Cleanliness and Drainability are among the most critical issues biopharmaceutical manufacturers or owner companies must confront with their process lines. Plants making active pharmaceutical ingredients (API) or ingredients used in the manufacture of pharmaceuticals are increasingly being held to the same sanitary standards as biopharmaceutical manufacturers. Therefore, optimizing fluid system components used in these systems must take both cleanliness and drainability into consideration.
Some manufacturers run one operation continuously. More often than not, manufacturers run multiple batches and must clean between them using SIP (steam-in-place); CIP (clean-in-place), which uses a chemical agent in the cleaning process; or both. In a properly constructed system, when a valve is shut off, the entire system downstream should drain completely, thereby minimizing residual puddles, reservoirs or entrapment along process lines or in and around valves or fittings.
Variables that will impact a system’s drainability and cleanability include: system slope; deadlegs; interior surface finish of tubing; valve and fitting selection and design; and fitting-to-valve ratio. Owners and contractors alike can take steps in the design and construction phase to enhance the cleanability and drainability of a system. However, the onus rests on the owner to make it known that drainability and cleanability are top-line requirements.
System Slope, Deadlegs and Interior Surface Finish
Some specific guidelines concerning system slope and drainability are given in AS ME-BPE (the American Society of Mechanical Engineers’ BioProcessing Equipment Standard, www.asme.org/Communities/ Technical/BPE/) section SD 3.12. Although this standard does not designate a specific slope, most companies use the guideline of a minimum ⅛ inch or ¼ inch per foot. In other words, for every foot of tubing, the line should drop a minimum of ⅛ inch to ¼ inch.
Deadlegs are sections of tubing (typically tees leading to valves or valve assemblies), characterized by a discontinuity of flow. When cleaning in place, chemicals or steam may not reach these locations, or fluid may be held up there and not fully drain, leading to contamination. Minimizing the number of deadlegs when designing a system is vital. Deadlegs can be managed in three ways, listed below in order from least to most desirable.
In Configuration A, a tee fitting with three welds creates a horizontal line to a valve. The deadleg is the area between the tee fitting and the valve. Of the three options, this one creates the longest deadleg because the valve’s proximity to the intersection is limited by the tee stub. With this configuration, the best solution is to choose tees whose stubs are shortest in length and widest in diameter. This type of setup will facilitate access when cleaning and will minimize the area for fluid hold-up.
In Configuration B, a valve is used instead of a tee fitting. The tee is created by boring a hole into the side or bottom of the valve, then welding a vertical line into the valve. The distance to the valve on the vertical line (the deadleg) is shorter than in Configuration A because the welded tee fitting is not part of the flow path.
In Configuration C, the best design solution, the deadleg is eliminated altogether through the use of a custom valve assembly. In these assemblies, two valves actuate from the same block, one controlling vertical flow and the other horizontal flow. Owners and designers should look into block body-package options, as these assemblies are often more cost-efficient than two separate valves.
The interior surface finish of tubing affects both drainability and cleanability. A smooth finish, with no porosity or pitting, provides better performance in both areas. Cleanability can be enhanced further by applying an electropolish, which adds a chemically inert layer to inhibit corrosion. Special tools may be used to measure interior surface finish, along with a visual examination.
Selection and Design
Careful consideration is needed for valve selection. One valve is not just as good as another. In critical shut-off applications, the two most common types of valves are the weir-style and the radial diaphragm. The weir-style valve is the industry standard, with a track record of solid performance in validated systems. However, the weir-style sealing design has potential for entrapment or contamination. The diaphragm is designed to seal on a bead outside the weir area. In the open position, though, the diaphragm lifts up and flexes, exposing the valve body along the perimeter of the bowl. As the valve closes, the diaphragm closes back toward the body of the valve, allowing small quantities of fluid to become trapped.
Figure 1. Computational Fluid Dynamics (CFD) show the effect of gasket
Newer radial diaphragm valve designs correct this imperfection. In these designs, the diaphragm seals along the edge of the valve’s bowl. At no time does the diaphragm lift beyond the edge of the bowl. As a result, entrapment does not occur. Further, the bowl shape, inlet, and outlets are configured to ensure that the flow path is cleanly swept and optimized for full drainability.
In choosing between the weir-style valve and a radial diaphragm valve, owners should carefully consider the sensitivity of the application as to drainability, entrapment, contamination potential and system flow requirements. For example, the equivalent-size weirstyle valve would provide a higher flow rate and be the appropriate choice for applications requiring a higher flow, while radial diaphragm valves are well suited for applications where cleanliness or high cycling is critical.