Tag Archives: Clean Rooms

By Hank Hogan

Spring may be around the corner, but the prediction is for a chill to continue for at least the first half of the year. After that, things might warm up. That’s the consensus forecast with regard to semiconductor equipment sales. There are those, however, who think the outlook is much bleaker. On a brighter note, cleanroom consumables used for semiconductor manufacturing–silicon wafers, wipes, gowns, and so on–should grow.

The difference arises because consumables are needed for daily production, while equipment is a capital expenditure. Thus, the former tracks semiconductor run rates and those look good.

“The expectation of a number of analysts following the semiconductor industry is for growth in both semiconductor units and revenues in 2008. Demand remains strong for electronics in general, thus semiconductor devices and the materials needed to fabricate such will grow in sync with that demand,” says Dan Tracy, senior director of industry research and statistics for the semiconductor trade organization SEMI (San Jose, CA).

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The latest SEMI predictions are for a 12.4 percent growth rate in 2008 for world-wide wafer fab materials, a category that includes wafers, chemicals, gases, and other items. That’s healthy, even if it is down slightly from the 15.3 percent estimate for growth in 2007.

In contrast, capital equipment spending is forecast to decline, at least for the first half of 2008. Based on data from 60 North American equipment companies, SEMI has been showing a book-to-bill ratio of less than one for months. The ratio has bounced between 0.8 and 0.9 since mid-2007, meaning that fewer new orders were booked than those that were shipped, or billed. Equipment orders for Japanese manufacturers have also declined over that same time frame.

Gartner (Stamford, CT), a technology-oriented market research company, predicts a 9.9 percent spending decrease, with sales falling from $44.8 billion in 2007 to $40.3 billion in 2008. Three-quarters of that spending will be in wafer fab equipment. The 10 percent decline is in line with SEMI’s recent book-to-bill ratio. Gartner expects sales to pick up in the second half of the year as DRAM memory chip supply and demand come into balance.

A number of reasons are cited for this lessened spending, not the least of which is that last year was a good one for equipment sales. “Even with the declining orders since early 2007, 2007 will be the second highest spending year for semiconductor equipment, second only to 2000,” says Tracy.

He adds that the ramp in 300-mm wafer technology has driven equipment spending and wafer sales over the last half decade. This year will be the tipping point, with 300-mm fab capacity finally surpassing that of 200 mm.

Not all firms are as upbeat as Gartner. Advanced Forecasting (Saratoga, CA), a semiconductor market analysis company, issued a warning about the upcoming year. President Moshe Handelsman notes that his firm uses only quantitative tools to generate its predictions, which it sells to clients. For that reason, he won’t go into detailed numbers, but the situation could be significantly worse than current expectations, says Handelsman. “The numbers are really negative.”

By Bruce Flickinger

The concept of disease prevention is simple–but not easy

Hospital-acquired infections (HAIs; also called nosocomial infections) are a distressing issue on two levels: one, it is a sad fact that many people leave the hospital with infections and associated problems that they were not admitted with; and two, these infections are, for the most part, largely preventable.

Common wisdom says the concept of disease prevention is simple but not easy. The complicating factor in the European Union (EU) is tremendous variability on several levels: patient populations; hygiene awareness; standards and practices; and most critically perhaps, the microorganisms themselves–those invisible, elusive culprits that have developed a singular proficiency for surviving and proliferating in even the most hostile environments.

These variable conditions conspire to hamper preventative efforts and provide a fertile foothold for infectious organisms, and if an experience reported this past summer in U.K. newspaper The Guardian is any indication, the battle to eradicate disease-causing organisms from our hospitals and health care facilities is far from won. In their first enforcement of the new U.K. Hygiene Code, National Health Service (NHS) officials noted that the violative hospital employed only one microbiologist working four hours a week on infection control. Even someone at the periphery of the problem knows that this is an entirely insufficient response to the problem of bacterial infection and resistance as it exists today.

Anecdotal evidence about infection control successes and failures abounds. Some European countries, such as the Netherlands, have some of the lowest rates of HAIs, while awareness and vigilance of the problem tend to lessen in Southern Europe and in the emerging infrastructures in Eastern Europe, where multi-drug-resistant tuberculosis is a problem. Fortunately, the overall trend is toward heightened government oversight and regulatory accountability–the U.K. Hygiene Code, which went into effect October 2006, is but one example. Larger pieces of hospital budgets are also going to hygiene infection control.


Figure 1. STERIS’s VaproSure™ sterilizer is effective for sterilizing targeted hospital room surfaces. Photo courtesy of STERIS.
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The bottom line, says Gerald McDonnell, PhD, vice president of Research and European Affairs with STERIS Ltd. (Basingstoke, UK), is that “life is a constant battle between humans and certain types of disease-causing microorganisms, which we attempt to control through vaccinations, our own immune systems, and good hygiene practices. When we are healthy we generally tend to win these battles, but the sad part is that oftentimes we lose.”

Standard practice, new perspectives

The tenets of winning the war against HAIs are well established. They include good personal hygiene practices; patient involvement and empowerment; instrument and equipment sterilization; isolation and infrastructure controls; and proper surgical and catheterization procedures. How effectively each and all of these are implemented in a facility and ingrained in the staff through education and training will impact infection rates.

