The best combination medical device makers select product materials, process steps, and monitoring strategies in the early stages of product development to ensure biocompatibility and product stability throughout the manufacturing process.

Click here to enlarge image

By Sarah Fister Gale
The drug-eluting cardiovascular stent has changed the landscape of medical device manufacturing. These small implantable devices, which incorporate a device that can prop open an artery with a pharmacologic agent that interferes with reblocking after surgery, were among the first successful products to combine two unique medical tools in a single package.

Prior to the drug-eluting stent’s success, few companies were producing or even talking about combination medical devices. Limited to cutting-edge research, they were solely the focus of forward-looking researchers and manufacturers. Today, however, combination medical devices are a common part of the medical industry lexicon.

The U.S. Food and Drug Administration (FDA) defines combination medical devices as products comprised of two or more regulated components, such as a drug and a device, or a biologic and a device, that are combined and produced as a single entity; or those that are comprised of two unique entities, but are packaged together, or packaged separately but intended only to be used together.

Manufacturers are increasingly combining novel technologies that hold great promise for advancing patient care and making treatment options more convenient, customized, and self-regulated. Drug and biologic products can also be used in combination to enhance the safety or effectiveness of either product when it is used alone.

Some more recent examples of successful combination devices include proteins incorporated into orthopedic implants to facilitate bone growth that can stabilize the implant, drug-device inhalation systems for insulin delivery, and implantable timed-release medication delivery systems.

Rapid growth

The recent rapid growth of the combination medical device industry is undeniable. Independent firm Navigant Consulting (Chicago, IL) estimates the market has grown 10 percent per year since 2004 when it was an estimated $5.9 billion, to hit $9.5 billion by 2009.

FDA has had an office of combination products since 2004, and there are a growing number of conferences and resources discussing the challenges and triumphs of the latest combination innovations. Christine Ford, event director for PharmaMedDevice, an annual medical device manufacturers’ conference (Norwalk, CT), reports that 30 percent of devices currently in development are combination products and that these devices have become the most popular topic at the events. “Every multibillion dollar medical device company seems to have a combination device in their pipeline,” she says. “And if they don’t, they need to know what’s going on because it’s a big trend.”

Cutting-edge device companies who want to find a foothold in this burgeoning market are scrambling to identify innovative ways to combine device technologies with drugs or biologics that meet a range of medical needs.

The category of products promises to bring new business to these firms–if they can figure out how to produce them successfully. “It has become an emerging growth area, particularly in the last few years, and many firms are looking at these devices as an opportunity for market growth,” says Sharad Rastogi, principal in the life sciences group of PRTM, a management consulting firm (Waltham, MA). “But it’s a high risk, high reward market.”

“It can test a company’s resolve,” adds PRTM’s Sam Baldwin, manager of the life sciences group, who notes that developing the first product in particular can be very difficult. “The time to develop is significantly longer and the cost is much greater than with conventional medical devices. But if you go in with your eyes open you have a good chance of success.”

Figure 1. Foster-Miller designed an ergonomic insulin injector pen for Becton Dickinson to treat diabetes patients (top) and worked with G.D. Searle to create a transdermal nitroglycerine patch for angina treatment (bottom). Photos courtesy of Foster-Miller.Click here to enlarge image

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Regulatory red tape

The rapid growth of this market has left the medical device industry in unfamiliar territory as it figures out how to characterize and regulate this hybrid category of products. Even FDA is struggling to define a roadmap for these devices. While its office of combination products offers guidance and development considerations to manufacturers, it has yet to clearly define a set of good manufacturing practices (GMPs) specific to this product category. That has left companies to define their own path using a combination of drug GMPs (21 CFR 210/211), biologics product standards (21 CFR 610), and medical device quality system regulations (QSRs; 21 CFR 820). Trying to strike that balance correctly is where the challenges begin to pile up.

“The combination product regulatory framework requires a unique perspective on both medical devices and pharmaceuticals/biologics,” says Steven Richter, founder and CEO of Microtest Labs in Agawam, MA. “The first step to producing one of these products on a commercial scale is determining which regulations impact which steps in the process and come up with a plan for process validation.”

A combination product manufacturer must have a robust pharmaceutical GMP system in place that addresses some of the issues with the device QSRs, but the main regulatory foundation must be the drug GMPs, Richter says. “There are a lot of factors to consider to meet FDA standards, and a lot of clean manufacturing environments for devices won’t be sustainable for drug manufacturing.”

Baldwin suggests that manufacturers partner with FDA in the early development stages to ensure they are making sound choices and documenting their progress. “The last thing you want is to get to the end of your project and discover you didn’t validate it properly,” he says. “Working with the FDA, you can make your case for your approach, and they can tell you if you are going in the right direction.”

Medicine takes precedence

Aside from meeting regulatory compliance, combination medical device manufacturing is complex, particularly because it combines two or more distinct and delicate elements that will ultimately be used by the most vulnerable consumers. Because of this, contamination control must be complete and provable at all times.

“Most people who do medical product development are familiar with issues such as temperature and humidity control, airflow maintenance, management of particulates and pyrogens, and gowning,” notes Clair Strow, senior engineer and program manager in the medical division of Foster-Miller, a technology and product development company (Waltham, MA). “But it’s more difficult with combination products because of the subtle differences.”

Devices that have been engineered from plastic, metals, silicon, or other materials have contamination control issues that will differ from the medical or biologic needs of the product. They can also create contamination issues, through off-gassing or particulates, that can contaminate exposed biologic or pharmaceutical material, damaging its efficacy, says Foster-Miller’s Bob Andrews, medical division manager.

Figure 2. A medical device sterility test vessel with a medical device immersed in TSB (Trypticase soy broth). Photo courtesy of Microtest Labs.Click here to enlarge image

Biologics are also more temperature and light sensitive and have shelf life issues that need to be considered–many biologics are only able to maintain stability for a few hours outside of a tightly controlled environment.

If the combination product uses multiple biologics or chemicals, cross-contamination among materials is an additional concern, Strow says.

If a technician is working with a nanoparticle in one cleanroom zone, it could contaminate biologics in another area if the facility uses a common air system. “The pharmaceutical industry is very sensitive to spills,” Strow says. “In a combination product, you have to be extremely careful, particularly of chemicals coming in contact with biologics.”

Depending on the delicacy of the product and the risks in the environment, that might mean the use of gloveboxes, laminar flow hoods, and control over the exhaust air around a fill station, or it could be as extreme as total isolation with separate air handling for the biologic component of the product to prevent particulates and other contaminants from the manufacturing process from coming in contact with biologic material.

