Life Sciences

I saw a tweet yesterday, which pointed to a great BioProcess International article, Biopharmaceutical Information Infrastructure 2.0 (Part 1 of 2). I sent the link to Emerson's Jonathan Lustri, who manages the Syncade smart operations management brand for his thoughts. I thought they were great and needed no further elaboration from me. Here's what he wrote back:

Regarding information management within a Biopharmaceutical operation, this article does a nice job of laying out information about data collection and visualization for postproduction analysis. Systems that do this may generally be categorized as manufacturing intelligence (MI) systems.

This is all well and good for applications where engineers and quality assurance (QA) people want to perform analysis on how to improve the process or investigate what went wrong. It misses all together the opportunity to use information to prevent errors and assure manufacturing efficiently. In order to truly gain benefits to eliminate human error and speed QA review and approval, information has to be applied within the context of performing manufacturing procedures.

So in addition to all of the points made in this article, biopharm processing should consider software systems that electronically dispatch work procedures to operating personnel and bring to them the information they need to correctly perform the procedure. In most Biopharm facilities, work procedures are coordinated with paper standard operating procedure (SOP) documents and Batch Production Records.

Depending on personnel to read paper instruction, correctly follow these instructions, and then manually record key information by hand in paper batch production records affords huge opportunity for error. Furthermore, even if a site has a well-developed manufacturing intelligence system, all the information recorded on paper either never makes it into the MI database, or requires the information to be transcribed at a later point.

There are software systems now available, such as Emerson's Syncade Smart Operations Management suite that include workflow engines that dispatch step-by-step work procedure guidance to operators to direct them how to perform the procedure. And, through integration with other systems, information can be brought to the operator within the context of the procedure to assure efficiently performing the procedure.

For example, a sampling operation may require a sample ID from the laboratory information management system (LIMS). By using a workflow software system to guide the operator on the steps to take the sample, we can increase the likelihood the procedure will be performed correctly and we can automatically provide the technician the sample ID if the workflow is integrated to the Lab information system and even automatically print out the sample bar code label.

Another value workflow execution systems can bring is in the coordination of work activities. If quality manufacturing requires two operators to perform different tasks which need to be coordinated, using paper-based batch records, such coordination can only occur by two technicians talking together to verify things are coordinated.

The result is that they may not talk and the activities may occur uncoordinated. Using a workflow execution system, the workflow engine performs the coordination and only dispatches work activities at the point in time they should be performed.

To summarize, data collection and visualization information systems for manufacturing intelligence provide significant value in postproduction analysis for investigations and process understanding. The biopharm industry should also look to workflow software systems to apply information within the context in process procedure execution.

The primary benefits of this are that it enables truly paperless operations, eliminates human error and increases productivity by eliminating many manual information look up steps.

It makes sense to reduce errors by automating the workflows where possible and practical.

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In an earlier post I mentioned how Emerson's Shenling Yang had taken an assignment in Shanghai, China. She's bringing her expertise in operations management and the Syncade software gained while executing projects as a member of the Life Sciences industry team. Shenling had some thoughts on the FDA Globalization Act of 2009 and its impact on pharmaceutical and biotech manufacturers across the globe.

The Formulary web site sums up the act:

The Globalization Act expands FDA's authority to inspect foreign plants, to block questionable imports, and to crack down on those who fail to comply. Regulatory "parity" is sought to ensure that lax oversight is not luring manufacturers from the United States to Asia. All registered manufacturers and importers--including generic drugmakers--will have to pay new user fees to support the broader oversight program, and manufacturers will ensure the integrity of product supply chains through electronic pedigrees. FDA also would gain the power to detain, recall, or destroy unsafe, adulterated, or misbranded goods. The act gives the agency added authority to subpoena records and to impose criminal penalties for drug counterfeiting.

The web site continues:

Ironically, legislation that increases FDA inspections of foreign drugmakers may reopen the door to drug importing. A group of leading senators is sponsoring a bill to allow nationwide reimportation of prescription drugs, claiming that the program would save $50 billion over 10 years. All of the imports would have to come from FDA-approved manufacturing plants in Canada, Europe, Australia, New Zealand, and Japan--a policy that assumes more frequent inspections and a viable pedigree system.