“Infection control, or more correctly infection prevention, is always a combination of a number of interventions to reduce risk,” McDonnell says. “It starts in the ambulance or emergency ward and goes all the way through to discharge. The sicker the patients, the more at risk they are, but vigilance by patients and staff mitigates this risk, along with good practice and products.”

In addition to hygiene practices, the misuse and overuse of antibiotics has become an acute concern. A 2005 report from the European Antimicrobial Resistance Surveillance System (EARSS), a database of test results reported from 30 European countries, notes that resistance is “most convincing” where orally administered antimicrobial compounds, which are preferred in ambulatory care, are used. That is, they are convenient and often overused. EARSS says, “The growing availability of third-line antimicrobial drugs as oral formulations is a matter of concern and underscores the need of locally or nationally advised prescribing practices for both ambulatory and hospital-based care.” A number of companies serving the health care market offer antibiotic management services, in which mismatched antibiotics can be identified and formularies adjusted accordingly.

Another topic gaining more attention of late is environmental surveillance, particularly of patient-contact surfaces. This is particularly salient in light of the emphasis that is usually placed on handwashing and personal hygiene. “A number of recently published studies have shown that contact surfaces can be contaminated with important pathogens such as MRSA (methicillin-resistant Staphylococcus aureus, VRE (vancomycin-resistant Enterococcus), and Clostridium spores,” McDonnell says. “In some cases, these organisms have been shown to survive for weeks on surfaces. With patient or staff contact, this becomes a significant source of infection.”

So while infection control professionals spend a lot of time teaching hospital staff and patients about the importance of handwashing in reducing hand contamination, “we should remember what happens to those hands after they have been washed, or even gloved,” McDonnell says. “Contact with contaminated surfaces such as bedrails or bedside tables can quickly recontaminate the hands/gloves and be a further source of infection.”

McDonnell says the merits of surveillance are “often a debated point,” but that it does “make sense for hospital administrators to at least understand the levels and types of contaminants or microorganisms that can be present in high-risk areas, wards, or patients, and in particular during outbreak situations.”

Quantifying the problem

Broadly speaking, the importance of epidemiological surveillance both for better understanding HAIs and for crafting appropriate responses to them cannot be overstated. Numerous local, national, and pan-European efforts, such as EARSS, are in place to carry out this work. Another is Improving Patient Safety in Europe (IPSE), funded by the EU Directorate General for Health and Consumer Protection, which oversees HELICS (Hospitals In Europe Link for Infection Control through Surveillance). HELICS, in turn, is an international network that collects, analyzes, and disseminates data about the risks of nosocomial infections in European hospitals.

Based on the 2006 HELICS survey, which encompasses results of hospital-wide surveillance programs throughout the EU, IPSE estimates that roughly 3 million patients acquire a nosocomial infection in the EU each year, and that 50,000 of these infections result in death. The most frequent infections are urinary and respiratory tract infections (28 and 25 percent prevalence, respectively), and surgical site infections (17 percent).

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Significantly, 20 to 30 percent of nosocomial infections are considered to be preventable by intensive infection prevention and control programs, according to ISPE.

The most prevalent offender continues to be MRSA, which is isolated in approximately 5 percent of all nosocomial infections in the HELICS database. EARSS confirms this. In 2005, the database included results from more than 27,000 isolates of invasive S. aureus. Prevalence of MRSA among these isolates was under 3 percent in only seven countries, around 20 to 25 percent for most of the “EU25,” and above 40 percent for eight, primarily southern European, countries.

While not as prevalent, E. coli resistance is “a disturbing development with seemingly inexorable vigor,” EARSS says. The pathogen’s resistance to both aminopenicillins and fluoroquinolones is increasing, and combined resistance is a frequent occurrence.

It is generally thought that MRSA strains are more frequently isolated from ICU patients than non-ICU patients. This again is supported by EARSS, which says that in some countries, such as Poland, Bulgaria, Croatia, Greece, the U.K., Cyprus, and Romania, the proportion of MRSA found among ICU patients reaches over 60 percent. These figures remain troubling, and ICU infection control procedures are often a main component of a hospital’s overall program.

McDonnell and others caution against making broad generalizations about the ICU being a key problem in the spread of HAIs. “Although HAIs are often identified within ICUs and some have been acquired in ICUs, in many cases patients are already carrying various pathogenic microorganisms when they come into these departments,” McDonnell says. “An example is the recent understanding that many strains of MRSA are actually community acquired. A patient may not know they are carrying these strains, but when they become sick, are put on antibiotics, or are immunocompromised they are more at risk from these organisms causing an infection that normally they could fight off. Patients in ICUs are very vulnerable to infection. They are very sick and predisposed to illness.”

On-site epidemiology

National surveillance figures provide important information, but hospital administrators also need a better understanding of how infectious organisms and antibacterial resistance pervade their own facilities. One new tool is MedMined™, a service offered through Cardinal Health (Birmingham, AL) that enables the automated collection and standardization of infection data throughout a facility. Management can use the information to track its own infection rates and preventive efforts and, because the data is fed anonymously into a national database encompassing all MedMined sites, an individual facility’s performance can be compared to others.

A surveillance component continuously scans the hospital for problems using data uploaded from a laboratory information management system. It then uses pattern mapping and a kind of artificial intelligence to track microbial populations, potential hot spots, and the effects of any interventions. Says Patrick Hymel, MD, vice president with Cardinal Health, “You don’t have to direct the system or ask specific questions like you do with manual epidemiology. It provides regular, standardized feedback about the effectiveness of infection control procedures, so people can see change almost immediately. They’re often surprised at the opportunities they have for improvement.”