Adding to the difficulty is that device material and biologics or chemicals can have conflicting requirements for stability in the manufacturing environment. “Humidity control for a device may be too high for a biologic,” Andrews points out. “But if humidity levels are too low, you can build static in the room that can affect the device.”

This is not an uncommon problem, adds Foster-Miller’s Strow, who recently worked with a client facing just such a dilemma. The client was developing a combination diagnostic product that included chemicals that would be stored in a nylon device. For the chemical to remain viable it had to be dispersed in an environment that maintained 1 to 2 percent relative humidity. The client was producing the product on a commercial scale, packing 100,000 units per 24-hour shift.

“In that environment at the low humidity level, there is a lot of static so materials need to be stable,” Strow points out. The nylon, however, became brittle in the low humidity, ultimately shattering.

Fortunately, they were able to create a solution that allowed the nylon device to be isolated in a 30 percent humidity room. The two elements of the device are now packaged separately using moisture barrier packaging that allows the chemical to remain at low humidity levels and the device to maintain higher humidity. Once the package is opened it must be used within 20 minutes, during which time the humidity levels won’t be an issue.

These kinds of problems can be avoided if proper product development planning is done with all of these issues given careful up-front consideration by the design team before establishing the manufacturing operation, says Andrews of Foster-Miller. “Once the room is assembled it’s much harder to make changes.”

Maintenance and monitoring

Controlling contamination in the environment during manufacturing requires an end-to-end process that ensures the cleanest materials go in and remain clean throughout the manufacturing process. The most successful operations begin contamination control steps well before materials ever enter the facility, says Richter, who notes that at Microtest, new batches of drug or biologic material are tested upon arrival for content, quality, moisture, purity, and contaminants before use.

Storage of device materials is also critical and must be closely evaluated when manufacturing processes are being established for combination devices. From an environmental control standpoint, you must consider both what a material is made of and where it has been, because the storage environment can affect how it performs in the cleanroom, says Strow.

“If I have a particular polymer piece that has been stored in a warehouse that has 90 percent humidity levels, then I bring it into a cleanroom with low humidity, that stored moisture will be sucked to the surface,” he points out. “If you seal a drug product into that polymer, you contaminate your final product.”

Strow suggests that materials be placed in isolation with environmental conditions comparable to the clean environment for 24 hours to stabilize them.

Once the material is in the environment and process steps are taking place, manufacturers should perform round-the-clock monitoring, not just of the cleanroom, but also of the building management system, with a focus on airflow, temperature, humidity, and any motor malfunctions that could compromise the manufacturing or storage spaces, says Microtest’s Richter. They should also include backup generators to ensure the process is continuous.

Richter notes that newer HVAC systems can include specialized levels of pre-filters to eliminate toxic contaminants before they can be released downstream of the manufacturing space. This is particularly important if the device contains hazardous chemicals, such as cytotoxic drugs that could be deadly to personnel.

Figure 3. An analyst inoculates a 96-well plate to perform an endotoxin assay on a combination product. Photo courtesy of Microtest Labs. Click here to enlarge image

Microtest has two 1,500-sq.-ft. manufacturing spaces, each with separate airflow systems and dedicated chillers to manage relative humidity and temperature. The facilities are also designed with walkways above the main room for maintenance and servicing. “It’s critical for the service people to be able to get above the cleanroom to pull filters, change traps, or look for problems,” Richter says. “We can do visual inspection and maintenance freely without compromising the cleanliness of the room.”

The product Microtest manufactures in this space includes a powder stored in an injection system, which makes the risk of airborne particles an issue. This is addressed in the design and management of the room: It incorporates a conductive ESD floor, and high humidity levels above 60 percent to prevent dryness. The HVAC system was designed with an integrated vacuum system to suck out any particles that are generated from equipment or process steps. The company also does ongoing monitoring with particle counters and air samples at critical control points.

To maintain cleanliness and avoid bacterial issues, the sanitation team regularly rotates the intermediate-level disinfectants used to clean the room to prevent resistance. If problems with microbial status of the room arise, a high-level sporicide is used.

Once processing is complete, samples of the finished product are analyzed for contaminants using high-performance liquid chromatography, and the product is bagged and terminally sterilized.

Sterility options

How the product is sterilized at the end of the manufacturing process is one of the most difficult decisions developers of combination medical devices will make, says PRTM’s Baldwin. It’s another decision that must be made early on in the product development process because it can affect every product development and environmental choice that will follow.

With traditional medical devices, sterilization can almost be an afterthought. A common sterilization process is the use of ethylene oxide, which is a potent antimicrobial agent that can kill all known viruses, bacteria, and fungi. But such a strategy could destabilize biologic or pharmaceutical materials that are a part of the product.

“Once you add the biologic or pharmaceutical component, your available sterilization options drop considerably,” Baldwin says, explaining why sterilization methods must be determined well in advance of production. “Sterilization can have critical implications on your design. The companies that have the most success are the ones that include the sterilization group from the start of the design.”

Some options include low-dose or low-temperature radiation; a dry heat sterilization process, which can be an option for most small-molecule combination products; or the drug or biologic may be lyophilized, or rapidly frozen, to stabilize it during sterilization to allow for additional options.

Engineers also need to think carefully about working in an aseptic environment, and they need to be very careful about the bioburden that is brought in on equipment, materials, devices, and most importantly on personnel, Baldwin advises. “That means better training programs, daily operator assessments using touch plates or hand swabs, and a design process that minimizes human interaction.”

Whenever possible, he recommends automating key processing steps to remove the possibility of human error and contamination from the system.

Working together

The willingness to look at each product as having an original set of needs and contamination control issues is critical to a successful design process, but that attitude comes more naturally to medical manufacturers than to device manufacturers, who are accustomed to more controlled decision making options. This cultural difference and the need for prioritization of medical materials represent significant challenges for companies looking to move into this niche industry.

“While both elements of a combination device have unique sets of requirements for the manufacturing environment, you have to defer to the needs of the biologic,” says Strow. “They are the key to the device.”

That doesn’t mean the non-biological material should be compromised. Rather, it means the device material, along with the assembly methods, airflow handling, contamination monitoring, room layout, and isolation methods should be chosen based on the requirements of the biology in the product, with device materials selected to complement or coexist with those choices.

The trick is ensuring that you have biocompatibility between the materials, chemicals, biological elements, and the fluids they might come in contact with, says Rob Hodges, biomedical business unit director for STMicroelectronics, a Dallas, TX-based global supplier of microfluidic devices. “In many cases, the things you worry about are easy to handle, and the things you think will be easy take a lot longer than you expected.”

