Proactive tactical planning will ensure adherence to standards

By Fran McAteer, Microbiology Research Associates

The obvious objective in effective cleaning is the removal of contamination acquired from daily activities in the cleanroom. In order to better perform a robust cleaning, it is necessary to evaluate and understand the sources of contamination. Implementing an effective cleanroom cleaning and sanitization program is based on some tactical considerations for pharmacists. Even though cleanrooms are designed and built to rigorous standards, each cleanroom is unique and is a function of the products, process, and people involved. Sterile product areas have their own unique characteristics. For example:

1. Some compounding cleanrooms have more staffing associated with them. They have more pharmacists and technicians. Therefore, potential sources of contamination may come from viable sources such as sweat, skin, hair, etc. From a microbiological viewpoint, this represents potential contamination from such bacteria as Staphylococcus, Streptococcus, or Micrococcus species.
2. Another type of cleanroom may have more refrigerators and freezers for medication storage. This equipment provides a large surface area for water condensation, which is based on temperature and humidity differences between the cleanroom and the equipment. The source of contamination from this compounding area may be water based. From a microbiological viewpoint, this represents potential contamination from molds and Gram-negative bacteria such as Pseudomonas species.
3. The third type of cleanroom may be more specialized, using automated filling equipment for transparenteral nutrition (TPN). The potential sources of contamination may be non-viable particles from repetitive movements and larger amounts of ingredients. From a microbiological viewpoint, this contamination may represent Gram-positive spore formers.

By evaluating the different sources of contamination in a cleanroom, the pharmacist can better choose a more effective cleaner and/or sanitizer. The basic requirement for implementing a cleanroom cleaning and sanitization program is the microbiocidal properties of the cleaners and/or sanitizers. The cleanroom contamination may require broad spectrum activity against vegetative bacteria; maybe fungicidal activities against yeast and mold contamination; or possibly sporicidal activity against spore-forming bacteria. These different types of “cidal” properties for different sanitizers may provide the cleaning efficacy that a particular cleanroom may need.

A second consideration centers on the creation or augmentation of an environmental monitoring program. Simply put, environmental monitoring tests for viable and non-viable levels in a cleanroom. Viable particle monitoring looks for microbial contamination on surfaces or in the air, while non-viable testing checks particle counts at specific sizes. Environmental monitoring goes hand in hand with an effective sanitization program. It provides the continuous feedback loop on the performance of the cleaning program. An environmental monitoring program should include samples sites, location maps, testing frequency, action/alert levels, and test procedures. An effective program must also be governed by standard operating procedures that document the purpose, responsibility, and procedures necessary for an effective program. Environmental monitoring results should be trended over time and by location to demonstrate overall effectiveness and control of the cleaning/sanitization program.

In formulating an effective cleaning program, a tactical risk assessment analysis should be undertaken. This strategy assessment will evaluate the overall impact of potential contamination on such factors as drug cost, prescription quality, and medication complexity. For example, a contaminated CSP will have devastating consequences to hospitals and compounding pharmacies, including patient harm, medication recalls, and malpractice lawsuits. The risk assessment tactic will provide hospital management with consequences, costs, and a clear indication of the levels and frequency of cleaning and sanitization needed.

In today’s regulatory environment with USP <797>, a key tactic is to review compliance and documentation. This is a critical concept. The cleaning and sanitization needs to be qualified, which incorporates methodologies such as cleaning validation and disinfection efficacy studies. These validation tests demonstrate the effectiveness of the program by utilizing proven compendial guidelines.

Proactive tactical planning will ensure implementing an effective cleanroom cleaning and sanitization plan that meets acceptable compliance and quality standards. Contamination potentials, monitoring programs, and risk assessments will provide overall objectives, critical measurements, and managerial justification for successful implementation.

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

I had some very interesting conversations at this year’s “SEMICON West” conference and exhibition in San Francisco. And I have to say this surprised me somewhat, since, to be honest, I have come to view the event as a little old and tired over the last few years. Obviously, my interest is largely restricted to contamination control developments and technology, but even looking at semiconductor manufacturing progress across the board, the pace of truly new technology implementation, or introduction, has been painfully slow. I mean, how excited can we get year after year about high-k/metal-gate technology, 45 nm nodes, and 300 mm wafer-scale tools?

That’s why I was so pleased to see at least one area of significant new progress. The very real challenge of molecular contamination has finally come to the mainstream in terms of the industry recognizing its impact on yield and its willingness to actually invest in new control systems and practices. Certainly, we’ve been talking about molecular contamination control in the pages of this magazine for at least as long as the semiconductor industry has been talking about “45 nm and beyond,” but I believe I now see the first signs of an emerging watershed in terms of an all-out competitive drive to address the problem with real solutions.

One clear indicator of the growing attention being paid to molecular contamination is the simple fact that semiconductor companies are increasingly loathe to discuss their individual activities in the area and certainly not willing to share any “solutions” being tried. But even more telling is the shift in focus of our own contamination control industry expertise away from simple broad-based filtration and other molecular contamination removal systems to detailed studies and analysis of process equipment designs and chemistries, molecular-level defects, and complex chemical and material interactions-all aimed at taking the science of molecular contamination control out of the realm of keep-your-fingers-crossed, black-magic solutions to well characterized and highly targeted solutions.

So if I’m seeing behind the curtain properly, molecular contamination control isn’t just an “important-down-the-road concern” for the semiconductor industry anymore but a real and expensive problem today-and one not being particularly well addressed as yet. Once this cat is fully out of the bag, and semiconductor companies accept they’re all sharing the same problems-and also all having the same limited success at implementing solutions-we should expect to see more open discussion and a further spike in cooperative research and investment activities. We should also see a larger and more varied group of potential solution providers participating in the process.

Even though I’m wary of overstating the impact and immediacy of any trend in the painfully cautious semiconductor industry these days, I do think this development stands a good chance of becoming the single largest, new opportunity for contamination control companies in the semiconductor sector in quite some time.

John Haystead,
Editor-in-Chief

The Institute of Environmental Sciences and Technology (IEST) continues to offer valuable online education classes in the ongoing Access the Experts series with its one-hour class, “Sustainability Considerations in Cleanroom Design and Operation,” and two-part online education tutorial, “Healthcare Airborne Molecular Contamination,” both to be presented in September. Learn from your desk, conference room, or auditorium without travel expenses. The per-location fee has no limit on the number of students who may participate at each location; access will be granted to one computer per location. Online registration is now available at http://www.iest.org/education/online.htm.