MedMined is currently in use in 250 hospitals across the U.S., and users have been able to document an average 13.5 percent reduction in infection rates in the first year of using the service, the company says.

“There are major changes coming in how payers will reimburse for complications from HAIs,” says Hymel. ‘It’s important for hospitals to know their true exposure, and it is hard to know this if they are using a strictly manual approach to case finding and tracking.”

Hymel adds, “Infection control departments have traditionally been viewed as a cost center at hospitals, but with improving practice over time, you can really transform the department into a significant source of cost savings that can be directly applied to the bottom line and improve the overall financial performance of the hospital.”

Good practice pays off

While HAI control and prevention is a complex, multi-factorial public health issue, with proper infection control implementation, such as hand hygiene, proper vaccination of staff, and sterile techniques, hospitals can save lives and minimize economic losses. This realization is turning health care into a strong market for contamination/infection control technologies and services, much like microelectronics was several years ago, observers say. Awareness and education are increasing concurrently.

“In the post-antibiotic era many countries employed medicine to treat disease, but not necessarily to prevent it. Now the focus is on prevention or controlling early, and the same should be held for infection prevention,” McDonnell says. “Medical staff should be spending significant time during training on infection prevention earlier in their careers. Some countries are doing this effectively today while others have a long way to go.”

Resources

  1. Surveillance reports and other information are available from the Improving Patient Care in Europe web site at http://helics.univ-lyon1.fr/
  2. The European Antimicrobial Resistance Surveillance System (EARSS) web site is http://www.rivm.nl/earss/
  3. Information about the VaproSure system and other STERIS technologies is available at http://www.steris.com/aic/aic.cfm
  4. Information about MedMined is available at http://www.cardinal.com/medmined/

The number one goal of this publication is to provide our audience of contamination control professionals the very latest and most useful information available. To do this, each month we provide a unique combination of staff-reported articles and a selection of contributed articles from leading industry experts.

What concerns me of late, however, is the limited number of contributions coming from the user community–you, our readers. While we certainly include the activities, expertise, and opinions of users in our staff-written material, the vast majority of technical article contributions are coming from the vendor/provider community.

I suspect the biggest reason for this is that many of you have simply become so busy actually implementing and managing your contamination and infection control solutions that you don’t feel you have the time available to write and share your accomplishments with the community at large. Of course, this is a legitimate concern, but it’s also a problem, because if successes, experiences, and lessons learned are not being shared, then everyone is operating less efficiently–duplicating efforts and repeating mistakes.

That’s why I’m writing this month to encourage our readers in the user community to record and publish your activities. We’re certainly willing to offer whatever assistance we can to make this as seamless a process as possible. One thing we’re doing right now is adjusting our long-standing editorial policy of not accepting “case history” articles. This policy was implemented because case-history-type articles are normally submitted by writers from the vendor community and tend to be specific to a particular company’s product or service. As such, unless readers already have the specific product described, or intend to acquire it (that’s what advertising is for), the article will have little to no value to them. On the other hand, case histories, or articles describing individual contamination control challenges, experiences, and accomplishments by end users, are extremely valuable to our entire readership.

So, while we will continue to cull out vendor-supplied case histories, this policy will no longer apply to anyone in the user community who wishes to contribute this type of article. By the way, before you call, I’m well aware that most contamination control vendor companies are also users of the technology, and we can work this possible conflict out on a case-by-case basis.

So please, let me and your colleagues in the contamination control community know what you’re doing out there. Remember, it probably won’t hurt to remind people in your own company how important your contributions are, either.

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John Haystead,
Publisher & Editor

Coming clean


March 1, 2008

By Bruce Flickinger

Cleanliness and critical environment controls are essential for the manufacture of modern automobiles. A new standard could help harmonize disparate testing practices in the EU

Quality management systems, embodied in recognized standards such as ISO and in the meticulous specifications used by individual manufacturers, have been integral to the resurgence and success of the automotive industry since the 1980s. Today, automobile manufacturing is among the most stringently controlled industrial sectors, driven by ever-rising demands for performance, safety, and efficiency.

Cleanliness and environmental controls clearly are paramount to meeting these goals. This is true not only for sensitive electronic components, but also for precision mechanical parts, such as those found in transmissions, fuel injection, oil circulation, and braking systems, as well as painting and finishing technologies. Across the spectrum of automobile assembly, there is a direct correlation between cleanliness and product defect rates. The term “cleanliness” has progressed to become a quality feature and is now often specified on component drawings or in quality agreements in the same way as size accuracy or surface roughness.

“Clean technology always trickles down, and car companies and OEMs [original equipment manufacturers] are finding they need to have controls that they didn’t need before,” says Duane McKinnon, president of Simplex Isolation Systems (Fontana, CA). “Twenty years ago, cleaning basically meant degreasing, and the engines being assembled in the plants could be assembled in your garage. Engine and transmission tolerances are so much tighter now that you need at least a Class 100,000 room to do the work.”

Metal cleaning and degreasing has become more complicated and demanding. With restrictions on the use of halogenated hydrocarbons as solvents, “resulting cleaning systems have become much more complex in order to achieve the same degreasing performance as before,” says Markus Rochowicz, PhD, with the Department of Cleanroom Manufacturing at the Fraunhofer Institute for Manufacturing Engineering and Automation (Stuttgart, Germany).


