Tag Archives: Clean Rooms

By Carrie Meadows

As a first-time attendee at an Institute for Environmental Science and Technology (IEST) Working Group session, one probably doesn’t expect an animated crowd of participants sticking neon Post-It® notes on the walls. But at the inaugural meeting of proposed RP-CC044.1, “Vacuum Cleaning Systems for Cleanrooms,” at ESTECH in May, that is exactly what took place.

Roger Diener, chair of the new Working Group and contamination control engineer at Analog Devices (Wilmington, MA), took an unusual approach to the brainstorming session, one that has actually been in existence since the 1960s. Instead of soliciting feedback via the typical orderly roundtable discussion, Diener handed out the aforementioned brightly colored notepads to participants, instructing them to jot down any user-related aspect of cleanroom vacuum cleaners and stick them to any number of poster-sized papers on the walls, which were labeled with broad headings such as “general background,” “features,” “performance expectations,” “portable unit design considerations,” “design criteria,” and more. This technique, part of the K-J Method (or affinity diagram) invented by a Japanese anthropologist as a way to discover meaningful groups of ideas in a raw list, enabled the dynamic that produced an entire set of core expectations for the group’s attendees to fill in at a later date.

“I did it because a lot of people do have a different idea of what a Working Group meeting is,” says Diener. He notes that some attendees are reluctant to participate in a conventional setting, especially when they are new to the industry or RP process. The Working Group is composed of IEST members who design, manufacture, and use the systems for various cleanroom applications. “There are many different levels of experience to be incorporated into a well-rounded group. Some participants can be intimidated by that. This way gets all the questions and ideas out there, from basic to advanced, without putting anyone on the spot.”

Diener says that vacuum cleaning systems had been on the “short list” of topics that needed someone to rally for it in order to get the RP process rolling. Once it was identified as a need and he volunteered to chair the group, it was time to contact the manufacturing experts and get users to participate. During the Working Group session, Diener had pointed out that “a cleanroom is not just a ‘clean room’–it’s the largest piece of equipment [in your facility], and people need to act accordingly.” The Working Group is tasked with moving the proposed RP forward, keeping in mind the purpose of the vacuum cleaning system itself: to aid in the removal of large particles, fibers, and debris without becoming a risk to the surrounding environment.


IEST members brainstorm an initial draft of the proposed RP-CC044.1, “Vacuum Cleaning Systems for Cleanrooms.” Photo courtesy of IEST.
Click here to enlarge image

“This document is intended to address the needs and issues you should understand when buying, specifying, and using a cleanroom vacuum cleaner,” he explains. “Let’s be clear: We’re not telling users, ‘This is how you should clean your cleanroom environment.’ With this RP, we’re recommending, ‘This is what you need to know about the [vacuum] equipment you’re bringing into the environment to keep contamination from becoming a problem.’”

The importance of these proposed guidelines lies in clearly outlining what is appropriate for a cleanroom vacuum cleaning system, agrees Ray McCarthy, a sales representative for industrial vacuum manufacturer Nilfisk CFM (Kingstown, RI) and a member of the Working Group. “I think it is important to note here that a vacuum is part of the whole cleaning process within a cleanroom environment. Each cleanroom is unique to whatever is being done within that cleanroom, whether it is a tableting process for the pharmaceutical industry or a fab within a semiconductor facility

SEMICON West 2008


July 1, 2008

JULY 14–18, 2008
MOSCONE CENTER, SAN FRANCISCO, CA

Event hours

Exhibits
Tuesday, July 15–Wednesday, July 16  10:00 a.m.–6:00 p.m.
Thursday, July 17  10:00 a.m.–4:00 p.m.

Conference program runs from Monday, July 14, through Friday, July 18

SEMI, the global industry association serving the semiconductor manufacturing supply chain, is hosting its 38th annual SEMICON West Conference and Exhibition from July 14–18. Attendees will have the chance to learn about the latest developments in nano and microelectronics, packaging/assembly, wafer processing, and more, including special topics such as sustainability and repurposing fabs. For a complete conference schedule, visit www.semi.org.

show highlights

Keynote: “Semiconductor Technology, A Convergence of Technology and Business Models”
Tuesday, July 15, 1:30–2:15 p.m.

Bernie Meyerson, vice president for strategic alliances and CTO, IBM Fellow, IBM Systems and Technology Group, will explore the relationship between silicon technology (scaling, in cost and performance) and the semiconductor business model. This talk will cover the extraordinary measures required to sustain both trajectories and the progress being made.

200mm Productivity Symposium: How to Breathe Life into Old Fabs

Tuesday, July 15, 12:30–5:30 p.m.

Fab repurposing is going on across the globe and spurring additional business and growth opportunities equipment and materials supplies, and their customers. At this SEMICON West Forum, companies up and down the supply chain will show how they are profiting from fab repurposing.

EHS and Sustainability Programs and Events

Energy Conservation in the Semiconductor Industry: Obstacles and Opportunities for Energy Reduction in Equipment and Fabs (Co-Presented by SEMI and ISMI)

Tuesday, July 15, 2:00–5:00 p.m.

Device Scaling TechXPOT Session: Advances in Device Manufacturing: Productivity, Process Control and Sustainability

Wednesday, July 16, 10:30 a.m.–12:30 p.m.

Growing public and corporate interest in sustainability and environmental issues are creating new challenges and opportunities for companies and individuals across the global microelectronics and related industries.

North American Photovoltaic Advanced Manufacturing Technology Conference

Session 1: Thin Film/Equipment
Tuesday, July 15, 2:00–6:00 p.m.

Session 2: Bulk Silicon/PV Manufacturing
Wednesday, July 16, 9:00 a.m.–1:00 p.m.

The Photovoltaic Advanced Manufacturing Technology Conference will focus on the solutions, manufacturing equipment, and technology that the industry is able to provide to wafer, cell, and module makers. Elements of the production process will be highlighted: integrated logistics and automation; quality control and traceability, (advanced) statistical process control, and preventive maintenance.

ITRS Summer Public Conference

Wednesday, July 16, 7:00 a.m.–5:15 p.m.

In addition to the Roadmap working groups’ highlights and key messages of the 2008 Update, the conference will include executive forums for two special topics. The morning breakfast session provides interactive discussions on global energy and how the ITRS can influence outcomes. An afternoon session focuses on the challenges of the industry supply chains.

The 450 mm Transition: When Will It Make Economic Sense for the Semiconductor Industry Ecosystem?

Thursday, July 17, 8:00–9:30 a.m.

Over the past few years, SEMI, through its Equipment Productivity Working Group (EPWG), has been studying the overall cost and benefit of a potential transition to 450-mm wafers. The goal of the study has been to develop transparent, objective analysis tools and data which would help the industry to determine what the potential outcomes a new wafer size transition would bring for the industry and what the right path might be for each individual company. A summary talk on the results of the analysis will be followed by a panel discussion from the team of experts who had a role in developing the model and analysis.

Exhibitor showcase

More than 1,100 leading companies and suppliers connected to the semiconductor manufacturing industry will display their innovations at SEMICON West 2008. Here are a few that will be of interest to the contamination control community.

Asahi/America, Inc.

Click here to enlarge image

Web: www.asahi-america.com
Booth 133

Click here to enlarge image

Asahi/America, Inc. is a manufacturer and distributor of a full line of corrosion-resistant thermoplastic fluid handling products, including valves, actuators, pipe, and fittings. Asahi specializes in providing solutions for fluid handling systems individualized to meet virtually any customer’s need. For more information, contact Asahi/America, Inc., 35 Green St., Malden, MA 02148. Call toll free (877) 24-ASAHI or (781) 321-5409, fax (800) 426-7058, or e-mail [email protected].

Web: www.das-europe.com
Booth 2522

DAS–Dünnschicht Anlagen Systeme GmbH Dresden

Click here to enlarge image

DAS develops, distributes, and services waste gas abatement systems for semiconductor, flat-panel display (FPD), and solar cell manufacturers, customized to process requirements with full customer support. DAS’s state-of-the-art technology, quality, and experience have been incorporated in modern manufacturing facilities in Europe, Asia, and North America. More than 2,000 systems have been installed worldwide thanks to a global network of specialists in China, Hong Kong, Japan, Korea, Malaysia, Singapore, Taiwan, and the United States. The company’s ESCAPE technology is featured in a burn/wet system for point-of-use (POU) abatement of all semiconductor manufacturing waste gases, which are environmentally harmful, toxic, and contaminated. The unit combines incineration, scrubbing, and monitoring in one system. AQUABATE technology is provided via a compact wet scrubber designed to scrub waste gases with water or reactive chemicals. The GIANT, UPTIMUM, and EDC systems provide waste gas abatement for FPD and solar cell manufacturing processes: incineration, scrubbing, and electrostatic dust collection.

Entegris, Inc.

Web: www.entegris.com
Booth 1021

Click here to enlarge image

As a materials science and contamination control expert, Entegris enables its customers to improve productivity, reduce cost, and enhance yield. At SEMICON West, Entegris will demonstrate new innovations in wafer handling, liquid and gas filtration, fluid handling, post-CMP cleaning, and specialty coatings applications. Featured products include Torrento™ 15-nm wet etch and clean liquid filters, Impact® 5-nm photoresist filters, IntelliGen® HV high-viscosity photoresist dispense system, LiquidLens® high-flow ultrapure water purification system for immersion lithography applications, Integra® high-temperature valves, Clarilite Certified reticle haze prevention systems, and 300-mm Prime and 450-mm wafer carrier and shipper products.

Lighthouse Worldwide Solutions

Web: www.golighthouse.com
Booth 6158

Click here to enlarge image

Lighthouse Worldwide Solutions will introduce its newest liquid particle counter, the NanoCount 50, at this year’s SEMICON West tradeshow. The NanoCount 50 is an ultrasmall-footprint liquid particle counter with a sensitivity of 50 nm. The unit measures just 9x 6x 9 inches and includes the sensor, counting electronics, and flow meter all housed in a NEMA rated enclosure. The small footprint permits the instrument to be easily integrated into process equipment for POU semiconductor process applications. Lighthouse Worldwide Solutions has also introduced new products for gas particle monitoring and air particle monitoring applications. The new HPC 1100 high-pressure controller enables sampling of high-pressure gas lines at 1 cfm without wasting extra gas. The 1CFM MiniManifold permits sampling of multiple locations with a single particle counter, offering a tool for cost-effectively partitioning particle problems and monitoring minienvironments.