“Healthcare Airborne Molecular Contamination” will be presented on Wednesday, September 5, and Wednesday, September 12, 2007, at 11:00 a.m. Central Daylight Time (CDT). Nosocomial infection, commonly referred to as health-care associated infection (or hospital-acquired infection; HAI), is a significant problem in health care environments around the world. In the United States alone, HAI claims nearly 100,000 lives per year and adds billions of dollars to the cost of care. There are numerous factors that are combining to make the struggle with HAI increasingly difficult. Living in what is becoming known as the post-antibiotic era, new methods are required to combat HAI and there is increasing pressure to employ them. This class examines the magnitude of the problem, discusses in general what factors are contributing to it, and relates how technology developed for ultra-clean manufacturing facilities can be utilized to help reduce the incidence of HAI.

Joseph McGill, the instructor, has 20 years of engineering and construction experience, 15 of which have been cleanroom related in the United States and abroad. He was a consultant to firms in the Science Based Industrial Park in Hsinchu, Taiwan, for five years, where he worked with numerous American, Asian, and European companies specializing in cleanroom design, manufacturing, and construction. With a background in semiconductor-related projects, he has become increasingly involved in the design and construction of health care facilities, with an emphasis on maintaining environmental conditions and controlling airborne contamination in critical spaces. He is a 1984 graduate of the School of Engineering at the University of Alaska Fairbanks.

“Sustainability Considerations in Cleanroom Design and Operation” will be presented on Wednesday, September 19, 2007, at 2:00 p.m. CDT. This live, one-hour class will provide an overview of the key elements of sustainability for cleanroom facilities and will focus on energy efficiency in cleanroom design and operation. The course will present real-world examples of good and bad cleanroom design and operation, provide guidelines on key considerations and opportunities to improve the performance of cleanroom buildings, and discuss caveats of rules of thumb or industrial document-specific recommendations.

Instructor Tengfang (Tim) Xu manages and performs R&D projects on energy efficiency and environmental performance of commercial, residential, and industrial buildings, including cleanrooms, minienvironments, and data centers, at Lawrence Berkeley National Laboratory, Berkeley, CA. Xu served as contamination control technical vice president of IEST from July 2005 to June 2007. At Berkeley Lab, he is involved in the development of innovative methods and protocols that are instrumental in formulating standards to characterize fan filter units. Xu’s interests and accomplishments include the production and dissemination of new knowledge and techniques to improve the environmental and energy performance of mission-critical buildings, such as cleanrooms and minienvironments. Xu is also a technical editor for the Journal of the IEST and serves on the editorial board of Building and Environment. He has received numerous national awards for scientific papers, publications, and professional services.

Cleanroom wipers and swabs are important to enhancing productivity and product quality in critical manufacturing environments.

By Bruce Flickinger

New technologies, chemistries and value-adds notwithstanding, cleanroom consumables are driven by two tenets for suppliers and users alike: They have to function properly and consistently, and they have to do so cost-effectively. For wipers and swabs, this means removing undesirable materials from the cleanroom without leaving undesirable material behind. These tools are critical to keeping environment and product contaminant-free, but their ubiquity and utilitarian demeanor tend to place them low on the list of considerations when a company is re-evaluating its operations for cost or quality reasons.

Where change is warranted, such as where rising defect rates or interruptions in the supply or quality of a particular consumable merit a revisiting of suppliers, performance evaluations are needed to compare products and make informed decisions. But change doesn’t come easily for critical manufacturing industries, especially those that are regulated, and audits, plant expansions, equipment upgrades, and the like usually are perceived as having a greater impact than revisiting the use of wipers and other consumables.

“Users aren’t likely to change their cleanroom procedures or products unless there is significant benefit to doing so,” says Kim MacDougall, research scientist with Kimberly-Clark Professional (Roswell, GA). “It is very difficult to bring about change in wiper usage in cleanrooms because many times consumables are a lower-priority product area.”

“If the time is available, a company will entertain the idea of re-evaluating the performance of their wipers and deciding whether other products should be considered for quality or cost efficiency reasons,” adds Howard Siegerman, PhD, director of technology for ITW Texwipe (Mahwah, NJ). “Users need to weigh the question, ‘If we start this performance evaluation, do we have the resources to carry it out? And what is the benefit in doing so?’ If it ain’t broke, don’t fix it is a prevailing attitude.”

Follow the money

This attitude is changing. Tolerances are becoming tighter across the critical manufacturing spectrum and in hard disk drive (HDD) fabrication, in particular, processing lines and equipment are becoming smaller, making particulate and ionic contamination a necessarily bigger concern. “With shrinking linewidths and 300 mm wafers in the semiconductor market, particle contamination will inherently increase in significance,” says Chris Roman, business manager with Milliken Anticon Products (LaGrange, GA).

In HDD manufacturing, John Westland, president of American CleanStat LLC (ACS; Anaheim, CA) notes that consumable suppliers have had to adopt new materials used for swab handles and different static-dissipative and chemical-resistant additives to foam swabs. “Some manufacturers are offering specific tools and tweezers that are antistatic or made of other inert tip and product materials, and new nitrile and polyurethane materials for gloves and fingercots are both static dissipative,” he says. “There has been a lot of pressure on packaging and wipers to reduce particles and static tribocharging by using ESD [electrostatic discharge] formulations that don’t outgas.”

The issue, Westland says, is that “these industries are high volume and these items are not made in large enough quantities to allow prices that are as low as the traditional non-ESD safe materials.” The situation presents a “push-pull” between cost and performance for HDD manufacturers, who are not only operating on slim profit margins but also face increasing competition as other types of memory devices-for example, optical, flash, and USB-erode the HDD marketplace.

Another related business driver is burgeoning overseas microelectronics manufacturing, fueled by inexpensive labor. Where operations are more labor intensive, wipers and other consumables figure more prominently in the costs-benefits equation.

