Saturday, November 5, 2016

Barrier Isolators and Microenvironments for Cleanroom Applications

Source: Absolute Control Systems
This presentation provides relevant information regarding the advantages of using Barrier Isolators and Microenvironments in cleanrooms, primarily in semiconductor and pharmaceutical applications. This narrative is a discussion regarding the need for the technology, followed by general equipment features common to both pharmaceutical and semiconductor industries. The Cleanrooms East presentation includes numerous viewgraphs covering this topic followed by examples of enclosure systems which were successfully integrated into clean manufacturing facilities.
First, a few unofficial definitions of terms used throughout this presentation. The term Process refers to the activity that must be performed. The equipment being discussed here is used to contain or isolate the process and process equipment for the purpose of protecting the process from the environment, protecting the environment from the process, or both.
A Barrier system is an engineered device which provides a simple, single method of separating a process from the surrounding environment. No environmental parameters are typically controlled; the operator can see the process, but can not touch it without defeating the device. Interlocks may be provided to prevent or stop a process within the barrier if a perimeter door is opened. The simple barrier assures that nothing impedes the flow of air from the cleanroom ceiling downward to the process.
A microenvironment is an engineered enclosure system used to maintain low-particulate environment around a semiconductor production-related process. Temperature, overpressure, relative humidity, air flow and make up air may be controlled. Interfaces are carefully designed to maintain the conditions inside the enclosure. The process may represent a hazard to operator and facility.
A Barrier Isolator is an engineered enclosure system used to maintain an aseptic / sterile, low- particulate environment around a pharmaceutical production-related process. Temperature, overpressure, relative humidity, air flow, and make up air balance may be manipulated to enhance aseptic conditioning efforts. Interfaces (a b or rtp) are carefully designed to maintain the conditions inside the enclosure.
A Containment Isolator is used to contain Potent, Hazardous, or Toxic (PHT) chemical compounds or liquids. Complexity of these systems varies depending on the level of hazard that must be contained. The enclosure is maintained at a negative pressure with respect to the surrounding room, in an effort to keep PHT compounds within the isolator system should a leak occur. In pharmaceutical production, powders, liquids, and slurries are routinely transferred from one container or vessel to another. Containment isolators have found utility as secondary containment between two vessels during make- break operations. Many finished pharmaceutical products retain the PHT properties after sterilization, and must remain pure for human consumption. Once sterile, the handling and packaging of these materials becomes a complex problem due to the requirement for isolation (aseptic / sterile) and containment (PHT) simultaneously.
Why consider barrier isolation technology in the cleanroom? The answer is that this technology is required to achieve full potential of modern process tools. Historically, hoods or clean benches have been used to provide localized "special" conditions within a clean manufacturing facility. Because hoods and clean benches work on the principal of dilution and filtration (respectively) combined with directional air flow, a large volume of air must be moved, which translates to energy cost. They are "single ended" devices, meaning they pull or push air, but not both. They require the facility to provide particle collection or make up air. The facility must be properly designed for the correct rate of air changes and volume of make up air, and system balance may be subject to transient upset due to movement of people, equipment, and product through the ballroom.
Small scale cleanroom
Raised floor cleanrooms use the principal of flowing (purging) filtered air over the process (and people), and collecting the return air, which helps remove particles from the suite. A properly designed enclosure system accomplishes the same thing, on a smaller scale. More air changes may be accomplished for a given energy cost by reducing the size of the zone of concern.
Cleanable Zone of Concern
Eventually, any open system collects debris. Sources include people, garments, process materials, process tools, and debris from system upsets. A closed system has the potential for higher levels of isolation and contamination control by removing non-essentials from the zone of concern and reducing that zone to the smallest area possible. Properly designed, a closed system can be cleaned better, and kept clean longer.
Plan ahead
Murphy's Law teaches that if anything can go wrong, it will, and at the worst possible time. A transient process upset, spill, or accident may spread contamination in the facility. My experience has been that for many clients who are currently using this technology, there is an first generation system which now resides in the "bone yard", because it can no longer be used. The overwhelming reason for this has been cross contamination and/or redeposition issues; the equipment became inadvertently contaminated by well intentioned individuals and circumstances. Proper design and forethought is of paramount importance. The closed system affords superior operator protection over open systems where significant hazard to the operator exists when properly designed.
Operator Protection
The topic of protection brings up two important points. If there is a hazard to the operator, simply removing the operator may solve the biggest part of the problem. Consider also that people can be hazardous to many processes, and removing them is again desirable. A common way to accomplish both is to contain the operator in a gown or air suit, and some operations cannot be performed without operator containment. The reason is usually that the equipment which is integral to the process is not designed for isolation. In most cases, the cost of gowning and airsuits is a major cost of operation, and they increase operator discomfort. It is desirable then to reduce the level of gowning from both a cost and operator comfort standpoint. Barrier isolation technology affords the opportunity to completely remove the operator from the zone of concern.
