Tag Archives: Clean Rooms

Particles


February 1, 2007

Compiled by Angela Godwin

Partnership to develop food-safety compliance system
Smart Online Inc., provider of Software-as-a-Service (“SaaS”) for the small-business market, will partner with FoodLogiQ, LLC, designer of workflow, compliance and traceability systems, to develop branded food-safety compliance systems for industry associations. Under the partnership, Smart Online’s business application suite will incorporate FoodLogiQ food-industry traceability and compliance functionality. The new application is expected to help farmers, food manufacturers, grocers and restaurants meet their business and compliance needs at the same time. It will be customized to provide anonymous, aggregate data to industry associations to confirm their memberships’ level of compliance. Through the application, audit results from the associations’ members can be scheduled and recorded to help assure compliance to label claims of quality and safety.

Lithography light source manufacturer opens new facility

Gigaphoton Inc., a lithography light source manufacturer for the global semiconductor industry, announced that it has completed construction of a new building at its headquarters campus in Oyama, Japan. The new facility will house a state-of-the-art, Class 1,000 cleanroom that features expanded research and development capabilities and laser light source maintenance training for field service engineers. The new facility will also house Gigaphoton’s customer support administrative functions, as well as a spare parts warehouse.

According to Dr. Yuji Watanabe, president and representative director of Gigaphoton, the company’s decision to expand its existing facilities was based on the increased demand for its advanced light sources. “Gigaphoton’s high-quality, extremely reliable, and high-uptime products enable chipmakers’ fabs to run at benchmark levels. As a result, customers continue to turn to us as they realize the benefits afforded by our advanced lithography light source solutions, for which we provide superior service and support,” said Watanabe.

Dates announced for STAR Center training

Baxa Corporation has published the 2007 dates for training at its STAR (Skills Training, Academics and Resources) Center, a facility designed for cleanroom and pharmacy practice demonstration. The center (www.baxa.com/starcenter) is located at the company’s world headquarters south of Denver, Colorado. Baxa Corporation built the facility to provide professional education on pharmacy practice, cleanroom principles and compliance to regulatory requirements.

The STAR Center’s initial course offering, “Compliance Tools and Aseptic Certification for USP <797>,” debuted in September 2006, with sessions repeated in October and November. The USP 797 course will also be held: March 20-22; May 22-24; July 24-26; September 18-20; and October 23-25.

The ACPE-certified training targets pharmacy and IV managers, as well as personnel who compound sterile products or who are implementing cleanroom principles and practices that comply with USP <797> and industry best practice. Topics include cleanroom physical design and layout, engineering controls and airflow science, media fill testing, and principles associated with workflow, staff training, cleaning, monitoring, validation and documentation.

The rapidly building need for standards is driving increased committee activity and frequency of meetings

By David S. Ensor, PhD, IEST Fellow and director of IEST SPC 7: Nanotechnologies

In 2005, Technical Committee (TC) 229, Nanotechnologies (ISO/TC 229), was established by the International Organization for Standardization (ISO) with the British Standards Institute (BSI) serving as the secretariat and Dr. Peter Hatto of the United Kingdom as the chairman. The formation of this ISO technical committee was in response to the extraordinary worldwide growth of the nanotechnology field.

In 2004, the expenditures for nanotechnology research and development were estimated to exceed $4 billion USD. Forecasts indicate that, in the foreseeable future, nanotechnology will experience significantly accelerating worldwide activity. It is clear that international standards tailored specifically to nanotechnology are needed to support commerce.

The United States, represented by the American National Standards Institute (ANSI), joined ISO/TC 229 as a charter participating country. The Institute of Environmental Sciences and Technology (IEST) joined the ANSI-sanctioned U.S. Technical Advisory Group (TAG) to ISO/TC 229 as a charter member to represent the fields of contamination control and environmental testing. The role of the U.S. TAG to ISO/TC 229 is to develop and represent the position of the United States in the ISO process. I have had the pleasure of serving as IEST’s representative since its inception.

Because of the rapidly building need for standards, the committee activity and frequency of meetings have been greater than most standards committees. ISO/TC 229 has been meeting biannually and national advisory groups have been meeting much more frequently. The U.S. TAG has been meeting bimonthly.

ISO/TC 229 currently has 28 “Participating” countries and 8 “Observer” countries. The inaugural plenary meeting was held in London, England, in November 2005. The United States delegation at this and the following plenary meetings was led by Dr. Clayton Teague, director to the National Nanotechnology Coordination Office and chairman of the United States TAG. At the London meeting, the scope of ISO/TC 229 was established as follows:

Standardization in the field on nanotechnologies that includes either or both of the following:

  1. Understanding and control of matter and processes at the nanoscale, typically but not exclusively below 100 nanometers in one or more dimensions where the onset of size-dependent phenomena usually enables novel applications.
  2. Utilizing the properties of nanoscale materials that differ from the properties of individual atoms, molecules and bulk matter, to create improved materials, devices and systems that exploit these new properties. Specific tasks include developing standards for: terminology and nomenclature; metrology and instrumentation, including specifications for reference materials; test methodologies; modeling and simulation; and science-based health, safety and environmental practices.

At the meeting in London, the following working groups were established:

  • Working Group 1-Terminology and Nomenclature, with the convenorship held by Canada.
  • Working Group 2-Measurement and Characterization, with the convenorship held by Japan.
  • Working Group 3-Health, Safety and Environment, with the convenorship held by the United States.

One principle established at the first meeting was that the interdisciplinary nature of nanotechnology will require liaison and coordination with a large number of other ISO technical committees and other international standards bodies. For example, I was elected to represent ISO/TC 229 as liaison to ISO/TC 209, Cleanrooms and Associated Controlled Environments.

As the nanotechnology industry matures, facility requirements will need to be defined for the development and production of the wide range of potential products containing nanomaterials. It should be noted that at the national level, IEST, in anticipation of the need for information on designing, constructing and operating nanotechnology facilities, organized in 2005 a new working group, IEST-WG-CC210: Forum for Nanoscale Research Facilities. This IEST working group is lead by Ahmad Soueid of HDR Architecture, Inc. and Hal Amick of Colin Gordon and Associates.