He notes that a big mistake companies make in their first attempt at a combination product is to design the elements independently of each other. “It’s not going to work if you design them separately then bring them together in the end. You need an integrated system from the beginning for the final product to work.”

However, many of the products coming to market now are the result of partnerships between medical device companies and pharmaceutical makers, who each bring a unique set of manufacturing skills and knowledge to the table. The gut reaction in these partnerships is to leave control of the key components of the product in the hands of the experts, who may work in separate labs or organizations. The medical device company designs the delivery mechanism, while the pharmaceutical team develops the drug or diagnostic. But if the two groups work in isolation with intent of combining the two elements later on, they are going to run into trouble, says Hodges.

“There is a lot of interaction between materials that can’t be predicted, especially when you work with biologics,” he points out, adding that engineers in particular don’t expect these kinds of problems because they don’t occur when working with pure electronics.

Hodges learned this lesson the first time he developed a combination product. Working with a diagnostics company, the two teams decided to develop their own sides of the product individually with the goal of bringing them together later on in the project. “We tried to avoid the biology for as long as we could, and we stuck to electronic consumables, because it’s what we knew,” he says of his team. “We later realized that was an impossible approach.”

Hodges learned through that process that many unpredictable problems can arise when you incorporate biologics or drugs into a product, and ST has since added teams of biologists, chemists, physicians, and engineers to its staff who work together in the R&D phase ensure they achieve successful convergence between the technology and the biology.

“Combination products are a nice fit for the semiconductor manufacturing process,” he says, now that ST has the development process figured out. “We are driven by quality. That’s the mindset of semi and it’s the mindset of the medical industry.”

Hodges is currently working on ST’s lab-on-chip combination device, which facilitates the diagnosis of specific diseases or the monitoring of food and water for bacterial contaminants by allowing the rapid detection of particular genetic material in liquid biological samples.

The lab-on-chip product includes a silicon-based MEMS microfluidic chip that is printed with DNA molecules using equipment similar to a very large ink-jet printer. The DNA is arranged in a microarray that requires precision and a contamination-free environment.

Figure 4. Semiconductor manufacturers such as STMicroelectronics are delving into the combination medical device market. The company’s In-Check lab-on-chip platform incorporates silicon-based MEMS microfluidic technology to facilitate the diagnosis of specific diseases or detect bacterial contaminants in liquid biological samples. Photo courtesy of STMicroelectronics.Click here to enlarge image

“The combination of our historical knowledge of microelectronics with other multidisciplinary teams gives us the potential to develop disruptive innovations,” he says. “It’s the kind of innovation we need for the growth of our future.”

Resources and contacts

Foster-Miller, Inc.
Waltham, MA
781-684-4000
www.foster-miller.com

Microtest Labs
Agawam, MA
800-631-1680
www.microtestlabs.com

Navigant Consulting
Chicago, IL
312-573-5600
www.navigantconsulting.com

PharmaMedDevice
Norwalk, CT
www.pharmameddevice.com

PRTM
Waltham, MA
781-434-1200
www.prtm.com

STMicroelectronics
Dallas, TX
512-225-6161
www.st.com

Barrier technology offers clean spaces for pharmaceutical
filling and packaging, as well as protection for operators

By Jack Lysfjord, Lysfjord Consulting LLC

Barrier technology is designed to replace the use of conventional ISO 5 cleanrooms in pharmaceutical filling and packaging (i.e., ampoules, vials, cartridges, and pre-filled syringes). The goal of barrier systems, isolators and restricted barrier access systems (RABS), is to segregate people from the product, ensuring that pharmaceuticals are not exposed to viable organisms or particulate contamination. When dealing with highly potent formulations, these systems can protect operators as well.

Isolators are enclosed, usually positively pressurized units with high efficiency particulate air (HEPA) filters supplying ISO 5 airflow in a unidirectional manner to the interior. Air is typically recirculated by returning it to the air handlers through sealed ductwork. Cleaning can be manual or automated (clean-in-place). Bio-decontamination occurs through an automated cycle typically using vaporized hydrogen peroxide. Access to an isolator is through glove ports and sterile transfer systems. Isolators can be located in an ISO 8 or better environment.

RABS also process in an ISO 5 environment, with varying degrees of contact with the surrounding room, which is generally classified ISO 7 or better. Bio-decontamination is performed manually in a RABS. Although doors can be opened, this is a rare occurrence, after which the system must be appropriately sanitized, a necessary line clearance performed, and the intervention documented.

Figure 1. Active RABS pressure zone. Photo courtesy of Bosch Packaging Technology, Valicare Division.Click here to enlarge image

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Key differences between RABS and isolators

Compared to isolators, RABS can allow for faster start-up and ease of changeover, and, accepting certain restrictions, offer increased operational flexibility and reduced validation and revalidation expenditure. Contract manufacturers tend to gravitate to RABS because of speed of changeover.

RABS air handling units operate in a fashion similar to laminar flow hoods (LFHs) in that they are fed clean air from fan units through HEPA filters and air vents from the unit into the RABS. Air exit is through openings to the room at a low level on the equipment. RABS provide separation by the barrier and by positive airflow. Isolator air handling requirements are more complicated because air is recirculated, necessitating return fans and ductwork. In order to maintain positive pressure, the air handling unit must be leak tight.

Figure 2. Aseptic powder filling in a passive RABS. Photo courtesy of Bosch Packaging Technology, Valicare Division.Click here to enlarge image

There are also differences in cleaning and bio-decontamination for RABS and isolators as mentioned previously. Cleaning must occur first, removing stoppers, broken glass, and spilled product 9the dirt), and then bio-decontamination can occur. RABS are typically cleaned manually, or a CIP system can be used after manual clean-up of commodities. Isolators are bio-decontaminated through an automatic sequence by injecting vaporized hydrogen peroxide (VHP). Validation of the manual cleaning is more challenging than the automated cleaning cycle of a CIP system.

Environmental monitoring is necessary to ensure the integrity of the ISO 5 environment in both systems. Monitoring in isolator systems can only be achieved though built-in sampling ports or sterile transfer of sampling devices. The environmental monitoring requirements of an isolator system are therefore key design considerations. These same methods can be employed in RABS, but there is also the option of using portable sampling devices inserted into the floor-level air exit openings.

Responding to current trends in the pharmaceutical market

There are a number of trends within the pharmaceutical industry that will make RABS and isolators critical components of any successful packaging and processing operation.