Figure 1. In addition to removing particles and spills, cleanroom wipers are used as applicators for disinfecting and sanitizing solutions. The wiper cannot contaminate the application process and has to be chemically resistant. Photo courtesy of Kimberly-Clark.Click here to enlarge image

“The semicon market is growing globally and developing differently than it has in the U.S.,” MacDougall says. “Labor and facilities are driving the biggest migration of jobs, and where operations are labor intensive, the use of consumables increases.” In the U.S., conversely, the trend in semiconductor fabrication is to “engineer out” consumables and the human workers who use them as much as possible.

As such, the consumable testing market has been relatively flat in the U.S. over the past two to three years, observes Carl Newberg, president of Micro-Stat Labs (Rochester, MN). “This can be attributed to a couple of things, namely a large portion of manufacturing moving to Asia; an increase in the numbers of independent laboratories in Asia, which work for a fraction of what labs have to charge in the U.S.; and the downsizing of quality departments. The typical engineer just doesn’t have time to worry about consumables.”

Providing the independent lab’s perspective, Newberg says that most of the major players in the HDD industry are moving to a 0.3 μm cumulative large-particle-count specification for many of the components that go into the drive. “While many of the consumables specifications haven’t changed yet, I expect them to in the near future,” he says. “The suppliers haven’t been hit with these new specifications yet; however, when they are, I would expect the number of qualified suppliers to drop somewhat.”

Suppliers obviously want to provide a high-quality product and avoid a blip in the end user’s productivity or product integrity that could be traced to a poorly functioning wiper. Superior but more costly products that provide lower contamination levels tend to make sense over the long term. “It’s important to consider the ongoing cost of utilization in terms of how quality or productivity is being affected,” says Texwipe’s Siegerman. “Suppliers have to prove savings through cost and use models, in reducing waste and saving money in the overall system.”

Other geographic challenges that weren’t always there are shaping business practices as well. “As off-shore manufacturing becomes more common, auditing becomes less practical. A company could contract a local lab to audit the supplier and conduct testing, but lab quality and the results they generate can vary,” MacDougall says. “Most customers prefer to transfer the burden of testing to their supplier. They typically aren’t equipped to do their own RP [recommended practice] testing.”

Recommended practice

“RP testing” refers to recommended practices developed by the Institute of Environmental Science and Technology (IEST), the U.S. standards-setting body for scientists and businesses concerned with contamination control. The analytical techniques used to detect ionic, particulate, and other contaminants in cleanroom wipers and swabs are specified in IEST RP CC004; this document’s current iteration is familiarly known as RP 4.3. First published in 2004, this RP describes methods for evaluating, selecting, and testing wipers used in cleanrooms and other controlled environments for characteristics related to both cleanliness and function. It is applicable to wipers, for the most part, although a companion swab RP document is wending its way through the same working group.

Test and measurement criteria addressed in RP 4.3 include particles (MM/m²), extractables (%), ions (ppm), fiber shedding (MM/m²), and composition. Specified analytical techniques include ion chromatography, liquid particle counting, or scanning electron microscopy; nonvolatile residues (NVRs) are to be assessed using gravimetric weight analysis or, where organic contaminants need to be identified, by Fourier-transform infrared spectroscopy or gas chromatography combined with mass spectrometry. These are sensitive, highly evolved techniques that not every manufacturing concern is equipped to conduct.

“There are also ASTM methods [American Society for Testing and Materials, recently renamed ASTM International] for general testing that are not specific to the lower levels that are of interest to many HDD and semiconductor cleanroom manufacturers,” Westland adds. The Electrostatic Discharge Association (ESD), for one, provides test methodologies to measure electrical properties such as surface and volume resistance, which directly affect static charge build-up and discharge voltage. Many companies also specify testing that addresses their own cleanroom personnel or operational needs.

RP 4.3 is due for review this month, but this effort had not moved forward as of this writing and details were unavailable from the RP 4.3 Working Group. Westland believes proposed changes will focus primarily on test method specifics, the amount of material to be tested, and the agitation or movement methods for particles. A standard test has been added for use with alcohol or acetone, he says, to show test results with solvents other than water. The working group also aims to standardize the particle sizes to test, types of equipment to use, and calibrations of blank samples and bracketed ranges for tests to be relevant and comparable. “Each lab interprets the test methods slightly differently and this creates differences among various labs, which can change results dramatically at 0.5 μm and smaller,” Westland says.

Seeking standardized testing

Variable test methods and results are cited as the foremost obstacle to objective wiper evaluations and comparisons. Siegerman expresses a common opinion that “the same testing methods are not being used, and individual facilities have their favored approaches to given tests, although we are reaching better commonality in our testing practices.” RP 4.3 is regarded as a meaningful and practical means of achieving standardization.

Most end users of cleanroom wipers are well aware of the IEST test methods, says Milliken’s Roman, and although not all wiper manufacturers follow these methodologies, IEST and ASTM methods “allow fair comparisons of wiper attributes and cleanliness profiles.”

The optimal way to assess performance of wipers and swabs is through a set of independent tests or through an evaluation of use and yields on finished products. But these “are not always totally independent tests,” Westland notes. “It is best for users to either run the tests themselves or have the tests run by an independent lab.” End users also can ask the manufacturer to run a current lot of material for tests and specify which lab will be used to do the comparative tests.

While highly sophisticated, leading-edge technology companies conduct their own consumables performance testing, many end users rely on their suppliers to do the work and provide the necessary documented quality assurances. Suppliers, in turn, conduct this testing in-house and, in the optimal scenario, invest in a third-party lab for independent corroboration. “The major manufacturers and major end users of cleanroom wipers perform their own in-house evaluations to ensure ongoing consistent quality with identical operators and test equipment,” says Bill Lynch, vice president of sales and marketing with Lymtech Scientific (Chicopee, MA), which enlists third-party test labs to verify test data.

“Users in the markets we serve have specific cleanroom wiper characteristic needs and requirements,” Lynch says. “Some of these specifications include qualification documentation regarding sterility validation, lot controls, product and process compatibility, along with independent third-party performance test data of ultra-low extractables, particle counts, and bioburden levels.”

Where products are being compared, the only way to do this fairly and accurately is to test all the products in the same manner using the same test methods, with the same test labs or departments doing the tests. “You cannot always correlate or rely on different manufacturers’ test specifications or results because they use different methods, labs, blanks and units of measure for testing all the variables that can affect sub-micron particle testing, outgassing, NVRs, or other parameters,” Westland says.

