First developed in the 1940s to contain radioactive materials and protect operators conducting research with hazardous materials, glovebox isolator technology has become a staple in many laboratory environments. Glovebox isolators consist of a sealed container designed to allow users to manipulate objects where a separate atmosphere is desired. Manipulation is typically performed through half suits or glove ports. While the technology stems from work in the nuclear industry, it has now found a home in pharmaceuticals, electronics, food processing, and more.
Despite increased adoption, many users still have questions about glovebox isolators, namely: what overall benefits does this technology offer over a traditional cleanroom? What attributes should they assess when purchasing this technology? And what glovebox or isolator technology is a “glove fit” for their facility or given application?
Benefits of glovebox isolator technology
Glovebox isolator technology offers greater overall operator safety when handling potent compounds, as well as greater sterility assurance during aseptic processing or testing than traditional cleanrooms. However, one of the greatest benefits of the technology can be seen from a cost perspective.
Controlled atmosphere gloveboxes maintain oxygen levels as low as 0.2 ppm and moisture levels as low as 1 ppm. Image: Labconco
Although the purchase of an isolator system is a large capital expense, this is balanced by operational costs that are significantly lower than traditional cleanrooms. Some areas where isolator technology can save money versus cleanroom technology, according to Gary Partington, manager of sales for Walker Barrier Systems, New Lisbon, Wis., include a smaller HVAC system which saves in utility costs and less filtration which saves in filter change costs. The technology can also help laboratories save on labor cost and investigation costs, with the elimination of false positive results.
A look at ergonomics
Ergonomics is a focal point for those looking to purchase isolator technology, as worker safety and comfort are important considerations. One key attribute to look for is a high level of protection for the operator that does not affect his or her ability to perform complex analytical procedures and compromise results or production procedures, says Thomas Peterson, president of Enviroflo, San Jose, Calif. Of upmost importance is the training of operators to use the instrumentation correctly. Users must be able to clean both the surfaces and interior of the technology in a laboratory setting, perform their given processes, and reach integrated equipment and materials inside.
There are a variety of solutions available for proper ergonomics of the technology, which Partington states, include gloves, half-suits, height adjusting stands, 3D modeling, and mock ups. Walker Barrier Systems offers 3D modeling in the design phase of the technology which eliminates interference with integrated equipment. They also offer mock ups which allow operators “to simulate the process and test reach, range of motion, etc. before the final isolator is made,” says Partington.
As systems evolved over years, vendors, such as NuAire, Plymouth, Minn., see more ergonomic designs; specifically designs with counterbalance interchange windows.
Proper cleaning and safe filter changes
While ergonomics is an important factor, how easily a system can be cleaned and maintained by its operators ranks high as well. All isolators, enclosures, or gloveboxes must be cleaned properly; and the highest risk of exposure to toxic compounds, according to Petersen, is during the changing of gloves or filters.
The filter stores the highest level of contaminated product and the safe-change must be quick and simple. “This can be achieved by a bag in/bag out mechanism or by a direct filter/duct change where the contaminated filter is not exposed to the operator,” says Petersen. The gloves must have a push-through mechanism that doesn’t expose the operator.
A sterility test isolator with an airlock provides an alternative to a “multi-isolator” approach. Image: Walker Barrier Systems
However, for easy cleaning to meet CIP validations, product changes, or instrument upgrades, every surface, joint, seal, and panel of an isolator or glovebox must be reachable. It is necessary to have a waste chute option to safely dispose of contaminants. “It is also advantageous if incoming and outgoing samples are isolated and easily cleaned before being handled,” says Petersen.
According to Petersen, the biggest advance in isolator technology has been in the containment levels reached during all aspects of isolator control. This includes filter-safe changing, safe-glove changing, and operator performance, which gives the operator with proper training full control for the lifetime of the instrument. New filter change mechanisms can now be achieved in five minutes, with no exposure to the filter; these filters can be easily changed by the operator with no requirement for an engineer, keeping costs down.
With the proper training, operators can change filters safely and easily, significantly reducing the total cost of ownership of the instrument with more modern ergonomic designs to improve stability.
Consider the materials
Improvements over the past five years to air handling systems, along with limiting absorptive materials in the construction of isolators, according to Partington, have improved decontamination cycle times—especially important in filling machine and sterility test isolators.
