By Michael Kopp
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Cleanrooms are not a one-size-fits-all proposition. If a room is under-designed, then expensive and time-consuming fixes may be required. And there is always the risk of distorted research data, economic losses and even catastrophic consequences due to compromised laboratory experiments, or from manufacturing contaminated products.
If over-designed, however, a cleanroom may be inefficient, overly complex and costly. This result could be needlessly higher operating costs at R&D facilities, and added barriers to a product's cost-competitiveness at a manufacturing facility.
Pending changes in regulations and standards can also affect cleanroom design. For example, the FDA is moving forward with its initiative, “A Risk-Based Approach to Pharmaceutical Current Good Manufacturing Practices (cGMP) for the 21st Century,” and the International Standards Organization (ISO) has issued a draft of ISO 14644-3, “Metrology and Test Methods.” While neither may be finalized for years, the necessary debate has already begun.
Regardless of use or precise wording of any particular regulation or standard, all successful cleanroom projects have these characteristics in common:
1. Clear definition of a purpose, and the performance criteria appropriate to achieving that purpose;
2. Systems and operating procedures that are conducive to meeting performance criteria;
3. Ways to monitoring adherence to performance criteria.
Addressing all of these characteristics during design reflects a comprehensive approach. It is not enough to accommodate key functions efficiently, nor is it enough to consider cleanroom design solely as keeping particulate counts within acceptable amounts.
The successful cleanroom design must also take into account its role within the entire building—even its relation with other company facilities around the world. Here's what to consider:
Clearly define the purpose and performance criteria
Start by clearly identifying the activities that must take place in the “clean” environment.
Microelectronics cleanrooms must prevent even the most minute contamination, which can result in defective manufactured components. Sources of contamination come from dust, static electric discharge and gases—even in trace amounts.
The emphasis in biotech, pharmaceutical and medical device cleanroom design is to keep critical systems sterile. This means that the process equipment, process utilities and the products themselves must be free of bacteria, viruses and other contaminants.
Nanotechnology represents a new direction that has the potential to merge both microelectronics and biotechnology. Within nanotechnology, two approaches are being studied: miniaturization, or looking at how assemblies and functions can be made smaller; and the use of molecules as building blocks—seeing what is possible by assembling bigger and more complex molecules.
The activity inside the clean environment determines what ways a particular environment must be clean, as well as the consequences if standards are not met. (For comprehensive coverage of cleanroom standards for various industries, go to cleanrooms.com.)
Establish an air flow strategy
Air needs to enter the room through supply registers and exit the room through return ducts as smoothly as possible. This means minimizing turbulence, eddies and dead spaces.
Typically, smooth “unidirectional” or “laminar” air flow is more critical in microelectronics and nanotechnology applications with ISO Class 6 or cleaner conditions. It usually requires ceiling diffusers, and perforated floors above a return plenum space.
Weighing/dispensing operations in biopharm facilities often require a “laminar” airflow, although it's usually contained in a fume hood or other smaller space that, in effect, vacuums dust particles before they can spread.
Biopharm cGMP facilities, however, typically have a mix of ISO Class 8 and 7 cleanrooms. The ISO Class 8 areas will require ceiling diffusers and returns, resulting in a mixed air flow. Class 7 spaces will need the ceiling diffusers and low-wall returns to minimize turbulence yet still be considered non-unidirectional.
Establishing and maintaining air pressure differentials
Establishing air pressure differentials between rooms is related to air flow strategy and protecting the cleanroom classification. In a typical scenario, the cleaner the space, the higher its air pressure relative to adjacent, less clean spaces. This keeps the higher level of particulates from being pulled in to the cleaner space. Air locks often serve as a transition between higher and lower levels of cleanrooms, and so have a pressure that is between the two.
Set the temperature and humidity range
Temperature and humidity ranges should be dependent on the conditions required to maintain the materials used in a particular research or manufacturing process.
In addition to identifying temperature ranges, it's important to determine an acceptable amount of time that a space can be out of its range due to excesses in outside temperatures that must be conditioned.