Biotechnology is having a big impact and reshaping the processing demands on pharmaceutical firms. Live vaccines, large molecules, and protein-based drugs are increasingly the trend and require highly aseptic conditions. These products are preservative free and are usually a growth medium; therefore, they are easily contaminated.

Toxic, cytotoxic, and otherwise highly potent applications–immunosuppressive cancer drugs are a key example–also demand stringent barrier technology to protect operators.

Broadly speaking, there is a trend toward smaller volume, higher value pharmaceuticals. Manufacturing in high-throughput, mass production systems that produce millions of dosages is declining and the ultimate cost-effectiveness of constructing a large ISO 5 cleanroom facility must be addressed in the long term.

Smaller systems that meet high regulatory standards and can be customized to small product runs are an increasingly attractive option. More compact, adaptable lines allow for flexible configurations and enable manufacturers to respond rapidly to changes in market demand.

Isolators are ideal for smaller facilities that employ flexible,
reduced-footprint systems. Compared to conventional cleanroom
processing, isolators offer pharmaceutical firms significant capital
and operational cost savings. Furthermore, with a smaller isolator system there are minimized gowning costs and reduced labor and maintenance expenses.

Regulatory issues to consider

The critical regulatory concern for barrier systems is so-called “open door” interventions in a RABS. Such interventions introduce undesirable variables into the operation and potentially compromise the aseptic environment and so should be avoided or minimized.

However, when such interventions are unavoidable, appropriate measures must be taken to ensure the aseptic environment is
maintained. Open door interventions inevitably prompt heightened regulatory scrutiny, demanding particularly scrupulous observance of standard operating procedures (SOPs).

Figure 3. FLC vial filling in a passive RABS. Photo courtesy of Bosch Packaging Technology, Valicare Division.Click here to enlarge image

When open door interventions are necessary, an ISO 5 vertical unidirectional airflow system outside of the RABS reduces risk of a breach in ISO 5 conditions and further safeguards the aseptic integrity of the system. Each intervention that requires opening of a door of the RABS is regarded and documented as an intervention. Interlocked RABS doors facilitate control and documentation. Following an open door intervention, appropriate line clearance and disinfection commensurate with the nature of the incident are required.

Challenges in implementing a RABS or isolator

Many companies forget the “systems” aspect of RABS and isolators. For successful implementation of these technologies, operators, maintenance personnel, and engineers must take an expansive, holistic view of their system, ensuring that it is integrated into its surrounding environment and instituting the appropriate maintenance and oversight regimes.

This includes appropriate surrounding building and room design, including HVAC and air handling systems. Proper disposal systems for bio-decontamination waste, both within the building and in relation to the exterior natural environment, are also key considerations. Drainage systems and building HVAC should also be taken into account. Building system utilities can impact isolator pressure control schemes.

Management oversight is indispensable. Proper gowning procedure, adequate training in current good manufacturing practice (cGMP), SOPs for interventions, and documentation protocols must be instituted, rigorously executed, and consistently enforced. Continuous system monitoring is also a must.

A RABS or isolator system should be understood not merely as a discrete piece of a larger manufacturing process but as deeply integrated with every other aspect of an operation. The line itself must be well integrated. Moreover, a holistic view encompassing all of these exterior concerns will ensure the successful implementation of a RABS or isolator system. Integration is easiest through the use of experienced vendors, especially those that can produce many components of the system. More vendors means more customer project management and more tasks to juggle, which can lead to potential project risk.

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Jack Lysfjord is principal consultant for Lysfjord Consulting LLC. He previously served as vice president of consulting for Valicare, a division of Bosch Packaging Technology (www.boschpackaging.com).

NASA planetary protection programs charged with keeping biocontamination out of space.

By Patrick Hogue, Johns Hopkins University, Applied Physics Laboratory

National Aeronautics and Space Administration (NASA) missions to solar system bodies with the potential to sustain life, or that could potentially contain life in a fundamental evolutionary state, have stringent requirements on the maximum spore count permissible on spacecraft surfaces; and these levels are likely to become lower as cleanroom protocols become more efficient. Several promising technologies can help contractors reduce spore counts to acceptable levels, provide for the rapid determination of microorganisms, and determine the genomic inventory of spacecraft microorganisms.

Establishing planetary protection policy

The need for planetary protection, and protection of Earth by sample return missions, was recognized at the dawn of the Space Age through the Committee on Space Research (COSPAR).¹ Article IX of the Outer Space Treaty of 1967 states, in part, “…parties to the Treaty shall pursue studies of outer space including the Moon and other celestial bodies, and conduct exploration of them so as to avoid their harmful contamination and also adverse changes in the environment of the Earth resulting from the introduction of extraterrestrial matter and, where necessary, shall adopt appropriate measures for this purpose.”²

NASA Policy Directive (NPD) 8020.7 establishes NASA policy for implementing planetary protection (PP), which includes protection of planetary bodies for future exploration and of Earth from extraterrestrial sources of contamination. Depending upon the target, implementation may range from obtaining a letter from NASA approving mission design as adequate planetary protection (e.g., New Horizons Pluto fly-by, category II) all the way to full implementation (e.g., Mars sample return, category V). For samples returned from a solar system body with the potential for life (e.g., Europa) mission design must “break the chain of contact”; furthermore, “for un-sterilized samples returned to Earth, a program of life detection and biohazard testing or a proven sterilization process shall be undertaken as an absolute precondition for the controlled distribution of any portion of the sample.”³ Depending upon the nature of samples returned to Earth quarantine up to Biosafety Level (BSL) 4 may be required.

In reaching these decisions, NASA seeks the opinion of scientific advisory groups such as the Space Studies Board of the National Academy of Sciences. NASA Procedural Requirement (NPR) 8020.12 delineates a uniform set of planetary protection requirements for all NASA robotic extraterrestrial missions and references NPR 5340.1, which provides a uniform set of procedures for performing microbial assays for enumerating bioburden levels of spacecraft and facilities used to assemble, test, and launch spacecraft with planetary protection requirements (it is written primarily for use by microbiologists). This year, NPR 5340.1 will re-release as NASA HDBK 6022, which will not set requirements but will list approved protocols. The two Viking Landers, which received dry heat sterilization at 125°C, are considered the gold standard for planetary protection.

Detailed microbial burden requirements

NPR 8020.12 allows alternatives to 125°C dry heat sterilization provided that procedures and quality controls are approved by the NASA Planetary Protection Officer (PPO). These methods are then spelled out in the approved PP plan. Flight hardware drawings may call for these unique microbial reduction methods by citing their specification numbers. Microbial barriers may be used to prevent recontamination of previously sterilized areas; a pressure of at least 1,244 Pa (5 inches H₂O) is considered satisfactory to prevent the entry of microorganisms. High efficiency particulate air (HEPA) filters (99.97 percent efficient for 0.3 µm) are also considered effective microbial barriers. NASA requires that spacecraft assembly occur in a cleanroom meeting ISO class 8 (Fed. Std. 209E Class 100,000) as a minimum.

