Antidote For High Cost: Electronic Simulation For Design, Construction, Documentation And Operation Of Pharmaceutical Cleanroom Facilities

The Sear-Brown Group will be demonstrating its Electronic Simulation Technology for Cleanroom Design at Interphex '99 (Booth #1389), April 20-22, 1999, Jacob K. Javits Convention Center, NY.

The life cycle costs of pharmaceutical cleanrooms and the processes they serve are many, including cost of design, construction, validation, operation and maintenance, renovation and decommissioning. Speed-to-market for the products produced in these environments is critical and is greatly influenced by the owner's ability to commission the required facilities on a timely basis. A streamlined approach to creating and operating a highly cost-effective and flexible facility exists in first creating the cleanroom using Electronic Simulation (ES), then using the ES at each subsequent stage, through and including decommissioning.

Contents
Development of Design Criteria
Process Flow Diagrams Developed
3-D Modeling, Recording, and Use of Database
Power of 3-D During Design and Construction Phases
Database at Work for the Owner
Summary

Development of Design Criteria

To achieve a cost-effective cleanroom facility, the pharmaceutical owner must begin with the end in mind. That is, the owner must understand the intended use and life cycle of the facility. The owner must know what products will be produced in the clean environment (such as research or production, parenteral, topical, or oral), the processes involved (aseptic, terminally sterilized, or lyophilized, formulating, component preparation, or filling), the staffing requirements of the facility (number of people, activities, occupancy schedule), the support facilities required (high-purity water systems, breathing air, clean steam, et cetera), and the future of the facility (renovation, expansion, decommissioning). Once these basic needs have been identified, more detailed consideration is given to each requirement of the facility to write specifications for contamination control, temperature and humidity control, control of hazardous materials, and process installation.

Pharmaceutical companies and designers of cleanroom facilities must integrate the requirements of various standards produced internationally, by federal, state and local agencies, and within the pharmaceutical industry such as PIC, FDA/cGMP, GRP, OSHA, Federal Standard 209, USP and EPA. Interpretation of these standards and the development of performance specifications for each cleanroom facility have a profound impact on the overall life cycle cost of the facility. For example, the cost of class 100 cleanroom space is approximately 10 times that of class 100,000 cleanroom space. Electronic Simulation is essential for developing design criteria that meets the applicable standards while minimizing the associated cost through avoidance of over-design. It is a disciplined approach to planning the work in advance—forcing the owner and designer to thoroughly examine the requirements and intended use of the facility while utilizing scientific and engineering methods for decision making.

Electronic Simulation of the cleanroom facility includes engineering models, intelligent drawings, and three-dimensional (3-D) design. Engineering models such as material handling, HVAC, and energy analysis of facilities are used to create highly-effective conceptual designs. By modeling the flow and exchange of product and people within the cleanroom, efficient process equipment selections and floorplans are created that avoid bottlenecks and accumulation of work in process (WIP) while reducing labor cost. Concurrent with floor plan development, HVAC modeling is performed to accurately model the loading on the HVAC system and thereby avoid over-design. Typically 50% of the cost of constructing biotech cleanroom facilities is related to mechanical systems and 90% of the operating cost is used to operate the HVAC and clean utility systems. Proper conceptual design and equipment sizing is critical for cost control.

During master planning of the cleanroom suite, processes are segregated such that occupancy of highly-controlled spaces is limited to the essential processes and personnel, while less critical processes may be located in more suitable environments. Cross-contamination of process is a major concern and is also addressed during segregation. For example, having modeled the material handling and production processes, aseptic filling processes are located in class 100 mini-environments that are located in class 10,000 rooms while component preparation and closed-system solution preparation areas are located in less controlled (and less expensive) environments. HVAC systems for the cleanroom suite and mini-environments are modeled using HVAC load calculations and energy analysis software. It is the combination of a thorough understanding of facility requirements and accurate load and energy estimating that allows a balance to be struck between space requirements, capital costs, and operations and maintenance costs. Similarly, the support facilities such as high-purity water systems and breathing air systems may be properly sized and planned based on the output of the original production modeling and consideration of future facility requirements.

