Applying the FDA’s PAT Initiative in Product Development
by Jim Cahill
Interphex2008, the Pharmaceutical and Biotech manufacturing conference is going on this week in Philadelphia. Before Emerson's Terry Blevins and Mike Boudreau left, they passed along the presentation they are giving on Thursday, March 27. It's entitled, Application of PAT in Product Development. They are joined by University of Texas at Austin PhD graduate student, Yang Zhang and Broadley-James' Trish Benton. Here's an excerpt from the abstract:
The Process Analytical Technology, PAT, initiative encourages innovation in pharmaceutical development, manufacturing, and quality assurance to enhance understanding and control of the manufacturing process. The challenge for many manufactures is to identify how best to address the opportunities that PAT offers. Broadley James, Emerson Process Management, and the University of Texas are working together to examine and quantify the potential to reduce cycle time and out-of-spec product through the use of high fidelity, dynamic simulation and multivariate analytics. The objective of this work is to show that the impact of PAT can be maximized through the integration of these tools during product development (PD).
In the presentation, Terry begins by discussing the U.S. Food and Drug Administrations' PAT initiative, which has a framework that identifies some of the tools they discuss in the presentation. These include:
- Multivariate data acquisition and analysis tools
- Process and endpoint monitoring and control tools
- Continuous improvement and knowledge management tools
Terry describes on-line process analytics including fault detection and quality parameter prediction. Tools for detection of abnormal operations vary for measured and unmeasured disturbances. For measured disturbances, principal component analysis (PCA) captures contributions that can be associated with process measurements. Deviations may be quantified using Hotelling's T-square statistic.
The residual space that is not captured by the principal component score space reflects changes in unmeasured disturbances that can impact operations. These deviations can be measured with the Q statistic, squared prediction error (SPE).
For the quality parameter estimation, detection of deviations is addressed using projection to latent structures (PLS).
Armed with these statistical tools, Mike shows how the basis for bioreactor process modeling. In the book Mike coauthored with Greg McMillan, New Directions in Bioprocess Modeling and Control, they present a first principal bacterial model that was developed for fungal, bacterial, and mammalian cell processes. The intent of the process model is to more quickly evaluate input step techniques and control strategies in the PD stage.
The BioProcess International magazine article, PAT Tools for Accelerated Process Development and Improvement describes this collaborative effort between Emerson and Broadley-James technologists and University of Texas researchers along with how these tools can accelerate life science manufacturers' PD phase.
Tags: bioprocess modeling
| Interphex
| process analytical technology
| PAT
| multivariate analytics
| first principal model
|
March 25, 2008 in Analyzers, in Control Strategies, in Life Sciences, in Simulation | Comments (0)
Recommendations for Increasing Heater Efficiency
by Jim Cahill
A great question came in on the Operating Fired Heaters More Efficiently and Reliably blog post:
Jim I work with natural draft heaters on a daily basis and have initiated several efficiency tests with improved burner internals. I am looking for an opportunity to optimize dual firetube treater by first off improving the combustion efficiency to 80% in each tube and then staggering the temperature controls so that one tube runs 90 to 100% of the time and the other tube only fire during high load requirements.
I sent the comment around our advanced automation consultants for any comments that they might have and I received a great reply from Lou Heavner whom you may recall from earlier posts. Lou describes how to approach optimizing these heaters:
Heater efficiency is calculated using heat loss or input/output method. Input/Output method is difficult because you have to account for lags and delays between fuel firing rate changes and the measurement of process heat absorption changes and in the specific case where there is incomplete phase change on the process side (e.g. partial vaporization) you cannot easily solve with reasonable instrumentation. The heat loss method measures heat loss in the flue gas and assumes any other losses are negligible and constant. If not, they need to be measured and added as well.
Heat loss requires knowledge of the supply air (and fuel) temperatures and the flue gas exhaust temperature as well as the composition of the fuel and flue gas, just like with a boiler. In perfect combustion, there would be no unburned fuel in the flue gas and no sensible heat losses. But due to practical considerations, there are sensible heat losses and to calculate them, you need to know the delta T between the exhaust and ambient and how much excess oxygen remains in the exhaust. Efficiency calculations made using this technique can be pretty accurate in a natural draft heater, but if there is air leakage after the combustion zone, tramp air will show up as lower efficiency due to increased O2. And there is usually an optimum cost operation where the trade-off between sensible heat losses and unburned fuel losses require some level of unburned or incompletely burned fuel leaving in the flue.
