Tag Archives: Clean Rooms

cGMP certification and FDA registration prepare PURE for production of SDC as an active pharmaceutical ingredient

September 5, 2007 — SAN DIEGO, CA — PURE Bioscience today announced the current good manufacturing practice (cGMP) certification by Peiser & Associates, Inc. of PURE’s manufacturing facility and process for the production of its pharmaceutical-grade silver dihydrogen citrate (SDC) concentrate as an active pharmaceutical ingredient (API). In addition, PURE has completed the Registration of Drug Establishment with the U.S. Food and Drug Administration (FDA).

“This is a necessary step for PURE to be able to fulfill our requirement to provide SDC as an active pharmaceutical ingredient to our current and prospective pharmaceutical development partners. Establishing the cGMP facility and production processes ensures that we meet the highest industry guidelines for the safety and quality of our API product,” states Michael L. Krall, president and CEO of PURE Bioscience. A facility with cGMP production certification is recognized as having the proper equipment, technical expertise, controls, and procedures to produce API for human applications.

Eugene S. Peiser, Doctor of Pharmacy and president of Peiser & Associates, Inc., comments, “Peiser & Associates, Inc. has inspected and certified many pharmaceutical manufacturers and distributors during our many years of operation (we established the firm in 1974), and in our opinion, PURE Bioscience can be considered one of the top producers of active pharmaceutical ingredients (API), and we are proud to present the firm with our ‘Certificate OF cGMP Compliance’ for the manufacture of SDC concentrate.”

About Peiser & Associates, Inc.
Peiser & Associates, Inc. is one of the oldest and most respected FDA compliance consulting firms in the United States. Established in 1974 at the request of FDA to assist in providing expert advice to firms regulated under state and federal good manufacturing practice regulations (CGMP), Peiser & Associates, Inc. has provided assistance to firms operating in the U.S., Puerto Rico, England, and Israel. To receive a Certificate of cGMP Compliance, a firm must be in substantial compliance with all FDA rules and regulations.

About PURE Bioscience
PURE Bioscience (PURE) develops and markets technology-based bioscience products that provide solutions to numerous global health challenges. PURE’s proprietary high efficacy/low toxicity bioscience technologies, including its silver dihydrogen citrate-based antimicrobials, represent innovative advances in diverse markets and lead today’s global trend toward industry and consumer use of “green” products while providing competitive advantages in efficacy and safety. Patented silver dihydrogen citrate (SDC) is an electrolytically generated source of stabilized ionic silver. SDC is colorless, odorless, tasteless, non-toxic, non-caustic, and formulates well with other compounds. As a platform technology, SDC is distinguished from competitors in the marketplace because of its superior efficacy, reduced toxicity, and the inability of bacteria to form a resistance to it. SDC also offers 24-hour residual protection against standard indicator bacteria. PURE Bioscience, headquartered in El Cajon, CA (San Diego metropolitan area), was incorporated in 1992. Additional information about PURE Bioscience is available at www.purebio.com.

August 29, 2007 — /PRnewswire/ — ST. LOUIS, MO — SAFC(R), a member of the Sigma-Aldrich Group, has announced a $4.5 million capacity expansion program at its flagship SAFC Pharma(TM) high-potency API (HPAPI) facility in Madison, WI. The program, scheduled for commission in early 2008, will add additional cGMP pilot plant and kilo lab capacity and complement the new XRPD (X-ray Powder Diffraction) analytical equipment for advanced solid-form testing due to become operational this month.

These developments build upon existing capabilities and expertise in potent compound handling at the Safebridge(R)-certified SAFC Madison facility and add to a $12 million, 38,000-sq.-ft. expansion program completed in 2006.

In the $4 million expansion, SAFC is adding additional capacity to its custom HPAPI manufacturing by introducing two 400-liter cGMP pilot plant reactors and two 100-liter cGMP portable jacketed reactors into a 1200-sq.-ft. dedicated, large-scale kilo lab. The addition will enable larger-scale chromatography for process purification, catering to future business requirements.

For solid-form testing and analysis, SAFC Pharma has installed and qualified a Bruker D8 Advance X-ray Diffractometer in a new dedicated analytical laboratory, providing U.S. customers with on-site cGMP and XRPD analysis of potent compounds. Rapid sample testing at the Madison site combines with data analysis and evaluation performed at SAFC Pharmorphix(TM) facilities in the U.K. Acquired in mid-2006, SAFC Pharmorphix specializes in solid-form research and is completing a multi-phase, $1.2 million expansion program at its labs.

SAFC president Frank Wicks comments, “As regulatory requirements align with the increasing complexity of drugs, solid-form testing, analysis, and optimization are becoming key elements in the drug development process. Additional and enhanced capabilities at SAFC Pharma’s Madison facility mark a timely expansion to the scope and value of our HPAPI offering and are reflective of SAFC’s ability to support its customers throughout the drug development cycle.”

SAFC Pharma is focused on cGMP manufacturing, process development, and contract services for small organic APIs and advanced intermediates, and the development of large-molecule biopharmaceuticals.

About SAFC
SAFC(R) is the manufacturing group within Sigma-Aldrich that focuses on high-purity inorganics for high technology applications, cell culture products, and services for biopharmaceutical manufacturing, biochemical production, and complex, multi-step organic synthesis of APIs and key intermediates. SAFC has manufacturing facilities around the world dedicated to providing manufacturing services for companies requiring a reliable partner to produce their custom manufactured materials. SAFC has four operating segments — SAFC Pharma(TM), SAFC Supply Solutions(TM), SAFC Biosciences(TM), and SAFC Hitech(TM) — and had annual sales of nearly $500 million in 2006. SAFC is one of the world’s 10 largest fine chemical businesses. For more information about SAFC, please visit www.safcglobal.com.