The second plenary meeting of ISO/TC 229 was held in Tokyo, Japan, in June 2006. The emphasis of the Tokyo meeting was on organizing the work of the committee. For example, because the effort in TC 229 is expected to become quite large, a Chairman’s Advisory Group (CAG) was organized to work on policy issues. The CAG consists of the chairman, working group convenors, and other national members elected by region.

At the working group level, the priority in Japan was to develop “road maps,” structures or strategies so that appropriate standards are developed on a timely basis. Development of a structure is particularly important in the area of ISO/TC 229 Working Group 1-Terminology and Nomenclature. Because of the wide range of disciplines involved in nanotechnology, vocabularies are currently being developed in a haphazard manner. This may lead to imprecision and confusion as the field matures, thereby adversely affecting commerce and safety considerations. The principle activity within the TC at this point is the definition and writing of work item proposals for the development of documents. These work item proposals are championed by various national organizations and submitted to the TC for a formal vote by the participating member countries for approval by ISO. Upon approval, these proposals become work items within specific working groups. The first approved work item within ISO/TC 229 was ISO/AWI TS 27687 Nanoparticle-Terminology and Definitions, submitted and lead by the United Kingdom in Working Group 1. This document will be derived from BSI Publicly Available Specification (PAS) 71:2005 Vocabulary-Nanoparticles.

The third plenary meeting of ISO/TC 229 was held in Seoul, Korea, in December 2006. The primary purpose of the meeting was to refine working group strategic plans. A survey conducted during the last six months was used to support working-group planning sessions. Work was continued on the second approved work item, Health and Safety Practices in Occupational Settings Relative to Nanotechnologies, lead by the United States in Working Group 3.

The national bodies of Japan, Korea and the United States within Working Group 2 were encouraged to submit work item proposals on the measurement of carbon nanotubes. Further development of liaisons with other organizations was an important item of business. For example, plans for coordination by ISO/TC 229 with the newly organized International Electromechanical Commission (IEC), a standards committee on nanotechnology related to electrical and electronic products and systems, are currently being developed.

The next planned plenary meetings of ISO/TC 229 will be held in Berlin, Germany, in June 2007 and in Singapore, Malaysia, in December 2007.

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David S. Ensor is the director of the Center for Aerosol Technology and an RTI senior fellow. Dr. Ensor received his PhD in engineering from the University of Washington. He has conducted contamination control, aerosol and indoor air quality research for over 30 years, and is a founding editor of Aerosol Science and Technology. Dr. Ensor has served as President of the American Association for Aerosol Research and the International Aerosol Research Assembly, and he is the convenor of ISO/TC 209 WG 7. Dr. Ensor is a Fellow of the IEST and of the American Society of Heating Refrigerating and Air-Conditioning Engineers.

About IEST

IEST is an international technical society of engineers, scientists, and educators that serves its members and the industries they represent (simulating, testing, controlling, and teaching the environments of earth and space) through education and the development of recommended practices and standards. IEST is the Secretariat for ISO Technical Committee 209, Cleanrooms and associated controlled environments, charged with writing a family of international cleanroom standards. IEST is also an ANSI-accredited standards-development organization. For more information, contact IEST at [email protected] or visit the IEST Web site at www.iest.org.

Additional resources

  1. http://www.ansi.org/news_publications/news_story.aspx?menuid=7&articleid=1389
  2. http://www.bsi-global.com/Manufacturing/Nano/index.xalter
  3. http://www.iest.org
  4. http://www.iso.org/iso/en/commcentre/pressreleases/archives/2005/Ref980.html
  5. http://www.iso.org/iso/en/commcentre/pressreleases/archives/2005/Ref978.html
  6. http://www.nano.gov/NNI_07Budget.pdf

ESTECH, the IEST’s 53rd annual technical meeting and exposition, will take place April 29-May 2 at the Indian Lakes Resort in Bloomingdale, Illinois. With seminars and tutorials focused on contamination issues, the event offers contamination control professionals a unique opportunity to learn from and network with their peers and colleagues in the industry.

New this year, a special seminar topic for contamination control professionals is avail-able. “Compounding Sterile Pharmaceuticals,” presented by members of the USP <797> committee and CleanRooms magazine, will focus on U.S. Pharmacopeia (USP) Chapter 797, Pharmaceutical Compounding: Sterile Preparations.

The American Society of Health Systems Pharmacists (ASHP) recommends that all “persons who compound sterile preparations should exercise their professional judgment to obtain the education and training necessary to prove their competence in managing sterile compounding facilities and in sterile compounding processes and quality assurance.” USP <797> is the first set of relevant standards to address this requirement.

Published in 2004, USP <797> is currently under revision. Proposed changes to the 2004 standards were released in May 2006 to address inadequacies and clarify ambiguities in the document and, as a result, new concerns and questions have arisen.

CleanRooms is very pleased to sponsor this special session at this year’s ESTECH,” said John Haystead, chief editor of CleanRooms magazine. “Hospital pharmacies, and specifically the compounding of sterile pharmaceuticals (CSPs), are among the most dynamic and expanding segments of the contamination control industry right now. Our live Webcasts on the topic have had unprecedented audience sizes and participation, and I’m certain this program’s topics and distinguished speakers will draw major interest as well.”

Presenting the seminar are members of the USP <797> committee, including Jim Wagner, president of Controlled Environment Consulting, and Eric Kastango, president and CEO of Clinical IQ. Also presenting: Kenneth Mead, research mechanical engineer for NIOSH, and R. Vijayakumar, consultant to the contamination control industry.

The upcoming seminar and panel discussion will provide a forum in which to explore the latest information on the status and implementation of USP <797>.

For more information on the seminars and tutorials ESTECH will offer, or to register for the event, visit the IEST Web site at www.iest.org.

World market for AMC control


February 1, 2007

Importance of controlling airborne molecular contamination impacts filter manufacturers and media suppliers

By Robert McIlvaine and Karen Vacura, The McIlvaine Company

Airborne molecular contamination (AMC) is non-particulate chemical contamination in the form of vapors or aerosols that has a detrimental effect on a product or process. The need for AMC control in cleanrooms continues to grow as technology advances.

A necessity in the lithography process, AMC control is becoming more important in other cleanroom processes. As processing moves to faster speeds, manufacturers are seeing increasing sensitivity to contaminants, affecting yields.