Mettler-Toledo Thornton

Web: www.mt.com
Booth 421

Click here to enlarge image

The 5000TOC sensor and 770MAX multiparameter analyzer provide fast, continuous measurement of total organic carbon (TOC), enabling online process surveillance in an economical analytical package. TOC can be monitored at critical, pure/ultrapure water treatment stages providing low detection limits in less than 60 seconds, which enables real-time correction of process excursions. The 770MAX transmitter provides the flexibility of interfacing up to two 5000TOC sensors, leaving additional channels available for measuring conductivity, pH, dissolved oxygen, ozone, or flow. Mettler-Toledo Thornton specializes in pure and ultrapure water systems with measurements of resistivity/conductivity, dissolved oxygen, ozone, flow, pressure, pH, ORP, temperature, and TOC.

Setra Systems, Inc.

Web: www.setra.com
Booth 541

Click here to enlarge image

Setra Systems, Inc., a manufacturer of variable capacitance vacuum and pressure transducers, will showcase its Model 730 capacitance diaphragm gauge (CDG) at SEMICON West 2008. Designed for semiconductor applications, absorption chillers, lasers, autoclaves, vacuum packaging, freeze drying, and vacuum distillation applications, the low-cost, compact (1.5×2.1-inch) CDG’s high-frequency bridge circuit design is fully RoHS compliant and yields extremely low noise, while maintaining the fast response time required for today’s critical control applications. The Model 730 provides a 0-to-5 VDC or 0-to-10 VDC output that is linear with pressure and independent of gas composition. A wide dynamic measuring range is ensured through percent of reading accuracy (

In the wafer fab, no matter how hard you fight, there are some battles you’ll never win. The best you can do is stave off your enemy–molecular contamination–for as long as possible.

By Sarah Fister Gale

Click here to enlarge image

Since the beginning of wafer manufacturing, cleanroom operators have waged war on contaminants, relying on a growing collection of filters, monitors, and enclosed environments to prevent particles from crushing their yields. But for every step forward they take in contamination control, the industry takes two steps back as shrinking geometries make delicate materials and processing steps ever more susceptible to even smaller contaminants in the environment.

In today’s fab, once harmless molecular contaminants can now damage surfaces and interact with energy, moisture, and other chemicals in the environment to create hazes on optics, attach to wafers, and even contaminate the minienvironments that were designed to protect them.

“It’s an evolving field,” admits Mark Camenzind, senior technical advisor in the Fremont, CA-based Balazs Analytical Services office of Air Liquide Electronics, an international industrial group specializing in semiconductor, industrial, and medical gases, chemicals, equipment, and related services. “As airborne molecular contamination (AMC) gets better controlled and analyzed, we’ve come to realize that it is hard to control completely. It’s like peeling an onion. Underneath every layer is another layer, and something else for us to learn.”

Unfortunately, while advances in manufacturing are allowing fab manufacturers to shrink their technology and produce more complex components at the micro scale, the tools used to battle contaminants in these manufacturing environments are not evolving as quickly.

“A complete and universal fix for AMC is still elusive,” says Steven Rowley, molecular contamination product line manager for Particle Measuring Systems, a manufacturer of air, gas, and liquid particle counters in Boulder, CO, “but companies are taking a more serious look at molecular contamination monitoring and control strategies to mitigate risks.”

Jitze Stienstra, director of product marketing in the San Diego, CA office of Entegris, whose contamination control solutions business unit specializes in these issues, agrees. “Contamination control is becoming increasingly important as decreases in line size mean more processes are affected,” he says.

Stienstra believes a multi-tiered approach to “total contamination control” offers the best solution. The combination of pre-filters for clean ambient air, chemical filters at the tool level, and point-of-use purifiers for purge gases in highly sensitive enclosed environments that cannot come in contact with ambient air, leads to the most robust system. “It starts with the fab ambient, then it goes to the tool level and the micro level,” he says.

Fab operators are also relying more heavily on real-time monitoring to get a more accurate sense of what, where, and when contamination is creating problems in the fab, particularly around photolithography tools.

“Every solution has to be customized to the needs of the fab so that operators can manage contamination and solve problems in an affordable environment,” Stienstra says.

Photolithography blazes a trail

The wafer manufacturing industry is quickly reaching the point where ambient air, even filtered ambient air, cannot be controlled enough to prevent yield loss in the cleanroom environment, so people are going more to cluster tools, enclosed environments, front-opening unified pod (FOUPs), and purge gases to avoid AMC exposure altogether. “Purge gas can be made very clean through purification, which means you don’t have to test it as often, vs. ambient air, which changes hourly and ideally would be constantly monitored,” says Camenzind. However, continuous monitoring at the low levels required by the International Technology Roadmap for Semiconductors (ITRS) is not always available, e.g., for sulfur oxides at pptv levels.

Acidic gas contamination from organic acids such as sulfonic acids can create particularly costly contamination problems if not controlled in the fab because of their reactivity with a number of other chemical species, says Rowley. This reactivity often occurs on surfaces that are very sensitive to contamination, including optical components within photolithography steppers and scanners. “In close proximity to the reduction lens’ final optical element, these species can play a significant role in the formation of films that can potentially adhere to and contaminate optical surfaces,” he says. “Not only can this contamination cause drifting of critical process parameters due to lens contamination and optical hazing, but also terrific costs may eventually be incurred in order to replace contaminated optics in steppers and scanners.”

Acidic gas contamination can also have detrimental effects on cleanroom materials, which may indirectly affect product surfaces, such as filters, sealants, epoxies, and plastics used in tools and components. For example, small amounts of acidic gases in the air, specifically hydrogen fluoride (HF), can cause HEPA filters to accelerate the release of boron.

Nowhere are these problems more of an issue than around the highly sensitive and extremely expensive photolithography tools, which are getting the most attention from contamination control experts because the optics cost millions of dollars to replace or repair and can lead to significant tool downtime and production loss, since the lithography tools are often rate limiting. For these surfaces, the AMC can become surface molecular contamination (SMC) when it either absorbs directly or reacts with light or other molecules to deposit on lenses, leading to optical problems not easily solved.

“In 300-mm fabs, most lithography tools have tracks connected to steppers with an enclosed FOUP-in and FOUP-out,” says Camenzind. “There is no direct cleanroom air exposure anywhere in the sequence,” and wafers only see air that is well purified by AMC filters.

Even so, molecular-scale particles and chemicals in purge gases or scrubbed ambient air can still allow for some surface contamination.

“SMC is a big issues for optics, steppers, lasers, and masks,” says Camenzind, who notes that even trace volatile contaminants, which normally wouldn’t stick to surfaces, can decompose, leaving a residue that ultimately causes hazing. Adding to the risk is the fact that many volatile compounds don’t get trapped in typical absorbents so it’s difficult to accurately assess their levels.

And as the tools utilize light at shorter wavelengths to accommodate smaller feature sizes they become more susceptible to contaminants from ambient air. “It only gets worse with extreme UV,” Camenzind says. “Previous wavelengths couldn’t break down these compounds, but in the future, they will break down everything and masks will have to be used in a vacuum.”

Issues that become more severe at smaller wavelengths include organic compounds reacting with light; refractory compounds leaving residues; and O2 and H2O absorbing light and assisting in haze formation on optics, which decrease imaging performance and lead to expensive repairs or even warranty invalidation.

“There is more concern about refractory compounds causing lens hazing then ever before,” notes Luke Lovejoy, manager of the analytic chemical laboratory in the Austin, TX office of Freescale Semiconductor, a provider of embedded processing and connectivity products to the automotive, networking, and wireless communications industries; and a member of the wafer environment contamination control subgroup of the Yield Enhancement Group of the ITRS.

Steppers generally have point-of-use chemical filters to scrub the ambient air before it enters the tools, but Lovejoy points out that they are not always enough. Many tools also blow purge gases such as high-purity nitrogen and compressed air, which are unlikely to have refractory compounds in them, across lenses with a slight vacuum to prevent contaminants from coming in contact with lens surfaces. This limits the risk of contaminants getting into the critical areas, but even in those scenarios, says Lovejoy, you can get some gas diffusion.

Purge gases are a popular choice because they are easier to control than ambient air, but they are themselves a potential source of contamination, including volatile and semi-volatile organics, volatile acids and bases, and refractory silicon and sulfur compounds.

“Every year is a new learning experience and there is a lot we still don’t know about hazing,” says Lovejoy. “People are working on developing tools to assess these compounds, but it could take years.”

Camenzind also points out that filtered air is still far more economical when it works, and it remains a viable choice for non-critical areas of the fab, such as pre-etching steps when wafers are less sensitive to contaminants. “You are stripping that layer off anyway,” he says.

Manufacturers drive change

Tool makers have had the most profound recent impact on the industry’s ability to understand, manage, and mitigate contamination thanks to stricter warranty requirements for contamination control. In order to maintain full warranty coverage for steppers, manufacturers require tool owners to meet explicit contamination specifications and validate that those requirements have been met.

“Most tool manufacturers require AMC at certain levels to meet warranty requirements,” Lovejoy says. “They also demand that operators use their accredited labs to measure levels or be able to prove that their internal labs are meeting warranty requirements.”

Meeting those requirements isn’t easy. It takes rigorous monitoring and stringent control methods, but it’s worth it because replacing these optics runs in the millions and even tens of millions of dollars–and neither the vendor nor the operator wants to take on that out-of-pocket cost.

Not only is there the hard cost of the lens, which can fall to the fab operators if they can’t prove they adhered to warranty requirements, but also the huge impact on production due to downtime for lens replacement and the challenges of removing the lens, which can weigh a ton and require a crane to move.

“The warranty requirements are driving the industry to do a better job,” says Particle Measuring Systems’ Rowley. “It’s forcing the industry to understand the impact of molecular contamination and value of contamination control strategies.”