About Sigma-Aldrich
Sigma-Aldrich is a leading life science and high-technology company. Its biochemical and organic chemical products and kits are used in scientific and genomic research, biotechnology, pharmaceutical development, the diagnosis of disease, and as key components in pharmaceutical and other high-technology manufacturing. The company has customers in life science companies, university and government institutions, hospitals, and in industry. More than 1 million scientists and technologists use its products. Sigma-Aldrich operates in 36 countries and has 7,700 employees providing excellent service worldwide. Sigma-Aldrich is committed to accelerating customer success through leadership in life science, high technology, and service. For more information about Sigma-Aldrich, please visit www.sigma-aldrich.com.

Contact:
Dr. Frank Wicks, president, SAFC
Tel: 314-286-8008

Richard Kerns of Northern Exposure
Tel: +44-161-728-5880
E-mail: [email protected]

August 31, 2007 — BILLERICA, MA — Millipore Corporation, a leading provider of products and services that improve productivity and results in biopharmaceutical manufacturing and in clinical, analytical, and research laboratories, today announced that Phase 1 of the plant modernization project is complete at its facility in Kankakee, IL. The Kankakee plant is dedicated to the manufacture of certain key products including Probumin(R) brand Bovine Serum Albumin and other products derived from bovine serum or plasma.

Phase 1 modernization included installation of new, state-of-the-art-control and processing equipment. These changes will result in enhanced control over product quality and existing proprietary and fully validated processes. Critical equipment was substituted “like for like” with modern equivalents of exactly the same configuration and processing characteristics, so customers will see no change in the reactivity or other characteristics of the affected products. This initiative does not impact the EX-CYTE(R) focus factory also located at the Kankakee facility.

Phase 2 modernization will begin immediately and will include enhancements to plant capacity and to filling and packaging capabilities.

“This modernization to our Kankakee processing plant demonstrates Millipore’s commitment to delivering the highest product quality through enhanced process control to meet the ongoing needs of our life science customers,” says Andrew Bulpin, PhD, vice president of Millipore’s Bio-Products and Technologies Business Unit. “Our many customers expect Millipore to maintain leadership in the area.”

Alan Doty, product manager for Probumin and EX-CYTE, adds, “By completing this modernization phase, Millipore has confirmed Probumin as the premier BSA brand for life science markets. Consolidating manufacturing into one modern facility means that our customers can continue to enjoy the high purity and excellent lot to lot consistency they demand from Probumin and all our bovine derived products.”

Millipore’s Bio-Products and Technologies Business Unit is a valued partner to leading life science companies worldwide. In addition to Probumin BSA, Millipore offers a wide range of products for media, diagnostic, cell culture, and microbial culture applications.

About Millipore
Millipore is a leading provider of products and services that improve productivity and results in biopharmaceutical manufacturing and in clinical, analytical and research laboratories. The company is organized in two operating divisions. Its Bioprocess Division helps pharmaceutical and biotechnology companies to optimize their manufacturing productivity, ensure the quality of drugs, and scale up the production of difficult-to-manufacture biologics. Its Bioscience Division helps optimize laboratory productivity and workflows by providing reagents, kits and other enabling technologies and products for life science research and development. Millipore has a deep understanding of its customers’ research and manufacturing process needs, and offers reliable and innovative tools, technologies and services. The Company is part of the S&P 500 Index and employs approximately 6,000 employees worldwide. For additional information on Millipore Corporation, please visit its website at www.millipore.com.

August 27, 2007 — TAMPA, FL — The first international Certified Pharmaceutical Industry Professional (CPIP SM) credential — made available through the ISPE Professional Certification Commission (ISPE-PCC) — has been awarded to four industry professionals, announced ISPE-PCC on August 24.

This new credential offers the first competency-based international certification for pharmaceutical professionals and is helpful to the pharmaceutical industry in general by qualifying professionals to a global competency standard through demonstrated education, experience, and a rigorous examination.

The following individuals have been conferred the CPIP:
* Mr. Anders Brummerstedt, CPIP, manager computer compliance, NNE Pharmaplan, Soeborg, Denmark
* Mr. Andrew A. Signore, PE, CPIP, CEO, IPS, Lafayette Hill, PA
* Mr. Damian Gerstner, CPIP, president, sys-tek, Blue Springs, MO
* Ms. Tiffany G. Tomlinson, CPIP, manufacturing manager, IDEXX Pharmaceuticals, Inc., Greensboro, NC

“We are pleased to bring this credential to the industry,” says Jerry Roth, PE, director of professional certification. “It supports the U.S. Food and Drug Administration’s acknowledged need for change within the pharmaceutical industry to improve drug product safety and quality and consumer cost-effectiveness. We are delighted that ISPE can continue to be a catalyst for change and help move the industry forward.”

Already, the CPIP credential is hailed by industry leaders as beneficial to team leaders, allowing the ability to impact greater quality and efficiency in their specific roles; along with using the CPIP credential to qualify project teams and support ongoing professional development. To learn more about the credential and how to apply for eligibility, visit www.ispe-pcc.org.

