Barrier isolation boosts biotech productivity
Isolated environments enable quick and efficient production of pharmaceutical and biotechnology products in a compact space.
By David Reese
Carter and Burgess, Inc.
In the 20 years since the first dedicated biotechnology companies were founded, the industry has expanded with the same multiformity as the biological processes on which it is based. Current industry earnings of $5.5 billion will seem insignificant by the year 2000 when a flood of new products is predicted. Already, nearly 200 biotech drugs are in the final stages of testing (four dozen aimed at cancer and 40 at AIDS and other infections alone), and at least 50 new biotech drugs will hit the market in the next two years.
The proliferation of new product applications has also spurred the need for different kinds of manufacturing facilities. For example, as biotechnology products move from testing to production, there is less need for human-intensive environments (e.g., research and development labs, pilot plants, large open multi-purpose work areas and gowning areas for technicians). As a result, automated production equipment can be integrated within isolated sterile environments or “barrier isolation systems” allowing pharmaceutical and biotechnology products to be produced more quickly and efficiently, almost literally “untouched by human hands.”
Tightening requirements
Contamination-control requirements are becoming increasingly stringent for both the pharmaceutical and biotech industries. As observed by Jack Lysfjord, vice president of technology and international sales at TL Systems (Minneapolis, MN), “many new pharmaceuticals, especially parenteral products, demand ever-stricter process cleanliness requirements. Where today`s standard is 10-3 (1 in 1,000 vials would fail a sterility test), the FDA encourages manufacturers to meet 10-6 (1 in 1,000,000 vials) or better.”
Lysfjord adds that the unique characteristics of biotechnology products add another challenge. “We`re winding down development of drugs that are chemically based,” he says. “A growing number of biotechnology products involve creating a drug for a specific purpose. For example, protein is grown in media that sustains growth but is also very sensitive to external factors such as temperature and airflow. As a result, the processing equipment has to provide an environment that is sterile as well as stable.”
Providing such environments using traditional cleanroom methods is both labor- and space-intensive. Alternatively, barrier isolation technology allows equipment to be oriented in a clean, more compact, three-dimensional space. With most human interaction now accomplished through remote-controlled tools or glove port holes, the width of a cleanroom can essentially be shrunk from 25 to two feet.
The cost of clean
In a recent Scientific American article, Ernst & Young estimated the value of the biotechnology research industry in 1994 at $41 billion, but observed that because production and operation costs are so high, profit margins are generally low. Therefore to attract the capital necessary to fuel further growth, biotechnology manufacturing firms must find ways to streamline their production operations wherever possible.
Barrier isolation environments offer several opportunities for cost control. For example, while conventional cleanrooms can cost as much as $700 to $800 per square foot, a typical isolated cube can remove roughly a third of these design, operation and maintenance costs by concentrating specialized mechanical/electrical systems in one area.
Barrier isolation technology can produce another 10 percent in savings through reductions in the amount of germ-resistant surface space required. Airlocks, impervious floors, walls and ceilings, joint sealers and fixtures must still protect barrier isolation systems, but as the available space is optimized, the amount of exposed surface area required to be kept clean and sterile is also minimized.
In addition, according to analyses by the LUMS group (a collaboration of Eli Lilly, Pharmacia & Upjohn and Merck), barrier isolation technology can cut personnel costs by as much as 66 percent through reductions in monitoring and control requirements. Since everything can be operated and monitored from less restrictive areas outside the cube, energy costs are also less than standard cleanrooms.
Lysfjord is quick to add that people also need to be protected. “The cleanroom is not suitable for many potent products, which are toxic,” he says. “Although you can add personal-protection measures, such as respirators, they are inefficient and uncomfortable to work in, and they limit movement. The best option, then, is to design equipment to be operated in its own stable environment and keep people outside.”
Maintenance is also an issue. While workers will still have to remove the isolation barriers to perform repair work, followed by an internal validation pro cess, maintenance in a barrier isolation environment will usually be performed on a scheduled basis as opposed to large cleanroom environments, which require constant attention.
Moving forward
While barrier isolation technology already provides many benefits and advantages, important issues remain to be addressed. For example, the rooms in which barrier isolation systems are operated represent one of the key areas of opportunity as the equipment and technology move toward validation. While most isolation systems are being designed to operate in a standard Class 100,000 environment (instead of the more restrictive Class 100 facility), the special high-efficiency particulate air (HEPA) filters that reduce airborne matter must still be able to operate over a long period of time and be contained if exposed to biohazards. Likewise, room surfaces must be decontaminated when necessary.
Other issues include routine preventive maintenance; prevention of microbial growth on valves, gaskets and rapid transfer ports; and maintenance of proper temperature and pressure in the internal environment.
“The FDA recognizes that the use of barrier isolation technology offers many benefits to the aseptic manufacture of pharmaceutical products,” says Dr. Ken Muhvich, who recently was a spokesperson for the FDA`s Center for Drug Evaluation and Research (CDER) on the use of barrier isolation equipment. “However, we must make every effort to ensure that potential contamination of sterile drug products has been addressed. Even if the systems operate in Class 100,000 areas — as opposed to unclassified environments — the cost savings will nevertheless be significant. It really comes down to what kind of environment a manufacturer can validate and maintain.”
Although barrier isolators are ideally suited to new buildings, even with their inherent advantages, they are not always adaptable for retrofit to many existing cleanrooms. One problem is that many enclosures, surfaces and building air systems are often left in place, even though they are no longer necessary. By building the design around isolator areas, a facility owner will have more flexibility in locating special equipment, mechanical/electrical systems and other operational functions.
The biotechnology industry has come a very long way in a short time with many of the products, and the technology that produces them, unthinkable a generation ago. As the industry continues to grow and mature, designers and builders can work with equipment manufacturers and biotechnology companies to deliver cost-effective facilities that will continue to support that expansion.
David Reese, AIA, is the director of the Advanced Technology Group at Carter & Burgess architecture/engineering/construction management firm. With more than 25 years of experience, his hands-on involvement keeps him aware of current standards, regulations and future directions for a broad range of highly technical industries.
 |
A barrier isolation environment at TL Systems/Bosch Group (Minneapolis, MN). Photo Courtesy of TL Systems.