Compiled by Sue Forsyth

Cleaning agents are used on walls, ceilings, floors and equipment in the cleanroom. A well-rounded systematic approach to choosing, evaluating and using cleaning agents is critical to maintaining control of contamination.

Sterile alcohols

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The TexShield Sterile 70% Isopropyl Alcohol and Sterile 70% Isopropyl Alcohol with water for injection (WFI) are easy and safe to use, cost effective, and maintain their sterility assurance level throughout prolonged normal use. The bottles are recyclable and the contents can be completely dispensed. The TexShield alcohol products are all packaged using the SteriShield Delivery System (patent pending). This system holds the liquid inside an ultra-clean, medical grade, polyolefin bag that does not allow air to be drawn back into the bag when the trigger spray mechanism is operated. Testing shows the contents remain sterile for three months after first operating the trigger. Packaged in one-liter and five-liter containers, the sterile alcohols are useful for surface cleaning, cleaning gloved hands in sterile suites, and wiping down items for pass through into a controlled environment. ITW Texwipe Mahwah, NJ www.texwipe.com

Sterilizing solution

The SimpleMix system is a sealed multi-chamber, handheld container that, when activated, mixes a sterilizing solution with USP water for injection (WFI) quality water. The side chamber contains the sterile concentrate disinfectant or sporicide, and the larger chamber holds the sterile UPS WFI-quality water. The system is available in either the 16-ounce trigger sprayer or a gallon-sized container for larger uses. All SimpleMix products are manufactured in a Class 100 GMP filling operation, filtered at 0.2 micron, double-bag packed per bottle, gamma irradiated, and lot sterility tested per current USP compendium. The SimpleMix system has been developed for the company's Decon Phene, Decon Phase, Decon Cycle, Decon Quat 100, Decon Clean, and Decon Spore 200 Plus. Veltek Associates Inc. Malvern, PA www.sterile.com

Point-of-use cleaning solutions

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The One Solution Vesphene Vesphene IIst system and One Solution LpH st system are complete, efficient, point-of-use cleaning solutions for critical environments. Each system includes a pre-measured, single-use formulation of Vesphene IIst or LpH st and one gallon of water for injection (WFI), double-bagged with linear tear strips for easy introduction into the cleanroom core. The systems are irradiated to a 10^-6 sterility assurance level. Steris Corporation Mentor, OH www.steris.com

Sterile alcohol solution

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The CiDehol ST 70% IPA solution is made to meet water for injection (WFI) specifications with regard to endotoxin levels. Endotoxin testing is performed on all lots of finished sterile alcohol products to ensure this claim and results are listed on the company's lot-specific document, which is shipped with each case. The sterile alcohol solutions are filtered to 0.22 µm, bottled and double-bagged in a Class 100 cleanroom, then gamma-irradiated and tested for sterility. Decon Labs Inc. Bryn Mawr, PA www.deconlabs.com

Increased funding for research into treatments, antidotes and vaccines against bioterrorism agents has sparked a building boom for biosafety facilities

BY BETSY ZIOBRON

When we think of cleanrooms, we think of controlled manufacturing environments utilizing contamination control processes to remove small particles of dust and debris that can wreak havoc on circuitry and electronics. But the war on terror has given rise to a different type of “clean” facility where contamination control takes on a whole new meaning.

Bio boom

Following 9/11 and the subsequent anthrax attacks, increases in homeland security funding have given rise to Biosafety Level 3 (BSL-3) laboratories for clinical, diagnostic, research or production work with agents that may cause serious or potentially lethal disease. Much of the funding is channeled through the National Institute of Allergy and Infectious Diseases (NIAID) with at least a dozen BSL-3 facilities in planning or development stages at various universities throughout the nation.

In October 2003, a new BSL-3 lab opened in Los Alamos, N.M., and in May 2004, the Food Safety and Inspection Service (FSIS) opened a $1.65 million BSL-3 lab in Athens, Ga. “As part of our efforts to enhance homeland security, USDA has implemented an extensive program to secure American agricultural production and protect consumers,” says Agriculture Secretary Ann M. Veneman regarding the Athens facility. “This new lab will enhance our surveillance program, while expanding our nation's capability to respond quickly to unforeseen events.”

CDC scientist showers in a protective suite before leaving a Biosafety Level 4 laboratory in Atlanta, Georgia, USA. Source: CDCClick here to enlarge image

As part of the antiterrorism infrastructure, President Bush signed the Project BioShield Act on July 21, 2004. Project BioShield is a $5.6 billion, 10-year program that expands both public- and private-sector research incentives to develop treatments, antidotes and vaccines against possible bioterrorism agents. This latest funding has sparked a building boom among public and private companies with proposals to build more than 35 new biosafety facilities. “Large commercial pharmaceutical companies were not interested in this work before because they couldn't make money working on vaccines and antidotes for diseases that don't even exist in our country,” says Thomas R. Reynolds, executive vice president science and technology at Commonwealth Biotechnologies Inc. (CBI), which recently announced completion of its new BSL-3 virology lab. “But now that the government is funding this work through Project BioShield, I expect we'll see a lot more of it taking place in the commercial sector.”

Changing focus

While biosafety labs are not classified as cleanrooms per se, both require strict policies and procedures and a unified commitment by everyone that enters. Accredited and audited by the Centers for Disease Control (CDC), biosafety laboratories range from BSL-1 to BSL-4, much like cleanrooms range from Class 10,000 to Class 1.

BSL-1 is suitable for work involving common agents not known to consistently cause disease in healthy adult humans. BSL-2 is similar to BSL-1 but involves agents of moderate potential hazard to personnel and the environment. BSL-3 involves agents that may cause serious or potentially lethal disease. A BSL-4 facility is required for work involving dangerous and exotic agents that pose a high risk of infection and life-threatening disease. “Diseases for which there is no medical treatment or cure are typically dealt with in a BSL-4 lab,” says Reynolds. “Only a handful of BSL-4 facilities exist at well-guarded sites and bases throughout the country, many of which keep their location confidential.” Workers in a BSL-4 lab are required to shower when leaving the facility.