Some common reasons for instituting AMC control are to prevent corrosion during processing and to protect reticles during transport or storage, according to Christopher Muller, technical director for Purafil, Inc., a leader in the engineering and manufacture of gas-phase air filtration media, systems and monitors. In leading-edge fabs, a large amount of outside air is pulled in for ventilation and pressurization purposes, and an even greater amount of air is recirculated, all of which needs to be monitored for molecular contamination. Additionally, reticles are at risk of damage due to haze formation from molecular contamination.

The International Organization for Standardization (ISO) has recently published ISO 14644-8, Cleanrooms and associated controlled environments–Part 8: Classification of airborne molecular contamination. This part of ISO 14644 covers the classification of airborne molecular contamination in terms of airborne concentrations of specific chemical substances (individual, group or category) and provides a protocol for test methods, analysis and time-weighted factors within the specification for classification. The document is designed for use in a wide range of industries, including microelectronics, pharmaceuticals and medical devices.

Applications for AMC control

AMC sources fall into two categories: internal and external. Some internal sources could be chemicals used in the manufacturing process, accidental spills, and off-gassing of cleanroom components. External sources vary by plant location and include factory emissions and auto exhaust. For example, in Taiwan, one fab’s exhaust can be the next fab’s intake. Proximity to farm fields can also raise the need for AMC control. In general, outside pollutants are removed from the make-up air, and indoor-generated contaminants are removed from the recirculating air.

AMC control is needed at different points in a facility, including: make-up air; re-circulated air in the ballroom, minienvironments and enclosed areas; fan filter units for localized control; and exhaust air. With the decrease in wafer carrier sizes, certain processes may only require AMC control in a smaller enclosed area, rather than for the whole ballroom. In a 200,000-square-foot semiconductor cleanroom, about 30 to 40 percent of the area is devoted to lithography processes. Only this area, roughly 60,000 to 80,000 square feet, needs AMC control.

According to Michael O’Halloran, director of technology at CH2MHill, engineering firms look at specifics for each application to find the most efficient and economical solution, balancing near-term and future costs. For example, engineers try to determine whether a contamination event is temporary, perhaps due to outgassing of new construction, or whether it’s a potential long-term problem.

CH2MHill uses a virtual airflow-modeling program, Computational Fluid Dynamics (CFD), to monitor contamination during process operations. This tool allows for the characterization of overall cleanroom airflow patterns, pressurization and temperature effects during the design phase of the cleanroom. The general approach is to improve the overall airflow patterns by minimizing recirculation zones that collect and transport contaminants, and to select areas for AMC control. CFD can also be used to track down the source of contamination in an existing cleanroom.

O’Halloran explains that the incorporation of a minienvironment into the lithography tool is part of a standard setup. Some tools require the background air to be controlled to a certain level in the cleanroom, and others rely on the minienvironment of the tool to do it. The life of the tool’s AMC filter is determined by the extent of challenges it receives: If the cleanroom AMC is controlled, the minienvironment filter will have a longer life.

Solutions and products

When choosing a system for AMC control, the most important consideration is what types of gases affect the process and personnel, and at what level. In general, AMC is specified to be less than 1 part per billion (ppb) over the service life of the system.

AMC control requires a combination of media and filter types, including prefilter usage, according to Purafil’s Muller. Types of common AMC filtration systems are:

  • Adsorption/Chemisorption: Adsorption uses granular activated carbon and/or activated aluminas. The removal capacity is directly related to total surface area. Chemisorbent systems use adsorption and specific chemicals added to activated carbons and/or aluminas.
    A reaction occurs with contaminants to form stable chemical compounds that either bind to the media or are harmlessly released into air.
  • Bonded media panels use granular adsorbents, such as activated carbon, bonded and formed into monolithic (single-piece) panels.
  • Ion exchange systems use synthetic polymers with positive or negative charged sites on pleated membrane or spongelike, flat sheets. This type of contamination control is mainly used in liquid applications but is finding specific niches as AMC control, such as for ammonia.

Practically all chemical filtration media today are manufactured from activated carbons and/or alumina. Specific chemical additives are utilized to impart special characteristics to the media. The target contaminant determines what chemicals are impregnated on the carbon or alumina. Potassium permanganate is a common, broad-spectrum chemical used almost exclusively on activated alumina since it cannot be effectively used with activated carbon. Pore size and structure of activated carbon can also affect how impurities are adsorbed.

Blended media for multiple contaminants are also used. For instance, alumina impregnated with potassium permanganate used in conjunction with plain or impregnated granular activated carbon provides a very broad-spectrum, gas-phase air filtration system. However, many manufacturers prefer to focus their AMC control on the specific contaminant type. Also, blended media have a shorter service life due to the reduction in the quantity of each media as compared to a system employing both media in individual stages. Filter life is based on capacity, with variables of temperature, airflow velocity, and contaminant.

Chris Hicks, a sales representative for Calgon Carbon Corp., explains that activated carbon works for most applications. Calgon manufactures several hundred carbon products to address almost any contaminant, and also offers activated alumina products. Hicks points out that AMC control needs to change as new exhaust regulations are passed. There is currently a shift toward adsorption from combustion. Calgon Carbon is starting to look at workstation filtration, targeting exhaust at site generation of contaminants. In this application, a separate module not integral to lab hoods would be employed.

Major suppliers of AMC filters are M&W Zander, Camfil Farr, and Purafil. American Air Filter (AAF) has developed a line of chemical filters as well. Asian companies Takuma, Takasago Singapore, and Taiwan Nitta also supply chemical filters, primarily aimed at minienvironments.

Cost considerations

Purafil’s Muller explains that costs can differ widely with application needs and whether the system is customized or integrated into an existing system. Chemical filter costs can range from $40 to $50 for a 24-inch x 24-inch x 2-inch outside

filter to $3,000 for a 24-inch x 24-inch x 12-inch tool filter. Chemical filters can have a higher pressure drop than HEPA filters, so increased energy costs should also be considered.

Monitoring filter life is another cost issue. According to Lighthouse Worldwide Solutions, depending on what chemicals are being monitored and how many locations are sampled, the cost can range from $3,000 for a single sensor to $400,000 for an entire system that samples multiple locations.

Performance and service life of filter systems differ with contaminant gas. CH2MHill’s O’Halloran says that monitoring must be a continuous process since failure load of chemical filters can be very sudden, over a span of just days or weeks. One efficient monitoring technique is to take a sample of the filter and test it; another method, although with less ability to predict future failure, is to monitor filter discharge.

