Knowing the flow
Flow measurement and validation in pharmaceutical plants

Accurate and consistent measurement of flow is critical, especially in pharmaceutical plants. This article explains the advantages of mobile calibration trolleys based on Coriolis mass flowmeters.
Modern pharmaceutical plants rely on accurate and consistent flow measurement to ensure that ingredient quantities are correct. Indeed, the regulatory authorities require that the accuracy of these delivery systems is established as adequate before the plant is licensed, and that there are procedures to ensure that flowmeters are calibrated regularly thereafter. Micro Motion Coriolis mass flow measurement systems from Emerson Process Management have been widely applied in modern pharmaceutical and biotechnology processes, particularly in batch manufacturing. Micro Motion mass flowmeters are highly accurate, have a wide turndown and are unaffected by
fluid composition, temperature or viscosity. The latest Micro Motion units are available with polished stainless steel external surfaces and electronics housings suitable for installation in hygienic areas, and with all the industry-standard hygienic process connections (Figures 1 and 2). With no difficult installation requirements, such as the need for flow conditioners or long straight pipe runs, these meters are easy to fit into compact skids or plant modules. This is attractive to pharmaceutical plant designers, who often try to make maximum use of standard modules.

The need for calibration
Quality control procedures and systems must ensure that the production control systems operate according to specification, to maintain product quality. A procedure to validate the accuracy of flowmeters and verify their calibration is therefore needed.
Emerson Process Management, one of the world’s largest manufacturers of mass flowmeters, has four manufacturing calibration facilities for Micro Motion products.
The Emerson Measurement Technology and Test Laboratory in Boulder, Colorado, USA, houses the Global Primary Flow Standard, the group’s primary flow test facility. This facility achieved ISO 17025 accreditation in 2003 at flowrates of 0.2–3200 kg/min, with a calibration and measurement capability of 0.014 mass percent.
The Global Primary Flow Standard is used to calibrate Global Reference Meters at each of the group’s four manufacturing calibration facilities. The Transfer Standard Metering (TSM) methodology used provides an uncertainty of 0.03 mass percent.
Industrial users can return their Micro Motion flowmeters to these four centers for calibration checks. Alternatively, calibration reference Coriolis flowmeters are available from the Measurement Technology and Test Laboratory in Boulder. These meters have a calibration accredited to ISO 17025 and are certified to an uncertainty of 0.03 percent. Several test houses worldwide have installed these meters as flow standards.
Trends in calibration
The best way to verify calibration of a flowmeter on a production plant is to do it on-site and in-situ. This maintains the integrity of the meter installation, avoids the chance of damage in transit, and helps preserve process cleanliness.
For many years, calibration service companies have provided mobile “prover vessel” systems for on-site calibration. Now, however, the use of portable reference flowmeters is becoming common. The reference flowmeter approach uses a mobile rig based around a flowmeter that has been calibrated on a high-accuracy, standards-traceable primary flow rig. The technique was developed some years ago in Scotland, mainly for the whisky distilling industry: J. E. Cockayne of Glasgow developed portable provers. Since the UK government collects excise duty on the quantity of whisky leaving the distillery, measurement standards are high. The required volume measurements are usually derived from Coriolis mass flowmeters, which in turn are calibrated using the portable provers. Based on experience in the whisky business, Emerson also started supplying custom-built portable flow verification units to pharmaceutical companies. These trolley-mounted systems (Figure 3) were used by the QA departments of the pharmaceutical firms; having an internal standard maintained business confidentiality and promoted confidence in the unit’s cleaning and service history. Like any calibration system, these trolleys needed to be re-calibrated themselves against a master flow rig at specified intervals.
Standard calibration carts
Demand for the original trolley-mounted units was such that Emerson developed a standardized traceable mobile calibration cart for use on Micro Motion products in the USA.
A typical customer was a pharmaceutical plant in Chicago that used three separate systems to validate liquid transfers. Weigh scales used in batch operations were calibrated with NIST-traceable weights. Precision turbine meters were employed as master meters for flowmeters on process lines of 50 mm or smaller. For larger lines, an outside metrology service used truck-mounted volumetric provers to calibrate meters up to 150 mm in size. The internal procedures were labour-intensive and time-consuming, while the external services were expensive. In addition, the turbine meters required exactly-specified test fluids and frequent recalibration. While the turbines were accurate to ±0.25 percent, they could only be used as standards to certify accuracy to ±1 percent, and this limited the company’s ability to satisfy FDA requirements.
The company replaced this poorly-performing system with calibration carts based on four sizes of Micro Motion Coriolis flowmeter, covering process lines from 12 mm to 150 mm. Weigh scales and flowmeters around the plant could now be calibrated using a simplified set of standard procedures, whatever the meter size. The Micro Motion meters are accurate to ±0.1 percent, allowing verification of process flowmeters and weigh scales to ±0.4 percent to conform to FDA rules.
Engineers soon found that they could use the carts to verify temperature as well as flowrate in CIP systems, since the Micro Motion transmitters measure temperature as well as density and flowrate, and to check the performance of pumps. Since the test meters are not sensitive to variations in process fluid composition, no special fluids are needed.