Deborah Cannon of the CDC’s Special Pathogens Branch processes SARS specimens. Photo by: James GathanyClick here to enlarge image

The underlying difference between a biosafety lab and a cleanroom is the contamination focus. Where cleanrooms utilize contamination control to protect product, the use of contamination control practices in biosafety labs is to protect workers and prevent microorganisms from entering the environment. However, because it's imperative to achieve quality results in the lab, the experiments must also be protected from contamination.

“We utilize the principles of working in a cleanroom where the air must be pure with no environmental contaminants,” says Reynolds. “While the typical cleanroom is concerned with contamination from oil, chemical, dust and debris, we need to prevent bacteria. Much of the work we perform is with tissue cultures, which is easily contaminated by bacteria.” Techniques deployed in the biosafety lab to ensure quality results include antibiotics in the medium, filtration, sterilization and basic decontamination practices.

Like a cleanroom environment, the main piece of contamination equipment is the exhaust hood using HEPA filtration. Class II, type B biological safety fume hoods utilize double HEPA filters and vent 100 percent of the air entering the hood to the outside of the building. These exhaust systems are typically completely isolated from the rest of the facility, and the air is never recycled.

In the biosafety lab, autoclaves are used to sterilize equipment and biological waste. “Nothing is removed from the BSL-3 lab that has not been autoclaved,” says Reynolds. “There's nothing that the autoclave can't sterilize, and we test for that by autoclaving test containers and then ensuring that they can no longer be cultured.” Once biological waste is autoclaved, a haz-mat collection group properly removes it from the premises.

“We conduct surface decontamination on a daily basis and on anything coming in and out of the laboratory,” says Reynolds. “It is very much like a typical cleanroom in that everything is done under extremely strict guidelines using a standard operating procedure that includes both a safety manual and a quality manual.”

People safety

Like those in cleanroom environments, workers in the biosafety lab are required to wear protective clothing, including sterile disposable gowns that cover the entire body, gloves, eye protection and, in some cases, respirators. Passage to the laboratory is through a series of two self-closing doors, and the sterile passageway often includes a clothes change room where workers dress in and out. The disposable clothing is autoclaved along with other biological waste.

“We're interested in keeping people safe, and the people that work in our BSL-3 facility come here because they want to do this type of work—it is their intellectual interest,” says Reynolds. “It's really no different than the risks faced by emergency room physicians on a daily basis, and we take the necessary precautions to protect ourselves.”

Personnel working in the BSL-3 lab are often vaccinated against the very disease-causing agent they are working with, and all are scientifically well versed in the characteristics of the organisms. The CDC monitors the number of lab-transmitted diseases each year, but cases are rare. “We've never had anyone become infected at our facility, and that's partly due to having extremely good safety practices,” says Reynolds. “We have a medical monitoring program through the nearby hospital for all of our workers.” CBI's medical monitoring program includes having local doctors aware of the various organisms and infectious diseases being worked on and who are responsible for administering vaccines. Each worker is monitored regularly by the doctors and whenever sickness occurs.

Other requirements of a BSL-3 lab include security and limited access with key cards, hand washing and safe handling requirements, insect and rodent control, hazard warning signs, construction that allows easy cleaning and decontamination, eyewash stations, showers and thorough documentation.

“This is good work we're doing here. It's an opportunity to make an impact, and it's patriotic,” says Reynolds. “If you're a scientist interested in pathogenic organisms, why not do work that provides some good for our country and the world?”

Work in progress

A 45-person company, CBI was established in 1992. The company built its first BSL-3 laboratory in 1997, and began working with pathogenic agents in 2000. In July 2004, they completed a new virology BSL-3 laboratory commensurate with the start of two contracts for the production of select agent viruses and assay of clinical samples stemming from a human trial of a vaccine targeting a select agent virus. “By expanding our facility to include a virology BSL-3 lab in addition to a bacteriology lab, we are now able to separate functions,” explains Reynolds. “Viruses and bacteria are handled differently. Previously with one lab, we had to decontaminate in order to start virology work. Now we perform both types of work simultaneously.”

CBI currently has biodefense contracts with both federal agencies and private companies involving analyses for select agent pathogens, detection of bioagents, including ricin and anthrax samples taken from mail sorting facilities, and vaccine development. CBI has also teamed up with DynPort Vaccine Company LLC, which is responsible for developing many of the vaccines for select agents. “We're working in vaccine development by providing tests for human clinical trials that determine vaccination response,” explains Reynolds. “In order to accept human samples, our BSL-3 lab must also operate under CLIA.” CLIA is the Clinical Laboratory Improvement Amendments through which all lab testing performed on humans in the U.S. is regulated. “We have the capabilities to do a lot of different things, and our reputation in biodefense is now well established,” says Reynolds. “Because we are for-profit and small, we have the ability to get work done quickly and cost efficiently.”

A scientist wearing a protective suit with helmet and face mask is seated at a biological safety fume hood as he conducts his studies. Photo by: James GathanyClick here to enlarge image

CBI also recently announced that it has initiated the sale of biodefense reagents. Under previous contracts from DynPort, CBI developed methods of expression and purification of proteins associated with select agent pathogens and antibodies directed against those same proteins. Under license from DynPort, CBI is producing and selling these proteins and antibodies to investigators in the biodefense community. “CBI has been working steadily towards this product line for the past year, ever since our first production contract from DynPort,” says Robert B. Harris, Ph.D., president and CEO. “It is essential that investigators in biodefense related work have access to all the necessary reagents and that these investigators work with common reagents so that the scientific community can evaluate the results.”

One of the few public for-profit companies involved in bioterrorism defense work, CBI foresees many more contracts and laboratory expansion in the future. “There's a lot of funding, and we're hoping for a small portion of that. Having the new virology lab is key to making us more attractive to new potential clients,” says Reynolds. “There's a growing demand in the biodefense sector for these services, and we're planning a further expansion of the BSL-3 suite to include a production bacteriology laboratory.”

With the funding available, we can expect to see many more of these “clean” biosafety laboratories popping up around the country. Unfortunately, the times we live in call for this type of work, but it's work that is vital to maintaining our country's safety, defense and freedom.

The following resources provide more information on biosafety labs:

• Commonwealth Biotechnologies Inc., www.cbi-biotech.com
• Biosafety in Biomedical and Microbiological Laboratories 4th Edition, U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, and National Institutes of Health. Available at http://bmbl.od.nih.gov.
• Biodefense Program, National Institute of Allergy and Infectious Diseases, www.niaid.nih.gov
• Centers for Disease Control and Prevention, www.cdc.gov.