AMC market forecast

Revenues for AMC removal have been projected based on the expected penetration in the microelectronics industry. A high penetration of the semiconductor industry and lower penetration of other microelectronics applications has been assumed. Other factors include filter life and cost.

Definition of the product is difficult. The filter element itself could be a stand-alone product or part of the total filter system. In either case, there is some additional ductwork, fan and housing cost for the extra treatment step. Forecasts for both filters and systems have been calculated.

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AMC filter sales are projected to rise from $50 million in 2006 to $67 million in 2010, with the bulk of the sales to the semiconductor industry (see Fig. 1).

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AMC system sales are projected to rise from $100 million to $136 million during the same period (see Fig. 2).

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By 2010, China will account for 7 percent of the sales but will also be increasing purchases at double-digit annual rates. Asian countries will account for the majority of AMC filter purchases (see Fig. 3).

Robert McIlvaine is president and founder of The McIlvaine Company in Northfield, IL. The company first published Cleanrooms: World Markets in 1984 and has since continued to publish market and technical information for the cleanroom industry. He can be reached at [email protected].

Karen Vacura is the air filtration market editor for The McIlvaine Company. She can be reached at [email protected].

References:

  1. Polen, Morgan, Peter Maquire. “AMC Measurement and Control,” Lighthouse Worldwide Solutions, application note, http://www.golighthouse.com.

The International Society for Pharmaceutical Engineering (ISPE) has released its latest technical publication, ISPE Good Practice Guide: Commissioning and Qualification of Pharmaceutical Water and Steam Systems.

The goal of the guide is to increase understanding of direct impact water and steam systems in the pharmaceutical and biotechnology industries. According to Alex Konopka, chairperson of the guide’s Task Team, “We’ve tried to pull together information that will allow practitioners to logically understand important considerations for the commissioning and qualification of these systems.”

The guide also describes how the capital project management process, commission-ing and qualification activities, and on-going monitoring work together in the Validation Life Cycle for direct impact water and steam systems.

For information on obtaining the guide, contact ISPE at (813) 960-2105 or via e-mail at [email protected].

Implementation of a compliance program improves pharmacy compounding quality at a major Boston hospital

By Fran McAteer, Microbiology Research Associates; William Churchill, John Fanikos, Michael Cotugno, and Caryn Domenici, Brigham and Women’s Hospital

The pharmacy services department of Brigham and Women’s Hospital (BWH), a major urban hospital in Boston, MA, has initiated a comprehensive USP <797> compliance program, the experiences of which stand to greatly benefit many other hospital pharmacy facilities and managers.

The BWH project began with the development of a detailed project management plan, called a GAP analysis, detailing myriad compliance issues and resulting in the decision by senior management to pursue a proactive strategy for USP <797> implementation. The project set out multiple phases and included a nonbiased expert audit of the hospital’s existing operation. This audit included:

  • a comprehensive review of quality documentation
  • interviewing compounding personnel
  • testing for viable particles
  • observing aseptic processing
  • monitoring the cleanroom environment
  • assessing the facility design
  • inspecting training records
  • reviewing quality management

Based on the results of the audit, a detailed project list was developed that further subdivided all compliance issues by size, scope, quality impact, and time of implementation. This was then developed into a project management plan and uploaded into the existing GAP analysis, making it a more proactive and focused document, and giving the pharmacy management team an overall customized assessment and implementation plan.

Turning words into action

The first step in the implementation phase was the establishment of environmental monitoring (E/M) capability within the sterile cleanroom where the compounding of sterile preparations (CSPs) would take place. Environmental monitoring standard operating procedures (SOPs) were also developed, including location-specific, sampling-site maps. The maps clustered sampling points around product critical areas.

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Microbiological sampling utilized specific media to exhibit both bacterial and fungal contamination, and sampling techniques and frequency were also delineated. Not only did environmental monitoring provide a feedback loop for overall cleanliness and sanitization of the cleanroom, it also provided trending data, which gave BWH pharmacy managers quantifiable performance management tools to help ascertain the quality of the sterile CSP area (see Fig. 1).

One immediate benefit of the environmental monitoring data was the clear demonstration that a stricter gowning policy for CSPs was needed. As a result, in addition to scrubs, booties, bouffants and gloves, gowning was upgraded to sterile, disposable, one-piece cleanroom coveralls. This proved to be a dramatic improvement over the ubiquitous blue scrubs and the new gowning requirements were stipulated in formal quality standard operating procedures.

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The CSP staff were trained in the new gowning procedures and gowning proficiency was tested using contact plates at multiple gown sites (hands, forearms, chest). Staff members who passed the gowning tests were certified to work in the sterile CSP cleanroom. The change in gowning procedures immediately impacted the viable particle environmental monitoring and a decrease in microbiological colony forming units (CFU) was observed (see Fig. 2).

In compliance with USP <797>, a formal quality unit for the pharmacy operation was established consisting of the associate director of pharmacy and the sterile product manager. The responsibilities of the quality unit include add-mixture review, environmental monitoring, documentation control, personnel training, final drug testing, and quality procedure enforcement. The quality unit has senior management approval and support, and multiple quality management procedures have been developed for documentation change control, review and approval. The quality unit is responsible for the review and approval of documentation, including all standard operating procedures, add-mixture records, and USP testing results. The quality unit also enforces gowning procedures, cleaning procedures, and environmental monitoring.

Another important element of the compliance program was the requirement that the pharmacy staff undergo USP <797> education and training. On-site training seminars were therefore conducted specific to CSPs and a 24-hour, 7-days-a-week operation. Topics included USP <797> compliance, aseptic processing, cleanroom gowning and environmental monitoring. The seminars are required before compounding activities may begin, and there are periodic updates for new personnel.

A formal cleanroom cleaning and sanitization program was also initiated. Since an outside vendor was used for this service, SOPs were developed for them, which included approved BWH sanitizers, appropriate dilutions, specific contact times for cleaners, application procedures, frequency of sanitizations, and a list of equipment and materials to be sanitized. The validation of the cleaning was conducted at both pre- and post-clean scenarios by environmental monitoring to demonstrate microbial reductions of various areas such as floors, walls, ceiling, laminar flow hoods, and equipment used in preparing sterile preparations. The validation demonstrated a successful cleaning process that adhered to BWH procedures and met acceptance criteria for microbial reduction.