Lovejoy agrees. “It’s helping to quantify the return on investment for the photolithography people,” he says.

It also may act as a lesson for other areas of the fab that may not currently be so susceptible to contamination risks, but that may be facing greater sensitivity in the future as shrinking geometries make other process steps more fragile.

“Photolithography has driven a lot of change and there are lessons to be learned from what they’ve gone through,” Lovejoy says.

“We see more and more process steps requiring additional contamination control steps,” adds Stienstra of Entegris, who predicts that optic metrology steps will be the next big contamination risk area, particularly below 65 nm. “We expect the number of contaminants that cause problems to increase, and the limits to decrease.”

Don’t be FOUPed

When materials aren’t in processing, FOUPs, pods, and reticle boxes are being used more commonly as a way to prevent delicate wafers and masks from coming in contact with contaminants in ambient air, but they too run the risk of creating new contamination issues through outgassing of the enclosure and carryover from past processes, which must be carefully controlled.

Camenzind points out that everything in the fab, from the materials and lubricants used on tools and containers to the process steps themselves, has the potential to create contamination that can impact yield.

“Whenever you find a solution you have to be sure the cure is not worse than the disease,” he says.

“Reticles and wafers can still be affected by molecular contamination during processing and storage,” agrees Jürgen Lobert, director of Entegris’s Analytical Services in Franklin, MA. “It’s not just happening in the tools. You have to look at everything.”

Stienstra adds that reticles are a bigger contamination concern than wafers because of the high cost of cleaning and/or replacing them. “To prevent reticle haze, reticles must continuously reside in an extremely clean and dry environment from the moment they arrive at the production fab.”

In the past year, he says, more emphasis has been placed on identifying the contaminants that cause reticle haze and how to prevent it. “There are 30 different species of molecules that cause haze, and they are all enabled by moisture,” says Stienstra.

Click here to enlarge image

He notes that Entegris currently offers a product line designed to prevent reticle haze in 193-nm lithography (see Fig. 1). The solution provides a continuous cleansing environment for the reticle, preventing the formation of haze by controlling and purifying the environment around the reticle between uses. The central element in the system is the integrated purifier and purge capability in the pod. The pod is purged in the stocker and again near the scanner where the reticle will be used.

Stienstra estimates that fabs can realize a four- to five-fold increase in mean time between reticle cleanings by using this system.

“Reticle haze is a multimillion dollar problem,” he says. “We find that fabs see a return on investment in a matter of months.”

The FOUPs also create problems because they can absorb airborne molecular contaminants, such as bromide from wafers, and outgas them onto other wafers. There is also the risk that wafers can contaminate slots in the FOUP. For example, copper contamination on the edges of wafers can carry over to the slots of the FOUP, contaminating the next wafer to be placed in that slot, says Camenzind, who believes the industry needs to embrace more stringent testing of the cleanliness of FOUPs to prevent cross-contamination. This is a new key focus for the ITRS.

Unfortunately, the industry hasn’t come up with the perfect solution and is still looking for tools to better quantify AMC in the FOUPs. “We are looking for abatement methods to measure, monitor, and purge the FOUP before issues arise,” Freescale’s Lovejoy says. “But it’s a challenge.”

Currently Lovejoy, and most other fab operators, must measure outgassing from FOUPs in a lab and wait hours or even days for results. “I want an analytical tool that is sensitive enough to measure the FOUP in real time,” he says, noting that several vendors are currently working on such solutions.

He also notes that operators and vendors need to do a better job of assessing the materials FOUPs are made of–from evaluating their potential offgassing and choosing materials that won’t absorb chemicals to selecting products that are easy to clean.

Go with the flow

Beside the enclosed environments, fab operators must also keep a close eye on their overall cleanroom environment and pay close attention to airflow, says Keith Kibbee, a mechanical engineer in the Portland, OR office of CH2M HILL, a full-service engineering, construction, and operations firm. Kibbee, who does 3D airflow modeling for cleanroom clients, notes that changes in the cleanroom (such as the addition of a new piece of equipment) can throw off the airflow, causing blockages or ripple effects, impacting fan filter unit airflow rates, and limiting optimal recirculation of air.

“In cleanroom remodels, I see a lot of bigger toolsets coming into the chase return and the expansion of clean space, which can create pressure problems and airflow migration,” he says.

Kibbee helps clients map out the impact of new tools or room changes using 3D modeling to identify airflow problems before they arise or to assess the effectiveness of possible solutions before they are implemented.

“You have to tweak the room to control negative factors, and the nuances are minute,” he says. “I can run 10 different cases to see which is the best fit. That would cost a lot more time and money to do it real time.”

One eye open

No matter what solution, or combination of solutions a fab uses to prevent, control, or mitigate contaminants, it all hinges on monitoring. And as smaller and lower levels of contaminants pose bigger risks, real-time online monitoring is becoming the norm–at least around critical processing and handling steps.

“You have to monitor something to know it’s there,” says Particle Measuring Systems’ Rowley, who predicts an ongoing shift away from periodic sampling to real-time high sensitivity monitoring in critical areas of the fab. “Once you monitor, you can correlate the data to your process yield, warranty requirements, the cost of downtime, and maintenance costs. If companies can get a handle on that data, they can see the value of monitoring.”

Some techniques available for monitoring molecular contamination in the air and on surfaces include ion mobility spectrometry (IMS), surface acoustic wave (SAW) monitors, impingers, and sorbent tubes. Particle Measuring Systems offers an extremely sensitive, part-per-trillion, real-time monitor that uses IMS technology to measure AMC before it can react with other compounds and accumulate on critical surfaces such as optics and reticles (see Fig. 2).


Figure 2. The AirSentry II surface molecular contamination monitor uses ion mobility spectrometry to measure contamination at ppt levels in real time. Photo courtesy of Particle Measuring Systems.
Click here to enlarge image

“Because AMC and SMC can fluctuate wildly throughout the day or manufacturing cycle, relying on periodic sampling may not deliver the most accurate information,” says Rowley. “Without real-time data, it is not possible to understand if AMC or SMC levels observed in the air or on optics, reticles, and wafers represent stable background conditions, a contamination event, or a low or high phase of a daily contamination cycle.”

Balazs’ Camenzind agrees that the trend is toward more routine online monitoring, particularly for ambient air which varies from day to day. However, he notes that in critical areas today’s online monitors may not be sensitive enough to give accurate readings at pptv levels.

“SO2 online monitoring works for makeup air, but after purifiers levels are required to be much lower, and online instruments do not have adequate sensitivity, so you still also need to do ‘grab sampling’ to get the lowest detection limits needed by the ITRS and stepper manufacturers,” he says. “Steppers, masks, and lasers all have similar and severe purity requirements in the sub-parts-per-billion to parts-per-trillion by volume range.”

He also urges fab operators to conduct routine air analysis for urea, a base that can contribute to photoresist problems, in addition to the usual suspects such as ammonia, amines, and amides.

“The only way to identify which contaminants will impact processes is with state-of-the-art measurement and sampling technology,” agrees Entegris’s Lobert. “Today’s applications require consistency and repeatability over time in the parts-per-trillion concentration range.”

Finding balance

“It’s a competitive advantage for companies to know how to manage and handle molecular contamination in the cleanroom,” says Rowley, who suggests that the industry has not gone as far as it should. “Most companies hold their AMC monitoring and control techniques and strategies close to the vest, because those who do it well gain critical tenths of a percent to a few percent gains in yield–which make huge differences in such a competitive industry.”

“In the end, reaching the extreme of no contamination whatsoever doesn’t make financial sense,” says Camenzind. “The most practical contamination control engineering is figuring out what the reasonable limit for each step is based on the process, then maintaining levels below that limit and monitoring to ensure you achieve it.”

Click here to enlarge image

The trick is figuring out exactly what those levels are and developing the tools to monitor and mitigate to these levels to ensure the environment is protected.

“It all boils down to yield and dollars,” says Rowley. “Most companies don’t have a good handle on the cost of poor contamination control and they may not know how much they are spending.” He explains, “Considering the costs associated with outfitting cleanrooms and lithography tools with chemical filtration and purge gases, costs of 193-nm lithography equipment downtime, as well as the additional costs embedded in warranty and service contracts, outfitting a cleanroom and 193-nm lithography tools with a complete AMC monitoring solution is minor in comparison.”

But as geometries continue to shrink, fab operators need to get a quantifiable measure of what contaminants impact their processes and how much that impact costs. Only then can they make an accurate assessment of the costs and benefits of contamination control decisions.

“Contamination is not going to be 100 percent controlled in our lifetime,” says Camenzind. “We’ve learned a lot about contamination control, but we still have a long way to go. Working together in interdisciplinary, multifunctional groups like the ITRS is essential to making the most progress in these areas, to keep the industry on track with Moore’s Law and new technologies.”

Contamination monitoring bolsters semiconductor manufacturers’ efforts to keep up with shrinking critical dimensions and cost and energy reductions

By Morgan Polen and Bill Shade, Lighthouse Worldwide Solutions

Contamination control in today’s production facilities is specifically targeted at loss prevention, cost reduction, and process control. As critical dimensions shrink and pressure increases for cost and energy reduction in manufacturing, contamination monitoring can be a useful tool to ensure that the cost reduction measures do not impact the production environment.

Various contamination monitors have been used in the past as indicators or watchdogs for contamination events. These have informed facilities, equipment, or process personnel about changes in contamination levels.

These same instruments are starting to be used to fine-tune the facilities, equipment, and utilities for cost and energy reduction. From the high purity water systems and bulk gas systems to the air handling systems and the air itself, contamination monitoring has become a more useful tool in cost and energy management.

Particle monitoring has long been a part of contamination control in semiconductor manufacturing. Optical particle counters are used to measure particle levels in the cleanroom ambient air environments as well as the gases, water, and chemicals used in the manufacturing process. As semiconductor manufacturing advances, new requirements are placed on optical particle counting technology and monitoring systems. This article explores some current trends in semiconductor manufacturing, optical particle counter technology, and monitoring systems, as well as contamination control applications in modern fabs.