About ISPE
ISPE, the International Society for Pharmaceutical Engineering, is the Society of choice for 25,000 pharmaceutical manufacturing professionals in 90 countries around the globe. ISPE aims to be the catalyst for “Engineering Pharmaceutical Innovation” by providing Members with opportunities to develop technical knowledge, exchange practical experience, and collaborate with global regulatory agencies and industry leaders. Founded in 1980, ISPE has worldwide headquarters in Tampa, FL; its European office in Brussels, Belgium; and its Asia Pacific office in Singapore. Visit www.ispe.org for additional society news and information.

About the ISPE-PCC
The ISPE Professional Certification Commission (PCC), an autonomous governing body within ISPE, develops certification programs to benefit credential holders and their employers, as well as government, academia, and the public health product consumer. The PCC is composed of 12 Commissioners: senior-level industry professionals representing Argentina, Australia, Japan, North America, and the United Kingdom, as well as academia, the U.S. Food and Drug Administration (USFDA), and the general public. Visit www.ispe-pcc.org for additional certification information.

August 27, 2007 — VALENCIA, FL — If you haven’t already heard about the use of UVC technology for air purification, you will soon. The use of UVC technology has been endorsed or specified by numerous federal, state, and local governmental agencies as well as various industry groups and standards bodies including some of the following:

  • Government Services Administration (GSA)

August 28, 2007 — SAN DIEGO — RASIRC(TM), the steam purification company, will feature a low-cost, safe, highly effective system to produce ultrahigh-purity steam at the European Photovoltaic Solar Energy Exhibition in Milan, Italy, September 3-7, 2007.

RASIRC technology improves many processes within the solar industry:

  • Passivation: eliminates hydrogen, reducing cost, reducing process time and improving safety
  • Interlayer oxide films: reduces electron recombination
  • Transparent conductive oxide: increases photon capture efficiency
  • Backside thick oxide: relocation of front electrode

Ultra-pure steam is needed to form transparent conductive oxide to improve solar energy capture. Steam is being used to grow thermal oxides on the backside for current isolation when used with backside contacts and form isolation layers between films and annealing of films to reduce defects and improve cell efficiencies.

RASIRC’s steam purification system replaces pyrolytic torches in the production of water vapor from hydrogen and oxygen. Torches provide good process control, but have limitations such as startup time, particulate generation under long-term use, purchase price, and it requires an excess of O2M or H2 to insure complete combustion of one constituent.

RASIRC generates ultra-pure steam from deionized water, which is inexpensive, widely available, and doesn’t burn oxygen and hydrogen. A non-porous hydrophilic membrane selectively allows water vapor and steam to pass through it. Contaminants in water such as dissolved gases, ions, total organic carbons, particles, viruses, bacteria, pyrogens, and metals are removed from the purified steam.

RASIRC steamer technology is installed on a 300mm Tempress furnace at the Fraunhofer Institute. The Steamer generates backside oxidation to improve electrical isolation between contacts on the backside and ultimately to generate leading-edge efficiencies. “There is great potential for ultra-pure water vapor in the solar industry,” says Jeffrey Spiegelman, president of RASIRC. “We are looking forward to discussing these possibilities with innovators at the European Photovoltaic Conference.”

About RASIRC
RASIRC products purify and deliver ultra-pure liquids and gases. RASIRC technology is the first to generate ultrahigh-purity (UHP) steam from deionized water. It reduces cost, improves yield, and improves safety. UHP steam has many applications in the semiconductor, nanotechnology, photovoltaic manufacturing, and related industries. Call 858-259-1220, e-mail [email protected], or visit www.rasirc.com.

August 29, 2007 — /PRWEB/ — MINNEAPOLIS, MN — The American Filtration and Separations Society (AFS) is offering short course training on Oct. 15 in Ann Arbor, MI.

To kick off the “Emission Solutions in Transportation” Conference, Oct. 16-18, 2007, that the American Filtration and Separations Society (AFS) is holding in Ann Arbor, there will be seven short courses on Oct. 15, 2007. Two of these courses are “Microfiltration Membranes” and “Ultrafiltration Membranes.”

In these two courses, attendees will learn in-depth knowledge of the various types of microporous membranes including strengths and weaknesses, performance characteristics, integrity testing, retention efficiency, ratings, and comparisons.

They will learn to differentiate between microporous, ultrafiltration, nanofiltration, and reverse osmosis membranes. These courses provides an in-depth study of the microfiltration and ultrafiltration membranes typically used in the pharmaceutical, microelectronic, food and beverage, water and waste water, chemical, laboratory, and medical markets.

Scott P. Yaeger is the instructor for both courses.He has more than 30 years of experience in the development, manufacture, sales, marketing, application, and management of membrane companies including Sartorius, Cuno, Gelman Sciences, Parker Hannifin, and PTI Advanced Filtration. Yaeger has held positions as vice president, engineering; vice president, sales and marketing; senior vice president and general manager; and executive vice president. In addition to his experience in membrane manufacturing companies, Yaeger has spent a significant part of his career working with membrane users in all applicable markets worldwide.

For information on the “Microfiltration Membranes” training go to:
www.afssociety.org/pr1/microfiltrationmembrane.htm

For information on the “Ultrafiltration Membranes” training go to:
www.afssociety.org/pr1/ultrafiltrationmembrane.htm

For information on the Emission Solutions in Transportation Conference go to:
http://afssociety.org/pr1/emissions.html

For information on other course offerings go to:
http://afssociety.org/pr1/

FDA is out of step


September 1, 2007

Sometimes epiphanies just jump out at me. For example, here’s one that just came to me recently. Why is the FDA continually sending out those public reports about various food and drug manufacturing companies that have failed this or that safety or quality inspection? Clearly, the agency is not giving adequate consideration to the inevitable big-picture consequences of such actions. I mean, has the FDA considered the potential liability that they are exposing these companies to from nefarious trial lawyers, or even the lack of faith and confidence that such reports will undoubtedly engender within the public at large when they hear about the health risks posed by these outed companies and the products they provide?