Drug testing of CSPs to strict current USP <71> sterility testing requirements and current USP <85> bacterial endotoxin testing were also initiated. This will be required for CSP in batch sizes greater than 25. Both outside and internal microbiological testing laboratories must also be compliant with GLP/GMP as well as USP <797>. Inhibition/enhancement testing per CSP formulation for USP <85> should be performed initially to validate test results, as well as bacteriostasis and fungistasis validation testing for USP <71> compliance.

Looking ahead, Brigham and Women’s Hospital will continue to build on compliance activities. For example, media fill validation testing has been performed on initial fill equipment (i.e., TPN) to demonstrate consistent sterility, and calibration of monitoring devices such as thermometer and chart recorders will be implemented to show traceability to USP standards.

In summary, the implementation of a USP <797> compliance program has improved overall pharmacy compounding quality. The improvements in technique, training, staff education, standard operating procedures, daily sanitization, and environmental monitoring have created a quality program with proactive performance feedback that enables Brigham and Women’s Hospital pharmacy to provide meticulous patient care in a fast-pace, high-volume setting.

Fran McAteer, MS, MBA, is vice president of Microbiology Research Associates (Acton, MA), a consulting laboratory for USP <797> compliance. He can be contacted at [email protected].

William Churchill, MS Hospital Pharmacy, is director of pharmacy services at Brigham and Women’s Hospital.

John Fanikos, MBA, is assistant director of pharmacy services at Brigham and Women’s Hospital.

Michael Cotugno is the pharmacy manager at Brigham and Women’s Hospital.

Caryn Domenici, RPh, is the sterile products room supervisor at Brigham and Women’s Hospital.

References

  1. United States Pharmacopeia. USP 29, Chapter 797: Pharmaceutical Compounding-Sterile Preparations. Rockville, MD, 2004.

A comprehensive set of standards for sanitary facility design has bolstered the food industry’s ability to fight foodborne pathogens

By Sarah Fister Gale

A few years ago, members from across the food industry did something radical: They set aside competition and worked together to find better ways to battle contamination in food processing facilities. Through a facility-design task force sponsored by the American Meat Institute (AMI), they came together with the common goal of developing a set of standards for the planning, construction and renovation of new and existing facilities, specifically aimed at combating the infiltration and growth of harmful bacteria and pathogens.

The task force included high-profile owners, operators, architects, engineers and contractors, including representatives from Land O’ Frost, Hormel Foods, Kraft, Sara Lee, Bar S, Tyson, McClier, Carter Burgess, Middough Consulting, The Stellar Group, Hendon Redmond, Hixson, Ram Market Solutions, Smithfield and John Morrel.

Bringing together members of industry to define these goals was a revolutionary step for an industry that prides itself on competitive advantage, closely guarding its secret formulas and original recipes.

“We all agreed that food safety would not be used in our industry for competitive advantage,” says Skip Seward, vice president of regulatory affairs for AMI (Washington, DC) and leader of the facility-design task force. “Everyone brought their best practices for sanitary design and their knowledge of where things can and have gone wrong in the past to create a set of principles that will ensure the safety of the production process. It was a remarkable experience.”

Like most industries, meeting with the competition to discuss process strategies initially sounded absurd. But, unlike most industries, food processors see contamination, especially of ready-to-eat products like deli meats or bagged salads, not as an issue of yield or competitive price, but as an issue of safety.

“The difference between food and semiconductors is that, in semi, if you have a contamination incident, the product gets pulled out during quality assurance. If it happens in food, people can die,” says Bob Hunt, a project principal for The Haskell Company, an architectural, engineering and design-build firm in Jacksonville, Florida, and a member of the task force.

Besides being remarkable for bringing competitive brand owners together, the task force was unusual in that it combined the knowledge and experiences of plant owners with the expertise of architects, engineers and contractors, creating a much more in-depth and well-rounded discussion, Seward says. “We wanted a broad approach that would enable us to look at the entire facility and everybody brought something different to the table.”

Owners deal with pathogen problems that occur over the course of many years at their plants, an experience with which contractors and architects are not familiar, while designers and builders undertake dozens of new and retrofit operations every year, making them more aware of the latest tools, technologies and design strategies to combat pathogen problems.

“No single person on the task force had all the expertise,” notes John Butts, vice president of research for Land O’ Frost (Lansing, IL), one of the nations largest producers of deli meats and a member of the task force. “We all learned a lot from each other.”

The sharing of knowledge and need was beneficial to all members of the task force and to the industry as a whole, adds Darryl Wernimont, director of process integration for The Haskell Company (Jacksonville, FL) and a member of the task force. For the first time, owners were sharing stories about what happens years after the architects and builders are gone. With that knowledge, these firms can identify better solutions, giving them a competitive advantage in the field of sanitary facility design and allowing them to better serve the long-term needs of facility operators.

Wernimont found the process to be extremely enlightening from an architectural perspective. “We gained an understanding of the true life cycle of the facility,” he says. “So much happens in the plant that architects never hear about because it happens long after they’re gone.”

By participating in the task force, his group was able to see what problems can arise later on in the life of a plant, such as the development of harborages in surface cracks when walls, floors or ceilings are not sufficiently durable, or the build-up of moisture in walls that are not properly sealed. “When we understand what went wrong in the past, we can make better design decisions to preclude these things in the future.”

The eleven principles

After months of collaboration, the group produced a document called The 11 Principles of Sanitary Facility Design, which was unveiled in 2005 at a workshop sponsored by the AMI Foundation.


Figure 1. Harborages and niches can cause serious contamination issues in food processing applications and should be avoided. Photo courtesy of Hixson.
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The document helps plant owners and plant designers avoid potential contamination problems in food-processing facilities by identifying during the planning phases high-risk areas or issues, such as places where moisture can collect in the plant, harborages and niches that can host pathogen growth, or material and personnel flow that can cause cross-contamination (see Fig. 1).

Along with defining the eleven principles, the task force developed a 107-point questionnaire to define specific criteria associated with each of the sanitary design principles, which designers can use as an audit tool during their planning stages to assess blueprints specifically for food-safety design standards prior to construction.