Standards for contamination and infection control are getting tougher, because a trip to the hospital shouldn't make you sick

BY HANK HOGAN

When the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) talks, hospitals listen. JCAHO is the oldest and largest healthcare accrediting body in the United States. More than 4700 hospitals nationwide voluntarily subject themselves to JCAHO's audits and accreditation. These inspections and certifications are done on a three-year cycle, which means the hospitals coming due in 2005 were last accredited in 2002. This time around those facilities will find a few changes in the JCAHO standards. The differences aren't a surprise but they are on the minds of those involved in controlling hospital contamination and infections.

“The new 2005 JCAHO standards for infection control and their patient safety goal #7 have certainly gotten the attention of healthcare professionals,” says Loretta Fauerbach, director of infection control for Shands Hospital (Gainesville, Fla.). She's also a member of the Association for Professionals in Infection Control and Epidemiology (APIC).

One reason for this attention is that the 2005 standards call for procedures and processes to have a measurable impact on infection rates and outcomes. The standards also outline audit methodologies that trace and confirm the implementation of those processes. A look at three areas—construction, sterilization and information management—shows what new contamination and infection control tools and techniques might come under the scrutiny of auditors.

Hard hats and surgical booties

As Shands' Fauerbach notes, there can be sterile fluids and instruments but not necessarily a sterile hospital. A clean hospital, on the other hand, is achievable. This might involve the use of techniques designed to rid surfaces of such organisms as drug-resistant enterococci and Clostridium difficile. The latter contaminates via spores, which makes it difficult to eliminate. In particular, notes Fauerbach, there aren't any hand antimicrobial agents that can kill the spores. The solution is to use gloves and conduct a thorough cleaning before and after a patient is in a room to minimize the spread of the spores.

But Jeanne Pfeiffer, APIC's national president, notes that achieving a clean hospital also involves overcoming a basic fact. Hospitals, unlike other contamination-controlled environments, aren't static structures.

“Hospitals are always under remodeling and redesign—always,” says Pfeiffer. “It's just a constant process.”

Tim Baugus is a project executive in the Portland office of Skanska USA Building Inc. (Parsippany, N.J.). The company was ranked number one in healthcare construction in 2002 by the Engineering News Record. Skanska USA, according to Baugus, does a lot of hospital construction and renovation. Baugus backs up Pfeiffer's assertion by noting that Skanska USA has been on some Portland-area hospital campuses continuously for 15 years. During that span the company might do a series of small projects intermixed with larger hospital facility expansions and replacements. While these projects, large or small, are underway, the hospital must remain open. That requires taking special contamination control measures and following specialized procedures during construction.

A technician uses a chemical indicator for sterilization assurance.Click here to enlarge image

These steps involve the use of HEPA filters, differential pressurization, entry and exit anterooms, surgical booties and sticky mats to ensure that the dust and debris kicked up during construction don't enter the rest of the facility. This is particularly important in hospitals because a form of the mold Aspergillus can be carried in sheet rock dust. Hospitals house people with compromised immune systems, those most at risk of developing one of the diseases related to the mold. Many of these contamination control requirements, Baugus notes, are covered in the mandated Infection Control Risk Assessment Standards (ICRAS) for construction.

“That's a fairly new requirement, although from our perspective we've been doing what the ICRAS guidelines tell you to do for the last 15 years,” he says. “There are a lot of contractors that don't do a lot of medical work; if they ever went into a medical environment, it would be a surprise to them what the requirement is.”

Baugus notes that airborne particle counts are sometimes done before and during construction. However, hospitals aren't controlled access areas and so it's difficult to get highly repeatable results. Thus, it's hard to draw an accurate picture of what's going on from a potential contamination and infection point of view. However, particle monitoring does have some advantages, especially when compared with the 24 to 48 hours it takes to culture a biological sample.

“Generally it's not wise to do biological monitoring. It's better to do particle counting. It's faster. It's an immediate answer. It's a lot cheaper, and we can do something about it once it's happening,” says APIC's Pfeiffer. “Biologicals take a long time.”

A clean machine

On the other hand, the time for a biological test has been reduced significantly for some applications. One is the monitoring of sterilization machines, which have seen the process times tumble six fold or more in some cases. These machines are used as part of the cleaning of endoscopes and other devices employed in minimally invasive surgery. Before such minimally invasive devices can be reused, they must be cleaned and any biological contaminants killed. Thus, the cycle time of the sterilization process and the time required to confirm that everything has been killed are a factor in overall surgical throughput.

Balaji Ramamurti, an industry analyst covering medical devices at the growth consulting company Frost & Sullivan (Palo Alto, Calif.), reports that the overall sterilization market is fairly mature. In 2001, the market stood at $647 million and for the most part was growing at a few percent per year. That wasn't the case with the segment that dealt with cleaning endoscopes, which was growing at 7.7 percent annually.

Vendors have attacked the reprocessing cycle time by cutting the time to test and time to sterilize. There are three types of sterilization technologies: steam, ethylene oxide and plasma based. The last is the newest approach, and in it an electrical plasma pumps up the effectiveness of chemicals. This improvement is achieved without boosting temperatures. Advanced Sterilization Products (Irvine, Calif.; www.sterrad.com) makes a line of plasma machines that use hydrogen peroxide.

“The killing power is the hydrogen peroxide molecules. The plasma decomposes or splits those atoms and removes the hydrogen peroxide as a residual from the load that's being sterilized,” explains Martin Favero, director of scientific and clinical affairs for ASP.

The cycle time, according to Favero, is less than an hour, and there are plans to cut that time in half within the next year or so. The devices to do this are already available outside the U.S. and the company is in the process of working its way through the Food and Drug Administration approval to sell the machines inside the U.S.

Besides the speed, which Favero says is four to eight times that of competing ethylene oxide sterilizers, the plasma-aided approach does not have any toxic components. Nothing is dumped into the environment other than water and oxygen and there's no need to wait for instruments to cool down or to be flushed of nasty chemicals.

On the testing front, in April the healthcare arm of 3M Co. (St. Paul, Minn.; www.3m.com) announced an extension of its Attest rapid readout biological indicator for monitoring ethylene oxide sterilization. The company's products are loaded into the machine and undergo the sterilization process. They're then removed and can provide proof of success in as little as four hours instead of the 48 or so needed for standard biological monitoring.

