When designing processes or facilities or specifying equipment for applications in the pharmaceutical industry, engineers must approach the task differently than they would for a project in the other chemical process industries. Although the basic design sequence and methods are the same, certain accommodations need to be considered for these projects outside of the chemical process industries. The high margins that many pharmaceutical products can command and the tight federal regulatory environment under which these companies must function mean plants must take measures to ensure the project and process will be profitable.
Pharmaceutical processes usually are batch-oriented and intensely manual. This environment affects not only the equipment that is used in these facilities, but also the design considerations of the workspace itself. Engineers assigned to the task of developing such a facility must be aware of these environment-related considerations and accommodate them.
However, designers must not abandon all of their experience gained in working on chemical processing facilities. Too often, lessons learned years ago are ignored in a pharmaceutical process because they do not transfer "directly" into this environment. This oversight is particularly important in light of the industry's expected growth and the projected capacity shortfall envisioned for the pharmaceutical industry in the next five years. Because of the numerous requirements of this industry, bringing new capacity on-line takes a significant amount of time.
One way to minimize the new plants' required size, as well as to make better use of the capacity already available, is to convert more aspects of pharmaceutical processes from traditional batch systems to continuous systems.
Batch vs. continuous
The pharmaceutical industry is dominated by batch-oriented unit operations. The reason is threefold.
First, plant personnel have an inherent preference for batch processes because they need to segregate "lots" of manufactured products. This method is the easiest and simplest way to conform to regulations and minimize waste from off-spec material.
Second, most pharmaceutical processes deal with relatively smaller amounts of material than with typical chemical processing operations, so batch processing equipment often is the easiest to use with these operations. Sometimes, an equivalent continuous-based unit operation that is small enough to accommodate the volumes of material to be processed is not available.
Third, most pharmaceutical processes come out of the lab where operations are predominately batch because the quantities are so small. These batch-wise processing techniques sometimes migrate to the larger-production scale.
In the chemical process industries, processes are inherently continuous because batch equipment used to conduct the same operation would be cost prohibitive. Note the differences in the footprints of the storage tanks and the processing unit in a typical refinery. The processing unit takes up a very small amount of space compared to the storage tanks, yet the processing unit is where manipulations can occur that add value to the final product.
The pharmaceutical industry always has been hesitant to use continuous processes for the reasons mentioned above. As a result, many operations in the industry are kept from realizing their potential. This need not be the case.
The case for continuous operations
One would not propose changing batch processes to fully continuous ones in pharmaceutical production--the products still need to be produced in "lots" to maintain the proper quality control--but continuous unit operations can be used to process a tank of material through one of its steps. For example, feed and product tanks on either side of a filtration step still contain a batch or lot of material. A continuous filtration method, such as a rotary drum filter, can be used instead of a batch method, such as a plate and frame filter, between the two tanks. When making this transition, plants will note that the actual piece of continuous equipment needed to conduct this operation is much smaller than its batch counterpart. The batch filtration equipment would need to be the same order of magnitude in size as the feed and product tanks, but the continuous piece of equipment to perform the same function could be one or two orders of magnitude smaller in size. Instead of operating a large batch filter for a relatively short period of time, continuous equipment allows the plant to operate a small piece of equipment for an extended time to process the same lot of material. Essentially, this transition involves trading equipment size for processing time.
Another example of making continuous unit operations work involves a two-phase extraction process sometimes used in drug production. The traditional batch approach to this step would be a simple mixer-settler that mixes two phases together in a tank before they are allowed to separate. This approach is similar to using a separatory funnel in an organic chemistry lab. This approach also suffers from the same batch problems as the filtration example, namely large equipment size and cost. In addition, the batch method provides only one "stage" of extraction contact.
In the continuous analog, a small extraction column could be used in which the two phases flow past one another countercurrently to facilitate phase contact. This continuous method can be conducted in a much smaller piece of equipment. It also provides numerous "stages" of phase contact, resulting in a more efficient and complete mass transfer operation. Further examples of this type also can be developed for fermentation, precipitation, crystallization and drying.
This conversion--from batch processes to continuous processes--would allow the use of smaller equipment with inherent lower capital costs. Continuous equipment also could be designed to be enclosed and cleaned easily, allowing the use of less costly production space because less of the environment would have to be controlled. Heating, ventilation and air conditioning (HVAC) and related costs would be minimized.
Because this equipment would operate at "steady state," it could be more easily automated, reducing labor costs. In addition, the equipment size reduction and the already inherently small amounts of material processed for many of these products, could allow the continuous equipment to be small enough to be manufactured from inexpensive disposable materials (injection-molded plastics) that could be supplied pre-cleaned, further lowering capital and operating costs.
When designing a new pharmaceutical process or modifying an existing one, process engineers depend on the same basic methods used in larger-scale sectors of the chemical process industries such as refining and petrochemicals. Namely, they specify the operations they want to conduct through the development of process flow diagrams (PFDs) and eventually piping and instrumentation diagrams.
The basis of the PFDs, of course, is the underlying chemistry and biology on which the process depends. These documents denote in detail the volumes, flows and manipulations that must occur. From this information, specifications for the equipment needed are generated and eventually sent to vendors for quote and purchase. For reasons mentioned earlier, these PFDs usually are based around batch processes, forcing the equipment to also be batch. Amplifying this push is the predominance of batch equipment by those marketing to the pharmaceutical market. These two forces make it difficult for more cost-effective continuous processes to be incorporated into many pharmaceutical production schemes.
If continuous operations are to become more common place in the industry, the process engineer must seek out and motivate specific manufacturers to furnish them.
The projected capacity shortfall for the pharmaceutical industry provides some opportunities to convert some key operations from batch to continuous. The challenge in using and designing these pharmaceutical facilities--and the equipment that is housed in them--is to accommodate the requirements for drug production and still take advantage of improvements made in the chemical process industries during the past 50 years. p
Kossik is a technical manager with Steadfast Equipment, Mill Creek, Wash. Contact him at (206) 409-7594 or via e-mail at [email protected]