Nonetheless, there was some skepticism early on about how competing brands could work together toward a common goal. “Going in, we weren’t sure,” Hunt admits. The group knew it couldn’t create specific regulations or set standards that would infringe on proprietary information, so it agreed to take the proprietary nature out of the equation and focus on identifying the problems rather than the solutions.

By focusing on problems, builders and operators can make their own decisions about how and whether they want to deal with certain issues, developing their own proprietary solutions that do not need to be shared with the group, notes Chris Harmon, senior vice president of project management for Hixson, an architectural firm in Cincinnati, and member of the task force.


Figure 2. Shown here, good corridor design. The aisle is wide enough to accommodate sanitation and maintenance activities, as well as movement of materials. Photo courtesy of Hixson.
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“We didn’t want to debate and limit people’s choices,” he says, noting that the principles only offer guidance on important contamination issues (see Fig. 2). For example, the document states that walls need to be durable and impervious to niches, but it leaves it to users to decide how to achieve that goal. “Maybe it’s with stainless-steel wall panels, maybe it’s with a Kynar finish,” Harmon says. “The principles don’t give them the answers, they point them in the right direction.”

Such guidance and framework for assessing risk areas help operators and designers look at their facility plans from a new perspective, launching conversations during the planning process that center on food safety, Seward notes. “It establishes a point of discussion between the company building the facility and the design/architecture firms doing the building. It gives them a forum for their decision-making processes and provides a rationale for certain design decisions.”

Land o’ food safety

Land O’ Frost was one of the first industry members to put the principles into practice, applying them to a new 182,000-square-foot, USDA-approved manufacturing facility in Madisonville, Kentucky, which broke ground in May 2005 and is currently up and running (see Fig. 3). Land O’ Frost designed and built the new facility following the eleven principles, with all design decisions based on sanitary-design concepts.

At the heart of its sanitary-design goals was the creation of a facility that could be kept dry, clean and cold, which meant they would need to strictly control air condensation and create a durable environment free from cracks, harborages, and corners or wells where moisture could get trapped.

“Science tells us that if something gets into a room, if that room is cold and dry, it won’t grow,” says Harmon, adding that in the last five years a much greater emphasis has been put on the dry aspect of that theory. “Everyone knows about cold, but today much more thought is put into the importance of dry conditions.”

Harmon goes so far as to suggest that someday science may show that, in optimally dry conditions, temperature would no longer be an issue, allowing facilities to operate at higher temperatures. “It’s a wild theory, but if it were true, it would change the whole product processing environment.”

In the meantime, the moisture control solution for the Land O’ Frost plant involved adding large, critical air-handling units in high-risk areas of the plant where exposed product would be handled, sliced and packaged. The air-handling units control humidity and dry out the facility after each daily sanitization.

When the facility shifts into clean-up mode, the air-handling units switch from their normal mode to using burners to rapidly heat fresh air and push it into the rooms while sucking the moisture out of the air and exhausting it through the roof. The rooms stay at a high temperature until the moisture conditions are acceptable. At the end of the cleaning shift, the air-handling units switch modes again, using cooling coils to condense the remaining moisture and push cool, dry air into the plant, bringing the temperature back to normal within 20 minutes.

The design team was able to further reduce the risk of moisture build-up in the facility by giving careful attention to the grade and drainage of the floors and surfaces. “Everything had to be self-draining,” Butts explains. “We couldn’t have corners or wall joints where water would pool. It was all sloped with precision.”

New technology makes drying a breeze

New technology is currently being developed to help facilities further improve efforts to reduce moisture by incorporating moisture-absorbing media into air-handling units. Called desiccant-based or desiccant-assisted air-conditioning systems, these cooling units do not need refrigerants and are effective for treating the large humidity loads resulting from ventilation air.

With desiccant systems, in the dehumidification/cooling cycle, the moist return air and some make-up air from outside are filtered and then passed through a slowly rotating, fluted desiccant media wheel, which absorbs moisture. The exiting warm, dry air is then passed through the air-handling unit to be cooled and distributed back to the processing area.

“With desiccant technology, you can keep the room’s relative humidity at 50 percent. That’s very dry,” Harmon says. It also dries the room incredibly fast after cleaning, in some cases reducing drying time by two-thirds, which means less downtime is required for completing sanitation procedures.

The downside, however, is that the technology is currently expensive and consumes an excessive amount of energy, Harmon says, so operators need to carefully consider which rooms would most benefit from these systems.

Although innovations in desiccant technology didn’t result from The 11 Principles, the focus on sanitary facility design has trickled down to material and equipment manufacturers, resulting in new products specifically developed to meet the goals of sanitary facility design, Haskell says. “It’s causing a ripple effect across suppliers.”


Figure 3. An exterior shot of Land O’ Frost’s new 182,000-square-foot, USDA-approved manufacturing facility in Madisonville, Kentucky.
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For example, one of the goals for food-processing operations is to have harborage-free, non-wood doors that can be repeatedly hosed down without damaging electrical components or allowing moisture to be trapped within. That need has sparked a new market and, thus, competitive opportunities in this area.

When The Haskell Company worked on the Land O’ Frost facility, it was a struggle to find a solution for its cold-storage door needs. Since then, two vendors have added non-wood doors to their product lines, says Hunt, and one coating manufacturer is working on a third product to meet surface durability goals for food processors.

The new Land O’ Frost plant also incorporated many existing design strategies, some of which were simply a matter of common sense once the design team looked at it from a food safety standpoint, says Butts. Some examples include eliminating wooden palettes for raw materials and designing a linear flow layout that keeps people, power, water and ingredients away from the high-risk processing spaces where product is open and exposed. “There is complete separation between raw and ready-to-eat products, with no flow-through areas,” Butts says of the design (see Fig. 4).


Figure 4. One of the eleven principles advises maintaining strict physical separations to reduce the likelihood of transfer of hazards from one area to another, as shown here. Image courtesy of The Haskell Company.
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All raw materials brought into the facility travel in identified paths outside of the processing space to eliminate cross-contamination. In the corridors, personnel move from left to right through the plant, also without moving through the processing spaces. Utility corridors are located above double ceilings that are accessed from above, and pipes and wires are dropped vertically into the processing areas, minimizing their exposure. When wiring conduits pass from cold to warm areas, they are wrapped with insulation to prevent temperature variances. The linear configuration also allows for future expansion to the left or right.