“It is important for end users to understand that it is very difficult to compare wipers with a side-by-side review of the manufacturers’ specification sheets,” Lynch adds.

Particulate trap

Testing is used to quantify a number of product attributes, but two broad performance criteria are of critical interest: the particle and fiber shedding characteristics of the wiper, and its sorbent rate and capacity. These respectively correlate to the wiper’s proclivity for leaving potential contaminants behind, and its aptitude for picking contaminants up. This information is critical not only for the end user but also gives the wiper manufacturer information about the consistency of its process.

Cleanroom wipers are used in close proximity to the end user’s products, sometimes even wiping the product itself, as is the case with medical device and some microelectronics manufacturing. Here, Siegerman notes, “The needs of medical devices are changing because devices such as stents are beginning to incorporate active pharmaceutical components.” Swabs, too, while commonly associated with environmental surface sampling, also contact product and are used for cleaning tight geometries in equipment and fabrication tools, such as slots, O-rings, and recesses in vacuum ports. A swab also can be used to capture particles by lightly touching the back of a wafer.

While essential requirements are the same, specific needs diverge somewhat between life science and microelectronics applications. “In cleaning a pharmaceutical aseptic fill area, wipers are used as applicators for disinfecting and sanitizing solutions. You need to dispense large volumes of liquid across broad surfaces,” Siegerman says. “The wiper cannot contaminate the application process and has to be chemically resistant. The usual fabric choice here is polyester knit, which satisfies both of these needs: It’s adsorbent, resists most aggressive chemicals, and will not contaminate surfaces.” Wipers dampened with DI water or isopropyl alcohol solution are also used to remove solutions and disinfectant residues from surfaces.

Figure 2. Cleanroom wipers are used in close proximity to the end user’s products, wiping equipment and fabrication tools-sometimes even wiping the product itself. Inset: The fabric used in most knitted wipers is formed by a series of interlocking loops of one or more yarns, wherein one continuous yarn runs crosswise in the fabric, making all the loops in one row of interlocking loops. Photos courtesy of Milliken & Co.Click here to enlarge image

Users in microelectronics and semiconductor manufacturing also tend to favor polyester knits, but in these environments the emphasis is on removing particles. Dampened-as opposed to saturated-wipers are the optimal means for doing so. Observers make the general note that it is important that wipers are not moistened to the point of saturation because if 100% of a wiper’s capacity is utilized, then there is no capacity to retain excess liquid and contaminants. “Pre-moistened wipers should be engineered to deliver a specific amount of cleaning solution and then to re-adsorb that solution along with any contaminants,” Roman says.

One point to note, explains Siegerman, “is that the ability to wipe a surface dry has nothing to do with the absorbency of the wiper; it depends on the mechanism of water pick-up.” Synthetic knit wipers that are surface-treated to pick up water adsorb the liquid, holding the liquid in the interstices of the knit, or on the surface of the polyester strands. Cellulosic wipers absorb water into the fibers of the wiper, causing them to swell. Wipers made from cellulosic materials offer better absorbency but typically aren’t found in clean environments better than ISO 7.

Although laundered polyester knits are used in as much as 90% of electronics and life science applications, the material’s main drawback is that polyester holds moisture via adsorption, which entails treatment with a surfactant during the manufacturing process. This process can leave residues and result in inconsistent sorbency among lots.

Figure 3. Dampened wipers are best for removing particles from most critical environments. It is important that wipers are not moistened to the point of saturation because if 100 percent of a wiper’s capacity is utilized, then there is no capacity to retain excess liquid and contaminants. Photo courtesy of Milliken & Co.Click here to enlarge image

Newberg affirms that some synthetic products that meet end-user requirements for ISO 5 or ISO 3 and better actually “don’t hold moisture very well and, in some cases, don’t do an optimal job of picking up debris, either. The dry synthetics also don’t have the ESD properties that some end users would like. This forces them to make decisions about their use in ESD-safe work areas, and how they perform their wiping and cleaning operations.”

Under control

Advances are being made constantly in materials and their treatments to improve particle retention and reduce ESD. One example is Milliken’s Particle Attraction Technology, or P.A.T., which involves proprietary chemical modification of the polyester yarn to impart increased sorbency and particle attraction within the fabric. The technology is used in the company’s line of Anticon wipers.

Figure 4. Texwipe’s Vectra Honeycomb 10 is a sealed-border polyester wiper designed for grit and residue removal in ISO Class 3-4 environments. Photo courtesy of ITW Texwipe.Click here to enlarge image

Unlike many suppliers of cleanroom wipers, Milliken makes its own base fabrics and thus can readily incorporate the P.A.T. treatment into its manufacturing process.

The company uses computer control to run its manufacturing process, from yarn texturing and knitting to finishing, wiper dimensioning, and cleanroom laundering. Statistical process control (SPC) is prevalent throughout all of the textile processes in the company’s facilities, as is the case for most wiper and swab manufacturers. “We provide lot test data to our customers and also do significant upstream process testing to ensure our processes are in control and that final results will be within specifications,” Roman says.

Similarly, at Lymtech, Lynch says, “SPC is a fundamental key component to ensure our manufacturing process is consistently and verifiably in control. Our end users are extremely interested in statistical process control, quality protocols, and process testing. Some of our testing includes dosimeter measuring of irradiation dosages, independent third-party sterility validation testing, and liquid particle counts, to name a few.”

End-user audits are also part and parcel of conducting business in cleanroom wipers, Lynch says. “The common practice is for a team of two or three quality auditors to review the entire cleanroom wiper manufacturing and packaging process. These auditors verify that we are strictly adhering to our stated SOPs, including use of the necessary forms, labels, tags, and other documentation.” Additionally, “some end users will have special requirements-for example, testing of specific ions that might be important to their people, product or process,” adds Lynch.

Working with wipers

While the emphasis of these efforts is on optimizing a wiper’s absorbency and affinity for offending particulates, the flip side of a wiper’s ability to attract and retain particles is that they become “very effective traps for airborne molecular contaminants,” Siegerman cautions. “It is critical to keep them bagged. Don’t leave them sitting out.”