Shenling provided her views on the legislation's impact on Asia:

It will impose higher costs on the Asia Pharma industry, because of its stringent quality compliance requirements, particularly the new requirements to secure entire supply chains. On the other hand, it might also help raise Asia Pharma industry's competitiveness on the global stage.

The Act may encourage Asia exporters to follow a more structured approach towards securing supply chain and higher quality standards. Hence, it might reduce the cases of non-compliance. Considering the growing export markets, maintaining the quality standards required for these exports might help Asia Pharma companies grow revenues to offset the costs of this legislation.

Shenling described how the ISA95 information model with automation like the DeltaV system and Syncade operations management can help with compliance.

One of the important aspects of the operations management is quality and compliance. By using the latest technology and adhering to the ISA95 standard, Syncade smart operations management suite integrates smart real-time, plant-floor data with your business processes. Through data and workflow management, Syncade suite reduces non-value added activities and variability. By identifying and correcting problems during the manufacturing process instead of post-process, this streamlined workflow improves the product quality and regulatory compliance.

DeltaV Batch uses the ISA88 standard, which helps batch process manufacturers to define a single recipe in a single engineering environment. It reduces time and cost during the documentation, implementation, and validation phases of a project, and enables manufacturers to quickly produce a quality end product.

Thanks for your perspectives on this legislation and its impact on pharmaceutical and biotech manufacturers, Shenling.

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I caught up the other day with Emerson's Shenling Yang, who is a senior project execution engineer in the Life Sciences and Food & Beverage (LSFB) industry group. You may recall Shenling from earlier posts.

She shared two pieces of news with me. The first is that the Critical Data Backup application developed by the LSFB team, and used for protection of DeltaV automation system configuration and critical process data, has been extended to the Syncade operations management software. Shenling has been working on a project with a pharmaceutical manufacturer implementing this application.

In one of the earlier posts with Shenling, Backing Up and Recovering Critical Control System Data, the goal of a biotech manufacturer was total recovery from a system failure in hours instead of weeks. For highly regulated industries, the scenario described was:

...the dreaded 3 am phone call from the plant with the news that production has stopped, people standing around and it's up to you to do something. Choice one is to go to the plant, to rebuild the automation system configuration, to revalidate the process, to lose a bioreactor batch that may have been running for up to 100 days, and then to hopefully resume production within a few weeks.

The Critical Data Backup application was the solution:

...to meet the 21CFR Part 11 compliance for backup, recovery and preservation of electronic records. It's a part of the overall disaster recovery plan, which includes files, spare on-site server hardware, physical separation of equipment and networks, and always-available support personnel on-site.

With the ISA95 Enterprise-Control System Integration standard, this critical backup need extends to level 3. The Critical Data Backup covers some of the Syncade Suite modules including: Document Control & Archiving, Security & Audit, Equipment Tracking, Batch Production Record, Recipe Authoring, Training and Development, and Manufacturing Information Portal. The backup extends beyond the operational and configuration data to include backup reports, style sheets, and behaviors.

I did mention there were two pieces of news. The second is that Shenling is moving to Shanghai to work with the Emerson Asia Pacific marketing team. She's promised to help me discover and tell stories of all the great work being done by our experts in China. I look forward to being able to broaden out the view of these Emerson experts around the world.

Safe travels and best of success in your new assignment, Shenling! And, make sure to show this post around to everyone that we've promised our readers some good stories.

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I'd like to welcome a new voice, Emerson's Alan Babbitt, to the blogosphere. Alan and team's purpose with this new blog, The Emerson Global Life Sciences Blog, is:

...to provide insight into the Life Sciences Industry from a number of perspectives. We will provide periodic updates on industry trends that include commentary on the state of the Life Sciences marketplace. Of particular interest is the current state of the economy and how we are all affected by change that is in our midst. Our blog will also speak to the value and importance of how the Emerson Team solves business problems at the automation and operations layers of the S95 context model. Readers will benefit from the many years of hands-on experience our team has realized, working with some of the largest pharmaceutical and biotechnology firms in our industry.

Beyond the initial welcome post, his second post looks at the Capital Contraction occurring and its impact on the Life Sciences industry. Alan writes:

Only 1 Biotech firm went public in 2008 and predictions are the Initial Public Offering (IPO) space will continue to be a tough year in 2009. The guess is there will be very few IPOs completed in 2009 and they will be the companies that have proven revenue growth coupled with limited risk. Gone are the IPOs with large technology or regulatory risk. Additionally, venture backed companies looking for more rounds of development capital will be questioning their outlook.

