Automation & Control

Getting the Most from Coriolis Flowmeters in Pharmaceutical Processes

Coriolis flowmeters can, or should, occupy many important positions in the pharmaceutical industry because of their natural compatibility with high-purity processes. However, they may not be the best choice for every flow measurement application.

By Vince Salupo, Eli Lilly & Co. and Franki Parson, Emerson Process Management, Micro Motion Division

This article provides discussion and suggestions on the role of Coriolis flowmeters in pharmaceutical and related processes. In addition to typical process considerations such as productivity, measurement accuracy and cost consciousness, the industry provides some specific challenges for flow measurement technology. With the variety of processing steps and the need for cleanliness, purity and rigorous accountability to consumers and regulators, there is a need for a flow technology that is reliable with high accuracy and low risk of causing contamination.

The information in this article is based upon research and field testing of Emerson Process Management’s Micro Motion Coriolis flowmeters and their capabilities. Where design and applicability similarities exist between manufacturers, the information in this article will be applicable to operation of other brands of Coriolis flowmeter.

Overview of Coriolis Flowmeters

Coriolis flowmeters measure mass flow directly by taking advantage of the Coriolis Effect. Simply stated, the inertial effects caused by a fluid flowing through a tube are directly proportional to the mass flow of the fluid. In a Coriolis flowmeter, vibration is induced in the process-filled flow tube(s), and then the mass flow rate is captured by measuring the time delay between the inlet and the outlet of the sensor.

Coriolis flowmeters also provide a direct and independent density measurement. The density measurement is proportional to the vibrational frequency of the tubes. Coriolis density measurement can be compared with a mass on a spring. As the process fluid becomes denser and heavier, the vibrational frequency of the flow tubes decreases.

Bent Tube and Straight Tube Basics

There are two basic styles of Coriolis flowmeter: (Dual) bent tube and (single) straight tube.

  • Bent tube meters
  • offer extraordinary accuracy and turndown capabilities. Two bent tubes in the meter are vibrated relative to one another. The vibration produces a sinusoidal motion along the length of both flow tubes. The sinusoidal motion of the flow tubes is measured at the inlet and outlet of the sensor. The Coriolis affect produces a time delay between the motion at the inlet and outlet that is directly related to mass flow rate.

  • Straight tube meters
  • are more rigid than their bent counterparts. The rigidity makes for a less sensitive flow sensor and a tradeoff in accuracy is needed to get improved drainability. The single flow tube is vibrated relative to an external reference tube. The two pieces move in opposite directions similar to the two tubes in the bent tube design. As with the dual tube device, the motion at the inlet is compared to the motion at the outlet. The time delay between the inlet and the outlet motion is a direct measure of mass flow rate. Straight-tube Coriolis flowmeters are less accurate than their bent-tube counterparts, but they are still more accurate than many other technologies.

Process Isolation

Coriolis flowmeters are well suited to many areas of pharmaceutical manufacturing. A particular virtue of the technology is natural process isolation. The only part of the flowmeter that is in contact with the process is the inside of the flow tubes, which are made of corrosion-resistant metal alloys. There are no fluids or parts that can be exposed to the process in the event of device failure.

Other technologies use components that can contaminate the process when the device fails. For example, a magnetic flowmeter’s liner and electrodes provide an entry point for contaminants; and the sensing element of a vortex flowmeter typically contains a fluid that can leak into the process.

Cleanability and Drainability

Most applications in pharmaceutical manufacturing require a high level of cleanability. Cleanliness in a pharmaceutical manufacturing plant is an indicator of product quality. Plants must control product mingling between lots and the growth of foreign organisms in the system. Where systems are cleaned-in-place, drainability becomes a required design consideration. Cleanability best practices rule out many popular measurement options (Vortex, dP, positive displacement) because they can trap materials in the crevices of the meter itself.

Coriolis meters are well suited to pharmaceutical manufacturing because the flow tubes contain all-welded metal surfaces. There are no crevices within the device or synthetic materials to absorb process chemicals.