Figure 5. Kimberly-Clark’s Kimtech Pure dispenser for pre-saturated wipers allows one-handed dispensing with no need to hold a package or reseal a closing flap. Photo courtesy of Kimberly-Clark.Click here to enlarge image

Users need to be mindful of this and other logistics of cleanroom wipers-their storage, cutting, or other preparation, unpacking, movement in and out of areas of different levels of cleanliness, ultimate disposal, and the like. Procedures governing all of these activities need to be in place.

Human variability in wiper use cannot be overlooked. “Some cleanroom personnel are very advanced in the use and control of wipers; they follow strict protocols for opening a package and bringing wipers into a clean environment,” says KC’s MacDougall. “Folding is important where you don’t double-use a side, and I’ve seen folding techniques just short of origami.” But other technicians are less skilled in the vagaries of wiper use, and “there’s always opportunity for improvement.”

One new option on this front is the “Kimtech Pure” dispenser for pre-saturated alcohol wipers, which allows one-handed dispensing with no need to hold a package or reseal a closing flap. The unit addresses two issues faced when dispensing wipers: “It is tough to pull out just one wiper, especially with a gloved hand, and packages can be difficult to reseal, causing pre-saturated wipers to dry out,” MacDougall says. “There is a definite perception of the potential for contamination with an open package of wipers.”

For additional cost efficiencies, some users repurpose used wipers from the cleanroom for use in less critical applications, such as maintenance. “We see a handful of end users who use a regrading system whereby the cleanroom wiper is used for its intended critical process, then the used wiper is relaundered and reused in a much less critical area,” Lynch says. “The relaundered wipers are packaged entirely differently than the original high-purity wipers. Regrading represents a contamination control risk factor in the sense that the relaundered wiper has lost all of its original purity and cleanliness and must never be confused with a high-purity wiper.”

Summary

From materials and testing to handling and use, there are numerous considerations when evaluating the cleanliness and effectiveness of new swab and wiper products, a task that ultimately falls upon the end user. This, in turn, entails evaluating the supplier and its proficiency at producing a quality, cost-effective product. And while wipers and swabs might not be foremost items on a company’s list of operational concerns or opportunities for change, they are critical contributors to the cleanliness of the manufacturing environment.

Resources and contacts

American CleanStat LLC
1596 S Anaheim Blvd., Bldg B
Anaheim, CA 92805
714-533-2827
www.americancleanstat.com

ITW Texwipe
300B Route 17 South
Mahwah, NJ 07430
800-TEXWIPE
www.texwipe.com

Kimberly-Clark Professional
1400 Holcomb Bridge Rd.
Roswell, GA 30076
800-255-6401
www.kcprofessional.com

Lymtech Scientific
60 Depot St.
Chicopee, MA 01014
800-628-8606
www.lymtech.com

MicroStat Labs-
River’s Edge Technical Service
3612 3rd Pl. NW
Rochester, MN 55901
877-204-2007
www microstatlabs.com

Milliken & Co.
201 Lukken Industrial Dr. W
M-836
LaGrange, GA 30240
800-762-3472
www.anticonwipers.com

Defining your cleanroom needs will help make sense of HEPA-filtered vacuum options

By Russ Seery, Nilfisk-Advance America

From pharmaceuticals to semiconductors, cleanrooms are highly regulated environments. Under the International Organization for Standardization’s (ISO) strict criteria put forth in 2001, manufacturers across the board have fallen under a great amount of pressure to keep cleanrooms clean and have been forced to evaluate and improve their housekeeping regimens. The risks associated with failing to do so affect a company’s efficiency, employee health, and, ultimately, the bottom line. So what is the best way to tackle contaminants when the very act of cleaning can affect a room’s ultra-sensitive environment?

Measurements taken in one cleanroom setting found that a dusting system using disposable cloths polluted the space twice as much as a system using a HEPA-filtered vacuum cleaner. Though wipe-down methods are necessary in many cases, vacuuming is often the most efficient method because particles are retained inside the machine with little chance of being exhausted into the atmosphere; however, not just any vacuum will be appropriate. There are many factors to take into consideration when choosing the right vacuum for your cleanroom.

The source

First, it’s important to pinpoint common cleanroom contaminants and how they can be prevented from entering the cleanroom in the first place. Contaminants are typically generated by three major sources: cleanroom personnel, materials, and equipment.

Personnel. Of course, one of the most common-and hard to control-contamination sources is people. While cleanroom gowns and other garments are designed to limit human contamination, it is impossible to regulate uncontrollable actions like sneezing and coughing. The typical working person generates approximately 1 million organic airborne particles greater than 0.5 microns per minute. In instances of human contamination, wipe-down methods are often the best, as they prevent contaminants from even entering the cleanroom.

Materials. Cleanroom consumables-such as gloves, masks, wipers, swabs, hairnets, booties, HEPA filters, and tacky mats-can be a breeding ground for contaminants if the proper preventive measures aren’t taken. For example, if employees do not decontaminate their gloves before entering the cleanroom, everything they touch may be contaminated-including the finished product. The costs of repairing such damage can be exorbitant. Once again, it is vital that all consumables be thoroughly decontaminated prior to cleanroom use.

Figure 1. The Nilfisk-Advance America IVT 1000 CR, equipped with an ULPA filter, addresses the cleanliness and hygiene standards required in cleanrooms in a compact machine. This unit is also available with Safe-Pak technology, a change system that allows for safe pick-up and removal of potent compounds.Click here to enlarge image

Machinery. Another potential source of contamination is the equipment already found within the cleanroom. The vibration of this equipment alone is often enough to cause a breakdown of particles, which then circulate in the ambient air.

The most efficient way to prevent this type of contamination is to keep all machinery as dust-free as possible, and this is where a HEPA-filtered vacuum comes into play.

What to look for in a vacuum

When selecting an industrial vacuum cleaner for the cleanroom, many people fail to recognize the key role of the vacuum filtration system. In essence, superior filtration is what you’re shopping for, not just a vacuum, and because available vacuum filter systems are different, it is helpful to know what to look for when choosing the right vacuum for you.

