy of Pharmacia and Upjohn.
Aside from the reasons, industries that rely heavily on contamination control have indeed come to the crossroads.
“It's going to happen; the industry is going to have both [cleanrooms and barrier isolators],” says Richard A. Matthews, founder of Filtration Technology Inc. (Greensboro, NC) and president of Micron Video International. “There's a dichotomy that's happening in the cleanrooms industry, everything is being driven by the process. So, on one side you have the need for an isolator for a smaller space and to keep costs down, and on the other you want the space-flexibility so you have available clean space.”
To date, however, those who have adopted the technology are mainly pharmaceutical companies. [See “Investing in isolation technology,” CleanRooms, August 1999, page 19.] In fact, you can count the number of companies that have made this investment on both hands, exclaims Dr. Peter Cooney, associate director for microbiology in the Office of New Drug Chemistry with the Food and Drug Administration's Center for Drug Evaluation and Research (Rockville, MD). “If you're going to make this kind of investment, you're a company that has a lot of capital as well as the ability to take a risk,” he says.
One company that uses isolators is Pharmacia and Upjohn Inc. (Kalamazoo, MI). It combined an older form of sterilization, ultraviolet radiation, with isolators for a process that has somewhat fueled the advent of a technology that simultaneously sanitizes and transfers medical products from a non-sterile to a germ-free environment.
“UV radiation has been used in Pharmacia and Upjohn isolator systems since 1992,” says Christopher Bell, a microbiologist for the sterilization technology division. “It has low operating and maintenance costs and short cycle times with no residuals.”
Bell, co-chair of the Parenteral Drug Association (PDA; Bethesda, MD) task force on container and closure integrity, was one of several speakers who presented abstracts on isolation technology at the 1999 PDA annual meeting, held in late November.
Cooney: Take a rick.
While Bell's presentation outlined how best to use and validate an ultraviolet radiation/isolation system, other lectures pointed to challenges and spotlighted issues surrounding the technology. Perhaps the greatest challenge is designing and producing an isolation system that can move large amounts of consumables without compromising their integrity or the reliability of the technology. On top of that, there is increasing debate over whether isolators are truly sterile and provide a better method than the conventional aseptic process.
Isolation systems, however, can be adapted to other processes, contends Austin McDonald, president of IC Technology (Livingston, NJ), a maker of sterile transfer systems. McDonald was on hand at the PDA conference, touting IC Technology's single-use, bag-like container transfer system for high-volume production.
“The technology is in the hardware, and when we developed it, we did not want to have to change the application,” he adds. “We can manufacture transfer systems to meet any application.”
While isolation may have some advantages over conventional cleanrooms, it does have some drawbacks, Cooney says. On the plus side, isolators eliminate the classic problem of microorganisms being inadvertently introduced to products by personnel. “Even though people are eliminated from the process, the problem is the process has not been proven long term, and areas of concerns are in the final analysis when products are sterilized by filtration,” he explains. “If you have a Class 100 cleanroom, the liquid portion of the drug product is filtered and there are problems associated with filtration. An isolator does not resolve those problems.”
Moreover, there is a strong contingent in the pharmaceutical industry that believes isolators should perform flawlessly.
“Some people have the expectation that [isolators] should be completely sterile. I do not hold that view,” James Agallocco, president of Agallocco & Associates (Belle Mead, NJ) said at an isolation technology interest group forum at the PDA conference.
Agallocco is also a PDA member who is leading an effort to establish a task force dedicated to hammering out a recommended practice for implementing isolation technology. The task force, he says, will attempt to answer such questions as are isolators truly sterile?, what makes them different than cleanrooms?, and do they provide a better method than conventional aseptic processes?
“We need a rational approach to isolation technology that says, 'Yes, it is better than cleanrooms,'” he adds.
Matthews, who chairs the International Organization for Standardization Technical Committee ISO/TC 209 “Cleanrooms and associated clean environments,” says the ISO is generating a generic standard to address isolation technology. Alas, he adds, a comprehensive approach for all aspects is needed.
“There should be industry-specific practices that address industry specific needs,” Matthews says. “The microelectronics guy is not going to care if the isolator is sterile, but the pharmaceutical guy is.”
Matthews also warns that barrier isolation may not necessarily be more economical than cleanroom, for each design has its limitations. “There's romance on the street that says isolation is cheaper and better. It might be appropriate for the process, but not for future changes,” he says. “The other issue is that a minienvironment is not always going to be cheaper.”