Figure 1. A Fabrinet operator works a complex manufacturing process under stringent disciplines required for cleanroom conditions. The company has expanded into the automotive sector from a base in high-density drive fabrication. Photo courtesy of Fabrinet.
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Furthermore, “chemical degreasing as a cleaning process has become insufficient to meet demands for the thorough removal of tiny amounts of residual particles of a few hundred microns. This has led to the development of cleaning systems equipped with more effective mechanical cleaning components,” Rochowicz says. These include ultrasound, intensive flooding of components, and lances that are “introduced into single borings and clean them by pressure-rinsing them with jets of water under pressures of several hundred bars.”

Tightening tolerances

Precision mechanical components must be cleaned and handled in the broader automotive assembly environment, where oil mist and metal particulates from robotics and other fabrication equipment pervade the air. “The focus is on setting up white rooms, or protection zones, to isolate paint and finishing, and critical manufacturing areas to prevent cross-contamination,” McKinnon says. “The airborne contaminants tend to settle and need to be kept out of areas such as engine and transmission assembly.”

In additional to supplying modular cleanrooms and industrial enclosures to automobile manufacturers, Simplex works with companies that make dash pods, air bag sensors, and door lock electronics, including new systems that incorporate fingerprint readers. “Dust and airborne particulates are the primary contributors to defects in these products,” McKinnon says.

A contaminating particle located in the wrong place on a component can potentially impair its function or cause it to fail. One example is diesel injection technology. “The rapid increase in performance since the second half of the 90s has led to constantly rising injection pressures as well as injection nozzles with smaller and smaller nozzles,” Rochowicz says. “The high-pressure pumps used are capable of pressures up to more than 2,000 bar and dispense fuel into the combustion chamber via apertures just 100 µm in diameter. Ensuring a high degree of cleanliness of the various parts, when manufacturing such systems, is no longer sufficient. Even the assembly processes need to be carried out under highly clean conditions.”

Injection systems speak to the fact that, while many automotive components must have a highly clean surface, these critical areas are often located in the part’s interior. Many parts are complex metal structures that are machined into their final shape after molding and contain media-conducting borings or inner surfaces that require a high level of cleanliness. The only way to check the degree of cleanliness of such parts is to extract any particulate contamination that might be present via a cleaning process and then analyze the cleaning fluid. To do so, particulate contamination is usually deposited on a filter membrane for microscopic or gravimetric analysis.

Learning from electronics

Particles of concern in the manufacturing environment typically are large enough that they tend not to be aerosolized, but rather drop onto surfaces, presenting a different air management scenario than that found in a semiconductor cleanroom. Still, the window of concern is getting smaller, and contaminants such as metal, fibers, skin flakes, and spittle–ranging from 80 to 120 µm on the large end, to smaller particles from 40 to 60 µm in size–need to be controlled. Users have the same goal as conventional cleanroom users: preventing visual and functional defects in the product.

It is not surprising, then, that some companies are expanding into automotive from a base in more traditional cleanroom sectors. One example is Fabrinet (Patumthanee, Thailand), a global engineering and manufacturing services provider of optical and electromechanical components, which has been able to parlay its success in DEL semiconductor and high-density drive fabrication into a burgeoning business supplying components to auto manufacturers worldwide.


Figure 2. Automobile manufacturing is characterized by constantly rising power and safety capabilities, coupled with lower pollution levels and reduced fuel consumption. Photo by Roger Job and courtesy of ACEA.
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“We felt we offered a compelling solution to our base of automotive customers: a real differential advantage in manufacturing,” says Mike Alarid, senior vice president, materials and overseer of Fabrinet’s automotive business. “We offered a more stringent, disciplined approach to manufacturing, along with a global delivery mechanism that the car companies were looking for from their contract suppliers.”

Fabrinet primarily operates Class 1000 and Class 100 cleanrooms throughout its operations, and uses a unique system of manufacturing bays in which individual conditions can be controlled and configured for different customers and their requirements. “The automotive components we were initially making didn’t need this level of control, but it’s more efficient to maintain a level of control than it is to rebuild down,” Alarid says.

He continues, “The industry has really transformed itself throughout the supply chain. Car makers look at every aspect of their contractors’ quality systems and their ability to manage that system.” Suppliers in Fabrinet’s space ‘need to manage to 0 dpm [defects per million] for the Tier 1 companies,” he says.

Testing standard evolves

Complex systems are, by their nature, more sensitive to particulate contamination, so while achieving lower defect rates becomes a greater challenge, it is the key business metric for any company along the automotive supply chain. ISO assurances, including ISO 16232 Cleanliness of Components, are just an entry point; manufacturers have much more stringent individual auditing systems and operate auditing groups attuned to their specific needs and standards.

“Just as with all other quality values, there is also a need to measure and document a component’s degree of cleanliness,” says Fraunhofer’s Rochowicz. Currently, however, there is no industry standard for testing cleanliness; the testing systems and standards used by different companies are convoluted with varying parameters, such as “the high number of possible cleaning methods and cleaning media which are implemented, and which give different cleaning results,” he says. “It is impossible to obtain comparable, reproducible residual contamination results in this way.”