3M's sterilization assurance product line includes sterilizers, indicator tapes and self-contained biological indicators. These products can help quality assurance laboratories document their results as part of a HACCP plan.Click here to enlarge image

Kevin Habas, marketing manager for 3M sterilization, says that the company also makes chemical indicators. These items verify that a sterilization load reached a certain temperature and chemical concentration. These indicators can be read very quickly.

“You'll get that result as soon as you open the door,” says Habas.

Depending on how sure a hospital is of its procedures, this quick test may be good enough. The strips used in the biological tests have a high concentration of spores and killing all of the spores is difficult. As a result, no growth, or a negative result, in the biological test is a more certain sign of killing success than the chemical indicators are.

Beyond biocides

Besides faster machines and tests, some hospitals are turning to other technologies for contamination and infection control. One of these additional techniques is based on a service offered by MedMined Inc. (Birmingham, Ala.; www.medmined.com). This method makes use of information technology to spot trends and uncover data buried within hospital and medical records. This is based on data mining, which MedMined chief medical officer Patrick Hymel characterizes as a form of artificial intelligence.

“Data mining is a process where you use very sophisticated technology to discover important patterns within data that may be unsuspected by a human user or a human analyst,” says Hymel.

According to Hymel, the process begins by scrubbing the incoming data to assure its cleanliness. Healthcare records have a lot of free-form text entry fields, where the same information may be entered any number of ways. The same term may be spelled differently, for example. MedMined uses an automated process, backed by human intelligence, to assure that the incoming data is clean. This information is then examined for what Hymel describes as patterns in patient results that indicate a process causing or placing patients at risk for infection. Examples could be patients that develop certain infections after undergoing surgery in a particular area.

The Sterrad 200 System, a large-capacity low-temperature sterilizer, can process up to 150 liters in 75 minutes.Click here to enlarge image

The system also can pick up problems that originate outside of the hospital. Hymel notes that the service has spotted health problems such as salmonella outbreaks before local public health officials have. Such discoveries, however, cannot be done immediately. Because the system is looking for patterns and not random, individual events, the analysis must look at a long enough time span. According to Hymel, the analysis window typically runs from two weeks to a month.

As for the future, Frost & Sullivan's Ramamurti notes a trend toward putting ultraviolet light in air ducts in order to clean the air circulating within hospitals of pathogens. Ultraviolet light of the right wavelength strikes at the foundation of life because it is absorbed by DNA molecules. That makes it more difficult for a DNA-bearing organism to evolve an ultraviolet defense, unlike antibiotics for which resistant strains have already appeared.

However, such techniques may not help in the destruction of prions, point-like particles that are thought to be the cause of bovine spongiform encephalopathy (BSE, or “Mad Cow disease”). Prions are proteins that reproduce without the need for nucleic acid. Because of this and other prion characteristics many of the standard detection and destruction techniques won't work. That's why reliably detecting and eliminating prions are the subject of research.

Ramamurti says, “Anything to do with prions, either detectors or some kind of indicators to let people know that there are prions in particular medical equipment or not, that could be helpful. Further down the line would actually be coming up with ways and means of destroying these prions.”

Development of a testing standard for fan filter units will go a long way in improving energy efficiency in cleanrooms

BY SARAH FISTER GALE

In the past five years, Fan Filter Units (FFUs) have rapidly replaced distributed air handling units and fan tower systems as the airflow technology of choice in new and retrofitted cleanroom environments.

The FFU, which consists of a small fan, a controller and a HEPA/ULPA filter enclosed in a box, maintains specific airflow, and is commonly installed directly into the ceiling grids.

The reason they've gained such popularity is that FFUs provide a relatively simple means of delivering filtered air to environments requiring high degrees of cleanliness. Smaller and more portable than traditional airflow systems, FFUs cost less to install, are more flexible and can be focused in targeted areas of a cleanroom environment for maximum performance without excess redundancy.

Unlike traditional recirculating air fans often used in cleanroom systems, such as larger plug or centrifugal fan units or vaneaxial fan systems, FFUs can be added easily to existing cleanrooms without major retrofitting. The compact FFU system makes it possible for owners to update contamination control systems in cleanrooms as their needs and the standards change, without having to raise the roof or tear down walls. They also can be easily mounted directly over key equipment or above workbenches to create temporary portable cleanrooms within manufacturing environments.

Airflow systems are energy gluttons

While FFUs are more efficient than traditional systems, even these smaller airflow units consume a significant amount of energy, adding to the already overloaded energy consumption rates of most manufacturing facilities. Due to the high air circulation rates and special environmental considerations, cleanrooms consume from 4 to 100 times more energy per square foot than conventional commercial buildings. As energy costs increase and power grids get overloaded, meeting higher energy efficiency goals and reducing energy use has become a serious priority for cleanroom facilities.

Within those environments, FFUs are a specific concern because they are an energy-intensive component of energy-intensive industries, according to Dr. Tengfang (Tim) Xu, project manager in the Environmental Energy Technologies Division of Lawrence Berkeley National Laboratory (LBNL; Berkeley, Calif.).

FFUs have become the poster child for improving energy efficiency in cleanrooms, winning interest and investment from high-profile groups, including LBNL, California Energy Commission and industry associations intending to improve cleanroom efficiencies. Much of the quality of “clean” in a cleanroom depends on the number of FFUs, and the filter types—high-efficiency particulate air (HEPA) or ultra-low penetration air (ULPA)—without which a cleanroom is simply a room. The lower the cleanliness class number the more FFUs are necessary to clean the air.

To meet Federal Standard 209(E) for Class 10 or Class 1 environments, a cleanroom will incorporate FFUs in every 0.6- to 1.2-m ceiling bay. These environments then have a laminar flow of clean air traveling downward at about 27.5 meters per minute, which ensures a positive pressure inside the cleanroom. The pressure blocks any influx of contaminants through leaks in the cleanroom wall or curtain, and guarantees that particles generated by people or process equipment inside the enclosure are quickly removed.

The airflow systems in facilities with cleanrooms drive an estimated 50 percent or more of the total energy use, with fan energy use accounting for 80 percent of total energy use in cleanrooms of ISO Classes 3, 4, or 5, which are the most electricity intensive.