Airborne particle counting

The ambient environment in today’s semiconductor fab is often comprised of a centralized cleanroom and the minienvironments for the process tools. This approach provides a high level of isolation that prevents contaminants from entering the wafer processing area. The cleanliness of these environments is strictly controlled to ensure that contamination does not impact yield and throughput in the manufacturing process.

Most fabs certify cleanliness periodically according to the ISO 14644-1 standard. In addition, today’s semiconductor manufacturing facilities frequently employ a centralized particle monitoring system for monitoring particle levels in the process tool environments. Typically these systems include multiple remote particle counters sampling in real time from several locations simultaneously or a single particle counter sequentially sampling from multiple locations via a manifold. The particle sensitivity of the instrument utilized depends on the cleanliness levels of the environments that are monitored.

The real-time application of remote particle counters places extreme requirements on the design for lower cost and high reliability since a fab typically employs a significant number of these in a monitoring system. In addition, as these instruments are used to monitor inside minienvironments, process tools, or stocking systems, their size can often become an issue. Figure 1 shows a 0.2-µm remote particle counter that can be used as part of a real-time monitoring system. The current state-of-the-art remote particle counters can have laser diode lifetimes of 20 years or greater.

A sequential sampling manifold system includes a manifold and portable particle counter. The manifold contains several ports that are connected to individual tubes routed to various locations in the fab. Figure 2 is a layout of a sequential sampling manifold system. The manifold mechanically samples from the various ports and delivers the sample to the portable particle counter. The current trend with these systems is to be able to control sample locations down to a few particles at 0.1 µm. Therefore, the manifold must be very carefully designed with flow efficiency in mind and no right angles in the flow path. This approach allows for better particle transport. In addition, the design must not generate any particles from either the internal mechanisms or from cross-contamination.

The portable particle counters employed in these systems are often used interchangeably in numerous other fab applications. These universal instruments are used as portable devices in a cleanroom monitoring plan or can be used for troubleshooting particles in a particular process tool or area. In addition, these devices are used for measuring particles in gases on-line or in a portable manner. Because these instruments are used in so many applications throughout the fab, they must be portable in nature and, as such, be as lightweight as possible and capable of running on a battery. They also must be easy to operate for personnel who are required to use them on infrequent occasions.

Today’s semiconductor manufacturing is composed of fully automated material handling and process equipment as well as minienvironments for isolating the product at all times from the central facility. These advances in the manufacturing process have created the need for optical particle counting instrumentation to facilitate the measurement of particles in minienvironments and stockers as well as to facilitate the troubleshooting and monitoring of complex automated process equipment. The result has been the advent of smaller sampling devices that permit the sampling of a handful of locations in a minienvironment, stocking system, or in and around a process tool using a single portable particle counter. Some of these devices use an ensemble averaging technique to draw in the sample from multiple locations simultaneously. Such sampling techniques cannot identify the specific location of the particle source. Other devices use sequential sampling techniques to monitor multiple locations. These devices have the ability to easily partition the particle measurement between different locations, helping pinpoint the source of particle issues rapidly. Figure 3 is an example of one such sampling device, which permits multipoint sequential measurement in a portable manner.

Gas particle monitoring

Another potential source of particle contaminants that can affect semiconductor product is the bulk gases used throughout the semiconductor manufacturing process. For this reason, many leading-edge fabs monitor critical high pressure gases for particles on-line. Historically this has been accomplished using particle counters specifically designed for measuring high pressure gases or using airborne particle counters in conjunction with high pressure diffusers. Current particle counters for measuring high pressure gases have relatively low flow rates and limited sensitivity. In addition, the complex design required for high pressure gas measurement results in a high cost-of-ownership due to periodic maintenance costs. High pressure diffusers use an orifice or series of orifices to reduce gas to atmospheric pressure. As such, these can be easily contaminated and can have long cleanup times. In addition, high pressure diffusers typically exhaust a significant percentage of the gas sampled, which is an added cost for this method of sampling.


Figure 1. Remote particle counters, such as this 0.2-µm device, can be used to monitor inside cleanrooms, minienvironments, process tools, or stocking systems as part of a real-time monitoring system. Photo courtesy of Lighthouse Worldwide Solutions.
Click here to enlarge image

As the industry moves to smaller linewidths, there has been a drive to improve the performance of optical particle counting instrumentation for gas sampling, including the sensitivity and sample flow rate. Recent advances in gas-sampling optical particle counting technology include the development of high pressure controllers. These devices reduce the pressure of the gas to atmosphere without any wasted gas and are less prone to contamination than high pressure diffusers. In addition, these devices have extremely short cleanup times. The result is efficient, reliable on-line gas measurement at 0.1-µm sensitivity and a 1.0 cfm flow rate using a universal airborne portable particle counter described previously.

Click here to enlarge image

In addition, because of the simplicity and rapid cleanup of these devices they can now be used easily in portable applications like checking incoming gas quality and filter performance as part of process tool startup and qualification. The use of these devices for tool startup and qualification can be expected to dramatically reduce startup costs and time.

High-purity water particle monitoring

In a typical fab several thousand gallons of high purity water come in contact with each wafer. For this reason, the output of the main high purity water plant is monitored extensively for several forms of contamination to ensure that the water does not impact product quality. Particles, TOC, dissolved oxygen, and silica are some of the forms of contamination monitored. The 2007 International Technology Roadmap for Semiconductors (ITRS) states the recommended particle levels at 50 nm are 0.3 particles/ml. This specification places extreme demands on the design of instrumentation to measure particles at these sensitivities and low concentration levels.

There are several industry trends that are likely to shape the future of particle monitoring for high purity water. Water conservation is one trend. The industry is developing specific goals to reduce incoming water consumption in the years to come, which is likely to lead to more recycling and reuse of water where possible. At the same time, local water purification solutions are emerging for specific processes where the purity of the water is critical. These trends are likely to drive the need for additional monitoring including point-of-use monitoring in key process steps.


Figure 3. A minienvironment monitor that uses sequential sampling techniques helps monitor multiple locations, easily partitioning the particle measurement between different locations. Photo courtesy of Lighthouse Worldwide Solutions.
Click here to enlarge image

In response to these changing requirements, optical particle counting instrumentation is advancing to reduce the background zero count levels to improve measurements at current and future concentration levels. In addition, instruments are now available that are truly portable so their application can be extended beyond the main DI plant into the fab and process.

Chemical particle monitoring

Optical particle counting is also used to measure particle levels in critical chemicals that are supplied to the fab by the bulk chemical delivery system. Current measurements are made at 0.065 and 0.1 µm with existing instrumentation. As the industry moves to smaller device geometries, it places demands on the instrumentation to improve sensitivities and/or background levels to provide reliable measurements in the near future. Given the current ITRS recommendation for critical particle size and number of particles, a 0.065-µm particle counter must measure particle concentrations at or below 1 particle/ml today. Clearly liquid particle counter instrumentation must continue to advance to meet the industry’s needs.

Fab-wide environmental monitoring systems

Fab-wide monitoring for particles and other environmental parameters is commonplace in most fabs today. These computer-based systems are composed of the various instruments previously discussed and other environmental instruments connected into a centralized data acquisition and analysis hardware and software system. Historically these systems have been used for environmental monitoring of the cleanroom.

At present, a number of additional applications for these systems are emerging that are in part being driven by a need to reduce costs and energy consumption. One such application is continuous monitoring per ISO 14644-2. ISO 14644-2 states that if a continuous or frequent monitoring system for particle counts and differential pressure is employed and these parameters are within the specified limits, then the cleanroom is in a state of compliance and does not require bi-annual or annual recertification. Therefore, users are starting to employ these continuous or frequent monitoring systems as part of their monitoring plan to reduce certification costs.

Another application that is being explored is realizing energy savings by using particle counts as feedback to control air handling units, thereby reducing energy consumption of the air filtration as much as possible. Given the cost of energy today and the present concern about preserving our global environment, this is an exciting application for these systems that is sure to be realized in the near future.

As fab-wide monitoring systems are utilized for more advanced, mission-critical applications, it drives the need to improve the overall performance of these enterprise systems. These systems must maintain higher uptimes, and that is now being realized through a number of system features being put in place.

At the instrument server data acquisition level, redundant controller architecture provides assistance in the event of any hardware or software failure on the main controller. At the database level, a clustered database deployed on multiple machines can dramatically improve the uptime of the database engine.

Another improvement in these systems is the development of open standardized interfaces. Modbus is commonplace at the data acquisition level and OPC is often an available interface to the data and instruments. These open interfaces permit these systems to be readily interfaced to building management systems that may need to perform advanced functions such as controlling fan filters or air handlers based on the collected data.

Summary

Semiconductor manufacturing is continuously changing as device geometries shrink in an effort to reduce cost and improve device performance. As the industry moves to smaller linewidths, there is continued focus on contamination control, including the use of optical particle counters and their fab-wide monitoring systems. The industry’s continuous adoption of these instruments and systems is in turn driving investment in the innovation of the technology and its application to realize additional cost savings and yield improvements.


Morgan Polen is vice president of applications technology and Bill Shade is vice president of marketing and engineering at Lighthouse Worldwide Solutions, headquartered in Fremont, CA (www.golighthouse.com). They can be reached at (510) 438-0500.

To maximize containment, all aspects of the glove and sleeve must be routinely inspected and tested

By Russell E. Krainiak, Integrated Containment Systems

As an isolator designer and builder ultimately responsible for operation, the question of the glovesleeve as a weak link is very complicated for this author. The application drives the wear, age, and how an operator performs the tasks to determine when a glove should be changed. A typical pharmaceutical user will ask “How many months?” in trying to determine when the glovesleeve is to be changed, but it isn’t that easy to determine from case history. The technology is still new to this particular industry that likes to know up front every detail of what to expect.

The intent of this article is to provide some of the details of glovesleeves, gloveports, and maintenance for keeping glovesleeves safe, thus keeping the entire operation safe and controlled. Testing is a very simple maintenance task, but some companies do not test the gloves and glovesleeves; examination is important, but they often are not examined. There are other factors to prevent actives from egress of an otherwise robust containment system. These will also be discussed.