VDA Volume 19 is an effort to bring some standardization to this complicated mix. The standard is the product of an industrial alliance formed in 2001 under the coordination of Fraunhofer IPA. Called TecSa (Technische Sauberkeit), this consortium comprises 25 companies, encompassing not only German automobile manufacturers and supplier companies but also manufacturers of cleaning systems and cleaning media. Volume 19 is now available through the Quality Management Center of the German Automotive Industry Association (VDA-QMC).


Figure 3. Unit injectors with piezo actuators for diesel engines being produced at Volkswagen Mechatronic GmbH & Co. KG (Stollberg, Germany). These are one example of the myriad precision components used in modern automobiles that must be manufactured in critical environments to ensure they are free of microscopic defects. Photo courtesy of Continental/Siemens.
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This standard, which is compatible with ISO 16232, establishes fixed procedures for each type of cleanliness test, specifies the analytical equipment to be used, gives recommendations for selecting a suitable test procedure, and states precisely how the procedure is validated. The overarching goal is to “detach all removable particulate contamination from the component in a single extraction process without damaging the part or the surfaces,” Rochowicz says. Depending upon the geometry of the test components, the user may choose one of four different extraction methods: pres-sure rinsing, internal rinsing, ultrasound, or agitation.

Another aim is “to avoid having to send parts to a few select laboratories for cleanliness analysis,” Rochowicz says. It stipulates the use of blank values adapted to components that compensate for the influence of external sources of contamination on the actual test, such as surrounding air, test set-up, test media, or staff. In this way, “the laboratory and test equipment are only as clean as the level required by the component itself. This allows most of the tests to be carried out in industrial laboratories.”

Rochowicz stresses that, in its current form, VDA Volume 19 is only concerned with testing the cleanliness of components and does not state how clean certain parts need to be in order to function correctly.

Educating an industry

Another point of emphasis is that “cleaning technology cannot be expected to straighten out mistakes made in preceding process steps,” Rochowicz says. The manufacture of technically clean products requires an integrated approach to development, construction, manufacturing planning, logistics, and quality assurance stakeholders. This, in turn, calls for concerted on-the-job and vocational training to better infuse the tenets of cleaning and quality throughout the manufacturing enterprise.

“In Germany, there is no specific training available in industrial component cleaning. Most of this knowledge is held by the manufacturers and users of cleaning technology in industry, along with a number of institutes focused on cleaning technology,” Rochowicz says. “Many of the problems that are currently being discussed have not yet been systematically investigated or solved, so there is demand for both knowledge transfer and increased research and development activities.”

Resources

Fabrinet
Patumthanee, Thailand
www.fabrinet.com

Simplex Isolation Systems
Fontana, CA
www.simplexisolationsystem.com

European Automobile Manufacturers Association (ACEA)
Brussels, Belgium
www.acea.be

Fraunhofer Institute for Manufacturing Engineering and Automation (IPA)
Stuttgart, Germany
www.ipa.fraunhofer.de

TecSa
www.technische-sauberkeit.de

German Automotive Industry Quality Management Center (VDA-QMC)
Oberursel, Germany
www.vdaqmc.de

Particles


March 1, 2008

compiled by Jason Andrukaitis

Foster Wheeler acquires Biokinetics, Inc.

Foster Wheeler Ltd. announces that it has significantly strengthened its position in the biotech and pharmaceutical markets by completing the acquisition of 100 percent of the stock of privately held Biokinetics Inc. from MPA Holdings LP. This acquisition enables Foster Wheeler to re-establish its position in the North American pharmaceutical market, and strengthens its position relative to key U.S. pharmaceutical companies seeking to invest in the U.S. and globally. In addition, this acquisition will provide enhanced capabilities to existing Biokinetics clients. Terms of the transaction were not disclosed. The acquisition is part of Foster Wheeler’s overall strategy to complement organic growth in its global engineering and construction business with highly targeted acquisitions.

Tiger Optics awarded patents for gas analysis technology

Tiger Optics LLC has received patent rights for five new innovations of the company’s continuous wave cavity ring-down spectroscopy technology. The new advances will enable Tiger Optics to offer more versatile and powerful sensors to a broader range of customers. The new patents improve analytical sensitivity and increase the range of species that can be measured, allowing the company to expand beyond gas analysis into the field of liquid analysis. Tiger Optics says it is now positioned to develop biological and chemical applications for such applications as Homeland Security and medical research, and sees its inventions as having strong potential for area monitoring and sensing of biochemical releases for use in liquid chemical analysis, cancer research, and additional safety and security applications.

Watson-Marlow acquires Flexicon A/S

Watson-Marlow has acquired Flexicon A/S through its parent company Spirax-Sarco Engineering. The acquisition includes Flexicon America, the company’s U.S.-based subsidiary. Watson-Marlow, well known in the biopharmaceutical industry for its expansive range of production-duty peristaltic metering and transfer pumps, now greatly expands its capabilities in filling applications. Flexicon has been marketing peristaltic-based aseptic filling and capping equipment for the past 22 years, specializing in filling systems for clinical-trial production. Utilizing peristaltic pump and tubing technology, Flexicon filling systems provide a completely disposable flow path, enhancing productivity and traceability while reducing maintenance as compared to piston type or time/pressure fillers.

Baxter provides update on heparin reactions

Baxter Healthcare Corp. is providing an update to its January 2008 heparin sodium injection 1,000 units/ml 10- and 30-ml multi-dose vial voluntary recall due to adverse reactions. Since the recall, Baxter has received reports of similar adverse reactions occurring in other lots of 1,000 units/ml 10- and 30-ml multi-dose vials; 5,000 units/ml and 10,000 units/ml multi-dose vials; and 5,000 units/ml single-dose vials when single doses were combined to create a larger bolus dose.