The good news is that there are many opportunities for improvement, according to Xu. “Optimizing aerodynamic performance in air recirculation systems appears to be a useful approach to improve energy efficiency in cleanrooms.”

The cutaway shows typical fan filter unit components.Click here to enlarge image

Larry Hopkins, engineering manager for Huntair (Portland, Ore.; www.huntair.com), a manufacturer of high-performance airflow systems, agrees. “When FFUs first came on the market price was the biggest selling point followed closely by noise control,” he notes. As a result, manufacturers made design choices to push costs down, and added sound blocking elements that restricted airflow. “They ended up with very inefficient models,” he says.

What end users didn't realize was that the cheaper models cost far more to operate because they required so much more power to produce the same level of airflow as the more efficient designs. For example, an energy-inefficient two-by-four FFU uses roughly 300 watts of power whereas an energy-efficient model may cost $100 more but could use as little as 50 watts. The up-front investment pays for itself in energy savings in as little as eight months (based on savings of 250 watts and 7 cents/kWh).

Computational Fluid Dynamics (CFD) analysis of an inefficient FFU (top) and a next-generation FFU (bottom). Areas in red show resistance to air flow.Click here to enlarge image

Huntair engineers tested several FFUs on the market to evaluate areas for improvements and were surprised by what they found. “The possibilities for improving energy efficiency on fan wheels alone is shocking,” Hopkins says. The problem is that suppliers have been using the same general FFU design since the 1990s, and, because the original designers did not prioritize energy efficiency, it is difficult to make these kinds of improvements. Hopkins believes that FFU efficiencies would increase tremendously if engineers started their redesigns from scratch. “If you add more-efficient motors, better fan wheels and change the design for noise control, you can develop a highly efficient FFU.”

Standards will drive better performance

Cleanroom owners are showing more interest in improving their energy performance, which is a good start, Xu says. However serious efficiencies won't be achieved until suppliers have a way to uniformly measure FFU energy consumption so that product comparisons can be made.

Today most FFU suppliers include performance test data regarding the noise, vibration and energy performance of their units with the product, but those numbers are impossible to validate. They are generally based on in-house tests that may have been conducted in empty isolated labs or warehouses that have little correlation to performance in a cleanroom. Even if the tests are relevant and accurate, there are no criteria to benchmark test data or decipher the test data as it relates to how it will operate after installation.

“None of the suppliers share test methods so there is no way to compare performance across the industry,” Xu says. “The industry needs a consistent and valid way to report test numbers.”

The first step, says Xu, is developing a set of standards to establish guidelines for testing FFU models. “To achieve high-efficiency FFUs, a standard test method needs to be developed for valid comparison.”

Xu is currently vice-chairman of IEST working group 36, which is authoring a set of standards called “A Laboratory Method of Testing Energy Performance of Fan-Filter Units.” The test standard is developed by LBNL, in collaboration with the Industrial Technology Research Institute (ITRI) of Taiwan and members of the Project Advisory Committee (PAC) for the high-performance building project supported by the California Energy Commission. “This project is a good start toward making the tool available and to gain industry's acceptance of the same document,” he says. “Using this standard, we can investigate the effects of various designs among different manufacturers. We can also produce baseline information through testing the FFUs in the market or under development.”

When the standards are complete, they will provide a uniform test procedure for laboratory characterization of FFUs by determining energy performance in terms of unit airflow rate, static pressure, electrical power usage, and total pressure efficiency. The object of the program is to provide a method for performance testing and reporting based upon consistent procedures. If the set of standards for FFU testing is approved, it will give suppliers a verifiable set of test procedures by establishing guides for third-party audits of FFU performance. This can then be referenced by and integrated into a relevant industry recommended practice.

In creating the standards, the IEST Working Group dealt with many testing issues, such as what the best testing methods would be, how airflow rates would be measured, and the impact of measuring vertical versus horizontal installations. There were many choices to be made, but fortunately there were few conflicts. “We are all in high degree of agreement on the standards tests,” Xu says, noting the industry's excitement and enthusiasm to push the standard forward.

The first draft of the document has been under public review since April, 2004, and is being fast tracked by IEST. “The feedback has been overwhelmingly positive,” Xu says. “Everyone in the industry wants a standard. This is a universal issue.” He expects the final draft to be available soon on the LBNL publication Website (www.lbl.gov/publications) and that hopefully it will be integrated into IEST's standard some time in the near future.

Suppliers gain credibility, users save money

When the standard passes, experts agree that everyone in the industry will gain some value.

Suppliers will benefit because a standard for testing gives them more credibility, says Paul Christiansen, director of sales for Envirco (Albuquerque, N.M; www.envirco.com), an FFU manufacturer. Envirco began working on energy-efficient FFUs five years ago to meet demands from clients in Asia who had stricter energy usage guidelines. According to Christiansen, the company's most successful energy-efficient FFU, the Mach 10 IQ, features a DC motor that uses 20 percent of the power of an AC motor, lowering its energy consumption to 80 watts. Christiansen also notes that in the past three years U.S. companies have begun making similar demands, increasing the popularity of the Mach 10 nationally.

Many other FFU suppliers have already begun offering more efficient FFUs, recognizing the growing demand from U.S. consumers. Along with Envirco and Huntair, Terra Universal (Anaheim, Calif.; www.terrauniversal.com) Airguard (Louisville, Ky.; www.airguard.com),

Click here to enlarge image

Cleanpak International (Clackamas, Ore.; www.cleanpak.com), Clean Rooms International (Grand Rapids, Mich.; www.cleanroomsint.com), and Lau Industries (Lenexa, Kan.; www.lau-ind.com) all offer FFU models specifically designed with energy efficient properties. GE Industrial Systems (Plainville, Conn.; www.geindustrial.com) is also marketing the GE ECM 2.3 series, which is a highly efficient FFU motor that performs 20 percent more efficiently than a standard induction motor at full load.

These FFU makers are all anxious to see the standards move forward so they can verify the validity of their test data and validate the efficiency ratings of their units. Several of the suppliers, including Envirco, are participating directly in the IEST working. “We are 100 percent behind the standard,” Christiansen says. “It will level the playing field for test procedures.”