Some bent-tube flowmeters drain well if they are oriented carefully; others do not drain well no matter how they are installed. Where drainability is critical and the higher accuracy of a bent tube meter is required, the meter should be selected with the help of the manufacturer. System drainability and/or meter performance can be compromised depending upon the orientation of the tube bends. For instance, low points can trap liquids and solids, while high points can trap gases.

Straight-tube Coriolis flowmeters drain well with proper installation. They can be oriented in virtually any direction. When straight-tube Coriolis flowmeters are installed in vertical process piping, the meter is fully drainable; flow should also be up through a vertically installed meter. If straight-tube Coriolis meters are installed in horizontal process piping, they must be sized and installed carefully. The ASME BPE-2005 Bioprocessing Equipment Standard, Part SD-3.12.1, gives guidance for ensuring full system drainability in horizontal piping and in-line measurement equipment, such as straight-tube Coriolis flowmeters.

Accuracy and Pressure Drop

In some applications, accuracy and repeatability are paramount to success. In others, accuracy is not as critical, but unrestricted flow is important to process efficiency. The accuracy of a straight tube Coriolis meter is determined by the material of construction and the sensitivity of the components used to measure time delay. At any flow rate, the sensitivity (accuracy) decreases as the sensor tube’s inside diameter increases.

The smallest working sensor for many installations may be a full pipe size smaller than the process piping. As a result, the flowmeter can create a significant pressure drop in the system. The choice of accuracy vs. pressure drop is for the owner to make. Consideration for the lowest measurable flow is needed. The smaller tube will be able to measure lower flows than the larger alternative. The larger sensor will reduce the drain time for the piping system.

Applicability of Flowmeter types to Specific Applications

Following are some guidelines for selecting (or not selecting) a straight-tube or bent-tube Coriolis flowmeter for the various phases of pharmaceutical manufacturing processes:

General Flow of Pharmaceutical Processes

Chemical (API) Synthesis

There are numerous opportunities for flow measurement devices during the chemical synthesis phase of production, which is characterized by large- to small-scale production of the Active Pharmaceutical Ingredient (API).

Raw Material Handling

Often, large quantities of raw materials must be received from vendors and accounted for as they enter the chemical synthesis process. There can be many different kinds of flow measurement devices scattered throughout the raw material receiving phase. Coriolis flowmeters are often not selected for raw material handling because there are many lower-cost solutions that can meet the minimal measurement requirements. However, Coriolis flowmeters are still the best choice in some cases:

  • Bent-tube
  • Coriolis flowmeters are desirable wherever highly accurate, reliable and rangeable mass flow or density measurement is needed.

  • Straight-tube
  • Coriolis flowmeters are desirable where raw-material contamination is a concern. Between runs of the same material or between runs of different materials it may be necessary to ensure that no cross-contamination can occur. Where cleaning is required, the straight-tube Coriolis meter offers an advantage.

These examples could account for 10 percent or more of the raw material applications.

Extraction or Fermentation, and Purification of the API

Achieving a purified API from processing methods is more delicate than raw material handling. There are fewer flowmeters overall involved in these processes, but nearly all of them are — or should be — Coriolis flowmeters. The Coriolis technology offers superior overall measurement accuracy, repeatability, multivariable capability and pharmaceutical-friendly materials of construction. When accuracy is secondary to drainability (about half of the time) straight-tube meters should be used. The other half of the time, bent tube meters should be used to make available the highest possible performance and repeatability.

Formulation

There are also some opportunities for flow measurement devices during pharmaceutical formulation, which is characterized by smaller-scale handling of the Active Pharmaceutical Ingredient (API) and/or other ingredients.