Nearly all reported adverse reactions have occurred in three specific areas of product use: hemodialysis, invasive cardiovascular procedures, and apheresis procedures. Some of these reactions, particularly profound and refractory hypotension, may be severe or life threatening. The manufacturer is conducting a thorough investigation to determine the cause of the increased number of reported adverse reactions.

Interphex


March 1, 2008

PHILADELPHIA
MARCH 26-28, 2008
Pennsylvania Convention Center

Interphex 2008™: Conference & Exhibition

conference hours
Wednesday, March 26: 9:00 a.m.

Battling biofilm


March 1, 2008
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The best sanitation programs are designed along with the product and aggressively implemented early in the manufacturing process.

By Sarah Fister Gale

The cleaning, disinfecting, and sanitization of a clean manufacturing environment determine the safety and effectiveness of the end product. These steps make the difference between a pristine product and a sullied reputation, yet product designers across industries tend to spend little up-front time designing and prioritizing sanitation programs in the product development process–and that can lead to costly delays in getting products to market and surprising sanitation issues down the production line.

Every industry has different procedures to ensure the cleanliness of its products and the processing environment based on the risks to the end user. And while a manufacturer of raw food products that will be cooked by the consumer may have more contamination leeway than those making injectable pharmaceutical products or implantable medical devices, they all have the same agenda: to produce consumable products free from bacteria and other contaminants that could ultimately harm the user and the brand.

The most successful manufacturers see the sanitization program as an integral part of the product design process, says Lisa Foster, vice president of Steripro, the consulting and laboratory services division of Sterigenics International, a contract sterilization organization in Corona, CA. “People think cleaning, disinfecting, and sterilization are the last act so they can be left till the end, but that’s a huge mistake, whether you are in pharmaceuticals, medical devices, or food,” she says. “You need to look at these steps up front in the product design process long before you get to manufacturing.”

She advises clients to consider attributes of cleaning, disinfecting, and terminal sterilization during product design and assess those goals against all materials, ingredients, and process steps in the product. She points out that it’s easy to select materials that won’t be compatible with your sanitization or sterilization choices–Teflon, for example, can’t be gamma sterilized. “If you want a Teflon stopper or a pre-filled syringe, the product can’t be closed prior to sterilization.”

If a material you want or need conflicts with your sanitization goals, you can make decisions during the design phase to address the problem before the manufacturing environment is established. In the case of the Teflon stopper, you could opt to pre-sterilize the components separately using an aseptic filling step followed by terminal sterilization of the outside barrier, or choose another material for your stopper.

“You need to determine what methods will work and design the product around that,” Foster says. “When you develop a product with effective sterilization processes from the beginning, you will save a lot of time and money during production phases.”

A clean education

Once a product is designed and the sanitization program is established, the only way to ensure it remains effective is through training. “Good sanitization is all about education, and reminding people of the little things that they may know to do but can forget when they are under pressure to get the job done,” says Chris Celusta, manager of food processing sanitization for Spartan Chemical, a Maumee, OH-based manufacturer of chemical specialty maintenance products and industrial degreasers. “But don’t inflict paralysis by analysis. Sanitation crew training has got to be simple, to the point, and ongoing.”


Figure 1. Gamma sterilization is one method for sanitization of materials. Shown: A radiation source glows blue underwater, where it is kept when not in use. Photo courtesy of Steripro/Sterigenics.
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Celusta points out that while senior management may be committed to a clean environment, sanitation crews are often less tied into the corporate goals and strategies. They often work in low-level positions with high turnover, despite the fact that they serve a critical role in the production process. To ensure they are as committed to sanitization goals as the rest of the team, sanitation training must also incorporate the reasons behind the cleaning program. “You can’t just tell your cleaning crew what to do; you have to explain why they are doing each step and what the result will be if they skimp on or skip something,” Celusta says. “Otherwise, crews may make assumptions that can result in problems.”

Those problems are not just issues of yield or delays. When sanitation crews skip steps dangerous bacteria, including E. coli and Listeria, can gain a foothold in processing facilities and lead to outbreaks of foodborne illnesses. Each year an estimated 76 million people contract a foodborne illness and 5,000 die because of food safety issues from bacteria that can be prevented with proper sanitation.


Figure 2. The Cobalt 60 radioisotope is used for gamma sterilization in the underwater chamber. Photo courtesy of Steripro/Sterigenics.
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Those outbreaks don’t just hurt one company or brand. Every time the public learns of a food recall it loses faith in the entire food production industry, says Celusta, who notes that consumer confidence in food safety is at an all-time low. “When you have a national recall, it draws a lot of attention to sanitation strategies throughout the food industry,” he says. “Company owners and consumers want to know you are doing what you are supposed to be doing, and that every ingredient in a product comes from a reputable source.”

Ready-to-eat products, such as lunch meat or fresh-cut produce, pose the greatest risks because they don’t involve a cooking, cleaning, or other “kill step” by the consumer. Whatever goes out the door on the product will be ingested.

“The

Designs can only be successful if the proper actions are taken to maintain cleanliness levels

By Thomas E. Hansz, AIA, Facility Planning & Resources, Inc.

