Planning high-purity manufacturing facilities
By Louis C. Leone, Process Facilities Inc.
Like other companies, high purity chemical manufacturers are seeking ways to differentiate themselves from the competition. To achieve this, better quality and faster cycle times are necessary. While raw materials and the manufacturing process are the primary drivers for improved quality and cycle time, the physical plant has a dramatic impact on performance. Today, more and more firms are utilizing high purity manufacturing (HPM) approaches to achieve these goals.
The early approach to HPM plants was to simply relocate existing “non-clean” manufacturing processes into cleanrooms. The reason: if the product was manufactured in a clean environment it would somehow remain clean. These early attempts failed for two reasons: contamination and costly cleanrooms.
The primary contaminants within most processes get there via raw materials, utility infrastructure, or people. Without a basic facility design and protocol to manage these elements, the only thing that was accomplished was contaminating the cleanroom itself with little or no improvement in the product cleanliness. Likewise, installing a large-scale process or system within a cleanroom is very costly from capital and operating cost perspectives. Therefore, the original efforts to sustain HPM plants were both ineffective and expensive.
Over the years, the HPM technology has evolved to meet the needs of the marketplace. Three significant design concepts that have made a significant impact on the development of state-of-the-art HPM plants are the following:
1. Transition design. A set of standards which address the design of the space between the clean manufacturing areas and the “outside” world. These design features along with the correct manufacturing protocols provide a barrier to prevent outside contaminant sources from entering the high-purity manufacturing zone.
2. Process ecology. An interrogative process that attempts to identify and document the potential impact between the external environment and the process reactants, intermediates, final products, etc. This protocol establishes a risk priority between the process and the external world interface. This external world includes materials of construction, temperature, pressure, etc.
3. Oasis design. This is a design approach that attempts to focus the maximum cleanliness levels in small areas where risk to the product is highest. This technique provides a framework for identifying those areas which require the most detail and may require the greatest cost.
Translating these concepts into a functional plant requires faithful dedication to detail during the design and construction of HPM plants. This dedication is required from early project planning, through design, into construction, and finally to operational protocols.
Trace levels of contamination can have disastrous impact on performance of the final product. The best design in the world will not protect ultrapure product, especially if the construction team has not maintained the proper clean construction protocols. Once constructed, the operational protocols must be developed which assure a clean operation, and finally, the owner of the plant must have the conviction to enforce the protocols. This last element is perhaps the most difficult to achieve. Clean manufacturing protocols require very structured, and sometimes tedious, approaches to doing every operation. The temptation to “invent a shortcut” should be avoided. All the elements which comprise the project must be carefully integrated to ensure a successful HPM plant. (See Figure 1.)
Like any project, the key to its success is the project planning phase. The front-end of an HPM project will typically take 25 to 50 percent more effort than a general manufacturing project. Because many criteria influence the product quality, it is critical each criteria be understood and prioritized. For example, construction techniques must be considered and documented as part of the early planning phase. It is strongly recommended that the construction manager and construction quality control specialist become involved during this phase.
Most projects begin with ideas brewing in the head of scientists, engineers, and the manufacturing managers. Initial planning efforts must focus on translating these ideas and needs into broad-brush concepts. Since each of the functional areas may have a different perspective on what the needs of the company are, it is important to document these ideas and needs without bias. From these brainstorming sessions, three things should arise:
1. Project precepts or “must haves.”
2. “Should haves,” concepts that make the project more maintainable, create a better image, improve efficiency, but are not necessary to assure product performance.
3. “Nice to haves” or concepts which specific people feel would enhance the project, but bring no real value.
These initial meetings between the customer and the engineer serve to document many divergent perspectives, and make sure that everyone`s ideas have been heard and considered. Typically, many hours are spent categorizing and prioritizing these ideas and needs. However, it is a crucial step in creating a strong project team that believes that everyone`s ideas will be heard, yet understands that all ideas and needs can`t become part of the project. In addition, it helps the project engineering team understand the needs of the project.
Up to this point, there is not much difference between an HPM project and any typical process plant project. The next step during an initial planning phase is to define the clean boundary limits and transition zones. At some point, raw materials, packaging, and so on, must enter the HPM from the “outside world,” and the products made in the HPM must exit to the “outside world.” Most times the product is on its way to another user with their own set of high purity protocols, therefore, it is necessary to provide a means for getting the product into the customers` HPM without compromising that facility. What is crucial to know is where the clean envelope begins and where it ends. For instance, is a product secured once it is put in a container and sealed, or must it have secondary packaging before it is considered secured for transition outside of the HPM? These boundary limits must be defined in detail. Figure 2 illustrates the general concepts of transitional design.
The transition zones must be clearly defined. These are operational areas between the HPM and the outside world. Issues to address include:
What activities get done in the transition zones.
What space requirements are needs.
Required material and people flow to assure cleanliness.
What infrastructure is needed and how are utilities delivered.
There is often too much effort placed on the integrity and the clean class of the operating area. Effort placed upon preventing contamination from entering the operating area is a more appropriate place to focus resources and creativity. The operating area should operate under clean protocols, and not contribute to contamination. But the operating area does not necessarily have to be certifiably clean unless there is an impact relationship between the environment and the product performance.
Product ecology and oasis design
Exposure of the product to the outside environment at some point in the manufacturing process is a fact of life. Understanding the impact between the environment and the product takes on importance as the product specifications become more restrictive. When designing HPM plants, every effort should be made to utilize closed-loop manufacturing systems wherever possible, however, in those areas where it is not possible, special attention should be focused on those “process oases” where the outside environment and the high purity product come in contact with one another.