First and foremost, any vacuum cleaner used in a cleanroom must be HEPA-filtered to ensure that 99.97% of all particles down to and including 0.3 microns are collected and retained. In addition, it is absolutely critical that the HEPA filter be installed after the motor to filter the exhaust stream. The motor’s commutator and carbon brushes generate dust, and if the exhaust stream is not filtered that dust will be released into the environment. A word of caution: Not all HEPA-filtration systems are the same. For example, a multi-stage, graduated filtration system uses a series of progressively finer filters to trap and retain particles as they move through the vacuum. The largest particles are captured first by coarser filters; smaller particles are then caught and retained by the finer HEPA filters. This multi-stage system protects the HEPA filters from blockage and excessive wear-and-tear, maintaining peak performance. (When equipped with an ULPA filter, the system should retain up to 99.999% of all ultra-fine particles, down to and including 0.12 microns in size). Additionally, the filtration system in your vacuum should use oversized filters, which slow airflow across the larger surface area and optimize the air-to-cloth ratio. This allows the vacuum to easily collect large volumes of debris over extended periods of time with minimal maintenance.

Besides having an exceptional filtration system, any vacuum used in a cleanroom should be constructed of non-particle-generating materials. For example, non-porous, stainless-steel vacuums-equipped with smooth hoses and attachments-enable personnel to quickly wipe down and decontaminate equipment for faster, simpler sanitization and validation. Many vacuums are also autoclavable, but be sure to check with your vacuum manufacturer first; otherwise you’ll destroy your investment.

Spill response should also be taken into account when purchasing a vacuum. At least one of your vacuums should be capable of wet and dry collection.

Central vacuum systems vs. portable vacuums

Another question manufacturers run into when purchasing a vacuum is whether a central vacuum system or several portable vacuum cleaners will be more efficient. The following pros and cons of both may help ease the decision.

Portable vacuums. Portable vacuums are best for cleaning around work areas where human contamination is prevalent, enabling personnel to effectively clean their area at the end of each shift. Many portables are designed for both wet and dry collection, while central systems are only capable of picking up dry materials. Due to their easy maneuverability, portable vacuums are often used to clean remote or overhead areas that the central systems’ hoses can’t reach.

However, unlike central systems, portable vacuums occupy precious cleanroom space. When purchasing a portable vacuum, look for a compact model. Emptying a cleanroom vacuum can be hazardous, especially when picking up potent compounds. When purchasing a vacuum, look for a unit that comes with a safe collection/ disposal container.

Central systems. The biggest benefit of a central system is that it enables personnel to take collected dirt outside of the cleanroom, where they can dispose of it without any threat to the manufacturing process. Because they are located outside of the cleanroom, central systems free up coveted floor space.

On the other hand, central systems don’t provide the flexibility you need to expand your operation because you may not have the appropriate vacuum capabilities to support a new area. Furthermore, if a contaminant enters the central vacuum system, the whole system may become contaminated-requiring a thorough, costly decontamination process.

Conclusion

Manufacturers must continuously evaluate their housekeeping regimens to ensure that all controlled areas are properly cleaned and maintained. Vacuuming with cleanroom-compatible machines designed specifically to collect and retain microscopic particles enables manufacturers to prevent airborne particulate contamination; ensure air and product purity; and safeguard the health of employees. There are many options out there, but when choosing a vacuum, be sure to know why you need the vacuum and what it will pick up, especially if you are using it to eliminate hazardous compounds. A quality vacuum manufacturer will be pleased to visit your cleanroom in order to assess the situation and match the correct vacuum and filtration system for your application.

Russ Seery is director of sales at Nilfisk-Advance America (www.pa.nilfisk-advance.com).

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Tips for keeping your cleanroom contaminant-free

Enlist multiple vacuums. If possible, purchase multiple portable vacuums and assign them to specific critical contamination-control points. Or install a central system backed up by several portable vacuums.

Educate your staff. To ensure the proper use of equipment (and that solid hygiene procedures are practiced), train all employees thoroughly. Don’t focus only on what they have to do, but why-if they are educated as to why certain procedures are necessary they will be more likely to follow them.

Insist on exceptional filtration. A multi-stage, graduated filtration system that filters both intake and exhaust is the most efficient method for capturing and retaining particles. Look for a filtration system that combines this capability with oversized filters for true efficiency.

Maintain equipment. Regularly check and clean all equipment used in the cleanroom, including vacuums and attachments, and replace parts as needed. Staying on top of equipment functionality saves money in the long run by preventing contamination.

Establish a schedule. Develop and enforce a strict maintenance and cleaning schedule that includes a comprehensive vacuuming of the entire facility after every shift.

Select your vacuum system carefully. Seek out vacuums designed specifically for cleanroom applications. Product lines should include essentials like food-grade hoses, cleanroom-packaged vacuums, wet/dry vacuums, and explosion-proof vacuums.

Biopharm manufacturers can see improvements in contamination levels, manufacturing costs, and production times

By Gary MacEachern, NP Medical

It’s no secret that biopharmaceutical companies are moving rapidly toward disposable products for the production of protein therapeutics and vaccines. In university and pharm/biopharm laboratories, disposables have been in use for more than 20 years because of their small scale, versatility, and lack of contamination issues. As the commercial demand for designer drugs has increased, drug manufacturers have increased their use of disposables in parallel. And for good reason: Biopharmaceutical companies are adopting a “fail early, fail often” business model, and therefore need faster, cheaper discovery processes and clinical trials. This compels researchers to not only drive out as much cost as possible early on but also to speed up the process so less time is needed in cleaning and validating expensive bioreactors before bringing them back on-line for the next project. Today, the use of disposables has become commonplace in 97% of biopharmaceutical companies.

Figure 1. Disposable fluid management components, like these unidirectional Luer valves, can reduce the cost of both disposable and stainless-steel bioreactors. Photo courtesy of NP Medical.Click here to enlarge image

When considering the design and construction of manufacturing facilities, biopharmaceutical manufacturers-and especially start-ups-need to consider several criteria.

Safety. Cross-contamination is a major issue. There is not only the possibility of chemical contamination from the water-based cleaning solutions in reusable systems but also that of biological/microbial contamination from fluid pathways and liquid transfers. Yeast, bacteria, mold, and viruses are all either used in producing drugs or can be considered biological contaminants. Disposable, sterile, pre-filled media bags and pre-sterilized fluid path components such as tubing, filters, connectors, and valves all offer significant safety advantages, save time and money, and increase efficiency.

Versatility. Most biopharm manufacturers can’t afford to be “one-trick ponies.” With fewer blockbuster drugs on the horizon, smaller markets, and target-specific treatments, product diversification requires a flexible research and manufacturing infrastructure that enables them to quickly change product development gears.