When you are ready to control, the goal is to minimize excess O2 while not allowing excessive fuel to go unconsumed. CO analyzers are often used to detect incompletely burned fuel and the goal is usually to keep it below 150 ppm or some lower target. O2 is controlled to stay as low as possible without exceeding the CO limit, which is usually 2% O2 or less for the fluegas.
You can do this with simple feedback control, but feed forward control can help do better. Information on fuel quality, if it varies, and process side temperatures and flows (the heater load demand) can be used to adjust the fuel and air for combustion to meet the heating demand at maximum efficiency. Fuel and air cross limits are often used to maintain fuel and air ratio without getting into a fuel rich condition in the firebox during load changes. But airflow is usually difficult to measure. Therefore, it is often inferred from damper position.
When evaluating an application, we would want to know what instrumentation already exists and what the process variability looks like. What efficiency are they currently obtaining? Then we would look at the control valves and any other contributors to variability to see if they warrant repair or replacement. We would similarly evaluate the instrumentation and analyzers to see if they need anything there.
Then we could evaluate the control strategy and performance and recommend reconfiguration or tuning as appropriate, which may include advanced process control (APC). The person evaluating the controls would have to weigh the cost against the improvement from better loop tuning, valve repair/replacement, CO analyzer, etc. to come up with the best solution. Dampers are often the weak link in fine control of a natural draft heater.
As my colleague Doug Simmers in Emerson's Rosemount Analytical business noted, "The commenter is probably correct with the strategy to fire one heater full out, and bring the second unit on only when needed. Running at full fire develops the best turbulence for fuel/air mixing, and the excess O2 can be kept lower." This is a load allocation problem when two heaters are firing simultaneously. If we can model heater efficiency for each heater as a function of load, then we could optimize the load allocation across both heaters when both must be fired. Actual testing would identify the models, uncover the best strategy, and verify or disprove this assumption."
He may also be interested in the efficiency calculator, developed by Doug's team.
Join the conversation and add a comment if you have experience to share.
Tags: fired heaters
| firetube
| fuel firing
| flue gas
| efficiency calculator
|
July 23, 2007 in Analyzers, in Energy Management, in Fired Heater, in Process Optimization | Comments (4)
Increase Energy Efficiency with Better pH Measurement
by Jim Cahill
Process manufacturers continue to seek ways to improve their energy efficiency, due to the high cost of energy. Corrosion and solids deposition in boilers, condensers, and steam turbines reduce the efficiency of this equipment and increase energy usage. This can also lead to unscheduled downtime if the conditions persist long enough to cause equipment failure.
One important way to minimize corrosion and the formation of solid particles is to have ongoing, accurate and reliable pH control in the boiler water, boiler feedwater and steam condensate, and main steam (carryover.)
The challenge is that these applications are often very low in conductivity. This is a challenge for continuous pH measurement due to the unavoidable formation of liquid junction potentials in the reference sensor. These cause offsets and instability in the pH measurement.
Emerson's Brian LaBelle, a power industry manager for Rosemount Analytical liquid analytical devices, explained these junction potentials are caused by spontaneous migration of ions from more concentrated to more dilute solution within a pH sensor electrode. What happens is a charge separation occurs among the various ions present. (At the word "ion", my mind raced back to those repressed memories of college chemistry lectures...)
Sometimes a severe junction potential occurs when there is an imbalance of negatively and positively charged ions across the liquid junction found in the basic reference electrode. The lower the porosity of the junction, the greater is the charge separation across this junction.
Sounds like we've gone a long way from the original problem of keep the equipment from corroding and being gummed up with solid particles.
Brian brought me to the solution by explaining that the technology team came up with the solution of replacing the diffusion junction with an open capillary (that's a hole for most of us.) Actually, this is not new or innovative, but what is innovative is that precise, laser drilling on a micro-scale of tens of microns is far more precise than what can be achieved with a twisting, mechanical bit. To minimize the junction potentials and provide more accurate measurement, the optimum capillary is laser-drilled at 25 microns in diameter. This capillary is also tapered outward to the outlet filter to help avoid clogging.
As we depart the micro world of ions and laser holes and return to our world of boilers, condensers, and steam turbines, the pH measurement with the Rosemount Analytical 3200HP pH sensor provides more accurate and reliable continuous measurement to ward off corrosion and solids formation. This means more reliable, efficient operations for this energy-consuming equipment.