Background

The nuclear industry has used gloveboxes for more than 40 years. In the early years, the glovebox was a necessary device to allow access to radioactive materials for the purpose of making and servicing a weapon. The nuclear industry shares many of the same problems as the pharmaceutical industry. Glovesleeves are used to access almost everything these technicians process and similar disciplines share the same concerns. If a glove leaks, will the product escape?

The first nuclear gloveboxes were transitioned to isolators by the manufacturers. There were many design changes to accommodate cleaning, which was not as critical in gloveboxes. Cross-contamination was not as much of a concern since the glovebox product was very different. The failings of gloves always raised the same questions: when, where, and why did it happen?

Some gloves on nuclear gloveboxes have been in place for five years without leaks. As demonstrated in papers presented and forums from the American Glovebox Society (AGS),1 this length of time before failure is possible with proper maintenance and sometimes by limited use. Training is cited as being critical to the safety of the operator.1 Some glovesleeves leak starting out of the new package, which most likely occurs due to storage problems.


Figure 1. Today’s isolators incorporate test programs to ensure glove and sleeve viability. Photo courtesy of Integrated Containment Systems.
Click here to enlarge image

One thing the nuclear industry understood from the history of glovebox usage was leaks can contaminate the room, the facility, and the outside. Monitoring equipment is used so operators cannot leave the facility without being cleared. There are other reasons for monitoring outside the scope of this article; if a glove has a hole or tear, the risk is imminent. Most pharmaceutical facilities do not routinely perform tests that detect active pharmaceutical ingredients (APIs) for operators working in the containment facilities. Some operations do require blood tests to determine past exposures, since it is the only way to determine exposure. Operators can go home, spend time with the family, and potentially spread APIs. For this reason, the pharmaceutical isolator must have certain additional safety features and qualities.

Glove materials and types

There are several glovesleeve designs and materials available for gloves. Deciding which is appropriate for an application is dependent upon the application. Hypalon, neoprene, and butyl are the most commonly used glove materials that withstand many cleaning chemicals. Chemical damage can occur and should be considered in the design phase. All chemicals–cleaning and process–should be checked for resistance with the gloves to be used. As an example, researchers use multiple chemicals in isolators as part of their daily operations. Every chemical should be checked against the materials of glove construction just like the isolator seals. Sometimes the gloves can be changed to another material, but there are some chemicals that degrade all available glove materials. For this reason, manufacturers maintain resistance charts as part of their web sites and company literature.

Another factor to consider is mil thickness of available gloves. A thin 15-mil glove is chosen for dexterity when doing intricate weighing (such as analog weighing). When the technician will perform scooping operations from a drum, a thicker 30-mil glove is chosen for its robustness.

Operations dictate the selection of glove type and thickness but also consider hand size. Multiple operators are another variable in the design, with hand size and dexterity as factors. The gloves are available in ambidextrous and left-right hand types. After the material is selected, the designer has to choose the type of glove, thickness, hand size, and whether it will be a left-right hand type. Note that some glovesleeve manufacturers only offer their gloves in certain sizes. When choosing a glove for multiple operators, the tendency is to go to a larger glove size to accommodate more users. Another type of glove is the changeable hand type. This allows changing only the hand glove portion of the assembly; the sleeve stays with the gloveport and allows more variety of hand sizes than a single-piece glovesleeve arrangement.

Gloveports

The gloveport is the attachment for the glove and is critical to the life of a glovesleeve. Friction from movement of the glove against the ring can lead to holes and tears. Most of this friction is caused by ergonomic problems that may have been designed into the isolator or result from continuous usage. Isolator manufacturers generally have proprietary designs that range from 8- to 14-inch diameters. Both oval and round versions are available. Most operators favor a large, round gloveport that provides more side-to-side and up-and-down movement. The first gloveports used on gloveboxes were 8 inches since shielding an operator’s chest was critical. Pharmaceutical workers can use much larger versions because they spend more time working in the gloveports and do not need radiation protection.

The two factors that lead to failure are repetitive motion and finger contact areas. These wear areas, like tires touching the road and wearing, are generally at the fingertips, which see the most contact and will eventually wear holes through the glove. One company manufactures a white-coated Hypalon urethane material that is a dark blue color. When the Hypalon wears off, this indicates the glove should be changed. The area where the glove constantly rubs against the ring is another wear point and should be examined and tested routinely; this is especially true for extreme reaching in an isolator. In the design phase, constructing a simple mockup to evaluate ergonomic problems in this area will allow design adjustments to be made accordingly.

Testing

Everything that fails does so for a reason. In the case of a glove, this is generally caused by repetitive wear or physical damage. What tests are available, how can you test a glove installation, and what is the best way? First you must understand how the glove works in an isolator.


Figure 2. Oval gloveports limit horizontal movement. Photo courtesy of Integrated Containment Systems.
Click here to enlarge image

A glovesleeve is maintained for containment isolators under a slight negative pressure, usually less than 0.5 inches water gauge during production. The pressure is imposed by the pressure drop across an inlet filter set up to flow around 100 fpm through a breached gloveport (“breached” meaning a glove completely removed for testing purposes). Although there is some pressure surge with an isolator, it doesn’t normally damage most glovesleeves. When gloves are moved for entry into a set of ports or exiting the ports, there is a surge that shouldn’t bring the negative pressure to a positive pressure but will be very close. If a leak exists in a glove, this is the moment that particles could penetrate through the hole, depending on size of the hole and the number of particles. Depending on the operator exposure limit (OEL) over time, an operator could be exposed to harmful amounts of substances. The size of the hole and how much can egress through it and at what velocity also varies. This is the justification for testing glovesleeves prior to use.


Figure 3. Round gloveports offer better range of motion. Photo courtesy Integrated Containment Systems.
Click here to enlarge image

Pressure is the most widely used method of testing gloves. Some will insert a plug on the outside of the ring and seal it. This is the best test method since it challenges the entire gloveport assembly in the installed, ready-to-go state. Pressure is applied to the plug and time is used to determine a preset pass/fail condition. Some test systems only challenge the glovesleeve, requiring the existing glovesleeve to be removed in order to perform the test, which works best with a new glove installation. The system uses pressure as well, but, again, only the glovesleeve is being tested, not the ring seals that lock the glovesleeve to the gloveport.

Following on the recommendation for daily testing of gloves used for low OEL applications, the trend has been to automate a glove and isolator pressure integrity test at startup of an isolator, prior to production or use. This can be a very simple way to maintain the safety of the operator; it allows a PLC to perform these testing functions by pre-validated pass-fail parameters. A PLC, unlike an operator, runs to a pre-validated program in a consistent manner that is not changed by the operator. The manual setup of an isolator for testing leaves room for error by depending on standard operating procedures (SOPs) being performed consistently. Most isolators that are set up manually are used for higher acceptable exposure applications. A PLC pressure integrity test for leaks is as simple as using the blower and inlet-outlet control valves to encapsulate the volume of trapped pressure. This helps identify the leaks on the isolator and glovesleeves. If it is determined that a leak exists for the glovesleeves, the next challenge is to determine which glovesleeve is leaking. A plug can be placed into the gloveport and sealed. A pressure line runs to a transducer to measure the pressure trapped in the glovesleeve and gloveport cavity plug. If the cavity shows negative pressure, it is leaking; if not, it is functional. These parameters can be set and controlled by the safety personnel. Using PLCs to perform the test function reduces time and money spent on testing and ensures the safety of the system. The other advantage, based on actual users in isolators, the unit passes the test most of the time, negating a “find the leak” element of the test since the glovesleeve is tested with the isolator as one volume.

Isolators

Isolators are predominantly built from stainless steel, with welded and sealed construction that can maintain the pressure boundaries that separate the worker and the API or hazard within. The openings, predominantly gloveports, are susceptible for one reason: This is where the wear and movement take place. The design of the isolator can add to the wear of the glovesleeves since a design that is not ergonomic can lead to stretching, yielding damage to elastomeric glovesleeves and tears that could result in exposures. Although the available materials are quite robust, continued and repetitive movements will lead to early replacement of glovesleeves.

Another glovesleeve failure observed by pharmaceutical companies includes extreme negative pressure, operating at around <1 inch water gauge. The excessive pressure will fatigue the operator, who must struggle with the glovesleeves for even the simplest movement. In this situation, the operator will have failures based on certain fatigue areas where creases are created and continually fold in the same location.

Training

Training is essential for any new installation and new technology. Training is conducted by the isolator suppliers because they are equipped to understand the operation and maintenance of the equipment. The weak link is how to do it safely regarding the gloves’ weaknesses and strengths. This supplier training is rarely conducted in any detail for each custom isolator project.

General training for operators is provided by the AGS at its annual conference. Attendees learn physical anthropology, how to work in a glovebox/isolator to avoid injury, and how to maintain the safety of the unit. Since many smaller pharmaceutical operations are not equipped to perform training within their facilities, this specialized training is a good start. Key information is given on how to visually examine gloves, how to avoid moves that might lead to glovesleeve damage, and safety related to glovesleeves. While this is a good starting point for a general “how to” training, it cannot replace understanding the specific equipment operations and procedures.

As noted, PLC control is used to incorporate most of the SOPs in the isolator program by the manufacturer and the user. This can further reduce training and operator setup responsibilities. Many programs include a safe setup or alarm for any failure. For example, if the isolator fails the pressure integrity test, the operator cannot use the equipment until it passes. The PLC simply locks out the operator. In the case of a leaky glovesleeve, the isolator will have a screen for pressure testing the gloveport and sleeve with the tester. Otherwise, an operator might use the isolator in an unsafe condition and risk exposure. This is common with older isolators that used manual operator setup. The operator could use the isolator without realizing a hole or tear exists on the glovesleeve.