A new standard will also provide the industry with a benchmark for continuous improvement and gives suppliers a way to establish a competitive edge by comparing their efficiency rates to other FFU manufacturers in the industry, says Patsy Dugger, industrial and agricultural program manager for the Savings by Design program at Pacific Gas and Electric (PG&E), California's energy utility company. “Rated, tested efficiency is a valuable marketing tool in a time when customers are increasingly paying attention to utility costs.”

End users will benefit, because they will finally have reliable consistent test data so they can compare the efficiencies of products across the market, adds Hopkins. Right now, companies either have to select an FFU model and hope for the best, or perform their own in-house evaluations, which is time intensive and expensive. “The IEST standard is absolutely needed,” he says. “You can't make an informed decision without reliable test data.”

Once the standard is in place, Hopkins predicts that many sophisticated buyers will start making buying decisions based on energy costs, which will drive design changes across the market. “Once the standard is in place, specifiers will demand more efficient models and that will push manufacturers to make design improvements if they want to stay competitive.”

California leads the charge

Besides suppliers and buyers, the push for change in the industry will benefit the communities where manufacturers are based because overall energy consumption rates will drop, lessening the burden on power grids and enabling them to put off building additional power plants, notes Dugger. This is especially critical in California, where high tech manufacturing has a huge presence and the state is battling an ongoing energy crisis.

The California Energy Commission (CEC) has prioritized reducing energy consumption in cleanrooms, and has put 'improvements in FFU performance' at the top of its list. “This could have a significant impact on public utilities in California,” says Tony Wong, senior mechanical engineer for the CEC. “If manufacturers reduce their energy consumption it could help manage the grid and reduce power outages.”

According to Paul Roggensack, the program contract manager of CEC, the CEC initially granted about $120,000 to this project to develop the draft FFU testing standard with the hope that it will spur more interest from the manufacturing industry in energy issues. CEC has a Public Interest Energy Research (PIER) program that supports public interest energy research, development and demonstration (RD&D) that helps improve the quality of life in California by bringing environmentally safe, affordable and reliable energy services and products to the marketplace (www.energy.ca.gov/pier/index.html#indust). The current FFU testing standard project is supported by the Industrial/Agricultural/Water End-Use Energy Efficiency program, which generally develops and demonstrates new technologies in this sector that increase energy efficiency and reduce emissions and manufacturing costs for California industries, agriculture and municipal water and wastewater systems. “Our goal is to reduce energy consumption and all studies focus on air systems as the primary target,” Wong and Roggensack say.

Choosing more efficient FFUs will also contribute significantly to achieving energy reduction goals set forth in the 2000 Technology Roadmap for High-Performance Laboratories and Cleanrooms, produced by LBNL in conjunction with CEC and PIER. The goal is to achieve 50 percent reduction in building energy use for comparable production in new construction while maintaining or improving productivity and safety by 2012.

To further incent end users to make more energy-efficient choices, PG&E is working with LBNL and the CEC to develop rebate programs for manufacturers. The utility has two programs—the New Construction Savings By Design and the Retrofit Standard Performance Contract—that could potentially offer incentives for installing efficient FFUs. In both programs, the incentive is based on the annual calculated energy savings over what is considered the program baseline. 700,000 kWh annual energy savings would be multiplied by the incentive rate for process systems, 0.10/kWh, to determine a potential incentive of $70,000, which would be paid after project completion.

“PG&E is very interested in being able to offer incentives for efficient FFUs,” Duggan says. “It is more cost effective for us to pay for a “nega-watt” through energy efficiency programs than it is to pay for a megawatt through generation.” The program would increase the benefit to customers who get the energy and cost savings of efficient equipment for the life of the equipment, and they can take advantage of utility incentives, which can buy down higher first costs. “Cleanrooms are increasingly looking for new methods and equipment to save energy in their production facilities. We're hoping that those who are not aware of potential energy and utility savings will be further educated through the expansion of our programs.”

But the programs can't be launched until the standards are established. “Before we can justify paying customers for using a certain piece of equipment, it would need to be tested for its operational efficiency and compared to other units.” The utility is awaiting approval of the FFU draft test procedure and is working with LBNL and the CEC to develop performance data on FFU performance before it launches the program. It is working directly with LBNL engaging FFU manufacturers to test unit performance so they can establish a baseline of test data for the program. “Once a critical mass of FFUs have been tested and we can establish a range of efficiencies, we can start to pay for the high-performance units,” Dugger says.

Every manufacturer that participates in the testing receives free test data regarding their products and their data remains anonymous in the final report, Xu says. “We are looking for industry's in-kind support to loan or give away units for our testing and for evaluating the test standard itself.” The group is still looking for more participants and Xu encourages all FFU suppliers to contact him about getting involved (e-mail Tim Xu at [email protected]).

The future

Xu emphasizes that having a laboratory standard for FFU testing is only the first step toward improving energy efficiency in the industry, and that there is still so much more that should be done. “Having this draft standard in place is just the very beginning of what we hope to accomplish,” he says.

Ideally, he'd like the standard to set off a domino effect in the industry. If the standard causes buyers to make more energy-efficient choices, that would encourage manufacturers to embrace best practices in cleanroom design and operation.

He hopes to find funding support in future FFU research, development and demonstration efforts that include conducting tests of additional FFUs of various types, with different controls, and different designs; resolving various technical issues surrounding refining the draft FFU testing standard such as airflow, uniformity, locations; and improving FFU designs through investigating factors contributing to actual performance levels, such as motor types, speed controls, housing, and fan wheel design. By working with IEST, he also hopes the industry will embrace a recommended practice guideline that will be accepted globally.

“Looking forward, I see that improving energy efficiency of FFUs has significant impacts on the energy market and the way suppliers and users would treat it.”

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Noise and vibration—still issues

No matter how energy efficient an FFU is, end users will still demand compact units that create the lowest amount of sound and vibration in the cleanroom environment. “Cleanroom tools are extremely sensitive to noise and vibration,” says Michael Gendreau, president of Colin Gordon and Associates (San Bruno, Calif.), an acoustics and vibration consulting company specializing in high tech facilities. From a vibration standpoint, FFUs are more desirable than traditional airflow models because they have smaller motors, but noise is a bigger problem. Because the units are compact there is little room within the unit to reduce the amount of sound it generates.