Tags: pH measurement
| pH sensor
| energy efficiency
| corrosion
| boiler
| condenser
| steam turbine
|
July 19, 2007 in Analyzers, in Boilers, in Measurement | Comments (0)
Simplifying the View of Smart Device Information with EDDL
by Jim Cahill
Automation World magazine recently had a great primer article on electronic device description language (EDDL) entitled, Device Descriptors Prove Merit. Application manager, Jim Gray, in Emerson's Rosemount Analytical Liquid division best summarized this important standard by saying:
...the most important thing about electronic device description language (EDDL) is that it makes managing process instrumentation easier.
If you're unfamiliar with EDDL, here's a short summary from an earlier news release:
An international standard — IEC 1804-3 — Electronic Device Description Language (EDDL) is a universal interface to diagnostic, real-time and asset management information contained in what is currently a growing installed base of more than 20 million field instruments from a host of manufacturers. With EDDL, a user can calibrate instruments, diagnose problems, provide data for user interface displays, identify process alarms, and obtain information needed for high-level software, such as MES, UI/SCADA, plant historians, asset management and ERP.
Virtually every vendor of process control systems worldwide supports the standard language and the information it describes is available in any HART Communication, Foundation fieldbus, or Profibus based instrument made since 1990.
ModelingAndControl.com's Terry Blevins is heading up the ISA-SP104 standards committee to continue to advance the EDDL standard.
I asked Jim for some examples of how this standard makes thing easier for automation engineers, operators, and maintenance technicians. As Jim sees it, the biggest advantage is that the presentation of the diagnostic and other information in smart field devices is separated from the actual data. This allows software applications to present information from a host of different device suppliers in a common, intuitive way.
The best analogy I can think of is RSS where the data resides in XML files on various websites across the internet. RSS Readers like Google Reader, Internet Explorer 7, Firefox, etc. handle the presentation of this information each in their own unique way. As a consumer of RSS feeds, it's much faster and easier to read the feeds in a common location in a common way with one of these RSS readers.
In the case of Rosemount liquid analytical smart devices like pH, conductivity, and dissolved oxygen transmitters provide EDDL files with their diagnostic, configuration and operating data and make this data available to software packages like AMS Device Manager to present the information. Like the RSS readers, AMS Device Manager presents this data in a standard way including device status, trends, gauges, and advanced device help to name a few. This is true for any suppliers' devices which support the EDDL standard. Also, other application software which supports the EDDL standard can present this information from Emerson devices which support this standard.
Jim sums it up rather nicely in the article:
The whole idea is to let the user know what is going on with the device and any actions that need to be taken, quickly and clearly, and to make configuration commissioning easier.
Tags: EDDL
| interoperability
| IEC 1804
| SP104
| analytical device
|
March 20, 2007 in Analyzers, in Interoperability | Comments (0)
Finding Process Analytical Technology Opportunities
by Jim Cahill
The growing conversation on the Food and Drug Administration's Process Analytical Technology (PAT) initiative continues. My persistent RSS search on PAT pointed to another great article, this time in Pharmaceutical Technology magazine. The article, The Five Steps to Starting PAT by Jacob Cook, discusses simplifying the process of getting started with a PAT initiative.
The five steps discussed were:
- Pick simple.
- Understand all the details and nuances.
- Evaluate the instrumentation you already have, and the information you can easily collect.
- Understand the appropriate intervals for collecting that data.
- Evaluate the tools available for reading and synchronizing the data.
Just last week we discussed the benefits of applying a structured approach to a PAT initiative to improve opportunities for initial success.
I passed this article by Christie Deitz, whom you may recall from earlier posts on PAT and ISA-88 (S88) projects. Like most initiatives, Christie believes having good data (step 3) is very important. The Life Sciences industry project teams use DeltaV Batch which integrates in a single location the data required for this analysis. This data includes: alarming, continuous and batch history, operator actions and other events. Having this information organized together around batches and campaigns can help identify PAT opportunities.
Where manufacturing execution systems (MES) like Compliance Suite are also used, exception-based reporting can also help with this process of analyzing the data. We discussed using XSL style sheets to do these reports in an earlier post. An example of this exception-based reporting is showing the batch reviewers only the alarm data that occurred during any particular batch run or campaign.
Christie also points out that where manufacturers have already implemented PAT analyzers, they can make decisions in electronic work instructions (EWIs) based on the analyzers' real-time data values to help verify its correct operation. For example, if a PAT analyzer is not reading the expected value based on other operating data, the work instruction can be to have the operator take a manual sample against which to compare the analyzer data value.
Whether you "pick simply" as a starting point or apply a structured methodology to assess the best opportunities to begin, analyzing your existing data is extremely important. The analysis process is less manually intensive when this data is either centralized or logically organized together in some manner to help better identify these opportunities.