Last month’s article on ISO 5 cleanrooms discussed the importance of establishing and maintaining the appropriate level of contamination control in a cleanroom. This holds true of cleanroom design at any level of cleanliness, and requires a close relationship between the cleanroom design process and the development of operational protocols. This is critical for whatever industry the cleanroom is intended to support.

Sticking to a cleanliness program

As cleanroom consultants, we spend a considerable amount of time in our clients’ facilities, documenting existing conditions and observ-ing operations. On one such opportunity, we were asked to correct a cleanroom design that was producing unacceptably high particle counts in an ISO 7 level medical device packaging line. During our investi-gation, we discovered that the cleanroom was properly designed and adequately equipped; however, one day standing outside the cleanroom, we soon discovered the real problem with the client’s contamination control. We watched as a cleanroom technician walked out of the gown room, proceeded down the hall to a vending machine, purchased a candy bar, and returned to the cleanroom, fully gowned. As we later interviewed the cleanroom staff, it was plain to see that operational protocols existed but were never enforced.


Figure 1. Proper gowning is the first step toward maintaining cleanroom protocols. Photo courtesy of Facility Planning & Resources, Inc.
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Contrast this to some operators who run what I will describe as “very basic” cleanrooms, yet achieve exceptionally low particle counts well below the cleanliness levels for which they were designed. In these cases, each cleanroom is operated in strict accordance to the established protocols, and they undergo daily vacuuming and cleaning. All cleanroom employees are focused on their work responsibilities, which includes maintaining the cleanliness level of their work environment.

One client has given the person in charge of daily cleanroom maintenance the authority to remove anyone from the cleanroom who does not follow the protocols or is not properly gowned. Dubbed the “Cleanroom Marshal,” he related with pride the time he stopped the president of the company and made him return to the gown room to put on a face mask, which was required for all persons with facial hair. It is no surprise to see that the facility’s production reject rates were so very low. Attention to cleanliness positively affects the bottom line.

Nanotechnology and industry applications

As discoveries in nanotechnology are applied to more and more industries and academic research, ISO 7 level cleanrooms (as well as ISO 8 and ISO 9) are becoming more prevalent. Once found only in integrated circuit assembly and test facilities and in pharmaceutical facilities, ISO 7 cleanrooms are commonplace throughout industrial sectors such as biomedical, biotechnology, medical device, automotive, advanced materials, metallurgical, and optical devices. Universities and colleges are also adding ISO 7 cleanrooms to support research programs in chemistry, biology, biochemistry, and biomedical applications.

Cleanroom entry and exit

Two of the more common mistakes in ISO 7 cleanrooms are the under-sizing of the gown room and the absence of supporting intermediate clean spaces. Cleanroom personnel should enter through a gown room that affords sufficient space for individuals to enter, gown up, and prepare to enter the cleanroom concurrently with individuals leaving and de-gowning. Airlocks should be placed between the gown room and the cleanroom as a final measure for eliminating particles from entering the controlled space. The air shower is characterized by a high velocity (6,000 fpm+) air stream scouring the garment of the person passing through into the cleanroom. In high traffic situations, an air shower tunnel may be used to accommodate a stream of people rather than a one-at-a-time air shower. When leaving the cleanroom, a separate door into the gown room is required because the air lock should only be used for entering the cleanroom.

Supporting intermediate spaces include pass-throughs and wipe-down rooms. Pass-throughs are installed in the wall separating the cleanroom from a non-controlled space, allowing materials, chemicals, and other items to enter the cleanroom without going through the gown room. Similarly, separate pass-throughs are required for finished work and wastes leaving the cleanroom. Pass-throughs have interlocking doors to prevent both doors from being opened at the same time. Airlock can vary in size from very small units–12 inches in height, width, and depth–to those large enough to accommodate lab carts. Special protocols should be developed as to the preparation and containment of items entering through a pass-through.


Figure 2. Flexible cleanrooms require designing in balanced airflow patterns. Photo courtesy of Facility Planning & Resources, Inc.
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Wipe-down rooms for equipment and materials to be unpacked and wiped clean are necessary where these items frequently enter the cleanroom. Although such spaces may seem like a luxury, their use can often prevent the cleanroom from becoming contaminated and requiring a thorough cleaning and reclassification. The principle at work is what we described last month as “islands of cleanliness.” Regardless of the cleanliness level, if the principle is followed and maintained, the chances of successful contamination control are very high.

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Let’s look at some of the basic physical components of ISO 7 cleanrooms: walls, ceilings, floors, airflow structures, and lighting.

Cleanroom wall and ceiling components

Class 10,000 cleanroom wall systems using vinyl-covered gypsum wallboard on steel studs have been around for years and continue to be quite popular due to their relatively low cost. However, due to the composition of the panel itself, they are not recommended for installations that require reconfiguration or frequent change-out of equipment or utilities. Many of the manufacturers of such wall systems proudly refer to the fact that their panels conform to Federal Standard 209 D, which has been superseded twice in the past 20 years.

In ISO 5 level and above cleanrooms, powder coated, aluminum honeycomb wall systems have been an industry standard for decades; they are anti-static, they do not shed particles, and they do not outgas. They offer other advantages as well: They are non-combustible, lightweight, and easily relocatable. Where these considerations are important, they make excellent wall systems for ISO 7 cleanrooms.