This is just not the way things are done these days, and I don’t understand why the FDA doesn’t take a few pointers from many of the state legislatures and boards of health across the country, where, far from going around willy-nilly handing out information to the public about the rate of hospital-acquired infections at individual hospitals, the state boards are quite responsibly keeping this information to themselves. What possible purpose can it serve to release this kind of disconcerting data to people trying to make an intelligent decision about where to take their loved ones for medical treatment? Isn’t it far better that they simply announce that while yes, thousands of people are dying from HAIs each year in their states, steps are also being taken to address the problem? There’s no reason to go singling out any particular hospital for criticism just because patients are dying there at a rate three to four times that of the institution down the street. After all, isn’t it enough that everyone is working on the problem to some extent?

Take Massachusetts, for example, where the state public health commissioner acknowledges that although his agency certainly has the authority to mandate the reporting of infection rates, his preference is for hospitals to provide it voluntarily. Quite sagely he observes that “we don’t want to overburden the hospitals with a heavy-handed regulatory requirement.” Well said, especially since, according to a state report released this month, Massachusetts hospitals are already overburdened to the tune of up to $473 million in medical costs annually from infections acquired in the state’s health-care facilities. What possible good can come from reporting the state’s share of the 90,000 patients who die annually in the U.S. from HAIs, or at which particular institutions they mostly died? This is the same good thinking guiding New York State’s Department of Health, which-while dutifully reporting the individual HAI data it collects-will not be identifying the hospitals it relates to.

California is even more responsible in its approach to reporting. Instead of boring the public with tedious infection rate data, this forward-thinking state will only be reporting the rate at which prevention practices are being implemented. Now that’s sensible, and painless.

The fact is that a great number of states have come up with all manner of clever ways to address the public’s concern about HAIs, which don’t include public reporting by facility. Isn’t it time for the FDA to follow their lead and stop with all the finger pointing? I mean, what we don’t know can’t hurt us. Right?

John Haystead,
Editor-in-Chief

Energy costs drive innovation


September 1, 2007

Facing pressure to reduce energy consumption, architects, designers, and operators are working from the ground up to build more efficient clean environments.

By Sarah Fister Gale

Energy cost reduction continues to be a driving force behind most of the innovations in state-of-the-art cleanroom design and construction. With the fuel price bubble refusing to burst, and environmentalists clamoring for industries to lighten their environmental impact, operators of cleanrooms-which are notorious energy gluttons-are anxious to find solutions for reducing energy consumption, both to improve their bottom line and their public image. Architects, designers, and operators are all seeking greater efficiencies through better room design, more efficient air handling and cooling systems, and advances in equipment design. Reflecting the global interest around this topic, the main theme of the CleanRooms Europe show in March 2008 in Stüttgart, Germany, will be structured around cost- and energy-efficient contamination control.

It’s no secret that cleanrooms consume huge amounts of energy in order to achieve operation standards. The combination of strict environmental controls-which require high air recirculation rates and stringent temperature and humidity controls-and the energy used to operate processing equipment and manage the heat generated by that equipment around the clock makes cleanrooms 20 to 100 times more costly to operate on a per-square-foot basis than conventional commercial buildings.

“The biggest trend across cleanroom industries is to improve the efficiency of operations and buildings to reduce energy consumption,” says Tim Johnson, senior project manager for Skanska, a global construction and project development firm based in Parsippany, NJ. “That has resulted in a lot more research into the return on investment of optimizing energy use.”

That research spans everything from adjustments to air handling systems; reformation of room layout; recycling systems for air, heat, and water; to more energy-efficient equipment design, he says. “It’s affecting everyone and everything.”

For owners, the desire to reduce energy use is about more than finances, claims Rod McCleod, head of the mechanical group of high-tech electronics for CH2M HILL, a global full-service construction and operations firm headquartered in Denver, CO. They want to cut their costs, but they also want to be perceived as good corporate environmental citizens, and that comes from making “green” business choices. “The decision to do the right thing for the environment by making decisions such as cutting energy consumption is becoming part of the corporate mission, especially for publicly owned companies,” he says. “They are always looking for ways to improve their public image.”

Achieving this demand for reduced energy consumption requires a paradigm shift, McCleod says. That means taking a different approach to return on investment and balancing up-front costs with operation and maintenance costs. “The payback paradigm is not the true measure of the cost of a system,” he says. “You need to take a broader look and factor in the life cycle of a system to get a truer picture of how that system impacts the bottom line.”

John Dunn, mechanical engineer in the Phoenix office of M+W Zander, agrees. He has worked with many clients to implement energy and cost savings systems in high-volume manufacturing facilities that had higher startup costs. For example, many wafer facilities are implementing dual-temperature chilled water systems so that they can use cooler 40° water to manage humidification, but 54° water to cool the rest of the facility. “The first cost of the facility is higher because you need two chiller plants, but when you look at operation costs the payback is there,” he points out. “The higher temperature allows the chillers to operate at much greater efficiencies.”