Process Flow Diagrams Developed into Piping and Instrumentation Diagrams and Construction Documents

Highly-effective Process Flow Diagrams (PFDs) are a natural product of the engineering models described under Development of Design Criteria. A PFD is an elementary diagram used in the development of pharmaceutical processes that is often rushed to completion without the appropriate level of effort. Decisions made at this crucial stage in process development cause a ripple effect with significant impacts on cost, space and operational effectiveness. For example, failure to recognize a material handling bottleneck may require additional equipment to be installed, requiring more cleanroom space and an expansion of high-purity water systems, and so on, as the ripple effect continues. The PFD resulting from study of engineering models is typically the best available solution to the process design problem. The time and engineering fees spent at this early stage of development are surely essential and repaid during detailed design, construction and operations.

The next step in preparing for construction involves the creation of Piping and Instrumentation Diagrams (P&IDs) and construction drawings. P&IDs are a more detailed representation of the process based on the PFDs. The P&ID includes conceptual pipe routing, locations of instrumentation and control devices (such as temperature and pressure indicators, and control valves and pumps) and illustrates how the system is to be controlled.

P&IDs are typically developed prior to construction drawings. As field conditions, design revisions, construction changes, or future renovation require deviations from the original drawings, all P&IDs, PFDs, and as-built revisions of the construction drawings need to be updated independently. This method of document management requires a high level of cost and effort. If all of these documents are not properly maintained, the owner is exposed to substantial liabilities local, state, federal and industry requirements.

3-D Modeling, Recording, and Use of Database

A more cost-effective approach to construction drawing development and document management is known as 3-D modeling. In 3-D modeling, as PFDs, P&IDs and construction drawings are created, an intelligent database file is written semi-automatically. This database records important data about each element of the design. For example, as a reaction vessel is introduced to the process flow diagram, the equipment is tagged with an identification number. Key data is recorded in the database including vessel dimensions, pressure rating, capacity, heat exchanger jacketing, material and thickness, and pipes to and from the reactor. Next, as the PFD is developed into a more detailed P&ID, that same data already existing in the database may be accessed. Details such as pipe size, material and schedule and instrumentation and control devices are added to the P&ID. Finally, a 3-D model of the process is constructed in computer-aided design (CAD) software that shows the equipment using correct dimensions and locations. The PFDs, P&IDs, and construction drawings are all linked to the design database.

The power and benefits of the 3-D model are realized during documentation for validation, construction, process safety management, operations and maintenance, renovation and decommissioning. All of the data mentioned above is typically included, in one form or another, in construction drawings or design reports under the conventional method of project design. Often the data is searched for and keyed into multiple locations over and over in order to create all of the required documentation. However, using the 3-D modeling approach requires that all of this information be reviewed and entered only once. The data is subsequently manipulated and displayed in different formats to satisfy requirements such as equipment schedules, design reports, validation documents and process safety management databases.

The process of 3-D modeling can be modified to fit many different applications. For example, if PFDs and PI&Ds already exist, it is still more cost-effective to create construction drawings using 3-D modeling. This is true because the CAD operator creates each design element only once, then selects and displays different views to produce plans, elevations, sections and details. Commitment to this process has shown that it is actually less expensive to create 3-D models of facilities and processes for the production of construction documents rather than utilize the conventional 2-D approach.

Most design firms regard 3-D modeling as an optional deliverable requiring additional fees. These additional design fees can make this approach cost-prohibitive, as most pharmaceutical clients must justify investments with a short financial payback. This need not be the case. Proper use of Electronic Simulation pays for itself before construction is finished.

Power of 3-D During Design and Construction Phases

Having established the need for thoughtful design criteria and the use of engineering models to arrive at effective design criteria, the availability of intelligent 3-D modeling linked to PFDs, P&IDs, construction documents, and central databases all for the same cost as conventional 2-D design, the power of that database at work for the owner may be introduced.