Most FFU manufacturers provide noise and vibration test information, however it's isolated data that doesn't take into account the specifics of the cleanroom environment. The acoustic performance of an FFU is best described by the outlet sound power, which represents the portion of the acoustic energy emitted into the workspace of a cleanroom.

“You have to determine how that will translate to your environment,” Gendreau says. “One FFU tested in a lab is very different from one installed in a crowded cleanroom where there is little absorption and a lot of reverb.”

Further complicating matters is the changing decibel level in cleanrooms. As cleanrooms age and more equipment is added, sound levels will gradually increase until it becomes an intolerant work environment for staff or causes damage to noise-sensitive equipment. FFUs become louder when their HEPA filters clog or fans fall out of balance, which means regular monitoring of units is also critical to maintain minimum noise levels.

Often end users have to make choices between efficiency, noise and cost, says Larry Hopkins, engineering manager for Huntair (Portland, Ore.; www.huntair.com), a manufacturer of high-performance airflow systems. FFU makers reduce noise by adding insulation and pans to block or absorb sound. “The added material reduces the noise, but it restricts airflow so much it chokes the fan and requires more power to pump the same amount of air.”

However, sometimes energy efficiency and noise reduction can work together in FFU installations—if good up-front investigation is done. Gendreau worked with a company that was able to reduce sound levels in its facility by installing twice as many FFUs and running them at half speed. Because the lower speed caused less wind drag, the energy costs dropped as well. “There is always a trade off,” he says of the cleanroom design. “The best thing is to find that middle ground.”

The cleanroom versus barrier isolator debate

This query was submitted by a reader to Doug Theobald, a frequent contributor to CleanRooms magazine, a certified facilities manager, and the Orange County-Los Angeles general manager of Controlled Contamination Services LLC (Anaheim, Calif.).

Question

I have read two of your very well written articles about the new 797 rules from USP.

We at this time do not have the space to put in a full-blown cleanroom. We are told by the barrier isolator salesman that an isolator is all you need.

It seems strange that the USP goes through all these requirements and suggestions and so on, and then an isolator in the corner of the pharmacy department meets all the 797 guidelines?

What is your take on being able to use a barrier isolator in a hospital environment versus [using] a cleanroom? Do you have the isolator in a separate room with an ante area, to reduce traffic, particles, etc.?

Tom Silver
Staff Pharmacist
Howard Community Hospital
Indiana

Theobald's response

Your question is very valid and not unexpected. First of all, the operative word here is “guidelines.” If you have read my articles [see “USP 797: Sterile compounding and room design,” CleanRooms June 2004, p. 12 and “USP 797: Contamination sources—control and remediation,” CleanRooms August 2004, p. 12], then you understand the “why” of USP 797, although you may not have personally experienced any sort of adverse problems in your own sterile compounding. Nevertheless, such events have occurred and the USP 797 guidelines have been drafted as a result.

The guidelines were developed with the intention of giving each state a “template” with which to work to either develop their own response or, as many have done and are doing, simply adopt. The criteria delineated in the USP 797 for all risk levels calls for an ante/gowning “area.”

Addressing your question: I do not know the status of the state of Indiana's stand on USP 797. However, I would like to recommend that you take a look at where you think they are going with it. The information that I am providing is designed to simplify the process and assist in the understanding of the (potential) requirements.

There are some basics that I recommend: A) the need to control the environment, B) the control of ingress and egress of personnel and products, and C) prevention and remediation of contamination. A barrier isolator is one component in achieving these basics. Obviously, each existing environment has its unique challenges. It is my hope that through this series of articles and subsequent communications I can aid in the cost-effective transition. Bottom line: stick to the basics and have a plan.

Douglas K. Theobald
Controlled Contamination Services LLC
[email protected]

There's no question about it. The future is nanotechnology. Just this year, worldwide expenditures in nano-technology R&D will reach $8.6B.

According to data from luxresearch's (New York, N.Y.), The Nanotech Report 2004, “the US government alone has spent $3.16B since 2000 on advancing nanotechnology, with proposed expenditures just short of another $1B for 2005.” And, in terms of corporate investment, North American companies will spend an additional $1.7B on nanotechnolgy R&D in 2004.

In addition to semiconductors, (bio)pharmaceuticals and medical devices, an ever-growing list of applications will play host to some implementation of nanotechnology. With each new application and product will come new opportunities for the contamination control industry.

But, how much of this home-seeded research will actually end up being home-produced? The report also notes that Asian firms are close behind North American companies in nanotechnology investment ($1.4B this year). And, most importantly, that “Japanese companies will productize nanotechnology more rapidly than the U.S. …because of their focus on product development rather than fundamental nanotech building blocks.” Beyond Asia, five non-U.S. (Europe/Australia) life-science companies already have nano-enabled products on the market or in FDA clinical trials.

Today, nanotechnology dollars are being spent on R&D, but production is where the revenue, jobs and investment will be. Inevitably, along with the export of production also goes production expertise and advanced production (including contamination control) technology. Though some will say that this point is irrelevant because the U.S. will remain a center of R&D and continue to innovate and develop next-generation science, I'm not so sure. U.S. companies, or rather the amount of world capital held by some U.S.-based investors, will no doubt continue to grow, but I'm not convinced that universities, research facilities and licensing fees can support the U.S. economy alone.

The advent of nanotechnology is not just another data point in the steady progression of science, it's comparable to the arrival of the machine and electronic ages—events which both clearly reshaped the world in just a few decades. The time is now to ensure that our Government and corporations invest not only in developing next-generation science and technology but also in the tools, facilities and people needed to turn them into U.S.-made products.

John Haystead
Editor in Chief

Compiled by Steve Smith

GMP pilot plant

OULU, Finland—A new Medipolis GMP pilot plant has been launched here, which will enter global biomedical markets with modern technology intended to help companies bridge the gap from laboratories toward successful clinical development of biopharmaceuticals.

The plant has state-of-the-art cleanroom technology and production equipment. The European medicinal agency, NAM, has granted a production license to the company and regularly inspects plant operations according to cGMP standards.

Medipolis GMP creates partnerships in R&D and cGMP production with biopharmaceutical companies to meet their process development and production needs in pre-clinical and clinical phases.