Much like the ModelingAndControl.com blog, I have subscribed to Alan and the Life Sciences team's blog and look forward to sharing some of their thoughts here at Emerson Process Experts.

If you have interests in the Life Sciences industry, the ISA88 and ISA95 models of information management, or industry perspectives of current global economic conditions, you'll want to subscribe too.

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Every industry has its special jargon that is like a secret handshake. If you're an insider, you can quickly spot the outsiders based upon their understanding of your industry's jargon and acronyms. For instance, my background was in the offshore oil and gas business back in the mid '80s. We had jargon like pigging (to clean out pipes) and Christmas trees (fittings and valves on the top of well casing which control the well production rate) to name a few.

My friends in Emerson's Life Sciences/Food & Beverage industry center are insiders in their industry jargon. What sparked this rambling opening was when I read a piece in the Asia Food Journal, Tackling CIP Automation with S88. Written by Emerson's Christie Deitz and Yogesh Rathi, they did a great job, right from the start, defining CIP for us outsiders:

Clean-in-place (CIP) is a method of cleaning vessels and lines without disassembling them. It involves delivering solutions of chemical detergents and rinses at specified flow rates and temperatures. Typically, a CIP skid creates the cleaning solutions and routes them to a user skid that requires cleaning.

According to Christie and Yogesh, CIP began in the 1950s as a manual operation. Over time, this process has been largely automated by most food & beverage, pharmaceutical and cosmetic manufacturers. The authors note that many common challenges exist whether CIP is performed manually or automatically. They include:

• Performing similar actions (acid wash, alkali wash) in an efficient way
• Managing CIP timing of available resources like process skids, and supply/return piping paths
• Minimizing CIP time cycle
• Managing distribution headers or transfer panels to process resources requiring cleaning
• For processes with portable CIP skids used in multi-product facilities, providing local control and easy point-of-use connects

Christie and Yogesh describe how the ISA88 (often referred to as S88) standard and terminology for batch control are applied to CIP processes to address these common challenges. The ISA88 model is comprised of both a physical and procedural model.

On the physical model side, one recommendation was to make the distribution headers and/or transfer panels into equipment modules that are independent of the CIP skid and the equipment it connects to in order to clean and sterilize. The path can be managed as a resource, which allows CIP skids to operate in a similar fashion.

The authors pointed out that the physical model helps to drive the procedural model. They wrote:

The sequences that operate the CIP skid equipment become phases on the CIP skid unit, and the sequences that operate on the user skid become phases on the user skid unit. Similar sequences can be modularized or made into reusable, flexible phases. The differences are handled with recipe parameters.

A final key point is that the ISA88 procedural model can be optimized to run phases in parallel to reduce the overall CIP cycle time for processes with fixed CIP skids. Their example:

...while circulating the pre-rinse solution from one of the vessels on the CIP skid to the user, the other vessel on the CIP skid can prepare the acid rinse solution.

Read the article for specific examples of physical and procedural models for fixed and portable CIP skids.

Understanding the jargon around batch processes begins with understanding the ISA88 terminology. Finding and reading articles like this is a good start as is the ISA website's ISA88 page.

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Recently, one of my RSS feeds alerted me to a new Micro Motion 2400S transmitter packaged in stainless steel for the ELITE Coriolis flow and density meter line. This 316L stainless steel packaging is:

Rated to IP66 and IP67, the corrosion resistant stainless steel housing is ideal for applications where instruments are subjected to regular caustic wash-downs, which are typically found in the food, beverage and life science industries. The 316L construction is also ideally suited for marine and offshore environments.

I caught up with Emerson's John Martin, a Food & Beverage industry manager for the Micro Motion family of products. I wanted to get the story behind the design of this product.

For those that have never been inside a food & beverage or pharmaceutical manufacturing process, John shared how you'll be struck by the bright, shiny silver look you see around the process. Hygienic standards are paramount in these industries and a mild caustic (e.g. sodium hydroxide) is often used to wash down the processing equipment. Standard painted-aluminum transmitter housings do not do well in this caustic environment. This new 316L stainless steel housing allows the transmitter to be integrally mounted with the Coriolis meter and provides a local display at the measurement point for the operations personnel.