Independent stainless-steel drains, square rooms with no dead-air spaces, exposed structures positioned away from walls, and smooth, sealed, cleanable, durable surfaces further contribute to the sanitary design of the facility. All surfaces are coated in a siliconized polyester paint that can endure the harsh cleaning and sanitizing chemicals used in the plant, as well as the extreme heat and radical temperature changes that occur during cleaning, and it won’t chip or break if surfaces are bumped or knocked by heavy equipment. The walls also feature thermal breaks using a curb design at the base with four-inch-thick, insulated, metal-skin wall panels on top to maintain temperature and condensation control between rooms with different temperatures. Metal wall panels were chosen over fiberglass because the latter can buckle during heat changes, making it impossible to waterproof, says Hunt.

Another critical design goal was to eliminate all empty, hidden spaces where moisture could collect unseen and pathogens could settle and grow. “The trick in a large facility is to avoid gaps in walls, ceilings and doors,” Butts says. “That’s something the building industry hasn’t yet embraced, which limits our ability to find solutions.”

Part of achieving that solution, says Butts, is educating subcontractors and workers on the job site not just about what the sanitary design choices are, but also why they are critical. “Some of the criteria in the design are executed in the field. If the contractors don’t understand why they’re doing it, they may make on-site decisions that look good from the outside but could be a time bomb on the inside.”

Butts is urging industry members to expand the education of sanitary design principles to the workers. “It’s so much easier when people understand why we make these choices,” he says.


The 11 Principles for Sanitary Facility Design

Principle 1: Distinct Hygienic Zones Established in the Facility
Maintain strict physical separations that reduce the likelihood of transfer of hazards from one area of the plant, or from one process, to another area of the plant, or process, respectively. Facilitate necessary storage and management of equipment, waste, and temporary clothing to reduce the likelihood of transfer of hazards.

Principle 2: Personnel and Material Flows Controlled to Reduce Hazards

Establish traffic and process flows that control movement of production workers, managers, visitors, QA staff, sanitation and maintenance personnel, products, ingredients, rework, and packaging materials to reduce food safety risks.

Principle 3: Water Accumulation Controlled Inside Facility

Design and construct a building system (floors, walls, ceilings, and supporting infrastructure) that prevents the development and accumulation of water. Ensure that all water positively drains from the process area and that these areas will dry during the allotted time frames.

Principle 4: Room Temperature and Humidity Controlled

Control room temperature and humidity to facilitate control of microbial growth. Keeping process areas cold and dry will reduce the likelihood of growth of potential foodborne pathogens. Ensure that the HVAC/refrigeration systems serving process areas will maintain specified room temperatures and control room-air dew point to prevent condensation. Ensure that control systems include a clean-up purge cycle (heated air make-up and exhaust) to manage fog during sanitation and to dry out the room after sanitation.

Principle 5: Room Airflow and Room Air Quality Controlled

Design, install and maintain HVAC/refrigeration systems serving process areas to ensure airflow will be from more clean to less clean areas, adequately filter air to control contaminants, provide outdoor make-up air to maintain specified airflow, minimize condensation on exposed surfaces, and capture high concentrations of heat, moisture and particulates at their source.

Principle 6: Site Elements Facilitate Sanitary Conditions

Provide site elements such as exterior grounds, lighting, grading, and water management systems to facilitate sanitary conditions for the site. Control access to and from the site.

Principle 7: Building Envelope Facilitates Sanitary Conditions

Design and construct all openings in the building envelope (doors, louvers, fans, and utility penetrations) so that insects and rodents have no harborage around the building perimeter, easy route into the facility, or harborage inside the building. Design and construct envelope components to enable easy cleaning and inspection.

Principle 8: Interior Spatial Design Promotes Sanitation

Provide interior spatial design that enables cleaning, sanitation and maintenance of building components and processing equipment.

Principle 9: Building Components and Construction Facilitate Sanitary Conditions

Design building components to prevent harborage points, ensuring sealed joints and the absence of voids. Facilitate sanitation by using durable materials and isolating utilities with interstitial spaces and stand-offs.

Principle 10: Utility Systems Designed to Prevent Contamination

Design and install utility systems to prevent the introduction of food safety hazards by providing surfaces that are cleanable to a microbiological level, using appropriate construction materials, providing access for cleaning, inspection and maintenance, preventing water collection points, and preventing niches and harborage points.

Principle 11: Sanitation Integrated into Facility Design

Provide proper sanitation systems to eliminate the chemical, physical and microbiological hazards existing in a food plant environment.

New factories support fast-growing demand for optical, automotive and medical products

January 22, 2007 — /BUSINESS WIRE/ –BANGKOK, Thailand — Fabrinet, a leading global manufacturing services provider of complex optical components, announced that its latest factory, completed in Nov 2005, is near capacity and that a foundation-stone laying ceremony for a new factory in its Pinehurst campus manufacturing complex near Bangkok, Thailand, will occur today.

The new facility of approximately 300,000 square feet will accommodate fast-growing demand for the company’s optical components, module manufacturing and system assembly services as well as anticipated growth in capital equipment, automotive and medical markets. Scheduled for completion in late 2007, the new building will raise Fabrinet’s global manufacturing capacity to over one million square feet.

The new factory’s numerous assembly lines can be customized to support Class 100,000 to Class 100 Clean Rooms for high precision opto-electronic manufacturing and sophisticated “Dry-Rooms” to meet the ultra-low humidity requirements of medical devices. Additionally, the factory will accommodate Fabrinet’s unique, customer-specific “factory within a factory” operations, ensuring complete IP security and exact adherence to each customer’s desired manufacturing processes.

“Our factory within a factory infrastructure and extensive quality process requires particularly large and flexible facilities,” said Tom Mitchell, chairman and CEO of Fabrinet. “The new building reflects the continued investment we’re making in Thailand which we believe continues to offer a compelling manufacturing value proposition for complex high-mix, low to medium volume products.”

About Fabrinet
Fabrinet is a global engineering and manufacturing services provider of complex optical and electro-mechanical components, modules and bulk optics serving data communications, telecom, networking, automotive and medical markets worldwide. A vertically integrated solutions provider, Fabrinet also designs and manufactures bulk optical components including glass and crystal through its operating subsidiaries’ Casix and VitroCom. With facilities in Thailand, China and the United States, Fabrinet is the number one choice for organization’s seeking to improve operational efficiency and reduce manufacturing costs for complex manufacturing requirements. For more information, see www.fabrinet.com.