Conclusion

To maximize the safety of the operator and facility, training, testing, history, and good isolator design features must be incorporated into a high-level containment system. Glovesleeves are fairly robust in most isolators and have been used for years by both the nuclear and pharmaceutical industries to successfully contain product. The pharmaceutical industry has a greater challenge in preventing egress of its products from the facilities. Gloves should be tested daily during production runs, along with visual examination to determine viability. Isolators should never be used if a leak is found as the risk is too great. PLCs should be used for any low OEL active, and a program should be established to minimize SOPs dealing with isolator pressure integrity testing and with glovesleeve/gloveport testing. This is the safest method and provides the greatest cost savings over time compared to manual testing with gauges and SOPs. The activity in the isolator, not necessarily the length of time on the isolator, will dictate how long the gloves remain on the gloveports. The other factor mentioned regarding chemical resistance should mandate that the material for the glove is compatible. Some chemicals will actually dissolve the glovesleeve. This failure could be catastrophic if an operator had their hands in the glovesleeves at the time. There is information available for news users from professional societies and technical forums to aid in determining wear and care of gloves.


Russell E. Krainiak is currently director of technology for Integrated Containment Systems, a design and build company of isolation and containment systems (www.integratedcontainmentsystems.com). He can be reached at [email protected].

Reference

  1. M. Cournoyer, C. Lawton, Los Alamos National Laboratory, “Why Good Gloves Go Bad,” pres. American Glovebox Society Forum, 2006 AGS Annual Conference.

ISO 21501 offers standard methodology for calibrating optical particle counters

By Tony Harrison and Bob Latimer, Hach Ultra Analytics, Inc.

ISO 21501 is a new family of standards describing the instruments and calibration requirements for determining particle size distribution using light interaction methods. It represents the culmination of work by instrumentation manufacturers and industry users and comes at a critical time for the life science industry with the increasing trend for real-time air particle monitoring in cleanrooms using light scattering air particle counters.

The ISO 21501 family of standards extends beyond air particle counters to include both scattering and extinction type liquid particle counters. The standard is split into four parts and all are available from ISO at http://www.iso.org.

ISO 21501, Determination of particle size distribution

The U.S. Food and Drug Administration (FDA) has cleared for marketing the Yulex® patient examination glove, which is made from a form of natural rubber latex derived from the guayule bush. Guayule rubber does not contain proteins associated with allergic reactions to latex products from Hevea brasiliensis, the source of traditional latex rubber, according to the Yulex manufacturer, Yulex Corp. of Maricopa, AZ.

As a result of several Type I latex allergy deaths, FDA initiated strict regulations of all products made with the Hevea rubber latex, including warning labels about the risk of allergic reaction on products containing latex. The U.S. Department of Agriculture

JUNE 8–11, 2008
WASHINGTON STATE CONVENTION AND TRADE CENTER

American Society of Health-System Pharmacists (ASHP)

Summer 2008 Meeting and Exhibition

Exhibit hours

Monday, June 9: 11:00 a.m.

Click here to enlarge image

Compounding pharmacies, equipment suppliers, and educators are all working to prove that USP <797> compliance is an attainable goal.

By Bruce Flickinger

Early in her career, Mary Monk-Tutor, PhD, spent many years as a home infusion pharmacist and for 12 years was a Joint Commission Home Care Surveyor. She remembers the time when home care patients were trained to mix total parenteral nutrition (TPN) formulations in their kitchens, and when nurses in hospitals compounded intravenous solutions on countertops. “We did this in the industry for years without infectious complications,” she says. “Obviously, these are not the safest or most appropriate environments, but it does show that it is possible to prepare at least low volumes of CSPs in uncontrolled environments without contamination.”

Things have changed in the past 20 years. Although avoiding contamination may be possible in such uncontrolled conditions, nobody now would admit to mixing intravenous and other sterile preparations on an open countertop. Doing so could cost a pharmacist his license and his livelihood, not to mention potentially compromise the safety of his patients and employees. Expectations for the handling and disbursement of compounded sterile preparations (CSPs)–loosely defined as manufacturer-supplied medicines (high-risk compounding can now involve non-manufacturer-supplied materials such as non-sterile bulk chemicals) that need to be mixed or modified by a pharmacist for patient use–have risen steadily among consumers, practitioners, and regulatory bodies. Standards for sterility and safety now have been codified in USP Chapter <797>, a federally enforceable standard introduced in 2004 and published in revised and updated form just this month.

Monk-Tutor, who is now professor of pharmacy administration and director of assessment with the McWhorter School of Pharmacy at Samford University (Homewood, AL), is among industry observers who say USP <797> is a long time in coming but still has a long way to go in terms of even, effective implementation. The standard, formally titled “USP General Chapter <797> Pharmaceutical Compounding–Sterile Preparations,” details the way sterile and high-risk pharmaceutical products should be compounded to optimally protect the safety and health of both patients and workers. It is incorporated to varying degrees in pharmacy accreditation programs and by individual state boards of pharmacy.

Like any federal mandate worth its salt, USP <797> initially prompted apprehension and procrastination in the pharmacy compounding industry, responses that have proved largely unwarranted and are for the most part dissipating. “While USP requirements are likely to become more stringent over time, they should be achievable for those organizations that have already put basic guidelines in place for compounding sterile preparations,” Monk-Tutor says.

In the wake of earlier consternation about USP <797>, two realities have emerged. The first is that the standard makes a clear demarcation between those pharmacies that want to do sterile compounding and those that do not. It is simply and primarily a business decision, one that expands the reach of care provided to patients but that requires a significant investment in training and infrastructure. The second is that education and training in sterile compounding needs to improve for those who do fall under the purview of USP <797> to achieve and maintain compliance.


Figure 1. State boards of pharmacy’s current USP <797> compliance status (direct, indirect, or no reference). Colors indicate whether the state’s pharmacy laws are harmonized with USP <797> (direct, green); include regulations for sterile compounding and/or parenteral nutrition but do not directly cite USP <797> (indirect, yellow); or currently include no regulations referencing USP <797> or sterile compounding/parenteral nutrition (no reference, red). Adapted with permission from ClinicalIQ.
Click here to enlarge image

Compliance clearly entails more than simply adding sterile compounding to a pharmacy’s slate of services or for the pharmacy to continue to compound CSPs the way it did five or 10 years ago. “Sterile compounding is a complex practice; it is not a simple matter to add sterile compounding to a hospital or community practice that dispenses manufactured products and compounds non-sterile dosage forms,” says Timothy McPherson, PhD, associate professor of pharmaceutical sciences in the School of Pharmacy at Southern Illinois University Edwardsville. “Rather, complying with USP <797> becomes a full-time, resource-intense commitment.

“I’ve spent some time with one pharmacy in the Midwest that specialized in non-sterile compounding for both humans and animals,” McPherson offers as an example. “A decision was made to add sterile product compounding, so they expanded their facility and added a state-of the-art cleanroom suite. They added a partner pharmacist to be in charge of the sterile compounding business, including all QC. I don’t see how a single pharmacist could reasonably handle the responsibility for both parts of this practice.”

Taking up the challenge

The independent community pharmacist is one of several players feeling the impact of USP <797>. Pharmacy compounding is a diverse practice that also encompasses hospital pharmacies, chain pharmacies, home health-care pharmacies, and specialty infusion companies, among others. Uptake of USP <797> varies among these establishments. Some of the best facilities in terms of compliance and overall quality practice are in community and specialty pharmacies “because they can implement changes much faster than hospitals can, provided they have budgets to work with,” says Loyd Allen, Jr., PhD, editor-in-chief of the International Journal of Pharmaceutical Compounding and professor emeritus of the University of Oklahoma HSC College of Pharmacy (Oklahoma City, OK).

“Some of the best facilities I have seen are in small- or medium-sized cities and even in some smaller towns. Most of the population lives in smaller cities and towns, and they require the same medical services as people in larger cities,” Allen says. Still, he notes that some pharmacists opt to forego their sterile compounding practice and focus on non-sterile compounding if it is not economically beneficial to invest in the necessary changes in their pharmacies. Some hospitals, too, are “outsourcing more sterile compounding to specialized companies, even to local pharmacies that have the required facilities,” he says.

One snapshot of the pharmacy landscape comes from a survey conducted by McPherson and his colleagues, results of which appeared in 2006 in the Journal of the American Pharmacists Association. His team surveyed 370 pharmacies in the Midwest and found that 94 percent of them provided compounding services. However, prescriptions requiring compounding represented less than 1 percent of total prescriptions filled for the majority (58.3 percent) of respondents. Overall, only 2.3 percent of prescriptions dispensed were compounded preparations, and “only about 5 percent of our respondents offered sterile product compounding,” McPherson says.

So while there is a market for sterile compounding, McPherson senses it is being met by businesses dedicated to the practice. “Most compounders we have come into contact with avoid sterile products. They generally refer patients requesting sterile products to a qualified pharmacy in the area,” he says.

One independent pharmacy that made the decision to specialize in compounding is The Compounding Shoppe, based in Homewood, AL. The Compounding Shoppe earned the Pharmacy Compounding Accreditation Board’s (PCAB) Seal of Accreditation in September 2006 and in the process became USP <797> compliant.

“Our goal was to become PCAB-accredited, so meeting USP <797> was mandatory for achieving this,” says Scott Wepfer, a registered pharmacist and owner of The Compounding Shoppe. “The commitment for any pharmacy that wants to bring itself up to USP <797> standards is significant, both in time and money. But if you are really serious about compounding and being in business 10 years from now, then it is simply a must-do.”

Wepfer adds, “I think that with the increased regulations and the increased costs of keeping up with these regulations, we will see fewer compounders doing more compounds and doing a better job of it than today.”

The Compounding Shoppe prepares capsules, creams, ointments, gels, suppositories, enemas, oral solutions and suspensions, sublingual (under-the-tongue) tablets, nasal sprays, ear drops, transdermal pain gels, and sterile injectables. A policy and procedure manual provides step-by-step instruction on every activity performed in the compounding lab for making these dosage forms.

“Definitely, the greatest amount of time was spent in writing policies and procedures,” Wepfer says. “We purchased non-sterile and sterile policies and procedures from a vendor, then combined the two and organized them in a way that was better for us.”

Chemicals used in compounding come from FDA-inspected chemical suppliers. Upon receipt, they are placed into quarantine until their certificate of analysis is verified by a pharmacist, who then creates a barcode to place on the container and adds it into inventory, Wepfer explains. “Formulas are stored electronically in our pharmacy computer system,” he says. “When we need to compound one of the formulas, we pull up an electronic log sheet in the lab where the barcode reader and even the electronic balance are all integrated into the computer system to literally create an error-proof compounding lab.”