Tags: Process Analytical Technology
| PAT
| Life Sciences
| Pharmaceutical
| Biotech
| electronic work instructions
|
March 12, 2007 in Analyzers, in Life Sciences | Comments (0)
Virtual Sensors Improve Quality in Refinery Crude Unit
by Jim Cahill
Emerson's Lou Heavner, a consultant on the Advanced Automation Services team, recently co-authored a paper, Using Neural Network Technology for Virtual Sensing in Crude Refining Units, at the recent ISA EXPO 2006. Lou worked with engineers from Russian oil refiner, Lukoil.
Always a great presenter, Lou not only shared his expertise on this project, but the fact he homebrews beer. I imagine this keeps his control application skills honed!
The paper describes the need to improve quality of refined products to improve upon the current process of taking lab samples once or twice a day. The operators would make changes to the process based upon the lab readings. They tried to control key temperatures and other process variables on the pre-flash, atmospheric, and vacuum columns by manipulating flows including reflux, furnace fuel, pump-arounds and product draws.
To make these quality adjustments more in real-time, the refinery engineers want to use something other than costly and maintenance-prone on-line analyzers. They decided to use neural network technology to build real-time inferential property estimators which could run inside the refinery's existing DeltaV controllers.
Lou work with the Lukoil engineers to build ten artificial neural networks measuring gasoline, kerosene, diesel, VGO, and residue on the pre-flash, atmospheric, and vacuum towers. They believe this application of virtual sensors to be one of the world's largest on a single crude unit.
The real work comes in collecting the data needed to train the neural networks. They needed around 100 lab samples for each model and the continuous historical data for process variables over this sample period. The DeltaV Neural software helped automatically perform the data collection and model training need to build and prove the neural networks. Up to 20 process variables were collected as inputs in training each of the ten neural networks. Any abnormal operating conditions were identifies to exclude the data from this time period from the model. Any of the variables that had little or no effect on the model outputs were eliminated.
The largest challenge in the data collection effort was in the lab data. It had to be accurate in terms of precise time of taken sample and the proper analysis of the sample. The quality of the neural networks is directly impacted by the accuracy of the samples. Another important factor is to make sure the process data is not filtered or manipulated, but instead a raw snapshot.
The resulting inferential sensors predicted what the lab results showed within a few degrees. The ones estimating lighter refined products were more accurate. The engineers have not closed the loop to run the control strategies based on these readings, but they do present the information to the operators to make adjustments more frequently then they could with samples coming only once or twice a day.
Tags: neural network
| virtual sensor
| lab sample
| crude unit
| refinery
| refining
| distillation
| ISA EXPO 2006
|
October 31, 2006 in Analyzers, in Distillation Column, in Process Optimization, in Refining | Comments (0)
Better Beer Quality by Measuring Dissolved Oxygen
by Jim Cahill
One of the workshops that caught my eye at next week’s Emerson Exchange meeting is Dave Anderson’s Dissolved Oxygen Measurements Improve Beer Quality and Lower Operating Costs. Dave is from Emerson’s Rosemount Analytical division. This probably caught my eye because I’m a fan of quality beer.
Dave helps us novices with the basics like what dissolved oxygen actually is. It’s the concentration of Oxygen (O2) in liquid phase remaining after exposure of gaseous oxygen to an aqueous solution. The process of brewing is aerobic where the yeast requires oxygen to convert the sugars to ethanol in the fermentation process. The dissolved oxygen measurement is important since too much oxygen can create unwanted side effects, including excess Dimethyl sulfide. This compound negatively impacts the beer’s taste.
The Rosemount Analytical Dissolved Oxygen sensors are designed to handle high pressure surges and not be as sensitive to flow rates. Most oxygen sensor can handle a few clean-in-place (CIP) operations which clean and sterilize the process vessels and piping. This sensor was designed to handle more than twenty of these CIP cycles.
Dave mentions the key process areas where brewers should measure dissolved oxygen. These areas include: brewhouse wort kettle, fermentation/aging tank, de-aerator vessels in the packaging area, and the utilities. Also, it is important to develop best maintenance practices to maintain highly accurate measurements over time.
Better control of the dissolved oxygen levels throughout the brewing process has great impact on the quality of the beer produced. And that makes us global beer consumers happy indeed. I hope to see a few of you next week in Nashville!
Tags: brewing
| beer making
| dissolved oxygen
| fermentation
|
September 26, 2006 in Analyzers | Comments (0) | Trackback (0)