Isolators are typically engineered from 316L stainless steel for the enclosure with laminated safety glass for viewing windows. Although the equipment is heavy and sometimes time-consuming to install, stainless steel isolators are more resistant to cleaning agents, solvents, and decontamination agents than other materials, says Partington. This translates to faster decontamination cycles—and stainless steel lends itself to unidirectional airflow.
Isolators can also be engineered from more flexible materials such as PVC and other plastic films. And while lighter in weight with good visibility, decontaminant agents can be absorbed into plastics resulting in long decontamination cycles. However, cleaning cycle time isn’t the main consideration when purchasing an isolator made with these materials. Bob Applequist, product manager of gloveboxes for Labconco Corp., Kansas City, Mo., says many glovebox and/or isolator customers are asking for simpler, less costly solutions for their containment needs. He states that in some cases gloveboxes constructed with polyethylene versus hand-welded stainless steel system have been found to meet application requirements in certain industries, such as the pharmaceutical industry, effectively.
Choosing the proper filtration
Purchasing a glovebox or isolator system is most often application specific. A well thought-out and thorough examination of application requirements is required before a selection should be made. “It is also economically advisable to review future or alternative application requirements which can spread the cost and enhance the return on investment for what can be an expensive capital equipment purchase,” says Applequist.
An applications approach to purchasing decisions raises other questions, mainly about filtration. Isolators provide a specific environment inside the isolator using either HEPA or ULPA filters for particulate control. The environment inside the isolator technology can be positive pressure or negative, can have humidity control, oxygen control, use of unidirectional airflow, or protect the operator from the product as with potent product handling. So the question becomes, which of these options serves the laboratory’s applications best?
The first consideration is to determine if particulate filtration is needed for both inlet and exhaust air streams. For many laboratory applications, the materials inside the isolator need protection from common environmental particulates. In that case, inlet filtration is required. If those materials generate hazardous particulates, then exhaust airflow must also be filtered.
Aseptic isolators create a positive pressure environment for compounding of non-hazardous drugs. Image: NuAire
If exhaust airflows must be filtered, the next choice is to decide between a HEPA or ULPA filter. “Many applications require supplying sterile air to protect the materials inside the isolator technology or glovebox,” says Applequist. While both HEPA and ULPA filters provide ISO 5 sterile air, ULPA filters provide a better capture profile when nanoparticulates pose a concern. One must also consider if the exhaust air needs to be vented outside. “Particulate filters do not trap these contaminants. If the exhausted glovebox air contains harmful fumes or gases, the answer will be yes, exhausting to the outside will be required,” Applequist notes.
Next one must analyze if the internal glovebox or isolator pressure should be positive, negative, or adjustable. Most hazardous particulates inside of a glovebox or isolator should be kept under negative pressure. “However, maintaining the cleanest internal environment inside of a glovebox or isolator may require a positive pressure operation,” says Applequist. If the material inside needs to be kept clean but is also hazardous, then a review of the leak tightness of the glovebox system is necessary. Applequist commented on this by noting that, “Many gloveboxes are extremely leak tight, and safety concerns regarding positive/negative pressure operations become a non-issue.”
A final consideration would be to determine if the filtered airflow maintains an internal sterile air condition. An important note is that volume sterility is not the same as surface sterility. While simply diluting the internal air volume with sterile air can ultimately produce a sterile air volume, this does not mean the internal surfaces of the glovebox or materials inside are sterile. “In order to maintain a total sterile environment condition, the airflow within the glovebox should be laminar,” says Applequist. The glovebox must also be connected to a vaporous hydrogen peroxide (VHP) system, which when used correctly can sterilize the materials inside the glovebox before operations begin. However, this brings along with it a determination about open versus closed sterile isolators and rapid transfer ports.
While there will always be a push for improvements to reliability, safety, ergonomics, and power consumption in isolator technology, control systems and cycle times have also evolved within the last five years.
“PLC use allows for direct communication with interface equipment and allows the control of such parameters inside an isolator like RH, oxygen levels, inert gases, and pressure,” says Partington.
Down the road for this technology the vendors see newer and cheaper isolators that can be converted from openface to gloved and recirculating, depending on the application. “These systems can be modified for temperature and humidity control for a fraction of the cost of a full stainless steel system,” says Petersen.
Lindsay Hock is the Managing Editor of R&D Magazine.
This article appeared in the March 2013 issue of Controlled Environments.