Design efforts should be tailored to each process oasis whether it is charging, filtering, packaging, etc. There are no cookbook design protocols for these “oases” since they become very situation specific, but since these areas carry the highest risk for product compromise, they should enjoy a greater attention to design details and creativity.
Operational economies and efficiency dictate that the size and number of “process oases” be kept to a minimum since they are normally more expensive from a construction perspective, and productivity within the oasis is normally lower than within a general manufacturing arena. The payback for this is in the form of less rework and improved product quality and consistency.
Design of a manufacturing plant to produce ultrapure chemistry is not magic, but it does require extreme attention to details. It also requires a great deal of attention to how the plant will operate when eventually constructed. One of the more interesting approaches, which should be considered, is to develop operating protocols and preliminary procedures before the plant goes into detail design and construction. All too often engineers will design a manufacturing facility which is technically good, but which “doesn`t work” from an operational perspective. The alternative is to develop preliminary manufacturing procedures once the preliminary layouts are developed. Using this approach provides assurance that the plant is consistent with how the customer expects the process and plant to work. It also ensures timely input from the members who will have to run the plant, which in turn, assures their support and participation in ensuring the success of the project.
The key to manufacturing products with a high level of consistency, and a corresponding low rework level resides equally in the design and construction of the manufacturing systems and controls, as well as the manufacturing procedural documentation. It is not uncommon to see a situation where significant attention is focused on the design effort for the manufacturing systems, and little effort directed toward the design of procedures and protocols for making the product. This documentation represents an important “bridge” between the plant design and the operational infrastructure.
With increasing participation of ISO 9000 certification, there has been significant progress in the area of manufacturing protocols, but these represent a “snapshot in time” of how things are done at a specific time. Under the best of circumstances, these procedures are kept up to date for existing processes and systems through good engineering change management.
What happens when new facilities are designed and constructed or when existing operations undergo significant renovation? Typically, the systems will be started up and commissioned by the engineer with involvement by the customers` engineers. This may involve mechanical start-up, water batching, or even process qualification. At the end of the effort, the customer is given a mechanical catalog, along with qualification documentation, and “proof of acceptance.” What is not available is a detailed set of documents that address the procedures for making and testing the products.
Manufacturing procedures are traditionally looked at as being the responsibility of the customer. The problem that arises is that the customer is focusing resources on making products, and when a new facility is completed, it is difficult to redirect those resources toward developing detailed manufacturing procedures without sacrifice elsewhere. Rather than having the manufacturing protocols tacked to the end of a project, where they can often drag on until interim procedures become permanent procedures by de facto, it is more appropriate to develop the procedures in parallel with the design and construction. It is also recommended that the engineering team be staffed to play an important role in the documentation development since they are most familiar with the manufacturing hardware.
Using this approach will unload a significant documentation burden from the customer, yet will provide customer input where it can provide the best leverage.
Clean build techniques
With ever increasing pressure on removing potential contaminants from the manufacturing environment, the construction techniques for HPM facilities are undergoing intense changes. As mentioned earlier, the construction team must be part of the early planning project and must step up as an equal partner in providing a facility that can manufacture ultra high-purity product. In the past, it may have been cliché, but today the reality is that the best design in the world will not yield ultra pure product if clean build protocols are not observed.
The first step in achieving clean build objectives requires selection of a construction management team familiar with clean build techniques, and then providing ongoing education and quality control of the construction trades. It is also recommended that a construction quality control specialist, who is independent of the construction team, be assigned to the project. This individual`s responsibility is to assure that all the clean build construction protocols are strictly followed, and that access to the clean construction site is controlled.
The owner must realize the lost productivity is the cost associated with strict adherence to clean build protocol where the highest level of cleanliness is required. Fortunately, it is often possible to limit the size and number of very high level clean areas (Class 100 and below) through careful design and integration of the manufacturing process and facility. The loss in construction productivity and associated increased construction cost is inversely proportional to the class of the clean area.
Even in the very high level clean areas, construction cost can be managed through careful phasing of the construction. It is crucial, however, that each phase be carefully defined, that specific build protocols exist for each phase, and that education and training of the construction forces be educated as to what is expected during each phase. A typical phased construction sequence for an ultra clean manufacturing oasis is shown in Figure 3.
Clean build requires getting construction partners involved early in the program, having detailed clean build protocols with clearly defined expectations, educating construction personnel, and investing in a construction quality control specialist.
There is no magic to the design and construction of clean manufacturing facilities; attention to detail and the application of common sense are the key ingredients. The primary difference in designing facilities for the manufacture of high purity products is the added importance on the requirements of the product, and the additional planning which must take place to assure alignment between the needs of the product and the facility. Teamwork and good communications throughout the life of the project will reap many rewards in cost, time and quality of the final project.
Louis Leone is director of high-purity manufacturing systems for Process Facilities, Inc. (Boston, MA), an engineering firm specializing in the design and construction of pharmaceutical and other advanced technology chemical manufacturing facilities. He has over 30 years of engineering experience in the pharmaceuticals, fine chemicals, and electronic chemicals arena. He has been responsible for facilities design and management in North America, Europe and the Far East. Prior to joining Process Facilities, Inc., Leone was director of facilities engineering and manufacturing for the Shapely Co., Inc.