Cost. When looking at the impact of disposables on cost, the savings with regards to sterilization alone are significant as disposable systems eliminate clean-in-place (CIP) and steam-in-place (SIP) sterilizing between batches and changeovers. Validation issues are also eliminated because all components are supplied sterile and certified. Cross-contamination is minimized, if not eliminated, by the use of unidirectional disposable valves and single-use filters.

Changeover procedures can often be reduced to essentially “stop and swap,” a significant reduction in time that enables disposable bioreactors to be up and running in hours-sometimes even minutes-compared to the weeks necessary to make stainless-steel reactors ready after a changeover. Validated cleaning, replacement of product-contact fluid path components, and sterility retesting that follows is time-consuming and expensive. Disposable component manufacturers now offer a wide range of unidirectional valves to help control flow and prevent backflow during fluid transfer and sampling.

Small vs. large scale processes

Currently, disposable bioreactors are best suited for small-scale R&D and manufacturing, in the range of several hundred liters. While large-scale disposable manufacturing is not yet feasible (production is still limited to about 2,000 L), scalable smaller-volume manufacturing is. In fact, it may be hard to push the size of disposable systems into the realm of large-scale manufacturing due to the inherent structural weaknesses associated with large plastic bags. However, with growing demand, new technologies for better yields and improved drug delivery, increased cost pressures, and a trend toward “boutique” therapeutics and personalized treatments, manufacturers have been driven to produce smaller batches while improving yields for higher volumetric productivity.

Biopharm manufacturers must improve production flexibility to meet periodic capacity shortages and produce smaller, higher yield batches, while dealing with reduced R&D budgets and health care reform constraints. This points to disposable bioreactors as an ideal solution. In some cases where manufacturing volumes are in the hundreds to low thousands of liters, manufacturers can simply run several, say, 200 L bioreactors in parallel, giving them the advantage of both the volume they need and the flexible scalability to increase or decrease production based on the products being run and the market needs at the time of manufacture.

What about retrofitting stainless-steel bioreactors?

With all the discussion about disposable systems, you’d think the death knell had been sounded for all those big stainless-steel systems, but to paraphrase Mark Twain, rumors of stainless reactors’ demise “have been greatly exaggerated.”

Rather, large, established manufacturers are beginning to use disposables to provide added flexibility and efficiencies to their existing stainless-steel facilities. By incorporating disposable components, particularly in the fluid path systems, they are able to reduce cleaning costs as well as turnaround time.

Disposables are also being used to cut lead time when performing product changeovers. With fixed stainless-steel systems, a changeover between drug runs usually requires piping redesigns and modifications that can take six to twelve months to complete. By using disposable fluid path systems to replace SIP stainless-steel connections, bioreactor lines can be reconfigured quickly, often cutting the project completion time by several months. Plastic tubing can be quickly and easily custom cut to fit a system and the process of cutting with a hot blade anneals the plastic to create a sterile seal. Retrofitting stainless-steel systems with pre-sterilized disposable pathways enables secure connections to be made in Class B, C, or even D environments while maintaining sterility-that means saving time and money even with expensive, reusable stainless steel systems by being able to operate them in less-than-optimal sterile environments.

Operating expenses

When discussing operating expenses, the conversation quickly turns to comparing the two types of systems in terms of the cost of consumables. Here the comparison between the two can get a bit murky because comparing consumables can be like comparing apples to oranges.

Stainless-steel systems actually use more consumables than most people realize-the cleaning chemicals and thousands of gallons of purified water needed for the cleaning process, along with their disposal expense, as well as utility costs associated with steaming and cleaning. In addition, there’s the cost of all the fluid contact components between drug runs-tubing, gaskets, valves, O-rings, filters, and connectors that are too hard to clean and revalidate. It’s less expensive to simply replace them. In fact, despite the conventional wisdom that a reusable stainless-steel bioreactor system has less environmental impact than a system that uses a lot of disposable plastics, studies show that the impact of increased plastic consumption associated with disposable systems is typically offset by the amount of reusable system cleaning water and chemicals and the utility service consumption required to process them.

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Approximately one-third of the labor cost for reusable systems is associated with cleaning and sterilization. By using disposables, critical, skilled-employee tasks such as testing and documenting validation associated with sterilization are eliminated, reducing the cost of labor. In addition, using disposable bioreactors, without all the CIP/SIP piping and components, decreases the complexity of the overall system, which may reduce the labor time involved in system construction and/or set-up.

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Time can also be considered a consumable and the use of disposables not only reduces the overall maintenance and operating time, it also enables biopharmas to simplify standard operating procedures (SOPs) and use less skilled labor for certain tasks. Pre-sterilized components, unidirectional disposable valves, and diaphragm pumps with in-line filters, in conjunction with simplified SOPs, enable workers to perform the work and avoid mistakes and contamination while transferring fluids and taking samples. Increased regulatory compliance requirements (and, in some cases, internal company policies) have increased the need and frequency of sampling. A variety of available disposable valves, such as pressure activated, Luer, and in-line check valves, would help facilitate a wide range of sampling-from single samples to multiple, extended-duration process sampling. The bottom line is an increase in the speed and efficiency of sample-taking and a reduction in labor costs and risk.

Making the case for disposables

While a case can be made that the cost-of-operation difference between disposable and reusable systems is not as great as often stated-upfront construction expense, consumables, and high cleaning and sterilization costs can offset some of the expense of disposable systems-the fact remains that disposables still have a higher cost-per-batch. Currently, a complete, small-batch disposable bioreactor costs about $200 to $300 per unit, including bags, tubing, connectors, valves, and mixing system. However, if time-to-market is crucial for successful production introduction, disposable systems are the clear winner when it comes to batch-to-batch speed and versatility. As we’ve seen, reusable systems, with lengthy sterilization, testing, and validation processes, clearly fall behind in the speed department. This can be mitigated to some degree by incorporating disposable fluid pathway components such as tubing, connectors, filters, and valves into the stainless-steel system. Only in this way can biopharmas reduce maintenance and operation time and speed up batch changeovers.

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But even assuming that it costs more to run disposable bioreactors vs. stainless steel, the economic stakes in drug development are so high, the cost difference becomes negligible. Put another way, if the potential is there for making dollars on an R&D investment that (relatively speaking) costs pennies, what’s a few cents more in the cost of operation between a stainless-steel system and a disposable one? Improved speed, efficiency, flexibility, and time-to-market more than outweigh a few pennies.