Click here to enlarge image

For a Mars Lander mission, the maximum spore count is 300,000 for the entire spacecraft (or <300 bacterial spores/m²); all other targets still have a probabalistic requirement. The quantity of 300,000 spores per total spacecraft surface area applies to non-special regions of Mars (most of the surface); the total allowed, including organisms inside hardware (e.g., encapsulated in potting) is 500,000. The Vikings, and spacecraft accessing “special regions” or looking for life, met/must meet 300,000 and then reduce the surface bioburden by 10,000 with dry heat sterilization–meaning no more than 30 viable spores total on the surface. Alternatives to dry heat are discussed later. Based upon Viking experience, NPR 8020.12 assumes spore content as shown in the table. Possible reduction methods are noted and also will be explained in another section.

Assessing microorganism levels

Most aerospace cleanrooms have unknown microbial deposition rates and surface microbial populations and usually do not have a microbiology laboratory readily available. While a proper microbiology laboratory is being created to implement NPR 5340.1, PP programs may choose to get a head start in making their cleanrooms as aseptic as possible. To this end an interim laboratory can be constructed, using a Class 100 (ISO class 5) flow bench with table-top incubator. Initial assays of the cleanrooms (including thermal vacuum chambers, acoustic, and vibration facilities) and associated equipment can be performed using commercially available settling plates (to capture microbial fall-out) and contact plates (to assay cleanroom surfaces) based on Tryptic soy agar (TSA). These procedures are designed primarily for the detection and enumeration of heterotrophic, mesophilic, aerobic, and anaerobic microorganisms; consult NPR 5340.1 for details. Microorganisms likely to survive space and planetary environments are halophiles, certain Bacillus species and extremophiles.

It is recommended that these initial assessment techniques, and others that may be recommended by local microbiology or pharmaceutical laboratory suppliers, be included in the PP plan and that they, along with the full NPR 5340.1 implementation plan, be approved by the NASA PP officer.

During this initial phase of assessing cleanrooms for fall-out and “hot spots,” a portable aerosol particle counter may be used to scan HEPA filter outlets for leaks and any repairs or replacements made before the start-up of PP program work. A rotary centrifugal impactor equipped with TSA strips can be used to validate the biological effectiveness of each HEPA outlet in the overall cleanroom. An alternative would be to place one settling plate for each HEPA outlet at a distance of approximately 1 m; of course, timely retrieval and incubation are essential.

If the trial-and-error methods described previously are not satisfactory for characterizing the cleanroom, then recourse can be made to real-time microbial particle detection technology. Most of these are based upon the fluorescence of energetic metabolic chemicals (e.g., adenosine triphosphate, or ATP, riboflavin) induced by ultraviolet light^4,5, although immunoaffinity-based phosphorescent sensors are being developed for detection of bacterial spores.⁶ Recently individual bacterial cells have been detected using Raman spectroscopy.⁷

Spot-checks of surfaces can be accomplished using commercially available portable systems based on the luciferin-luciferase reaction produced in the common firefly. These methods usually consist of reagent-dampened sterile swabs that lyse (chemically open) living cells and then react with ATP, the energy currency of living cells, to produce a brightly colored species that can be quantitatively measured with a luminometer. This kind of spot-check was recently performed on the Space Station surfaces using a NASA-developed variant called LOCAD-PTS, which is expected to become an approved protocol in NASA HDBK 6022 (see Fig. 1).⁸

Rapid microbial detection using filter-based media with ATP bioluminescence enumeration by a CCD camera equipped with a microchannel plate photomultiplier can reduce assay times from 72 hours to 5 hours or less as demonstrated by NASA/JPL.⁹ A recent addition to this technology is the use of a 16-base RNA probe that can be used to identify specific organisms after the non-specific fluorescence enumeration measurement is accomplished.¹⁰

Implementation of NPR 5340.1

The cost of a fully equipped microbiology laboratory to support a spacecraft program with full PP requirements–a Mars Lander, for example–is estimated to be $50,000 and will require at least two technicians, preferably three, to provide 24/7 coverage.¹¹ The cost associated with PP implementation is estimated to have added 2 months to an 18-month assembly, test, and launch operations program for Mars Polar Lander (MPL) and required 1,200 assays.¹² Viking program PP cost was 10 percent or about $7 million.¹³ A successful PP implementation hinges on the following:

1. Careful and thorough integration of PP into all aspects of the program
2. Management buy-in and support of the PP engineer
3. Universal personnel training (including purchasing and support groups)
4. Pre-planned bio-assay database that parallels the assembly flow
5. Lessons learned from the MPL program:
   • Daily change of cleanroom garments
   • Purchase of 200 new sets
   • Strict enforcement of aseptic techniques–a departure from the usual
   • Sterile, powder-free cleanroom gloves
   • Daily janitorial service (IPA used instead of ammonia for floors and walls)
   • Facility modifications to better isolate anteroom
   • Special cleaning and isolation techniques for vibration, acoustics, and thermal vacuum facilities
   • A standard assembly drawing note: “Perform bio-assay sampling prior to close-out”
   • Launch site processing facilities needed similar steps to maintain spacecraft biocleanliness; assessment of these facilities may occur early in the program
   • A portable clean tent was needed for the launch site
   • It is important to flow PP requirements to subcontractors–anticipate helping them understand and properly implement PP requirements for their hardware elements
   • Integration and test planning staff should strive to have parallel paths so that a delay associated with bio-assay could be accommodated by a shift in tasking
6. MPL lessons learned that were successfully applied to the Phoenix program:
   • Daily management briefing that includes PP lab lead
   • PP assay database must be robust and web-based for easy access
   • Program PP engineer should coordinate with JPL or NASA counterpart
   • Phoenix robotic arm (complex geometry) was sheathed in easily cleaned/verified biobarrier (it tears through this barrier when deployed)
   • Be prepared: NASA’s independent bio-assay testing might require re-cleaning or re-sterilization of spacecraft–could impact launch date

Reducing microorganism levels

Several technologies are available that have the potential to reduce airborne and surface bioburden levels.

