By Robert McIlvaine and Betty Tessien, The McIlvaine Company
Cleanroom devices are mostly thought of as modular laminar-flow systems, also called benches. However, the definition can be extended to cover everything from gloveboxes to microenvironment cleanrooms. In fact, the growing emphasis on microenvironments for the semiconductor industry is blurring the distinction between devices and rooms.
The current definition of enhanced clean devices (ECDs) as developed by ISO/TC209 Working Group 7 is as follows: Equipment utilizing physical and/or dynamic barriers to create improved levels of separation between the inside and outside of a defined volume. While the term minienvironment is used in the electronics industry, people in the healthcare industries use the term isolator, and glovebox is the accepted term in the nuclear industry.
Richard Matthews, president of Filtration Technology, Inc. (Greensboro, N.C.), explained in CleanRooms magazine (January 1999), “The term ECD arrived out of a necessity to coin a term that generically represented all of the above without favoritism to a particular industry or end-use application. This newly coined term also had to be unique so it wouldn’t conflict with closely related terms or acronyms.”
ECDs utilize physical or dynamic barriers, which can be curtains of air or solid steel walls, to create separation. The devices typically integrate personnel interface. They can be 100 percent self-contained and can have built-in glove sleeve systems and associated transfer devices. They are clean environments, but they are not cleanrooms.
Pharmaceutical compounding activities are classified as low, medium, and high risk. Each risk level has associated criteria for the compounding environment and storage conditions. United Stated Pharmacopia (USP) Chapter 797, effective January 1, 2004, requires that compounding be performed in a cleanroom environment providing ISO Class 8 (Class 100,000) air quality conditions. A “primary engineering control,” such as a clean bench or biological safety cabinet, must also be used within the cleanroom to provide ISO Class 5 (Class 100) air quality. A glovebox may offer an alternative means for aseptic processing.
According to James P. Agalloco, president of Agolloco & Associates (Belle Mead, N.J.), several firms endeavored to find a means to obviate the perceived inflexibility of isolators caused by difficulties relating to decontamination, leak testing, ergonomics, and flexibility of access. Thus, the restricted access barrier systems (RABS) concept was developed. RABS aim to provide the sterility assurance benefit of an isolator with fewer complications. Agalloco and James E. Akers, president of Akers Kennedy & Associates (Kansas City, Mo.), developed a description of an ideal RABS for advanced aseptic processing that would include fully automated aseptic processing systems with no requirement for human intervention. The system would operate in a predominantly unmanned cleanroom, and the entire cleanroom and RABS enclosure could be decontaminated with vaporized hydrogen peroxide or an equivalent technology. In addition, the RABS enclosure would be ISO 5 at all times and positive to the surrounding ISO 6 or ISO 7 environment. All maintenance could be accomplished through gloves, with no direct or open human intervention.
Benches
Cleanroom working areas or workstations are used in many places where air-transported particles, germs or other contaminating material could affect products, working processes and analysis results.
The basic concept of the workstation is to take air through a blower system, pressurize a plenum, and force air through the HEPA filter. Since the filter is subject to extreme air pressures, it must be strong and well built. The air then passes over the central work area, driving out airborne contaminants to provide a contamination-free environment for particular specifications.
The laminar flow clean bench is generally described as a workbench or similar enclosure characterized by its own filtered air supply. In recent years, the use of clean benches has spread from research and manufacturing to other fields such as aerospace, bioscience, pharmaceuticals, and food processing. The laminar flow clean bench can be found in a variety of facilities, including medical research laboratories, manufacturing, hospitals, and other clinical and research settings. Applications include syringe filling, sterile preparation, plant tissue culturing, and media preparation. In addition, the clean bench is used extensively in the electronics industry for testing, assembly, and inspection of products. According to Keith Landy, vice president of Germ Free, Inc. (Ormond Beach, Fla.), “Gloveboxes are often used to handle chemical hazards and are starting to be used instead of fume hoods.”
Gloveboxes
Gloveboxes are used mostly for difficult or dangerous operations. They provide protection to workers handling hazardous materials, such as those required for blending or mixing processes. Gloveboxes are also used for washing contaminated process equipment and for preventing cross-contamination in multiple process blending areas. Gloveboxes are easy to manufacture and, with the addition of tools and technologies, can provide a cost-effective alternative for small-environment contamination control. Newer gloveboxes utilize robotics for further safety and efficiency.
According to The Baker Company (Sanford, Maine), a leader in the design and manufacture of biological safety cabinets, clean benches and fume hoods, gloveboxes with air quality that is the same as, or better than, a cleanroom offer design advantages such as occupying less floor space, lower start-up and construction costs, lower operating costs, better working conditions for pharmacy personnel and greater sterility assurance due to the physical barrier.
Biological safety cabinets
As research and related work in the life science field has increased during the past few decades, the importance of protective equipment in the workplace has similarly increased. The need to prevent accidental infection of personnel and to protect the environment and the product have resulted in the development of a wide variety of biological safety cabinets. In addition, a diverse array of new procedures and scientific applications has made biological safety cabinets increasingly desirable.