Life science and pharmaceutical operations usually require wall systems that are thoroughly washed on a regular basis. The finished surface must withstand cleaning and sanitization with various chemicals that resist fungal and microbial growth. Another consideration for life science and pharmaceutical wall systems is to have a curved base where the wall meets the floor. This follows current Good Manufacturing Practice requirements for maintaining aseptic and/or sterile environmental conditions.

For ISO 7 cleanrooms, composite wall systems are available in a variety of options. Wall panels can have interior cores of aluminum honeycomb, paper honeycomb, expanded polystyrene, or isocyanurate insulation. In addition to the powder coated aluminum surfaces, many cleanroom wall manufacturers also offer high pressure laminates, melamine, vinyl, stainless steel, and PVC. It is recommended that the cleanroom ceiling panels be of the same finish as the wall panels. Either the ceiling panel or the ceiling suspension system needs to be capable of supporting the fire sprinkler system. With so many options, it is important to select a wall and ceiling system that supports the work, as well as complying with federal regulations and other requirements.

Windows are another consideration for the cleanroom wall system. Windows should be flush to the wall on the clean side to prevent accumulation of particles. Designs are available for flush windows on both sides of the wall, a particularly useful feature for windows between adjacent clean spaces. Whether for a corporate, institutional, or academic cleanroom, window placement is important for visual safety, permitting supervision from the outside. Windows are also important for supporting marketing tours that invariably include looking into the cleanroom.

Floor surfaces

Floors on grade are frequently covered with a high-solids epoxy finish applied to an appropriately prepared concrete surface. Vinyl tiles and vinyl sheeting, with standard, static dissipative, or conductive characteristics, are also used, depending on the application. Whether to use a raised floor or not for your cleanroom depends upon factors such as the volume of recirculating airflow, the need for under-floor utilities and/or exhausts, and the criticality of regular cleaning.

Airflow

The table of airflow guidelines (Table 1) relates the cleanliness class to a range of air change rates that increase as the ISO cleanliness class becomes more stringent. The table presents ranges of values to underline the notion that this is not an exact science. The final selection of air changes per hour is based on the process to be protected, the number of people working in the cleanroom, the activity and movement of those people, and the ratio of acceptable yield of finished work.

For ISO 7 cleanrooms, notice that the two variables in the chart are the airflow velocity and the number of air changes per hour. Other factors that need to be taken into account are the uniformity of the airflow pattern within the room and the configuration of the room itself. So to successfully provide the ISO 7 level of cleanliness, the HEPA filter coverage can vary from the 20 percent recommendation. It is important to remember that the following rates are recommendations, not hard and fast rules. We have been very successful in building
ISO 7 cleanrooms with varying percentages of filter coverage.


FIgure 3. Floor air returns should be strategically placed near major pieces of equipment. Photo courtesy of Facility Planning & Resources, Inc.
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It should be mentioned that the design of the air pattern relies on careful filter placement in the ceiling as well as careful air return placement at the cleanroom floor. It is important that the cleanroom designer fully understand the process within the cleanroom to ensure that an optimum design is created at the lowest cost.

Temperature

The temperature to be maintained in the cleanroom is driven by either comfort or by the process. Comfort in an ISO 7 cleanroom can generally be met by maintaining a temperature of 72

February 28, 2008 — /BELLEVUE, WA/ — Pharmacy OneSource, creator of the Simplifi 797 quality assurance web application, is pleased to announce that industry expert Eric S. Kastango, MBA, RPh, FASHP, CEO of Clinical IQ, has updated the included policies and procedures reference section in Simplifi 797 to match USP’s revised chapteron pharmaceutical compounding, “Sterile Preparations.”

The revised chapter was finalized in December 2007 and tightened standards and conditions for sterile compounding over the previous version of Chapter 797. These revisions will become official on June 1, 2008.

“Policies and procedures are the foundation for a robust compounding quality system,” says Kastango. “I’m very excited that Simplifi 797 has these updated policies and procedures to complement the outstanding software that provides pharmacists and technicians the tools to be successful.”

Simplifi 797 is a web-based application that automates, integrates, and streamlines the quality activities and documentation required to meet USP Chapter 797. Simplifi 797 manages task scheduling and monitoring, and automates the reporting of exceptions and compliances.

About Pharmacy OneSource

Pharmacy OneSource is pharmacies’ number 1 software-as-a-service provider. Its 50 innovative team members provide best-in-class SaaS solutions to current and future challenges within health-system pharmacies worldwide. Its SaaS solutions contribute to high performance pharmacies through better outcomes, lower costs, and system-wide results. More than 1,000 healthcare organizations worldwide utilize the company’s HIPAA compliant web-based services, including Accupedia,Amplifi, Quantifi,ScheduleRx, Sentri7, Simplifi 797, and UnitStock.

Visit www.pharmacyonesource.com

About Clinical IQ

Clinical IQ, LLC is a privately held consulting company based in Florham Park, NJ. It is led by Eric Kastango, MBA, RPh, FASHP, President and CEO, who is seen as an expert in many areas of the pharmacy industry, but particularly in USP Chapter processes. Clinical IQ, LLC aims to serve as the trusted source for pharmacy information services and product solutions for all its customers who range from local start-up operations to established national companies in the hospital, home care, and specialty compounding industries. With this aim, Clinical IQ creates software, classroom training, web based training, audit tools, and many other informational products to make sterile compounding and related areas of pharmacy safer.

www.clinicaliq.com