Gary MacEachern is director of marketing/new product development at NP Medical (www.npmedical.com). He can be reached at [email protected].

New high-speed doors minimize potential contamination and maximize production efficiency

By Matjaz Sentjurc and Vladimir “Benny” Bernard, Efafl ex-CZ s.r.o.

Beginning about 35 years ago, manufacturers began to recognize that to achieve greater productivity, they would need faster, more efficient internal factory transportation and logistics systems. The result was the development of all kinds of new, fast forklifts, cranes, conveyors, and other means of transport. But there remained a weak point—facility doors. Even when operated automatically, access doors were slow to open, and transport vehicles were held up waiting for them, wasting valuable time.

In addition, the slow-operating doors also had a negative impact on the factory environment, particularly for doors opening to the outside. In winter, conditions could not only become very unpleasant for workers, but also cause potential damage to manufacturing materials from continuous temperature and humidity change.

Figure 1. The “SRT-CR” high-speed, roll-up door for tight cleanroom closures features closed guidance of the curtain to minimize air loss; no screws or overhangs for particle adhesion; emergency release via electric button instead of pull-cord or crank handle; anti-static curtain; and integrated control within the frame to save space. Photos courtesy of Efafl ex-CZ s.r.o.Click here to enlarge image

To solve these problems designers developed a new type of fast-opening industrial door—doors that opened and closed so fast that their operation was transparent to transport operations. Similar principles are now being applied to cleanroom doors and pass-throughs with the goal to both minimize potential opportunities for contamination as well as maximize production efficiency.

From high-speed industrial to cleanroom doors

In general operation, cleanrooms are just like other industrial rooms, but with special demands for contamination controlled production—whether pharmaceutical, electronic, fine mechanical, or other products. As such, the requirements driving door and pass-through design are also similar.

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For example, in many highly automated semiconductor fabs, where the processing and transfer of materials is completely automatic, including the use of automatic guided vehicles (AGVs), fast-moving cleanroom doors can significantly reduce the time of processing and transfer of materials and even increase the cleanliness class of the room.

Not all the principles guiding the design and implementation of fast-opening industrial doors apply to cleanroom doors, but there are many common requirements. For example, one of the challenges that needed to be addressed in the development of the high-speed industrial door—the sheer size of the door leaf being operated—must also be addressed for cleanroom doors.

The door must be able to handle both the rapid acceleration of a large-mass door leaf as well as the very rapid deceleration needed to stop it at both full open and close. This requires large and highly stable drive units and components, but by meeting this operational requirement, designers have also achieved significant durability improvements and increased the average life expectancy of the doors. Today, fast-opening industrial doors have top speeds of more than 4 meters per second and a life expectancy of up to 1 million operations.

Safety is another common consideration for door designers as both personnel and equipment must be protected from possible collision with the fast-moving door leaf. Hence, several safety systems have been adopted such as contact edge, light barrier, light wall, light grid, etc.

Sophisticated control units have also been developed using sensors and computer systems to send, receive, and process impulses from different opening devices (activators), other doors, conveyor systems, and other control units. In the event of power failure or other emergency, backup mechanical counterbalance systems have also been developed to ensure doors can be opened without an external power source.

Special requirements

There are also special demands for high-speed doors intended for cleanroom applications. For example, in cleanrooms, multiple doors are usually arranged and installed in an airlock configuration with control units programmed to ensure that one or more doors remains closed at all times. These airlocks can be relatively large with standard doors for transport of large equipment and personnel or small access ports or cabins for passing materials and product.

The basic cleanliness requirements and criteria for designing and manufacturing high-speed doors for cleanroom applications include the following:

Air tightness. Each cleanroom or clean area is continuously refreshed with clean air, so the room maintains either a constant positive or negative pressure. The amount of air to be delivered into the cleanroom depends on the tightness of the entire room. High-speed industrial doors are therefore of great importance, since they are the only element in the cleanroom (sometimes in addition to a personnel pass-through) that is not permanently fixed.

Figure 2. In the STT-CR model, single-walled, transparent lathes, which are kept at a distance when rolled up in the patented spiral-door blade, remain transparent and free of wear and tear for years. Photo courtesy of Efafl ex-CZ s.r.o.Click here to enlarge image

Even if it is accepted that the cleanroom door is not completely tight, it is important to know how large the leakage factor is. Sometimes, a small, controlled air leakage can be welcome, but this should be known in order to most efficiently design the HVAC system and ensure that the room’s required pressure differential is maintained.

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Particle sources. A high-speed door—including its frame, drive unit, and the door leaf itself, which regularly opens and closes—must be designed so it will not produce any particles. The door’s components must therefore also be constructed from suitable materials.

Surfaces. Horizontal surfaces should be avoided in the design of the doors components, as these can provide places where particles can accumulate. All sources of potential electrostatic charge must also be eliminated.

Cleaning. The surfaces of door components should be at and very smooth, without any corners or crevices. This helps ensure regular effective cleaning of the door. Manual activators, if used, are also specially designed to meet this requirement. All metal parts are made of stainless steel. Frames can also be constructed of powdered galvanized steel and door leaves from eloxed aluminium, acrylic glass in aluminum frames, or laminate, depending on the door type.

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Because not all cleanrooms are the same, there are also different types of fast-moving cleanroom doors for different applications. Table 1 on page 35 lists some common important considerations.

International manufacturing and safety standards

To ensure commonality in product manufacturing and safety standards an important consideration especially in the European market, where every country has its own laws, standards, and demands the guidelines and standards in Table 2 have been applied to the design, production, and installation of fast-opening industrial doors.

Finally, anyone operating a cleanroom should certainly be familiar with U.S. Federal Standard 209 cleanroom classification criteria and standards and the follow-on ISO 14644-1 document, which combines the best features of the different base documents available from Europe, Japan, and the U.S.

Matjaz Sentjurc is project manager and Vladimir “Benny” Bernard is sales manager at Efafl ex-CZ s.r.o., a German-based manufacturer of high-speed spiral, roll-up, and folding doors for indoor applications and inlet/outlet bays in various facilities. Bernard can be reached at benny.bernard@efafl ex.cz.