Cleanroom operators also need to adhere to new and pending government requirements for reduced energy consumption. There are currently two programs in the U.S. and the U.K. for the optimization of energy use in cleanrooms and wafer fabs that many companies are using as a measure against which to adjust their own operations. “Most wafer fabs in the U.K. are already auditing their energy efficiencies and are looking at ways to optimize efficiencies,” CH2M HILL’s McCleod says.

The Carbon Trust is a private company, set up and funded by the U.K. government in response to the threat of climate change, that was established to accelerate the transition to a low carbon economy. The trust works directly with businesses and the public sector to cut carbon emissions and supports the development of low carbon technologies.

The International Technology Roadmap for Semiconductors (ITRS) committee is also researching ways to reduce energy consumption, particularly through exploring acceptable ranges for temperature and humidity in the wafer fab. The research could allow looser specs for these factors, which can translate into lower operations costs. This is a delicate balance, however: Poor environmental control, particularly in respect to humidity, can directly affect the yield. If humidity levels are too low, static charges can build up, and high humidity levels promote corrosion or product degradation.

One solution that is gaining popularity is using high pressure water systems for humidification, says Dunn. Traditionally, facilities use a combination of condensed air and low pressure water to circulate humidification through the facility; however, the use of high pressure water-at up to 1,800 psi-doesn’t require condensed air, making it far more energy efficient, he says. “The water pumps may need part replacements every few months, but the energy savings from not running the air compressors is worth it.”

In industries with less stringent cleanroom humidification controls, such as solar wafer manufacturing, operators have many more energy-efficient choices for humidification systems, adds Jeff Baldel, a mechanical engineer at CH2M HILL. He notes that evaporative media systems, which act as a filter within air handling systems, can be installed and operated for one-thirtieth the cost of steam systems. “They don’t give the same controllability, but if a cleanroom can be operated to within plus or minus 5 percent of spec, it is a much less costly solution.”

Solutions are small but significant

There are no silver bullet solutions for cutting energy use in the cleanroom, says Bill Acorn, principal of Acorn Consulting Services, an engineering design and consulting firm in Tucson, AZ. The environmental requirements are specific and require a lot of energy to operate; however, adjustments can be made, he says. “The solutions aren’t radical; they are incremental.”

One of the most obvious and easiest ways to reduce waste in water and energy use is by implementing sleep mode on equipment, fan filter units (FFUs), and vacuum pumps when they are not being used instead of running them constantly, he points out. In some cases, auto-control FFU systems that automatically lower power consumption during non-use hours are saving facility operators energy while increasing the life of the filter and decreasing the amount of heat generated in the environment.

“It’s a circle of life. The energy used to operate the tool creates heat that requires cooling, which impacts air and water handling systems,” Acorn says. “Every time you put a cubic foot of air into the environment you’ve got to treat it, and that has a huge ripple effect on energy use.”

M+W Zander’s Dunn adds that FFUs are much more energy efficient than traditional air handling units and are more flexible. “If you discover an area in the cleanroom that is generating a lot of particles, it’s easy to move fan filter units closer to that area to solve the issue,” he says.

As the rooms get bigger and more equipment is added, the impact increases considerably. But small adjustments, such as using the “sleep mode” for tools, can have impressive results. According to a 2005 study by the International SEMATECH Manufacturing Initiative (ISMI), the global semiconductor industry could save nearly $500 million per year in energy costs by making modest improvements to its tools and facility support systems. ISMI found that many of its largest members were already seeing significant savings from reductions in cleanroom air velocity, air conditioning optimization, ultra-pure water reductions, use of high efficiency motors, and various other energy conservation activities.

The ISMI energy conservation study was prompted by member company and industry concerns over rapid spikes in energy costs, coupled with a continuing commitment to environmental best practices established by the World Semiconductor Council. The data, compiled by ISMI’s Environment, Safety and Health (ESH) program, also showcased success stories at member companies that adopted the consortium’s recommended practices.

ISMI has since published 26 technology transfer reports documenting best practices for energy and resource conservation, which include enabling and using the sleep mode in vacuum pumps; optimizing exhaust flows on tools; lowering cleanroom airflow through HEPA filters; optimizing nitrogen use and on-site nitrogen generation; and measuring key tools to optimize heat removal.

For example, ISMI’s ESH engineers have found that low-energy vacuum pumps use less than half the electrical power of current versions and can be idled during non-productive periods for an additional energy savings of 30 percent. Similarly, technologists have discovered that exhaust flows can be reduced by 30 to 80 percent without impacting yields or exposing workers to harmful emissions, for an annual savings of $600,000 per fab.

M+W Zander’s Dunn has seen a growing trend in high-volume manufacturing facilities to cut back on filter coverage in wafer fabs. “Because the product is isolated in cassettes and minienvironments, and due to the increasing use of automation, operators are dropping their coverage.” The reduced coverage cuts the startup costs of filters for a facility and reduces energy costs because less air is recirculated. “In the past there may have been too much coverage. With minienvironments we can move away from that.”

However, Acorn notes that cleanroom operators are not relaxing cleanliness standards as much as some industry reports would suggest. “We are still seeing a lot of ISO 4 and 5 spaces,” he says, noting that fear of the unknown is a contributing factor to the hesitation. “Even though the cost of keeping a room cleaner than it may need to be is significant, it is nowhere near the cost of a shutdown due to contamination,” he says. “If you make a $3.5 million investment in building a manufacturing facility, you don’t want to make a choice that loses you $100 million in yield. No one wants to be the first to fail.”