Cleanrooms and other facilities used for PP hardware can be sterilized using commercially available fogging systems based on hydrogen peroxide (H₂O₂) or a combination of H₂O₂ and peracetic acid (CH₃COOOH); chlorine dioxide is also very effective. Compatibility of these chemicals with materials of construction should be verified with the supplier prior to use. Spore strips are used to determine the effectiveness of the kill. H₂O₂ fogging of spacecraft followed by immediate vacuum bake-out is one possible method of meeting the 10,000 spore reduction for probes accessing “special” regions or that search for life.

Various sterilization techniques exist for air streams: free radicals with scrubber; glow discharge; non-thermal corona discharge; ultraviolet light to lyse organisms (254 nm) and oxidize residue (185 nm); water impingement to mechanically entrain particles; electrostatic precipitation; biocidal filters; and ozone infusion.

Figure 1. Astronaut Suni Williams, Expedition 14/15 flight engineer, works with the Lab-on-a-Chip Application Development IEST marches on to nanotech beat January 1, 2008 IEST sets goals for new nanotechnology Recommended Practice Working Group activities. By John R. Weaver II, Senior Member, IEST The Institute of Environmental Sciences and Technology (IEST) is taking a leading role in addressing the needs of the important nanotechnology discipline through the formation of relevant Recommended Practices. The IEST Nanotechnologies Standards and Practices (S&P) Committee has defined its scope as follows: “To take the lead in the development of Standards and Recommended Practices and to establish related educational efforts in the field of nanotechnology by building on the established experience and expertise of IEST’s membership. In addition, the Nanotechnologies S&P Committee will strive to enhance IEST’s participation in this field by seeking out experts outside of the IEST from business, academia and government.” Working Group 200 (WG-CC200) is developing an overview document, “Nanotechnologies Overview: Planning, Design, Construction, and Operational Considerations for Facilities Engaged in Research or Production at the Nanometer Scale.” This work is well underway and should be completed and ready for publication in 2008 as a Recommended Practice/Guideline. In addition, Working Group 205 (WG-CC205), “Nanotechnology Safety: Applying Prevention through Design Principles to Nanotechnology Facilities” has recently been formed and held its inaugural meeting on November 14 at the IEST Fall Conference in Chicago, with a subsequent meeting planned for ESTECH 2008. The National Institute of Occupational Safety and Health (NIOSH), through the Centers for Disease Control and Prevention, has indicated its interest in participating in this Working Group’s activities through a Memo of Understanding (MOU). End users, vendors, and governmental and public participants are encouraged to attend the nanotechnology working group meetings. ESTECH 2008, the 54th annual technical meeting and exposition of IEST, will be held May 4 Cleanroom Garments January 1, 2008 Compiled by Carrie Meadows Since human-generated contamination plays a large role in critical environments, special care must be taken to provide appropriate garments to minimize the human impact on the cleanroom. Other important factors include specialty fabrics to safeguard technicians, as well as proper laundering and care of reusable attire. Chemical-resistant gloves with new grip technology Click here to enlarge image Ansell offers AlphaTECTM gloves, the first chemical-resistant gloves to incorporate Ansell Grip TechnologyTM. Designed as a liquid-proof product requiring less force to grip oily or wet objects, the gloves integrate microscopic channels in a patented ultra-thin nitrile layer to direct fluids away from the grip surface, leaving a significant dry contact area that provides almost the same grip that is possible under fluid-free conditions. This improved adherence promotes greater worker comfort while minimizing stress and fatigue. The production process ensures an exceptionally safe chemical barrier. The gloves’ polymer coating does not penetrate into the liner during the manufacturing process, which results in consistent protection for the skin. The nitrile coating is also designed for greater flexibility. For more information about new AlphaTEC gloves or any of Ansell’s line of protective gloves and apparel, visit the web site or contact Customer Service at 800-800-0444. Ansell Red Bank, NJ www.ansellpro.com Cleanroom garment tracking service CleanTrakTM is ARAMARK’s proprietary web-based garment management system, which provides high information availability and timeliness. CleanTrakTM provides customers with an easy-to-use web interface that allows them to manage their garment program online. The information is actual data taken directly from ARAMARK’s i barcode system, Garment Tracking System (GTS). CleanTrakTM is easy to use with almost no instruction. The web-based system allows the customer to see garments that are assigned to their inventory by item code or barcode; weekly in and out counts by line item; individual barcode history; a customer report that provides a five-week summary that can be downloaded into an Excel file or viewed onscreen; and receiver review. To learn more, call 800-759-0102 or visit the web site. Click here to enlarge image ARAMARK Cleanroom Services Burr Ridge, IL www.ARAMARK-Cleanroom.com Custom garment and consumables programs available Ameripride and Canadian Uniform Services announce their CleanStyle Cleanroom Division. CleanStyle represents fine reusable and consumable cleanroom services and products. With multiple certified ISO 4/Class 10 cleanroom laundry facilities in the United States and Canada, and service locations throughout North America, the company provides comprehensive service solutions. The CleanStyle Superior Apparel Management System (SAM) using state-of-the-art RFID tracking for reliability is exclusive to Ameripride and Canadian Uniform Services and provides an immediate data history, enabling the company to track the life of all reusable garments. Cleanroom technical support and vast experience allows CleanStyle to assist with customers’ growth and provide new solutions and flexibility as needs change. On-site inventory management programs ensure excellent product availability and accountability while saving both time and money; and CleanStyle’s large product inventory of cleanroom reusable and consumable products makes it an ideal single source provider for cleanroom requirements. For more information, contact a cleanroom specialist at 416-849-5100 or toll free at 866-539-7575. Click here to enlarge image CleanStyle Cleanroom Division Vancouver, BC, Canada Garments provided with recommended clothing standards Click here to enlarge image Connecticut Clean Room Corporation provides quality cleanroom garments for many different industries including cleanroom, critical manufacturing, industrial, and any environment that requires sanitary standards. Choose from lab coats, coveralls, frocks, aprons, isolation gowns, bouffants, hoods, face masks, and covers. The company carries TyvekTM, DuPont SuprelTM, KleenGuard*, Vidaro, Worklon, polypropylene, and SMS, and offers both disposable and reusable garments depending on your needs. The Customer Care Team provides information on Recommended Cleanroom Clothing Standards and will help you to select the right garment for your specific application. Modifications may be required according to individual processes and other factors affecting garment usage and frequency of change. All garments meet or exceed the stringent requirements needed in a critical environment ranging from Class 100,000 to Class 1. Connecticut Clean Room Corporation Bristol, CT www.ctcleanroom.com Extensive in-house quality testing on garment offerings Click here to enlarge image Established in 1979, Dastex Reinraumzubeh New Products January 1, 2008 High-purity foams for insulation and construction applications Kynar® PVDF-based closed cell foam is the first polymeric foam to meet the requirements for Factory Mutual (FM) 4910 test