Contacts
Fabrinet
Pam Crowley, 408-529-9655
[email protected]

January 22, 2007 — /PRNewswire-FirstCall/ — VIENNA, Va. — CEL-SCI Corporation (AMEX:CVM) has signed a letter of intent with BioProperties, Inc., a privately held real estate firm specialized in the biomedical sector, to acquire and build out to CEL-SCI’s specifications a turn-key CGMP drug manufacturing facility for CEL-SCI’s cancer product Multikine(R). CEL-SCI was recently given the green light by the FDA to start a Phase III clinical trial of head & neck cancer patients with Multikine.

This manufacturing facility is an integral part of moving Multikine into the Phase III clinical trial and later commercialization. The commitment, subject to a final contract, is for $15 million. The facility is expected to cost about $12 – 14 million, to be paid through a long-term lease agreement.

According to Stan Wendzel, Managing Director of BioProperties, Inc., “CEL- SCI has made tremendous progress advancing their Multikine product candidate towards FDA approval. We are very excited to be providing a facility to CEL- SCI that will allow them to complete the Phase III trials for Multikine and ultimately bring this important product to market.”

Geert Kersten, Chief Executive Officer of CEL-SCI said, “This facility represents a huge step forward for our Company. We will be able to produce our drug Multikine in our own CGMP facility for Phase III trials as well as for sale once marketing approval is granted. From a regulatory perspective and for the control of the manufacturing process this is the most prudent way for the Company to proceed. An additional benefit of having this facility is that, during the Phase III study, it may also be used for contract manufacturing work with other biotech companies and/or the U.S. government since it will contain a clean cold-fill suite. The ability to aseptically fill in the cold is rapidly becoming very important for many bio-defense and other biologic drugs, and is aimed at avoiding the large biological activity losses seen in these products when cold aseptic fill is not available.”

The CGMP drug manufacturing facility design and use plan have been reviewed by the appropriate regulatory bodies and all recommendations received were incorporated.

CEL-SCI Corporation is developing new immune system based treatments for cancer and infectious diseases. The Company has operations in Vienna, Virginia and Baltimore, Maryland.

When used in this report, the words “intends,” “believes,” “anticipated” and “expects” and similar expressions are intended to identify forward-looking statements. Such statements are subject to risks and uncertainties, which could cause actual results to differ materially from those projected. Factors that could cause or contribute to such differences include an inability to duplicate the clinical results demonstrated in clinical studies, timely development of any potential products that can be shown to be safe and effective, receiving necessary regulatory approvals, difficulties in manufacturing any of the Company’s potential products, inability to raise the necessary capital, inability to get American Stock exchange approval for any transaction and the risk factors set forth from time to time in CEL-SCI Corporation’s SEC filings, including but not limited to its report on Form 10- K for the year ended September 30, 2006. The Company undertakes no obligation to publicly release the result of any revision to these forward-looking statements, which may be made to reflect the events or circumstances after the date thereof or to reflect the occurrence of unanticipated events.

CONTACT: Gavin de Windt of CEL-SCI Corporation, +1-703-506-9460
Source: CEL-SCI Corporation
Web site: http://www.cel-sci.com/

January 22, 2007 — /PRNewswire/ — ENGLEWOOD, Colo. — Baxa Corporation has published the 2007 dates for training at its STAR (Skills Training, Academics and Resources) Center. The STAR Center, a premier facility designed for cleanroom and pharmacy practice demonstration, is located at the company’s world headquarters south of Denver, Colorado. Baxa Corporation built the STAR Center to provide professional education on pharmacy practice, cleanroom principles and compliance to regulatory requirements.

The initial class in the STAR Center, Compliance Tools and Aseptic Certification for USP < 797 >, debuted in September 2006, with sessions repeated in October and November. 2007 Program Dates for the USP 797 course will be: 23 – 25 January; 20 – 22 March; 22 – 24 May; 24 – 26 July; 18 – 20 September and 23 – 25 October. Class participation is limited to 18 to ensure that professionals have hands-on experience and a small student-to-trainer ratio.

The ACPE-certified training will be filled on a first come, first served basis. Current programming targets pharmacy and IV managers, and provides value to all personnel who compound sterile products or who are implementing cleanroom principles and practices that comply with USP 797 and industry best practice. Topics include cleanroom physical design and layout, engineering controls and airflow science, media fill testing and principles associated with work flow, staff training, cleaning, monitoring, validation and documentation.

Baxa Corporation sponsors the STAR Center to further best practices in hospital pharmacy. The STAR Center brings together professional and industry partners to provide participants with a range of experience in equipment, technology and design. Tuition charged for STAR Center training covers the cost of providing participant meals and training materials, ACPE accreditation and professional speakers’ fees. Future class offerings will be determined through professional interest and facility requirements. Contact Baxa Corporation at www.baxa.com/starcenter for more information.

About Baxa Corporation
Baxa, a customer-focused medical device company, provides innovative, solution-based technologies for fluid handling and delivery. Its systems and devices promote the safe and efficient preparation, handling, packaging, and administration of fluid medications. Privately held, Baxa Corporation has subsidiaries and sales offices in Canada and the United Kingdom; direct representation in Belgium, Denmark, Finland, France, Germany, Luxembourg and The Netherlands; and distribution partners worldwide. Further information is available at www.baxa.com.

About the STAR Center
The STAR Center is a state-of-the-art cleanroom, pharmacy and training facility located at the Baxa world headquarters in Englewood, Colorado. The center was purpose-built to support training in aseptic technique, pharmacy workflow and practice, cleanroom design and maintenance and USP < 797 > compliance among other topics. Classes will be taught by industry-recognized subject matter experts. Further information is available at www.baxa.com/starcenter.

Contact:
Marian Robinson, Vice President, Marketing
Baxa Corporation: 800.567.2292 ext. 2157 or 303.617.2157
Email: [email protected]

Maggie Chamberlin Holben, APR
Absolutely Public Relations: 303.984.9801 or 303.669.3558
Email: [email protected]

Source: Baxa Corporation
Web site: http://www.baxa.com/
http://www.baxa.com/starcenter