Figure 1. The need to reduce energy consumption has produced more efficient air handling designs. Above: This Compac Vane Axial fan system combines 85 percent efficiency with less static to offer customers lower brake horsepower and significant energy savings over the life of the unit. Right: Multi-fan arrays such as this Multipak system offer greater reliability with fan backup: In case of fan failure, the other three will speed up to maintain the system set point, and the failed fan can be replaced or maintained from outside the unit without shutting it down. Photos from M&I Air Systems Engineering, courtesy of EI Systems.
Click here to enlarge image

The additional reliance on minienvironments in order to relax cleanliness standards outside of the equipment offers further concerns for maintenance issues, adds Allan Chasey, associate professor at Arizona State University in Tucson, and director of Construction Research and Education for Advanced Technology Environments (CREATE), a research consortium of 25 companies representing the advanced technology design and construction industry. He is also head of the ITRS Facilities Group. “When you open the machine, the ambient air is not as clean,” he explains. That creates problems for maintaining standards.

Chasey believes that cleanroom designers and architects need to be more closely aligned with equipment manufacturers to establish tighter tolerances for installation, maintenance, and operation. “It all needs to operate like a Swiss watch.”

Air handling solutions

The demand for energy efficiency is also pushing air handler manufacturers to pursue more energy-efficient designs, says Richard Spradling, vice president of EI Systems, a technology solutions provider headquartered in Houston, TX. “The cost of energy is pushing innovation,” he says. “Engineers, architects, and owners are demanding more efficient systems and the market is responding.”

Spradling has seen dramatic im-provements in energy-efficient fan systems for high and low static recirculating fans and high static makeup handling systems. For example, M&I Air Systems Engineering’s Compac Space Fan System, which integrates noise absorption and flow control within the inlet and outlet components of the assembly, achieves up to 80 percent static regain of the axial fan’s annular velocity pressure, reducing energy consumption by up to 50 percent. “That translates to significant cost savings,” Spradling says, noting that an overseas client who pays $0.20 per kilowatt saved $400,000 in annual energy costs using 18 of these units.

Low-cost FFU control systems that are customizable and easy to install, as well as replacing traditional single-fan operations with multi-fan arrays, are also gaining popularity, especially in smaller facilities. Multi-fan arrays, such as Huntair’s Fanwall, or M&I’s Multipak system, break the air output load for air handlers into several smaller units for greater reliability and better operational efficiency.

Multi-fan systems offer many benefits, such as built-in redundancies, says Tim Loughran, managing partner for AdvanceTEC, a cleanroom design and construction company in Richmond, VA. “With a single, larger air handling unit, if it goes down the cleanroom goes down until you can get a replacement motor. That can take anywhere from four hours to two weeks,” he says. “But with a multi-fan system, if you lose one motor the others can compensate.”

Multi-fan arrays also allow for faster and easier replacements of motors because they are smaller and can realistically be stored on site; they also give operators the ability to customize the system to accommodate issues such as changes in filter cleanliness and airflow rates without affecting fan efficiencies.

With a single-fan environment, even highly effective, larger fans lose significant efficiency when they are run at lower load conditions. With a multi-fan array, operators can turn off individual fans so that the remaining operating units still function at peak efficiency rates.

The addition of heat-recovery chilled water systems, water reduction, recycling, and reclaim strategies and the use of variable frequency drives on large motors for increased efficiency all further help improve energy conservation in new and retrofit facilities.

Faster is still better

Along with reducing energy costs, cleanroom operators are still seeking ways to ramp up in less time for less money, and they want to achieve desired efficiencies faster than ever. Some designers in the industry are facing increasing frustration over the unrealistic expectations that can be laid at their feet by owners who want facilities up and running in record times.

“These facilities are more complex than ever, but they still want everything faster and cheaper,” says CREATE’s Chasey. He notes that facility sizes are increasing, with more equipment and more complex processing steps to support. The introduction of new production materials, gases, and chemicals into cleanroom operations-all of which create additional airborne molecular contamination issues and waste problems to deal with-makes these rooms increasingly complex. The continuous push to reduce geometries that require new equipment and all of the associated control designs that go with them also makes new and retrofit operations more complicated than ever to design and build. “Cleanroom owners want these facilities to be built in eight or nine months and they feel like the market should respond,” Chasey says. “It’s gotten to be absurd.” He would like to see the wafer fab industry embrace a stricter line increase in cleanroom complexity rather than the exponential growth that it currently supports.

Modular cleanrooms offer designers a faster ramp-up time because many of the pieces are prefabricated in the factory, taking less time to assemble, AdvanceTEC’s Loughran says. “Modular rooms take 50 percent less time to build, which substantially decreases the construction time on site.”


Figure 2. Modular cleanrooms offer faster ramp-up due to prefabrication that simplifies installation, walkable ceilings for easier maintenance, and utilities that are built in and connected after construction. Photos courtesy of AdvanceTEC.
Click here to enlarge image

Modular rooms also offer maintenance benefits because ceilings are walkable, and electrical and piping can be built into the system and dropped in after the room is constructed.

Air flow

In the meantime, designers are identifying ways to reduce the ramp-up time for new facilities, and the solutions are often found at the beginning of the design process, when alterations can be made before structures are built. At CH2M HILL, engineer Andy Solberg has found that computational fluid airflow dynamics software tools enable him to help clients cut weeks off of ramp-up time by running models of airflow patterns and how they will be impacted by room design and equipment layout decisions-prior to any construction.

“Often in the design phase, people confine their concerns to their specific part or area of the cleanroom without thinking about how their work impacts the entire bay,” he says. “For example, designs for photolithography can push air into other areas of the room.”