Single-wafer strategy

ALLENTOWN, Pa.—Akrion's subsidiary, Goldfinger Technologies, has received an order for a 300-mm advanced front-end-of-line single-wafer clean tool. The customer in Japan will use the Goldfinger Mach2 for final clean on its 300-mm wafers.

The Mach2 features patented megasonics for particle removal without etching, and built-in Sahara Dry allowing for watermark-free drying. The tool is available in 200- or 300-mm configurations, and can serve as a bridge tool with wafer size conversion typically taking approximately one-half of a work shift.

Medical manufacturer makes major move

SAN DIEGO, Calif.—In a move that consolidates its manufacturing facility and corporate headquarters, specialty pharmaceutical and medical device company Artes Medical Inc. (www.artesmedical.com) has begun operations at a new site in this city. The maker of ArteFill, said to be the first permanent injectable wrinkle filler to complete FDA clinical trials, is now located in a 35,000-square-foot facility formerly operated by DURA Pharmaceuticals and ELAN Pharmaceuticals.

Included in the manufacturing facility is 14,000 square feet of FDA-compliant, cGMP cleanroom manufacturing suites, plus 15,000 square feet of manufacturing support laboratories. Artes Medical expects to begin production and marketing of ArteFill early next year. The company anticipates it will add 55 more employees before the product launches.

Rice research renovation

HOUSTON, Tex.—Two cleanrooms are part of a recent design/build renovation project at Rice University's Abercrombie Hall (www.ruf.rice.edu/~che/), designed to provide nanotechnology researchers with a clean environment for studying minute mechanisms and configurations.

The 3,000-square-foot facility, built by Dallas-based McCarthy Building Companies Inc., (www.mccarthy.com) includes a Class 100 and Class 1000 cleanroom, conference area and lab support space.

Shanghai surveyed for semi subsystems

MENLO PARK, Calif.—Ultra Clean Holdings Inc. (www.uct.com) says it plans to begin construction of a manufacturing facility in Shanghai, China, early next year. The company develops and supplies critical subsystems for the semiconductor capital equipment industry.

The plant will be located in Shanghai's Kangquiao Technology Park, and will include Class 100 and Class 1000 cleanroom areas for the welding and assembly of gas delivery systems and other major modules of the semiconductor process tool.

Best dressed Senators

Click here to enlarge image

Senators Bob Graham (back), D-FL; John Glenn (front left), D-OH; John Kerry (front center and inset), D-MA; and Bill Nelson (front right), D-FL, show off their cleanroom attire during a tour of the Orbiter Processing Facility (OPF) at the Kennedy Space Center, Fla. Even U.S. Senators are required to don the apparel prior to viewing the orbiter Discovery, currently being prepared for the next space shuttle mission.

PHOTO CREDIT: National Aeronautics and Space AdministrationClick here to enlarge image

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BY STEVE SMITH

ROCKVILLE, Md.—Ozone treatments to reduce harmful pathogens during food processing and handling may be a good thing, but until proven, the Food and Drug Administration (www.fda.gov) is recommending that apple juice and cider processors establish their own documented validation study—or choose another treatment method.

With the fall months ushering in increased interest in apple products, the FDA's guidance is targeting juice and cider producers in the wake of an outbreak of cryptosporidiosis found in apple cider in Ohio last fall that sickened 148 people. The illness' key symptom is severe diarrhea, caused by the protozoan parasite Cryptosporidium parvum.

Ironically, the affected cider was traced to a local orchard that had reportedly treated the juice with ozone. While the FDA acknowledges that ozone treatments can be effective in reducing levels of such harmful pathogens as E.coli, and is approved as a food additive that may be safely used as an antimicrobial agent, the agency says the approval “does not establish the effectiveness of ozone as an antimicrobial under particular conditions of use.”

The FDA's message seems clear to at least one state agriculturist. “Cider makers who choose ozone treatment must either do their own validating studies, or run the risk of non-compliance with the [HACCP—Hazard Analysis and Critical Control Point] regulation, and the liabilities that might result from an incident of foodborne illness,” says Richard Uncles, bureau of markets supervisor for the New Hampshire Department of Agriculture, Markets and Food.

Ozonization, as part of a water treatment, has been used by some produce growers and processors because, when incorporated correctly, it has been found to be safer and more effective than other treatments. In some cases, ozonization has also been found to be effective in attacking fungi that can kill produce or reduce its shelf life.

But because of variables in the ozonization process, the FDA is urging juice and cider processors to include an ozone validation method that will clearly document, at a minimum, a 5-log reduction of the most resistant organism likely to occur in the juice. (Each log is a reduction of 90 percent, so a 5-log reduction means that juice and cider processors must use treatment steps to ensure that 99.999 percent of a pathogen is destroyed.)

Variables of the ozone process that are worthy of validation, says the FDA, include:

• Total concentration of ozone introduced into the juice;
• Flow rate of ozone into the batch tank;
• Treatment time;
• Appropriate batch volume;
• Degree of agitation needed to ensure that the ozone is uniformly dispersed in the juice.

In making its recommendations, the FDA argues that “compositional factors, such as the amount and type of juice solids present (e.g., sucrose and organic matter) can vary among different apple juice and cider products, and may affect the efficacy of a process.”

A scientific validation study is needed to establish how these factors need to be controlled to ensure the “efficacy of the ozonization process,” says the FDA, acknowledging that it is unaware of any published scientific study that establishes conditions for ozonization of apple juice or cider to achieve 99.999 percent pathogen reduction.

“The clear inference I get from the document,” says Uncles, “is that since ozonization for apple cider has not been the subject of validation studies (to FDA's knowledge), and since validation is a requirement of a HACCP plan's 5-log pathogen reduction requirement, the FDA is not supporting the use of ozone at this time.”

New Hampshire has approximately 65 apple cider producers, but Uncles indicates that most are staying with less expensive or otherwise proven contamination-control methods. After talking with one producer about ozonization, Uncles says, “their conclusion was that ozone was not an option at this point, owing to the tone of the FDA recommendations.”

While it may be that the FDA's guidance impacts mostly larger apple juice/cider producers, Uncles says most of New Hampshire's producers “are resigned to a retail-only mode until such time as cost-effective methods of pathogen reduction, such as ozone, are proved efficacious. Hopefully, validation studies will be conducted to demonstrate the effective use of ozone.”