Any compounding that involves working with powders is done in one of four containment hoods in the lab. Policy dictates that hoods are cleaned between each project to prevent cross-contamination. For sterile compounding, a Class 10 barrier isolator, from Containment Technologies Group (CTG; Indianapolis, IN), is used. “Rather than investing in the typical cleanroom setup with open-faced hoods, we decided to invest in a sterile isolation barrier. While the upfront cost was higher, the daily consumables cost is much lower,” Wepfer says.

Clear choices

Facilities and equipment requirements, including deciding among barrier isolators, laminar airflow workbenches (LAFWs), and enclosed cleanrooms, were cause for much confusion when USP <797> was introduced. People said they were unclear about the chapter’s requirements regarding equipment, positive and negative air pressure, and the segregation of hazardous and non-hazardous drugs, among other things. And if they weren’t unclear, practitioners were concerned that the infrastructure upgrades were too expensive for the typical pharmacy. A popular position at the time was to “wait and see”–that is, to do nothing until the standard wended its way through the comment and revision process and became more widely applied by regulators.

The current set of revisions, two years in the making and incorporating more than 500 comments, allows the use of both LAFWs and barrier isolators (called compounding aseptic isolators) in an ISO Class 7 buffer zone. However, if the manufacturer of a barrier isolator can prove that the isolator provides complete separation from the surrounding environment during dynamic operating conditions, the isolator does not have to be placed in an ISO Class 7 room. In total, the revisions “emphasize the personnel training and testing as well as the air quality and equipment and facilities necessary to meet the standard,” University of Oklahoma’s Allen says.

In his travels, Allen has noted a mix of cleanrooms with LAFWs and barrier isolation technology being used. “Generally, if a large volume of sterile preparations or IV admixtures is prepared, then workbenches with laminar airflow are easier to work with. If economics is an issue and the workload is low, then isolator systems are often selected,” he says.


Figure 2. The MIC-EDU barrier isolator from Containment Technology Group is the result of four years’ collaboration with STERIS Corp. and is offered in both single- and dual-chamber models. It has a static airlock that allows for residence time for decontamination agents and for performing automatic decontamination of the compounding environment. Photo courtesy of CTG.
Click here to enlarge image

The isolator at The Compounding Shoppe is one of CTG’s MIC units, a line of equipment that incorporates a static airlock, which allows for residence time for decontamination agents. “Our documentation package for compliance to the 2008 revisions to USP <797> contains a study showing that the static airlock approach results in at least [a 30 percent reduction] of microorganisms compared to a dynamic airlock when using 3 percent non-sterile hydrogen peroxide,” says Hank Rahe, technical director with CTG. “We attribute the reduction of microorganisms to the airlock design and the airflow pattern within the isolator chamber.”

Rahe points to two primary factors that influence a pharmacy director’s decision to choose a cleanroom instead of isolator technology: the perception that compounding in a cleanroom is more efficient and that it requires less change or disruption to familiar staff routines. “The idea that an isolator represents change and tends to slow down compounding activities is the most common reason cited for not using isolator technology,” he says. “We addressed this issue early on and published a study that concluded that, when proper procedures are followed, an isolator is as productive as conventional engineering controls.”


Figure 3. A pharmacy technician uses a Class 10 barrier isolator for sterile preparations. Photo courtesy of The Compounding Shoppe.
Click here to enlarge image

Another criticism is that, when using barrier isolators, people tend to relax their vigilance of protocol and other environmental controls because they feel the isolator will compensate for them. While isolators are less procedurally dependent than open cleanrooms, “good aseptic technique still needs to be practiced, and a properly trained staff understands the importance of maintaining the integrity of the environment in which sterile preparations are compounded,” Rahe says. “The isolator simply does not allow inadvertent touch contamination that can occur in open hoods.”

Monk-Tutor of the McWhorter School adds an important point: “Technique is always the key. The best equipment and cleanroom in the world will not make up for poor technique; they can only enhance correct technique,” she says.

On the pro-isolator side, reasons such as cost, flexibility, staff preference, safety, and increased sterility assurance typically are cited by pharmacy directors as reasons to use barrier isolators, Rahe says. Space utilization issues are common in hospital sterile compounding areas, and equipment design must accommodate these concerns. “Even though isolators are a less costly option, the flexibility an isolator offers is many times the deciding factor in selecting an isolator over a cleanroom,” Rahe says. “Cleanrooms represent a fixed asset and do not have the flexibility to relocate within a given facility or between facilities.” Furthermore, as opposed to being restrictive, isolators can actually be seen as enhancing the movement of pharmacists and technicians among different jobs, he says.

Other stipulations

Both isolators and LAFWs are referred to generically as primary engineering controls, or PECs, in USP <797>. Both must provide ISO Class 5 levels of cleanliness, but equipment specifications are just one part of the chapter’s scope. The net outcome of the chapter is that all CSPs be prepared in a manner that “maintains sterility and minimizes the introduction of particulate matter” and that final compounded products “maintain their labeled strength within monograph limits for USP articles, or within 10 percent if not specified, until their BUDs [beyond use dates].”1

The chapter addresses a number of different scenarios and types of products under the CSP umbrella. Hazardous drugs are one example. Using any PEC, hazardous drugs must be compounded in a negative-pressure buffer room, while non-hazardous drugs must be compounded in a positive-pressure buffer room. In addition, hazardous drugs must be stored separately from other inventory in a negative-pressure area.

“Hazardous drugs are a part of a pharmacist’s life: As long as a patient needs a hazardous drug that has been prescribed by a physician, pharmacists have the obligation to prepare it,” Allen says. “Safety precautions are now addressed in much more detail than they were years ago, so we now have good standards, practices, and new equipment to better handle hazardous drugs.”


Figure 4. Cintas offers the same cleanroom garments and services to compounding pharmacies that it offers pharmaceutical manufacturing companies. These include sterile reusable coveralls, hoods, boots, and frocks constructed of its Integrity 1800 antimicrobial fabric. The company also supplies technician suits (cleanroom undergarments), sterile consumable products, and sterile disposable garments. Photo courtesy of Cintas Corp.
Click here to enlarge image

The concept of a segregated area is new in the revised chapter. Along with hazardous drugs, the chapter includes a section on compounding low-risk-level CSPs with 12-hour beyond-use dating in an ISO Class 5 PEC within a segregated area. The chapter similarly provides an Immediate Use Exemption from ISO Class 5, in which compounding with direct contact contamination in an environment lower than ISO Class 5 is permitted when no more than three sterile ingredients are prepared or combined for administration that begins within one hour and is completed within 12 hours of completing the CSP.

Realistically, Allen notes, “some pharmacies may be able to do low-risk but most probably end up doing low- and medium-risk work. High-risk is more limited but is necessary in many situations; it just depends upon the workload and market the pharmacy serves as to which risk level is utilized.”

Jan Eudy, corporate quality assurance manager with Cintas Corp. (Cincinnati, OH), affirms that building a cleanroom capable of handling the variety of CSPs encountered is a key challenge to achieving both USP <797> compliance and good quality systems in the pharmacy setting. “Examples include separate areas for chemotherapy or hormonal mixtures in a closed cleanroom system vs. nutritional mixtures in a laminar flow hood system,” she says. “These require proper segregation of product and processes.” The pharmacy must also be ready to “make the financial commitment to maintain the calibration of the equipment and the cleanroom cleanliness levels required,” she adds.

“Cross-contamination is constantly a concern due to the number of people working in the cleanroom and the variety of products and processes in the cleanroom,” Eudy says. “This issue is addressed by creating a comprehensive cleanroom cleaning/sanitizing program that addresses the contamination from personnel working in the cleanroom, the products and processes in the cleanroom, and any mechanized equipment used in the cleanroom.”

Back to school

Although USP <797> devotes extensive attention to the provision, maintenance, and evaluation of air quality, it is clear the avoidance of direct contact between gloves and surfaces in ISO Class 5 areas is paramount. The chapter states unequivocally, “Compounding personnel must be meticulously conscientious in precluding contact contamination of CSPs both within and outside ISO Class 5 areas.”1

This speaks directly to aseptic technique and the proper preparation of sterile drugs. The chapter specifies that compounding personnel must be adequately skilled, educated, instructed, and trained in the following activities: antiseptic hand cleansing and disinfecting of non-sterile compounding surfaces; selecting and appropriately donning protective garb; maintaining or achieving sterility of CSPs in ISO Class 5 PEC devices; protecting personnel and compounding environments from contamination by radioactive, cytotoxic, and chemotoxic drugs; identifying, weighing, and measuring ingredients; manipulating sterile products aseptically; sterilizing high-risk-level CSPs; and labeling and quality inspecting CSPs.

So where does one become educated and trained in these skills? University curricula, continuing education, and on-the-job training are options, but none of them, individually or in concert, are doing a particularly good job in filling the knowledge void created by USP <797>. Efforts are underway to improve the situation, of course, and most recently the American Pharmacists Association published its official education and training policies that reflect many of the issues raised by USP <797>.

“The level of training has been a problem for at least 20 years,” Allen says. “Pharmacy students today do not have the scientific and laboratory background that they used to obtain during their education. So many of them attend specialized training programs to obtain the education required to meet the <797> standards. This is one reason that the <797> committee is emphasizing personnel training and especially personnel testing in performing operations such as media fills and fingertip testing. This is a good and necessary step for ensuring proper procedures are followed.”

“Some states require CSP certification through a CE program that includes a test and a skills demonstration, but, in my experience, these programs only cover very basic skills and are not sufficient to provide any proficiency,” Monk-Tutor says. “Some involve as little as 10 or 15 minutes “under the hood.’ So, I do see a national skills certification program coming some time in the future, either through a national pharmacy organization or through a private company.”

For an assessment of the current state of affairs among U.S. schools of pharmacy, Monk-Tutor conducted a survey to assess the extent of didactic and laboratory instruction related to CSPs. Results published last November in the American Journal of Health-System Pharmacy showed that, overall, instruction varied widely and only about a sixth of respondents believed that their students were adequately trained in CSPs before graduation.