People are Dirty
Because people cannot be sterilized, and don't stay really clean for long, they carry undesirable particulate and biological contamination in and out of the clean area. The isolation system, on the other hand, can withstand vigorous wash down, sanitizing, or other operations due to the hard materials of construction. Unique atmospheres may be introduced in high concentrations, and then removed to extremely low residual levels. Temperatures, pressures, humidity levels that humans and pathogens cannot withstand may be manipulated within the enclosure. The materials of construction and methods of finishing result in a non shedding, non porous, non reactive wetted surfaces in the zone of concern.
Superior Environment Control
Precise control over environmental parameters is achievable within an enclosed system, such as precision temperature control. One example for the need for precise temperature control is precision metrology, where the Absolute Control Systems temperature is of less importance, but the established temperature must be rigidly maintained (+/- 0.1 degree, for example) regardless of external influences. Other environmental parameters may be controlled and manipulated. Class 1 particulate levels are routinely achieved using ULPA grade filters. Low oxygen or moisture atmospheres measuring less than 1 part per million (<1 a="" allow="" anaerobic="" are="" atmospheres="" by="" compartments="" different="" exist="" for="" handling="" hygroscopic="" if="" materials.="" multiple="" of="" on="" or="" ppm="" produced="" pyrophoric="" range="" reactive="" required="" scale="" sections="" small="" system="" the="" to="" with="">
What to Expect
Without providing a detailed cost analysis, your can reason that by reducing the zone of concern to the smallest reasonable area, you should anticipate an overall reduction in operating costs, right? Well, maybe. Most production equipment is not yet designed for isolation, and such equipment is not an "off the shelf" procurement. Plan on becoming a "quasi-expert" on this technology to implement it to its fullest potential. Clearly, an enclosed system must be a fully engineered system to properly address all aspects of the critical service which is required of it.
Increased product yield and quality is the ultimate goal of most manufacturers. Increased yield pays the bills. The use of this technology is a capital expenditure, so there is a cost-benefit argument. Other studies have shown that initial costs are higher per installation than conventional ball room suites, but the cost of operation is somewhat lower. It is clear that this technology is not driven by a need to reduce costs, rather by the need for increased performance.
There are other benefits. Installing a great looking piece of equipment, that enhances the capabilities of your facility, can potentially bring additional work or recognition to your site and yourself. A properly designed environmental enclosure or workstation will be smoothly integrated into the facility.
Competition and Regulation
Eventually your competition will implement this technology, and you'll have to react to keep up. After all, competition drives the marketplace and regulation constantly raises the bar.
Current FDA regulations required extensive documentation, testing and validation activities take place prior to use of pharmaceutical production equipment. The approval is site specific, so if the process is moved to another location, the validation and certification activities must be performed again. The future holds the possibility that fully enclosed and integrated systems may eventually be approved for use prior to being shipped to a remote site.
Safety is Important
As concern for personal injury litigation is at an all time high, there a responsibility to provide "best available" technology with regard to worker safety. Regardless of whether the hazard is an airborne powder in a pharmaceutical facility or a class 4 invisible laser used in a wafer fab, the fact is that worker safety concerns exist shoulder to shoulder with production concerns in many cleanroom applications.
Do I need One? 
The use of Absolute isolation or containment is based on need. To determine when to employ this technology, I offer a simple rating system. If you apply a one to five scale, with five being the most acute hazard or sensitive process, then these systems are intended for the highest level of concern, ratings four and five. Level One concerns are handled in open areas with operators wearing the minimal level of personal protection, perhaps with a simple barrier method. Level Two and Three concerns typically are handled in controlled areas with operators wearing the appropriate level of personal garb, and utilizing clean benches, hoods and biosafety cabinets to maintain the facility.
Product properties that may indicate the need for isolation / containment.
  • Flammability
  • Nuisance dust
  • Explosive dust hazard
  • Corrosive properties
  • Irritants
  • Allergens
  • Sensitizing agents
  • Toxins
  • Carcinogens
  • Mutagens
  • Biohazards
  • Low bioburden
  • Germ free
  • Live virus
  • Visual hazard - laser
  • Physical hazard - moving components
  • Volatile Organic Compounds (VOC) - Emissive agents
  • Sterilants
  • Extreme Absolute environment - vacuum, pressure, temperature, moisture
  • ULPA class environment
  • Anaerobic
  • Unique inert gas backgrounds
  • Cross contamination between products
  • Precision cleaning - microcontamination
In summary, Absolute Control Systems containment and isolation is a maturing technology that offers advantages to operators of clean manufacturing facilities. A properly designed and constructed process isolation system offers the potential for tighter control of multiple environmental parameters surrounding a sensitive process than can be achieved in an open cleanroom.
Like any emerging technology, there is no one set of standards. The project professional who elects to utilize this technology in his or her facility must be aware of the potential pitfalls as well as the merits. Bring in experts early in the development process. Develop a detailed performance-based specification and review it with your operations and maintenance personnel. Select a competent design / build vendor with a proven track record. Thorough planning in the early stages will assure success. Good luck in your project.

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