The purposes and functions of a safety cabinet include protecting personnel from harmful agents inside the cabinet; protecting the work, product, experiment, or procedure performed inside the cabinet from contaminants in the laboratory environment or from cross-contamination inside the cabinet; and protecting the environment from contaminants contained in the cabinet.
The latest federal engineering and design requirements for biological labs are published in the fourth edition of Biosafety in Microbiological and Biomedical Laboratories, a guide jointly published by the Center for Disease Control and Prevention and the National Institutes of Health1. The guide defines four biosafety levels (BSL), with Level 1 being the least restrictive. Containment labs have BSL-3 and BSL-4 designations. A Class III biological safety cabinet is a specific glovebox for use in a biomedical lab.
Minienvironments
Minienvironments allow localization of contamin-ation control to specific tools or process areas within the cleanroom
The simplest minienvironments are enclosures designed to separate processes from contaminating sources (people and other equipment) within the cleanroom. In these installations, barriers extend from the cleanroom ceiling filtration system and surround the process equipment.
More complex, integrated minienviron-ments create localized environments in which specific factors-including contamination levels, hazardous vapors, temperature, pressure, humidity, molecular contamination, electrostatics, electromagnetic radiation, sound, and vibration-can be controlled more precisely than in the general cleanroom.
The contamination control achieved in minienvironment technology by the physical barrier between wafers and cleanroom environment allows the use of ISO Class 5 (Class 100) or ISO Class 6 (Class 1,000) cleanrooms, as well as less expensive cleanroom garments. As a result, the investment and operating costs of a cleanroom decrease and the working environment becomes friendlier for the operator. Moreover, the physical isolation of the product, such as wafers, results in a reduction of particulate contamination and, subsequently, an increase in product yield. Various minienvironment users have reported remarkable yield increases. This is considered the main benefit of minienvironment technology, especially during the ramp-up phase of the line when some equipment is functional while adjacent equipment is still being installed.
Isolators
In the pharmaceutical industry, the use of isolators for filling lines and sterility testing has gained acceptance. A trend toward more toxic drugs is turning attention to designs that can provide product containment as well as aseptic conditions to protect operators from product contact.
Regulatory concerns also drive isolator technology. Europe has pioneered the use of isolator-equipped filling lines, but the number of installations in the United States and Japan is growing. The number of isolator-equipped filling lines installed each year started out slowly, peaking at 17 in 1997, and currently hovers around ten per year.
Isolation technology allows the complete removal of personnel from the environment. In advanced isolator technology, operators perform only a limited number of tasks. Gloves are hermetically sealed to the isolator wall, providing a barrier between the critical environment and the operator. The use of isolation technology does not preclude the use of aseptic techniques; thus, direct contact between the gloves and materials is not acceptable.
Isolators reduce the required floor area of a facility by 15 to 35 percent and drastically cut air handling requirements by eliminating the need for ISO Class 5 (Class 100) space, segregated rooms for each product, changing rooms and airlocks. Regulatory agencies seem to be most comfortable with positive-pressure, high-transfer-integrity, chemically disinfected designs, especially when these systems are combined with good ergonomics and a well-planned and strictly enforced operator training program.
Modern isolators feature modular designs configured to process specification, radius corners for easy wipe-down or sterilization, process-gas generation and analysis, vacuum control, static control and ISO Class 3 (Class 1) cleanliness levels.
Before products can be marketed, most sterile processes performed in isolators will need to be validated by DHSS for FDA. Therefore, isolator users must be able to demonstrate reliable and reproducible sterilization cycle results.
At 30 to 70 percent above that of a manned cleanroom, the cost of isolation technology has been a concern. However, savings in utility consumption, gowning materials, labor use, decontamination, and environmental monitoring offset the expense.
Markets
Clean devices are used in the complete range of industries utilizing cleanrooms. In 2006, the semiconductor industry will account for nearly 25 percent of the total purchases of clean devices worldwide (see Table 1).
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The pharmaceutical industry will be the second largest purchaser. The maturation of biotechnology as it moves from pilot to production facilities will be one of the major contributors to growth in this segment.
The rapidly growing flat panel industry has now surpassed disk drives to rank third.
The category “cleanroom suppliers” includes all companies providing cleanroom hardware and consumables (which are manufactured in cleanrooms). This also includes cleanroom laundries.
The market in Asia is growing faster than in other regions. In 2010, the U.S. will still be the leading purchaser of cleanroom devices, but the next six rankings belong to Asian countries (see Table 2).
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China is rapidly expanding its purchases and will eventually compete with the U.S. and Japan for the top spot. Growth will be slow, however, in western Europe.
The market for devices will grow at a slightly higher rate than that of the cleanroom industry in general. The trend toward increased use of clean devices will be at the expense of some of the growth in garments and processing as people are removed from the clean environment.
Notes
1. Biosafety in Microbiological and Biomedical Labs (BMBL), 4th edition is available online at http://www.cdc.gov/OD/OHS/biosfty/bmbl4/bmbl4toc.htm.
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Robert McIlvaine is president and founder of The McIlvaine Company in Northfield, Ill. The company first published Cleanrooms: World Markets in 1984 and has since continued to publish market and technical information for the cleanroom industry. He can be reached at [email protected].
Betty Tessien is the cleanroom publications editor for The McIlvaine Company.