“Ideally, every school of pharmacy would have a state-of-the-art cleanroom and at least one faculty member who is experienced in infusion therapy and knowledgeable about USP <797> to teach students,” Monk-Tutor says. “Unfortunately, few schools have the financial resources and/or space available to build out a cleanroom, not to mention maintain it.” Another deficiency in her mind is that many pharmacy schools “do not seem to have an expert in infusion on faculty.”

Further findings from the study seem to put the onus on continuing and on-the-job education: Although only 13 percent of schools felt that their students had adequate CSP training before graduation, nearly 90 percent of them believed that students could only become fully competent in these skills over time in actual practice.

“In my experience and based on the literature I have seen, most continuing education programs on infusion are minimal and on-the-job learning varies drastically by site,” Monk-Tutor says. “Even though great resources, like those provided by ASHP [American Society of Health-System Pharmacists] and NHIA [National Home Infusion Association], are available to help train employees, not all organizations use these tools. One great way to get appropriate training in all schools of pharmacy is for schools to partner with local hospitals or infusion providers.”

Learning by doing

Equipment and service suppliers are also an important educational resource. Many of them also work with biopharmaceutical manufacturers and can apply the knowledge and experience from this industry to their clients in sterile compounding.

Cintas, for example, includes education and site assessments as part of its overall offering. A supplier of cleanroom garments and disposables, Cintas provides an education program based on IEST recommended practices and ISO 14644 guidelines on cleanroom protocol. This includes design of cleanroom linear product flow with line clearance; donning and doffing cleanroom garments; behavior/working in the cleanroom; cleaning of the cleanroom; environmental monitoring and testing of the cleanroom; and documentation and auditing of the cleanroom management program.

A sterile garment/gowning program should not be overlooked. “A cleanroom garment program that is USP <797>-compliant needs to replicate the cleanroom garment program currently in use by pharmaceutical manufacturers,” Eudy says. “This includes the recommended garment items, the validated laundry process, the validated sterilization process, and the assurance of consistent quality of product and services required by USP <797>.” Cintas’ Cleanroom Resources Division currently provides sterile consumable garments and supplies to a large compounding pharmaceutical company with 23 different locations throughout the United States, as well as to smaller compounding pharmacies.

CTG also offers a pharmacy assessment service that provides two types of information to the pharmacy. The first helps them understand the number and types of isolators that will best fit their given needs, and the second advises them how to configure the isolators economically to meet the facility’s volume of work. “Using the data the pharmacy provides, we can determine with our database the proper configuration of isolators and provide an economic analysis comparing the cost of a cleanroom to the isolators. This includes both capital and operating costs,” Rahe says.

To be sure, numerous companies design and build compliant cleanrooms for the various compounding risk levels; programs are available for training pharmacists and technicians and for providing continuing education; services exist to certify cleanrooms and laminar flow hoods; and analytical labs provide product QC including sterility and pyrogen testing.

“None of these are free, of course, but the essential component is a commitment by the pharmacist in charge to avail him/herself of these services and conscientiously carry out the QC program,” McPherson of Southern Illinois University says.

On this point, some observers find disconcerting the apparent reluctance to reach out to the pharmaceutical manufacturing community and translate some of its accumulated knowledge to pharmacy sterile compounding. “Some pharmacy consultants seem to have taken the position of “NIH’–“not invented here’–because they feel compounding is somehow different,” Rahe says. “While some aspects of compounding sterile products are different, a great deal of knowledge could be transferred from manufacturing experience-based individuals. One wonders what is the true motivation in not taking advantage of an outreach to other communities of knowledge.”

Reference

  1. United States Pharmacopeia, “USP General Chapter <797> Pharmaceutical Compounding–Sterile Preparations.” The revised USP <797> is available online at www.usp.org/pdf/EN/USPNF/generalChapter797.pdf.

Deciding what type of disinfectant will provide the greatest efficacy for your application requires a back-to-basics approach.

By Lisa Strickland, Contec, Inc.

It might not be too dramatic to state that bacteria, viruses, fungi, and spores represent a unique, insidious, and dangerous class of contaminants: unique in that under the right conditions the contaminant population can multiply over time; insidious in that these organisms can penetrate into small openings and crevices that can persist for long periods of time; and dangerous in that they can affect human health. So these contaminants must be destroyed and/or removed to achieve the desired cleanliness and aseptic condition. That’s the role of disinfectants.

If there were only one chemical agent–i.e., one disinfectant–available to accomplish our objective, life would be simple. Unfortunately, there are many products to select from. So how do we choose? Do we base our decision on chemical structure? Personnel protection issues? Type of organisms to be destroyed? In this article, we’ll focus our attention on these questions and others.

Chemical agents that destroy microorganisms can be termed “biocides”; it is useful to categorize them in terms of potency. Sanitizers, such as alcohols, can reduce microbial contamination by as much as 99.999 percent (known as a 5-log reduction) but are ineffective against spores. Disinfectants, such as phenolics and quaternary ammonium compounds, provide 100 percent kill of vegetative bacteria, some fungi, and viruses but are also ineffective against spores. To destroy spores and achieve 100 percent kill of all microorganisms requires sterilants–aldehydes or strong oxidants such as bleach or hydrogen peroxide.*

Finding the optimal chemistry for each environment is critical to removing these complex microorganisms.

The great bug hunt

Every facility must determine the resident micro flora unique to each environment. The United States Pharmacopeia (USP) provides guidance on microbial control and testing. Specifically, USP <1072>,“Disinfectants and Antiseptics”1, and USP <797>, “Pharmaceutical Compounding–Sterile Preparations,”2 provide guidance on identifying key organisms in critical areas. Testing to determine the organisms down to the genus and species level is crucial. Identifying the type of microorganisms and the number will provide the framework on which to build a microbial control program.

Now what?

Once the microorganisms have been identified, the cleanroom operator can select the proper biocide solution for the environmental isolates and surface materials. Things to consider:

  • Spores and surface sterilization. Did you discover any spores in your testing? If so, it is critical that a surface sterilant be employed.
  • Personnel safety. Many biocides are eye and skin irritants, unpleasant to use, and toxic. It is very important when choosing the application mode (fogging, spraying, wiping, mopping, or immersion) to be aware that these applications can create situations that are hazardous to personnel.
  • Surface contact time and material compatibility. Dwell times can vary significantly depending on the particular biocide and the specific isolate to be destroyed. The effective contact time can be determined by following the biocide’s label recommended claims or performing an in situ sanitization validation.
  • Chemical disinfectant media. Several formats of chemical disinfectants are available for convenience: ready to use, concentrates, and pre-saturated wipers. Sterile solutions of biocides are commercially available as well. These solutions are aseptically sterile-filtered and/or gamma-irradiated to provide the requisite Sterility Assurance Level (SAL).

There are three important components to chemical selection: chemical effectiveness, compatibility with substrates, and safety to personnel. There are numerous biocides available that can offer a broad spectrum of activity to kill susceptible pathogenic species. Arranged alphabetically, and described more fully below, are some of the most commonly used biocides found in critical environments.3,4

Alcohols are sanitizers commonly used as a skin antiseptic. Of the available alcohols, isopropyl alcohol (IPA) is most often employed. Typical IPA concentrations vary between 60 and 85 percent. Most commonly used is 70 percent IPA, because there is enough water in the solution to allow it to effectively penetrate the pathogenic cell. A minimum contact time of 10 minutes is recommended when using IPA. The quick evaporation of IPA is a major disadvantage as a biocide, because the concentration diminishes before the recommended dwell time can be met. Conversely, because of the volatility, IPA is an excellent option to clean and dry equipment without leaving a residue.5,6

Aldehydes are powerful and aggressive disinfectants that can be used effectively as a sterilant. In concentration aldehydes are highly toxic to personnel and require long contact times for sporicidal claims. A typical aldehyde, gluteraldehyde, can require up to 10 hours of exposure at a concentration of 2 percent to kill Bacillus subtilis. Aldehydes are ideal for use on equipment that can be submerged for a period of time, under conditions that can keep irritating vapors at a minimum. Some countries have banned or restricted the use of aldehydes because of their safety profile as carcinogens.5,6

Inorganic chlorine and chlorine compounds solutions are broad-spectrum biocides that can be used as a disinfectant or a sterilant. Chlorine chemistries are inexpensive, readily available, and relatively fast acting. However, these chlorine solutions are corrosive, unstable over time, and rapidly lose activity in the presence of heavy metals found in the environment. Chlorine solutions have a high toxicity profile and must be used in well ventilated areas. Sodium hypochlorite (NaOCl), the most commonly available chlorine solution, can be found in a range of concentrations from 1 to 35 percent. Typically concentrations for sodium hypochlorite are 1 to 5 percent. A 1 percent solution provides approximately 10,000 ppm of free chlorine. As little as 5 ppm will kill vegetative bacteria. Unfortunately, to kill spores the concentration must be 10 to 1,000 times greater.5

Hydrogen peroxide is a potent biocide that is environmentally friendly because it degrades to water and oxygen. Peroxides are rendered ineffective in the presence of organic and inorganic soils, so pre-cleaning is required to achieve the desired reduction in the microbial population. Disinfection can also be achieved with lower concentrations of peroxides.6 In concentrations as low as 0.5 percent, hydrogen peroxide can be combined with other ingredients to dramatically increase its germicidal potency and cleaning performance. These chemistries are effective with short contact times and offer an excellent health and safety profile.7 Sterilization can be achieved with hydrogen peroxide concentrations of 35 to 50 percent. Peroxides used in the vapor form, vaporized hydrogen peroxide (VHP), are very effective in sporicidal cleaning at low concentrations.6

Hydrogen peroxide blended with peracetic acid (PAA) is very effective at low concentrations and degrades to acetic acid and water. It is more effective than peroxide alone because it is not inactivated in the presence of soils. When high concentrations of this biocide are present, adequate ventilation is required. The combination of hydrogen peroxide and peracetic acid is an unstable solution; therefore, concentration testing must be performed prior to application.6

Phenolics are broad range disinfectants that are used on environmental surfaces. Substituted phenolics (e.g., p- t