Before any construction is begun, Solberg’s team looks at issues such as filtration coverage; floor layout; under-floor barriers due to exhaust systems, utilities, and conduits; and the spaces blocked or left vacant around them.

Solberg notes that by doing airflow modeling prior to construction and incorporating the potential impact of different design choices into the airflow design, the team and client can avoid expensive and time-consuming mistakes during ramp-up, such as moving conduits or utility lines. “After you spend a lot of money building a new cleanroom, you don’t want to think about making changes,” he says.

The airflow in these rooms can typically be balanced in a matter of days, instead of the weeks it normally takes, he says, and all of the rooms CH2M HILL designs using this airflow modeling technique are certified as meeting clean requirements with minor or no alterations.


Figure 3. With its computational fluid dynamics models, CH2M HILL can help clients cut down ramp-up time by showing how the airflow will be affected by room design and equipment layout decisions. These images show calculated particle tracks in a ballroom-type cleanroom with 33 percent ceiling filter coverage. Images courtesy of CH2M HILL.
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Using computational fluid dynamic models, CH2M HILL has been able to prove airflow distribution with particle, temperature, and pressurization data, and the models are used to develop specialized air handling systems, HEPA filter and ceiling systems, and flooring systems.

Cleanroom performance levels achieved through CH2M HILL’s design include stringent temperature and humidity specifications. Solberg also uses these models to develop site airflow characterization studies, plan for facility exhaust and air intake locations, and evaluate potential contaminant migration that could cause odor or molecular contamination issues. Using the tool, his designers can determine appropriate exhaust and intake locations, with necessary stack heights and exit velocities.

Interface plates accommodate expansion

Striving for longevity in new or retrofit construction, cleanroom designers are also seeking ways to design for future uses of expansions in the operating space to avoid costly shutdowns when equipment is added to an operation.

One promising solution involves installing interface plates throughout the cleanroom that allow for plug-and-play installation of new equipment for specific process steps that might someday be installed. “For example, in a new facility that will house eight etch tools for lithography, the designer may install another 12 interface plates in the bay for future expansions,” CREATE’s Chasey says. The interface plates are placed in the floor and include outlets for gases, electricity, water, and exhaust. “All you need to do is plug the new equipment in.”

Not only does this give the hefty investment in a new cleanroom a longer life cycle, it avoids the expense and mess of shutting down to install new tools, which otherwise requires tearing down walls to implement wiring and piping. “With interface plates, the final connections can be made and qualified as soon as the tool arrives.”


STMicroelectronics demonstrates how ‘clean’ can be ‘green’

Semiconductor giant STMicroelectronics’ public commitment to environmental responsibility has won it publicity, praise, and more than 50 international awards, including the European Business Award for the Environment and the inaugural Low Carbon Leader Award presented by the Climate Group. The company has also saved more than $60 million by cutting its energy usage and more than $20 million by reducing water consumption below baselines set in 1994.

“The foundations for our choice to be a sustainable business are ethical, social, and based on our interest in leaving a better world for our children,” says Reza Kazerounian, corporate vice president and general manager of ST’s North American region. “But we also believe that this commitment can make us stronger financially and help us attract the most responsible and competent people.”


STMicroelectronics’ Phoenix, AZ-based facility features a 20-kilowatt rooftop
solar array to help manage energy usage. Photo courtesy of STMicroelectronics.
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ST’s drive for “zero impact on the environment” has social and economic benefits that are laid out in its publicly available “environmental Decalogue,” which outlines its goals to exceed regulatory requirements in both degree and timing. The Decalogue is a set of ten quantified, timed, and measurable targets that include minimizing the impact of its processes and products on the environment, maximizing the use of recyclable or reusable materials, and adopting renewable sources of energy where possible. Some specific goals include reducing total energy consumption (kWh per production unit) by at least 5 percent per year through process and facilities optimization, conservation, and building design; reducing water draw-down (cubic meters per production unit) by at least 5 percent per year through conservation, process optimization, reuse, and recycling; and reducing total emissions of CO2 due to energy consumption by at least 5 percent per year.

Over the past 15 years, STMicroelectronics has saved the equivalent of one nuclear power plant by lowering its energy needs, has planted 10 million trees to offset its CO2 production, and, in 2006, saved the equivalent of drinking water for 70 million people. The company is on track to achieve its goal of CO2 neutrality by 2010 by using more renewable energies, such as wind and solar, and by buying a greater percentage of its power from heat and power plants, which are more efficient and emit less CO2 per unit of energy. Part of achieving that goal resulted from building a 20-kilowatt solar power plant on the roof of the manufacturer’s Northeast Phoenix, AZ, facility.

“As a consequence of adopting sustainable business practices, we believe that well run corporations will necessarily be more profitable,” Kazerounian says of ST’s business case for its green initiatives. “We are convinced that environmental responsibility is compatible with the ability for ST to compete in the marketplace.”

Enforcing adequate aseptic procedures will ensure patient and personnel safety

By Fran McAteer, Microbiology Research Associates

Compounding sterile preparations (CSPs) are made utilizing aseptic technique. Aseptic technique is a microbiological term referring to the prevention of microorganism contamination. The procedure involves the use of specialized equipment, sterile apparel, meticulous processing, and continuous cleaning.

Historically, asepsis was a startling revelation and was demonstrated in the work of great scientists such as Lister and Pasteur. Over time, aseptic technique has been developed, improved, specialized, and harmonized. Today, aseptic technique is the basis of good manufacturing practices (GMP), quality system regulations (QSR), and USP Chapter <797>, “Pharmaceutical Compounding-Sterile Preparations.”

