A Biopharmaceutical Vessel - A World of its Own

by Pietro Perrone


When one thinks of a tank or a vessel, the first ideas that come to mind are simple items that are present in our everyday life such as a jug/basin for holding water, a bottle for holding wine, or a coffee pot/cup. However, when one refers to containers or vessels used in the pharmaceutical environment, one must be ready to understand that these vessels are complicated systems that play a critical role in storing, transporting, and treating products - truly a world all their own.

The typical vessel also has a variety of components attached to it that are critical for properly monitoring and treating its contents. These include pressure and level sensors, mixers, analytical instruments, steaming and heat transfer components, spray balls, dip tubes, and sampling ports. This article introduces the various features that contribute to a vessel’s unique characteristics and adapt it for the specific purposes it needs to fulfill.

Vessel Shape

Typical tanks are vertical cylinders with specialized tops and bottoms. The tops are of an elliptical or spherical dish shape and customized to handle the fluid entry ports (e.g., process and CIP liquids, nitrogen, air, steam), view ports, and ports for access and instrumentation (e.g., pressure sensors, level sensors, mixers). The top can be either removable or welded. A removable top provides the best accessibility, but adds to cost and complexity.

Tank bottoms also are customized for specific applications. Although most of the larger vessels have a dish bottom, the smaller vessels are often conical in shape or may have a smaller, sump-type chamber located at the base of the main tank. These alternate bottom shapes aid in fluid management when the volume in the tank is low. In all cases, it is imperative that the tank be fully drainable to recover product and to aid in cleaning of the vessel. Often this is accomplished by using a tank bottom valve positioned to eliminate any “dead sections” that could arise from drain lines and to assure that all contents will be removed from the tank upon draining.

The height-to-diameter ratio is also a critical factor in vessel design. Although a symmetrical vessel maximizes the volume per material used and results in a height-to-diameter ratio of one, most vessels are designed with a higher ratio. The range of 2-3:1 is more appropriate and in some situations, where stratification of the tank contents is not an issue or a mixer is used, will allow still higher ratios to be used in the design.

Inlets and Outlets

Most liquid inlets are designed to aid in fluid management. Dip tubes or low-foam inlets are used to minimize the gas-liquid interface and protect components in the liquid. Entry tubes can be directed so that liquid mixing is either enhanced or attenuated as the fluid enters the vessel. Spray ball inlets are located in specially designed locations to aid in CIP operations. Outlets include rupture disk/relief valves, nozzles, product recovery connections, drain connections, and sampling ports. Drain connections should be sized so that the draining of the vessel contents occurs within a reasonable amount of time. Vents are used for transfer of gases in or out of the vessel and are critical to minimize either positive or negative pressure buildup.


Pressure and temperature monitoring instruments are important for maintaining safe operation. The level in a vessel can be viewed through the view ports. However, instruments such as floats, radar, ultrasonic, differential pressure (dP) sensors, or weigh cells are often used to get a more accurate measurement of the contents of the vessel. Typical analytical instruments that are added to a vessel include those for conductivity and pH measurements.


Cleaning of the vessel is a critical operation. A proper CIP program addresses the removal of product and contaminants from the vessel. The multitude of inlets and outlets as well as any protrusions into the vessel can create hard-to-clean areas. A major factor in getting all sections of the vessel cleaned is the application of strategically placed and sized spray balls. Although at least one spray ball is a must for any vessel, multiple spray balls are used when the vessel is large, contains hard-to-access areas, or when the level sensor guide, dip tubes, mixer shaft, or other protruding components create shadows in the vessel. The spray balls must be provided with a cleaning fluid at sufficient flow and pressure; this often requires that spray balls be custom designed for specific vessel geometries and cleaning conditions.

CIP is such a critical operation that riboflavin testing is often applied to confirm that all areas of the tank have been thoroughly cleaned. This test consists of spraying the internal surface of the vessel with a water-soluble compound (such as riboflavin) that is easy to observe if not fully removed by the cleaning process. After spraying, the solution can be allowed to dry on the vessel surface or the vessel can go immediately to a cleaning protocol. At the end of the cleaning, the tank is inspected with a light that causes any residual trace of riboflavin to be brightly displayed.

Heat Transfer

In addition to holding the fluid, a vessel is often employed to adjust the fluid’s temperature. This is done by jacketing a portion or the majority of the vessel’s surface. Most jackets are applied on the cylindrical portion of the vessel. This is typically the most cost effective way to adjust the temperature of the fluid in a vessel. Some situations require the jacketing to be done on the bottom of the vessel; there is also the rare need to jacket the top of the vessel. Jacketing the top and the bottom of the vessel is typically a more costly option due to the number of connections present in those areas.

The addition of heat is typically done by one of three sources: steam, glycol, or an electrical resistance element. The removal of heat is done by either glycol or chilled water. To control the heat distribution throughout the vessel, the jacket is usually set up with either a dimpled layout or with half-pipe channels to guide the heat transfer fluid. When a common jacket is used to add and remove heat from the process fluid, one must consider the heating and cooling fluid interface that will occur in the jacket as one fluid displaces the other during the transition from heating to cooling and vice versa.

A vessel that is used for handling the temperature extremes that are present in a heating/ cooling operation needs to have a specialized design to minimize stresses on the jacket’s welded joints. In addition, all jacketed vessels are insulated to protect the operators and to maintain temperature stability. Insulation also can be used to maintain temperature for vessels without a heat transfer jacket.


Two types of mixers are typically used: the topmount mixer and the bottom-mount, magnetic mixer. Each has advantages in fluid handling that need to be analyzed for the specific application and vessel design. Gas sparging, although effective for mixing, is not typically used, other than in bioreactors, due to the damaging effects of the gas/liquid interface. Design of the vessel needs to accommodate the removal of the mixing equipment for replacement and/or maintenance. The analysis of the mixing requirements in a vessel also needs to consider the use of baffles or vortex breakers that can help to control the level of turbulence within the tank.


The addition of steam to a vessel requires a methodical approach that can achieve consistent results. The steam should be introduced so that it displaces the air without the creation of stagnant sections within the vessel. One needs to consider that steam is denser than air when designing the steaming path and that residual air can result in cool spots in the vessel. The large temperature variation during steaming causes expansion/contraction of the fluid and necessitates a vent inlet/outlet. This port is typically fitted with a sterilizing filter and allows sterile air/gas to enter the vessel to prevent the formation of a strong vacuum.


Most vessels above a specific volume and for operation above a specific pressure must comply with one of the following codes: American Society of Mechanical Engineers (ASME) “U” Stamp, Canadian Standards Association (CSA), Canadian Registration Number, or Pressure Equipment Directive (PED) of the European Commission. Although the codes are similar, it is imperative that the locationspecific codes be followed depending on where the vessel will be used. Following these codes will provide safety for the user and compliance with the regulatory requirements that must be met before utilizing the vessel.

In summary, a vessel is more than just a storage container. It is a complex environment that protects and manages valuable fluid products and a critical piece of equipment that needs to be carefully designed to maximize its value for a specific process.

About the Author

Pietro Perrone is a Business/Projects Manager at Millipore Corporation. He has a degree in chemical engineering from Tufts University and more than 20 years of purification/ separation technology experience in process development/optimization, equipment scaleup, and project management.

Copyright © 2018 ISPE