Handling of the Pure API

Once the purified API is achieved, cleanliness becomes an even bigger factor than it was during chemical synthesis. Anything new that enters the process at this point ends up inside of the finished product — and affects final product quality and ultimately the amount of discarded product. Coriolis flowmeters have no moving parts exposed to the process. Many other technologies could expose the pure API to contamination from the meter or its surrounding environment. Because of the high value of the pure API, the more accurate, bent-tube Coriolis flowmeter is a better choice than straight tube, but the latter may be required if straight-tube virtues (e.g., better drainability) are important.

Where disposable piping systems are used, a bent tube meter may be the better choice. For fixed piping systems that rely on clean-in-place, the straight tube meter is preferred.

Indirect Processes

In addition to processes that contribute directly to the production of pharmaceuticals, there may be other places where a Coriolis flowmeter is a good choice. High-purity water is one example.

Using a Coriolis flowmeter to measure the flow rate on a simple distribution loop is unwarranted when an adequate, less expensive technology like a vortex flowmeter is available. However, in cases where the use of water (inventory) is to be monitored, two straight-tube meters on a loop may replace a flowmeter at each use point. This can save considerable money and improve the overall accuracy of total water usage. The primary complaint of users is that a totalized water flow rate is erratic when the water line must be completely drained. This is true for vortex, magnetic and Coriolis meter technologies. Maintaining two flow sensors that are kept full produces consistent results.

On water-for-injection, the purity of the water cannot be compromised. The failure of vortex or magnetic flowmeters can expose the water to particulates and impurities. In these cases, the use of any style Coriolis meter is preferred for flow rate.

Other Coriolis Flowmeter Considerations

Weighing Cost vs. Performance

Coriolis flowmeters are more expensive than most other flow measurement technologies. The additional cost is justified by considering the functionality only a Coriolis meter provides:

  • Accuracy specifications from 0.5%-100% of range that allow setpoint optimization without replacing a flow sensor;


  • Zero internal fabrication joints, polished interior and straight-tube design facilitate cleaning and draining;


  • All metal surfaces eliminate risks from leachables and particulates from the breakdown of synthetic materials;


  • No internal fluids to leak into the process;


  • A direct mass flow rate or total.

Alternate technologies are generally preferred when the flow rate to be measured is kept in a small range, the process fluid is a consistent density, and the flow rate is volumetric.

Overcoming Transient Flow

There has been much recent attention given to the difficulties associated with transient flow (two-phase flow, entrained gas, slug flow, empty-fill-empty, and flashing). Generally, transient flow refers to processes where there is continuous or intermittent mixture of gas, liquid, and/or solids in the process. In pharmaceutical manufacturing, the high degree of batch processing coupled with cleaning practices leads to many situations where a flowmeter will start empty, then be filled and emptied again by design. There are also instances of bad hydraulic design in the piping that leads to gas entrapment and entrained gas flow.

Virtually all technologies, including Coriolis flowmeters, suffer unacceptable levels of error when subjected to significant transient flow. Hardware- and software-based solutions to transient flow in the current generation of Coriolis meters reduce the impact of transients. Still, in processes with known transients, the problem is best solved by application-specific consultation with the flowmeter manufacturer. In addition to making the best measurement choice, there are many simple system modifications that improve the accuracy of the flowmeter in these situations.



About the Authors

Vince Salupo is an Engineering Consultant for Eli Lilly’s Manufacturing facilities worldwide. He is leader of the instrumentation standards team that selects the flowmeter standards for Eli Lilly’s global pharmaceutical manufacturing operations. He has a B.S. in Chemical Engineering from Case Western Reserve University. He is a licensed professional engineer and member of ISA. Salupo can be reached at v.salupo@lilly.com.

Franki Parson is the Life Sciences Industry Manager for Emerson Process Management, Micro Motion Division. She has a B.S. in Chemical Engineering from South Dakota School of Mines and Technology. She is a member of AIChE, ISPE and is a participant on the ASME Bioprocessing Equipment Standard Task Group for Measurement Instrumentation. Parson can be reached at franki.parson@emersonprocess.com.

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