protocols for cleanroom materials flammability. The flame propagation and smoke generation values obtained for the foams were well below the requirements imposed by the FM protocols. The high-purity foams are easily cut without creating dusts or particles and have very low thermal conductivity and a wide operating temperature range. The foams also resist mold and fungi, as well as most solvents, chemicals, and typical sterilization methods. In addition to cleanroom pipe and duct insulation, Kynar® foams can also be used to construct lightweight, sound dampening structures and partitions, seals and gaskets, and chemical wet benches. They are suitable for use in pharmaceutical, biological, nuclear, semiconductor, or chemical industries, and can be used in processing food, dairy and cosmetics. Arkema, Inc. Philadelphia, PA www.arkema-inc.com Dusting system and microfiber wipers Click here to enlarge image Kimberly-Clark Professional has introduced a new line of KIMTECH SCIENCE* brand products for laboratory maintenance: the KIMTECH SCIENCE* dusting system, lens-cleaning microfiber wipers, and large microfiber wipers. The products are designed to pick up more dust in more places, meeting the cleaning needs of laboratories and other controlled environments. The dusting system features a duster head, with 380,000 soft, flexible, dust-trapping polyester fibers that change shape for dust pick-up in crevices and contours where dust cloths can’t reach. The environmentally friendly system dusts without the need for chemicals and leaves no residues. Large, disposable microfiber wipers have excellent wet and dry strength and excellent water and oil absorbency (absorbing 4.5 times their weight). The lens-cleaning microfiber wipers are designed for high-end optical lens cleaning. Both types of wipers are extremely low-linting and clean without streaking, smearing, or scratching delicate surfaces. Click here to enlarge image Kimberly-Clark Professional Roswell, GA www.kcprofessional.com Nitrile, powder-free exam glove Click here to enlarge image Sempermed, a leading manufacturer of hand protection, now offers the SemperCare Tender TouchTM nitrile powder-free exam glove, as an alternative to natural rubber latex. The product delivers fit, feel, tactile sensitivity, strength, and value in a latex-free glove. The company designed the glove to improve comfort to help customers reinforce hand hygiene, compliance, and safety at their facilities. SemperCare Tender TouchTM is 4.0 mils in the textured fingertips. A standard-sized box holds 200 gloves. Sempermed Clearwater, FL www.SempermedUSA.com Custom-colored hose allows quick identification of process lines Click here to enlarge image AdvantaPure’s APSM reinforced silicone hose is now offered in custom colors for easy line recognition. APSM is used for applications involving elevated pressure levels in pharmaceutical, bioprocess, biomedical, food, beverage, chemical, cosmetic, and pure fluid transfer. The hose is constructed of a core of low volatile, platinum-cured silicone for purity. APSM is durable and heavy-duty yet flexible for pressure-rated discharge applications. It may be sterilized by autoclave, CIP, SIP, and gamma radiation processes. The material has undergone extensive testing and meets USP Class VI, FDA, ISO, European Pharmacopoeia, and 3-A standards. In addition to custom colors, AdvantaPure offers a wire-reinforced version of the same hose, called APSW. AdvantaPure Southampton, PA www.advantapure.com Wet-vacuum sample collection system Click here to enlarge image Microbial-Vac Systems®, Inc., an innovator in pathogen surface sampling, has released a new tool for pathogen collection. The Microbial-Vac (M-VacTM) wet-vacuum collection system utilizes LAMDACTM principles (Liquid and Air-assisted Microbial Detachment and Capture) to collect laboratory or field samples–typically from 1 to 2 sq. ft. of surface area per sample in 100 Planning and installing an environmental monitoring system January 1, 2008 The latest regulations call for a shift in particle monitoring strategies. By Mark Hallworth and Edward Applen, Particle Measuring Systems For aseptic manufacture of pharmaceutical products there has been a shift, primarily due to legislative regulations.1 Traditionally, monitoring has involved the classic portable monitoring of a cleanroom. New regulations have led to a requirement for an automated, remote monitoring solution. Various steps must be undertaken to implement an automated monitoring solution for a non-viable particle counting system. The steps also apply if you later enhance the non-viable system to include a viable monitoring or other environmental parameter component. There are several steps to be followed for the implementation of a system and the Good Automated Manufacturing Practices (GAMP2) guidance for the validation of these systems certainly forms the core of the requirements. A typical project follows the format design, build, install, test, and validate. Each of these has its own timeline. Building the timeline The key to a successful project is to ensure that all phases of the implementation are executed in a timely manner. The identification of each of the major steps can be presented as a GANT chart, which will also identify when obstacles, such as shut downs, need to be accommodated. Figure 1 shows a typical timeline GANT chart for a complete project. Figure 1. Project plan outline as a GANT chart. Image courtesy of Particle Measuring Systems.Click here to enlarge image Each of these summary tasks can be broken down into individual tasks so that resources–both material and labor–are available. This becomes more critical when multiple components of a project are encroaching on each other. This often occurs during installation when different trades are vying for the same space and during validation when deadlines are tight. System design There are several documents3,4 that identify how best to design a particle monitoring system. Considerations include selection of sample points, which hardware to use for each application, and the relationship between risk vs. instrumentation. Figure 2 shows a typical system designed to monitor the environmental conditions within a cleanroom. The driving factors in designing a cleanroom monitoring system should be defined in the User Requirement Specification (URS), the contents and format of which is fully described in the GAMP guidance documentation. Any changes required to a system that make it user-friendly should be incorporated as early in the project as possible to avoid costly changes to project scope later. When the speed required to implement a system does not allow sufficient time for the generation of a “perfect” URS, it can be subcontracted to a design company for preparation. It is important to ensure the end users or system owners review the document because the liability of using a system lies with them. System installation As can be seen from Fig. 2, there are many components to the installation of a monitoring system. Click here to enlarge image Wiring. The infrastructure of wiring includes power cables (24 VDC, 120 Experts cite missed opportunity in NIH risk assessment of BSL-4 lab January 1, 2008 By George Miller A National Research Council (NRC) committee of experts provided a boost to neighbors opposing construction of a biocontainment research lab at the Boston University Medical Center by declaring in late November that a draft environmental impact report concerning the facility is “not sound and credible.” The declaration compounds the complexity of a labyrinthine approval process whose players span neighborhood activists to officials at the city, state, and federal levels, all resulting from Project Bioshield legislation enacted following the 9/11 and anthrax letter attacks of 2001. The NRC experts viewed the report as an opportunity to quell fears about the safety of biocontainment facilities. The National Institutes of Health (NIH) is now implementing a construction program that will complete four new BSL-4 facilities–including the $200 million BU lab, now 70 percent complete–as well as 14 BSL-3 facilities within the next few years [see “Lab Biosafety