To design a system that always stays within specified ranges will require allowing for extremes that can be economically impractical. As a result, you must make allowances for extremely hot and/or humid summer days, and for the coldest winter days when the temperature plunges well below design parameters. This could mean allowing for suspension of operations when conditions exceed tolerable ranges.
Determine the electrical classification
The National Electrical Manufacturers' Association has a wide range of classifications for providing various levels of protection against dust, potentially explosive vapors, sparking, and moisture.
An appropriate level must be determined in each case, depending on the exposure. Also take into account protection during cleaning procedures, which may be more severe than the typical use.
Provide systems and procedures conducive to maintaining performance criteria
It's important to understand and plan for required maintenance procedures, and to design your cleanroom to facilitate follow-through. Microelectronics facilities typically have separate spaces for accessibility outside of the fabrication area. Often, these spaces are cleanrooms, but their air quality is less clean and they can be accessed and serviced without entering the “fab” area itself.
In cGMP manufacturing, it may be necessary for maintenance personnel to gown up each time they perform their duties, thereby disrupting clean operations. The use of “gray” areas adjacent to cleanrooms is one approach to minimize this problem—exposing the “backs” of equipment in locations where they are accessible for repairs, but without having to enter the clean room.
Ease in cleaning is an important criteria when selecting a wide scope of equipment, finished surfaces, and even electrical outlets. From casework to ductwork, light fixtures to grout, everything in the cleanroom must be easily decontaminated of harmful vapors, dust, or microbial or viral growth.
Develop written protocols for operations
Consistency is a key to good performance, including maintaining high levels of cleanliness. It's essential to have a method for documenting tasks that have actually been performed, and it's required for any validated procedure in cGMP manufacturing.
Understanding what those protocols will be during the design process will go a long way to assuring their implementation once construction is complete. This also applies to emergency procedures; conduct “hazardous operations” reviews during the design to identify all possible emergency scenarios and the method for addressing them.
Design air-handling systems to be balanced
The basic concept here is that the amount of air being supplied equals the amount being returned, with allowances for deliberately-designed pressurization differentials. Typically, areas of higher pressure are cleaner, and expel air into adjacent areas of lower pressure that have a lesser air classification level.
Consider “barrier isolation” technology
Simply put, this is the idea of a smaller volume of space having the proper conditions inside a specialized piece of equipment, rather than have a much larger room volume conform to the same conditions.
An example of “barrier isolation” in the microelectronics industry is through the use of a standard mechanical interface (SMIF); in the biopharm industry, “barrier isolation” can often be found in fill/finish equipment and operations.
“Barrier isolation” technology offers a cost savings by not having to meet the most stringent cleanroom standards in large quantities, plus improved quality control. Users, however, are often reluctant to allow the space surrounding a piece of equipment to fall to a lower quality condition. Consequently, both the equipment and its room meet the same quality, thereby defeating benefits of “barrier isolation.”
Document conformance to procedures
This is the written record-keeping that shows that maintenance and operations protocols have been followed—it's closely related to validation. A design that facilitates maintenance and operation procedures goes a long way towards assuring there will be follow-through.
Validation
Even before design is started on a cGMP facility, it's important to understand that its installation, operation, and performance must be continually monitored and documented for conformance to prescribed standards.
Preparing adequately detailed design documents is the first step to verifying that the facility was built the way that it was designed, operates according to the design, and consistently performs by producing products per design and operational requirements.
Quality of cleanroom construction
Poor quality control, whether through lack of inspection or execution by the construction team, can lead to numerous adverse consequences.
Follow-through in testing and balancing air pressure, for example, is essential for quality control. Projects with weak checks and balances among the contractor, owner and architect/engineer result in a space that has a high probability of not meeting specifications. This can lead to expensive remedial alterations for the owner, or a project that cannot be operated successfully.
Understanding that cleanroom design is much more than controlling particles in the air goes a long way to assuring its success.
Michael Kopp is a project manager and architect in HDR's Alexandria, VA office. He can be reached at [email protected]