In sterile compounding, aseptic technique is contributing to the prevention of nosocomial infections and thereby improving patient care. It is providing sterility, safety, and efficacy to CSPs, especially various aqueous injections for patients. Due to the routes of administration of these injections directly into the bloodstream, microbial contamination has a more deleterious effect on this target population and these preparations represent the greatest risk to patients from potential contamination. CSPs produced using meticulous technique, personnel gowning, and repetitive cleaning procedures dramatically reduce the opportunity for potential contamination.

Competent aseptic technique compounding procedures reduce contamination risks. The technique is divided into several general categories.

  1. Controlled environments
  2. Personal gowning
  3. Visual inspection
  4. Cleaning/sanitization
  5. Procedural manipulation
  6. Disposal

Aseptic technique is performed in a controlled area such as a cleanroom, laminar flow hood, and/or isolator. Each type of environment reduces both surface and air contamination to minimum levels. These environments are encased with smooth surfaces such as stainless steel and/or Lexan. Surfaces that are easily cleaned and composed of a material such as 316 stainless steel show a higher imperviousness to scratches, which provide a good hiding spot for microbes. The critical environments are equipped with high efficiency particulate air (HEPA) filters that remove 99.9 percent of microorganisms by continuous filtration. The higher air velocity moving through the filter and the number of air changes reduce bacterial levels. These controlled areas provide the foundation for successful aseptic processing.

Personal gowning specifies the type of garb worn by personnel while performing aseptic processing. This can refer to bouffants, booties, gloves, sleeves, hoods, masks, glasses, goggles, boot covers, suits, aprons, lab coats, beard covers, and scrubs, to name a few. The exact items and gowning sequence needed to successfully perform asepsis in various compounding activities should be specified in the standard operating procedures (SOPs). The SOP will stipulate types of acceptable gowning, frequency of changes, and garbing sequence. Some procedures will also specify a gowning certification in which the pharmacist or technician must demonstrate proficiency in donning cleanroom apparel before being permitted to work in the clean zone. This type of proficiency-based training further enhances meticulousness of personnel in complying with cleanroom gowning procedures. Certification testing is accomplished by utilizing contact TSA plates to test hands, forearms, and shoulders after gowning. This certification process helps exhibit aseptic competency to regulators.

Personal gowning also includes hand washing and hand disinfection. Remove jewelry, watches, bracelets, etc., before cleansing. Wash hands, up to the elbow, with an antibacterial soap, scrubbing to remove dirt-especially under fingernails-and ensure a good contact time (30 seconds). Be careful not to touch the face, clothing, or surroundings. Many compounding sinks are set up with knee or foot pedals to eliminate a potential touch contamination. If applicable, immediately put on gloves as specified in SOPs. Gloves should be frequently sanitized with 70 percent isopropyl alcohol (IPA) during aseptic processing.

Visual inspection is another integral part of aseptic technique. Pharmacists and technicians should visually inspect their work zone, gowning, equipment, vial closures, IV bags, syringes, needles, and so on for clutter, debris, trash, vial defects, septum penetration, and disposable package integrity. If there is an out-of-specification observation, then remove the impediment and resanitize the work area. If it is a vial closure issue, then inform the supervisor and obtain a new vial. Visual inspection of the admixture preparation for particulates is very important. Precipitate, flakes, and dust particles can indicate potential hazards in the medication. Visual inspection should be emphasized during new hire training and upon media proficiency requalification. Visual inspection should also play a role in personal gowning. A mirror in the anteroom will let technicians observe and inspect for proper attire.

Aseptic technique is enforced by strong cleaning and sanitization procedures. It is critical to disinfect the work area on a daily basis, if not more frequently. This cleaning and sanitization should be documented in datasheets or logbooks to demonstrate compliance. Using 70 percent IPA is the easiest choice. It is effective against most bacteria but not spore forms such as gram-positive rods. Adding a second sanitizer such as peracetic acid, hydrogen peroxide, quaternary ammonium, or phenol will provide more robustness to the cleaning efficacy. A rotation of these sanitizers is certainly a suitable strategy.

Procedural manipulation is a term indicating preciseness and meticulousness in performing compounding procedures. It refers to manipulations that minimize contact with critical product surfaces such as septums and needles. When contact is made, the surface should be immediately wiped with 70 percent IPA. The preciseness of procedures limits movement, which reduces particle generation and contamination potential. Procedural manipulation is best done through repetition and demonstrated by media proficiency testing.

Disposal and cleanup of the work area after completion of the admixture is critical in maintaining asepsis. If spillage is not wiped up immediately, it can create both a safety and contamination hazard for the immediate compound and other CSPs made in that work area. When compounders’ hands leave the sterile field, it is imperative that they are resanitized with IPA before re-entering the laminar flow hood. For disposal, spent materials used in the preparation of sterile compounds should be removed and the work area resanitized with IPA before leaving the area. Datasheets showing the date and workers’ initials are a good way to demonstrate compliance.

Aseptic technique is a process limiting potential contamination in the compounding process. However, it is very subjective and a function of the skills of the pharmacist, which should be reinforced with education, training, and proficiency.

Fran McAteer is vice president of quality at Microbiology Research Associates, Inc., an FDA-registered contract microbiology testing laboratory specializing in USP testing for pharmaceuticals, biologics, and medical devices. The author has expertise and experience in implementation of USP <797> programs for hospital pharmacies and acts as a consultant for many hospitals.