Hearings Conjure Cold War Fears,” CleanRooms, December 2007, p.7. Differences in biosafety level protocols are shown in the accompanying table]. Neighbors who oppose the facility question BU’s ability to protect their Boston neighborhood while running a BSL-4 facility, given the institution’s track record: At an existing BSL-2 lab in 2004, for example, researchers violated safety procedures and became infected with tularemia; at an advanced biomedical research building in early 2007, a medical waste fire led to the building’s evacuation. Click here to enlarge image Chief among the NRC expert committee’s concerns is the lack of inclusion of highly infectious agents in the NIH draft assessment, and the subsequent lack of a credible worst-case scenario. “A more acceptable analysis would have included agents that are readily transmissible and would have demonstrated that the modeling approach used recognizes biological complexities, reflecting what is known about disease outbreaks and being appropriately sensitive to population density,” according to an NRC statement. The BU Medical Center BSL-4 biocontainment lab facility, now about 70 percent complete, is part of the Biosquare II project on Albany Street in Boston. Image courtesy of Boston University Medical Center.Click here to enlarge image In addition, the draft assessment contains too little information to compare the risks associated with alternative BU campus locations in suburban (Tyngsborough, MA) and rural (Peterborough, NH) settings for the laboratory. Considering pathogens that spread more easily would improve analyses of how risks vary depending on location, the committee said. It was also dissatisfied with the draft assessment’s consideration of environmental justice issues and how the biocontainment facility could affect the inner-city population in particular. Missed opportunity Expert committee member Gary Smith, chief for epidemiology and public health at the University of Pennsylvania School of Veterinary Medicine, said that, given the type of model that NIH researchers used in preparing the draft statement, “this seems to have been a missed opportunity, especially when the three locations were considered.” The NIH draft could have presented a more refined analysis of the risks presented by a facility like BU’s, he said, and evaluated comprehensively the impact of a worst-case scenario event on public health and safety. Doing so might have provided greater assurances for the neighbors and might also have been viewed as relevant to assessments for other biocontainment facilities. The experts question whether the NIH fully exploited the agent-based model used in the analysis. The committee writes that such models are “particularly good at revealing the influence of heterogeneities in the host population.” Relevant examples, with respect to comparing the three locations, include host characteristics that may affect susceptibility and case fatality rates. “But there was no reference to expected or plausible differences on transmission probability for those at special risk (the very young, the very old, those with preexisting conditions, and those with compromised immune systems),” according to the report. In addition, NIH appears to have made the assumption in its model that each person has 10 contacts per day, regardless of the population density of the location. “This assumption about the number of contacts further reduces the opportunity for transmission and effectively eliminates one of the most important differences between locations,” the report said. Environmental justice concerns NRC expert committee member Gigi Kwik Gronvall, assistant professor of medicine and senior associate at the University of Pittsburgh Medical Center’s Biosecurity Center in Baltimore, added during the NRC press conference that the draft NIH document also took into account neither the health status of the population, nor the Boston neighborhood’s status as a U.S. Environmental Protection Agency environmental justice community. “We didn’t see accommodations for public health access in the report,” she said. “We don’t know if it makes a difference. We just want to know that it was addressed.” The neighborhood is acknowledged to have among the highest rates of HIV infections in Boston, as well as a high rate of intravenous drug use and correspondingly high incidence of hepatitis C. “One of several things that affects how diseased one becomes during an outbreak is health status [of residents],” said expert committee member Smith. That status varies with age distribution, pregnancy rate, and proportion of immunocompromised individuals, among other factors. The experts make clear in both their report and cover letter that their conclusions concern only the “scientific adequacy” of the NIH draft supplementary risk analysis, and not the previously submitted, original risk assessment and site suitability analysis document submitted by NIH as a standard part of the NEPA process. “It is important to recognize,” the experts write, “that these conclusions are based solely on the committee’s technical review of the [NIH draft], and thus they should not be viewed as statements about the risks of proposed biocontainment facilities in Boston, or in cities more generally. The Committee acknowledges the need for biocontainment laboratories in the United States, including BSL-4 laboratories, and recognizes that BSL-4 facilities are being operated in other major urban areas.” The NIH, while acknowledging via e-mail correspondence that “the NRC has raised important concerns,” makes no apologies for the document it drafted: “NIH followed the NEPA procedures in preparing a final environmental impact statement and in issuing a record of decision” on the BU lab, according to a statement issued after the NRC report was released in late November. NIH said it will continue to follow the standard NEPA process and will consider and respond to all comments received, including those of the NRC experts. For its part, the Boston University Medical Center said in a statement, “We recognize that the NRC report states concerns regarding the NIH methodology and analysis and are confident that the NIH will address those issues in its final report. In the meantime, we stand ready to provide whatever information we can in order to respond to questions and concerns, and to document that the South End site is as safe as or safer than alternative locations.” Particles compiled by Carrie Meadows Gerbig Engineering introduces new cleanroom construction feature Minnesota-based Gerbig Engineering, a specialist in the design, build, installation, and certification of cleanrooms, now offers a raceway that is integrated into the framing system of its cleanroom constructions. The raceway allows wiring, cabling, and plumbing to be threaded throughout the cleanroom and remain totally hidden. The system will work for both hardwall and softwall systems, and for portable or stationary cleanrooms. Existing AireCell Cleanrooms can be retrofitted with this raceway system. New England Peptide opens instrumentation lab New England Peptide, LLC (NEP), a company that designs and produces custom peptides and polyclonal antibodies for drug and vaccine discovery organizations, has opened a new production instrumentation laboratory at its Massachusetts facility. NEP’s engineering staff will use the dedicated lab to develop new instrumentation, qualify newly acquired production equipment, and efficiently bring instrumentation offline for maintenance. David Savage lands at Ultra Clean Ultra Clean Technology, a developer and supplier of critical subsystems for the semiconductor capital equipment industry, announced the appointment of David Savage as president and CEO, effective Jan. 8. Leonard Mezhvinsky retired from the position of president as of Dec. 31. Savage brings to Ultra Clean more than 20 years of executive experience. Before joining UCT, Savage was CEO of Litel Instruments, Inc., a semiconductor optical metrology business. He has also served as president of the Electronics Division of Meggitt USA, Inc., and as CEO at DigMedia, a media delivery business focused on broadband service providers.