Regardless of the attention to detail during conceptual design phases, design changes almost always occur during detailed design and construction. Having completed a 3-D model, these changes are executed with much less effort. For example, if the size of a storage tank needs to be changed, the database is updated with the new capacity, dimensions, pressure rating, and other applicable data. The 3-D model is then updated to reflect this design change. Because the database and 3-D model are linked to the PFD, P&ID and construction drawings, they are all updated with no additional effort. Furthermore, the designer avoids manual updates to plans, elevations, sections, and details because the 3-D model is the basis of those views and automatically updates them.

Another benefit of 3-D modeling is user-friendliness. 2-D drawings can be difficult to interpret and can easily confuse readers who do not spend a large portion of their time on construction projects. Scientists, regulatory agency representatives, end users and even construction contractors find 3-D models very easy to visualize and are more able to understand and add value to the design.

A major speed-to-market advantage is gained in design cycle time. Because designers from multiple disciplines may all view and work on the 3-D model simultaneously, most interferences are avoided. Also, because equipment data is written to a database, duplication of effort is avoided. For example, because the mechanical designer has entered pump data including make, model, flowrate, pressure, motor speed, electrical service, and power rating, the electrical designer avoids having to record electrical service and power rating in a separate file. Further time savings is achieved because the owner can view the 3-D model while it is under development and receive critical feedback from operators, maintenance personnel, and environmental health and safety (EH&S) personnel.

Another major improvement in speed to market is realized during construction. The construction bidding and negotiation period can be substantially reduced through use of the 3-D model. The database may be used to automatically generate bills of material for the various construction trades. This is a laborious task usually performed by the construction contractor (and ultimately paid for by the owner). Negotiation with construction contractors is usually faster and easier when the 3-D design approach is used because the construction drawings and bills of material leave fewer risks in pricing and there is less administrative work involved. Finally, because the construction drawings are based on a 3-D model and the existing field conditions, fewer interferences exist in the construction drawings. That is, mistakes are found at the CAD station instead of in the field, thereby drastically reducing the cost and time penalty associated with construction change orders.

Finally, the 3-D model is a cost saving tool during subsequent renovation and decommissioning. Existence of an accurate field-conditions model drastically reduces the time required to field-verify prior to renovation of an existing area. That is, if 3-D modeling were used to design and construct an existing facility, that model is re-used and modified during future work. Also, the database associated with the 3-D model can be used for environmental documentation during facility decommissioning.

Database at Work for the Owner

Finally, the database created during the design process continues to work for the owner throughout the life of the cleanroom. The information in the database can easily be manipulated or exported because it uses a common platform such as Microsoft Access or Lotus Ascend. The time and effort required for the following activities may be drastically reduced because all of the important information already exists in the design database:

• Validation – design criteria, equipment selections, key flowrates, et cetera
• Process Safety Management – basis of design, baseline material thickness, relief valve settings, pressure vessel information, inspection and testing intervals
• Preventive Maintenance – equipment tags, inspection intervals, spare parts listing, maintenance history may be recorded, maintenance instructions, maintenance contracts, et cetera
• Statistical Process Control – equipment calibration requirements, critical process variables
• Renovation and decommissioning – the 3-D model becomes the baseplan for future work

Summary

Electronic Simulation is a valuable method for first creating a pharmaceutical cleanroom in a model before creating it in fact. This simulation forces careful evaluation of intended use and future uses of the facility. The time and effort spent on the electronic simulation is paid back in the form of a more effective final design.

A few engineering firms with diverse experience in pharmaceutical cleanrooms have invested the resources in Electronic Simulation to bring the method to competitive grounds with the conventional 2-D design approach. These firms can provide this low-cost, high-technology alternative while forming the backbone of the following programs for no additional investment: intelligent drawings, database linkage, bill of materials, formatting for validation, process safety management, preventive maintenance, statistical process control and other key activities.

The owner is then free to utilize the database to meet the requirements of these programs or to retain the original creator of the database to administer them. Either way, for essentially the same cost of a conventional 2-D design, the owner is positioned to receive a product from the design firm that continues to provide value throughout the life of the facility.

For more information: Daniel P. Collins, Corporate Facilities and Industrial Manager, The Sear-Brown Group, 85 Metro Park, Rochester, NY 14623. Tel: 716-475-1440. Fax: 716-272-1814.