The biopharmaceutical
industry relies more and more on portable systems to perform a range of
manufacturing processes. For example, liquid chromatography systems used for
purification are often mounted onto portable skids with rollers allowing it to
be moved around the production site. Likewise, single-use bioreactors and
portable mixing systems may be similarly configured. Portability saves
manufacturers tens of thousands of dollars in permitting, construction and piping
costs. At the same time, portability presents its own set of special challenges
including power sources, wiring, connectivity to the transmitters and communication
with the distributed control systems. Another interesting challenge is proper
electrical grounding for the transmitters. The pH transmitters must be
electrically grounded correctly or erroneous readings will occur (also known as
ground loops). Many of these problems, however, can be overcome with the simple
addition of new technology – wireless.
Although not all
measurement devices utilized on portable skids are available via wireless today,
some are – notably the liquid measurements such as those for pH, conductivity
and temperature. What users are finding is that installing even a few wireless
devices on a portable skid can significantly reduce wiring costs and the need
for power sources, as well as improve reliability and performance.
Today’s Wireless
Before making a
“wireless” decision, a manufacturer will responsibly ask if the technology has
progressed to the point that it is reliable in critical applications such as biopharmaceutical
manufacturing. The answer is an emphatic yes. Over the last couple years, the
industry’s first wireless transmitters for pH and conductivity measurement have
entered the market. These transmitters utilize the WirelessHART 7 communication
protocol – an open platform that is rapidly becoming the defacto standard for
wireless communications. The analyzers, therefore, seamlessly integrate into
any network of WirelessHART devices. Perhaps most important, the WirelessHART
protocol allows wireless transmitters to operate in a “self-organizing”
network. In this configuration, every wireless device on the network acts as a
router for nearby devices. This means that all devices work together to
identify and use the most efficient communication path for each message, and in
the event of a problem with any single device, other devices are equally
capable of carrying the message. The network dynamically reconfigures itself
without manual intervention and without disrupting the flow of data. This makes
for very high data reliability and availability, characteristics essential in
biopharmaceutical production.
Security is, of
course, a huge concern and the new pH and conductivity analyzers take full
advantage of multilayered security features available in the WirelessHART
standard. These include encryption with automatic key rotation, device
authentication, and data verification. External interference is mitigated by
spread-spectrum broadcast and automatic channel selection that avoids the noisy
spectrum. Consequently, wireless networks can now offer security and
reliability comparable to hard-wiring.
An additional
benefit of the WirelessHART protocol is availability of diagnostics through the
wireless signal. These diagnostic signals are relayed along with process
variables to the plant’s asset management system, providing operators with a
quantitative means of evaluating the validity of the measurements. This data
sophistication aids in scheduling of maintenance and creation of the required
calibration audit trail.
The Measurements
Analytical
measurements play a critical role in several steps of pharmaceutical
manufacturing. Key among these is in chromatography and purification systems designed
for separating and purifying proteins and bio-engineered products. Conductivity
is one of the key determinants of when to start and end this collection
process. Tighter conductivity controls increase purity yields and may improve
secondary collection processing steps. pH also plays an important role in the
purification procedure, providing feedback control of buffer and effluent feed
through the column. Three analytical control points (two conductivity, one pH) are
included in most chromatography systems.
Bioreactors
depend upon pH measurements and temperature transmitters to control acid
addition within the process. Often, reactions must occur within an optimal pH
range in order to maximize yields and minimize unwanted byproducts that would
have to be removed by downstream purification. Portable mixing and buffer
preparation skids are used in a number of biopharmaceutical processes such as
cultivation, fermentation, purification and chromatography. These systems rely
on pH and conductivity to maintain optimal pH salt content and other parameters
of biologics within a desired range.
Portable Wireless Systems – An Example
It’s easy to see
that wireless technology and portable single-use systems are a match made in
heaven. A study done by BioProcess International™
asked users for the deciding factors in their decision to implement single-use
systems. Among the leading answers were cost savings and increased flexibility.
The addition of wireless technology to the portable skids forwards both goals.
Wireless
analytical systems utilize field-replaceable lithium thionyl chloride power
modules, requiring no external power sources or additional wiring. The life
expectancy for the power module is six years based on a once-per-minute update
rate at 25ºC.
The most obvious result is a substantial reduction in costs, power
requirements, and an increase in true portability. Wireless also makes possible
the collection of process data that might be too expensive to collect in a
wired system.
The less obvious
result of wireless technology, however, is a boost in measurement accuracy due
to the improvement in grounding. Portable skids are on rubber wheels which
don’t make good contact with the ground and can result in what’s called a
“floating ground.” Without a well-grounded instrument, the cabling on a wired
system can pick up interference from the motors, causing noise or readings offsets,
resulting in less accuracy and reliability. Wireless transmitters substitute RF
signals for twisted pair wires and, therefore, are significantly less
susceptible to noise interference. In addition, they have no external power
sources to create more potential noise.
As a way to
reduce the number of wired connections and thus save money, some pharmaceutical
processing plants have tested wireless to wired pH and temperature analyzers in
applications such as cell culture manufacturing in small scale bio-reactors.
The only notable difference in the operation of the wired and wireless
instruments has been the fact that while the wired transmitters provide updates
once per second, the wireless transmitters can be configured to update the primary
variable less frequently. However, if the primary variable exceeds the
pre-determined set points – in this case pH – the primary variable is updated
more frequently on an exception reporting basis. This method, known as “Trigger
Burst Mode,” communicates the process variables only when a measurement value
changes significantly since the last communication, or if a required reporting
period has been reached. This approach, sanctioned by the WirelessHART
standard, optimizes the power module’s life.
The purpose of
these tests in each case was to determine if there was any difference in the
wired versus wireless systems. The result showed no difference in performance. Rosemount
customers have uncovered an interesting bonus in the wireless operation, however.
Because the wireless transmitters are self-powered, they are isolated from
spurious ground-loop potentials that get introduced into any reaction vessel
from a number of different sources. These potentials dramatically affect the
accuracy of pH sensors. In tests, when a ground noise induced spike appears on
the pH signal, it is not present in the wireless transmitter output.
Noise reduction can
lead to significant qualitative improvements in the control of bioprocess
applications since improvement in signal equates to better process control.
Temperature, pH and dissolved oxygen are the basic measurements needed for
high-value pharmaceutical reactors and wireless technology can become a key
differentiator for a company providing portable systems.
For manufacturers
of single-use portable systems, the integration of wireless analytical
instruments is as close to a “no-brainer” as can be imagined since it meets the
goals of cost reduction, increased flexibility and improved performance. It’s
even possible to retrofit some existing systems with wireless capability. For
pharmaceutical manufacturers, wireless technology only increases the advantages
of portable systems.
About the Author
Dave
Anderson is the industry marketing manager at Emerson Process Management,
Rosemount Analytical. He has more than 20 years experience in various process industries.
For more information, please visit www.RosemountAnalytical.com.