John noted that normally, transmitters with aluminum and painted-aluminum housings had to be mounted remotely, in stainless steel enclosures or control rooms, to avoid the corrosive environment. This installation method meant more engineering and installation costs.

This 2400S transmitter supports DeviceNet and Profibus DP communications. These are common digital bus communication protocols used by PLCs and other automation systems like Emerson's DeltaV system. Across two wires, these transmitters communicate process and diagnostic information back to the controllers. From the press release:

The result is that one instrument can provide flow, density and temperature measurements, eliminating the need for multiple sensors and the wiring/configuration costs associated with them. In addition, digital communications unlock instrument diagnostic information, such as drive gain, meter verification and other alarms.

John also shared with me that other industries like offshore oil and gas and other marine environments have corrosive environments caused by saltwater and salt in the air, making them good candidates for this stainless steel transmitter housing.

I do know from my days back as an engineer working on offshore Gulf of Mexico oil and gas platforms, that we put the instruments with painted aluminum housing inside 316 stainless steel junction boxes to protect them from the corrosive, salt-air environment. This packaging option might have reduced the size/number of junction boxes required.

Update: I just saw a Twitter "tweet" from @timalosi who reminds me:

there is more to hygenic than stainless. draining is much more important. the Housing is just for looks

Tim, point taken and all in 140 characters or less!

Twice here at Emerson Process Experts, I've featured the work of Shenling Yang. The first was in her role as member of the DeltaV technology team and the second as an integration specialist in the Life Sciences industry center. Shenling shared with me a presentation she is developing with a biotech manufacturer for the Emerson Exchange on backing up and recovering critical process data. This is a huge requirement for regulated industries like pharmaceutical and biotech manufacturers.

The scenario they will present is the dreaded 3 am phone call from the plant with the news that production has stopped, people standing around and it's up to you to do something. Choice one is to go to the plant, to rebuild the automation system configuration, to revalidate the process, to lose a bioreactor batch that may have been running for up to 100 days, and then to hopefully resume production within a few weeks. To give you a sense of the value of saving a batch, it's important to note that the medications being produced in these bioreactors save lives and any loss of a batch means a delay for a patient who needs this medication.

Choice two is to load the data backed up from the critical data backup application, have the operator restart the plant, verify normal operations and save the running batch in the bioreactor. Obviously, choice two was the way to go. It is vital to protect and recover control system data because human error or system failure can wipe out years of work, experience, plant operations information and process records.

The U.S. Food and Drug Administration (FDA) regulates and requires fully validated backup and restoration solutions for critical data. With the FDA's 21CFR Part 11 electronic record provisions include the accurate and ready retrieval of control system information through the record retention period. The FDA's 21CFR Part 210 & 211 good manufacturing practices (GMP) require this retention period be at least one year after the expiration date of the batch.

The goal established by this biotech manufacturer was to be able to recover and be back up and running 100% with minimal loss in three hours or less. They were looking for something with minimal customization that would automatically back up the configuration and version control databases without any operator intervention. The solution was to use the Critical Data Backup application (CDBA) developed by the data management services team to meet the 21CFR Part 11 compliance for backup, recovery and preservation of electronic records. It's a part of the overall disaster recovery plan, which includes files, spare on-site server hardware, physical separation of equipment and networks, and always-available support personnel on-site and at their Emerson local business partner location.

The backup system includes a server, tape carousel and gigabit network to link multiple DeltaV systems and transfer large files quickly, safely and efficiently. This application help formalize the backup process which was not as diligent or documented as it should have been.

Like anyone who administers a server or even backs up the family PCs can attest, you don't know how good it will work until you have to use it. The day came when this site lost two hard drives in a RAID array. They were able to put a new server in the rack, transfer data using CDBA, do a warm batch restart and be back up in an hour with no loss to the batch.

This sounds like a great presentation to catch if you need a way to formalize your system backup and recovery effort.

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.

Continuous manufacturing processes have long benefited from the application of advanced process control (APC) in their processes to improve upon their regulatory control. Batch manufacturing processes have recently been able to take advantage of these technologies. I received an email the other from Lou Heavner, part of Emerson's Advanced Applied Technologies team. We've featured Lou's work here a few times in the past.

I'll summarize a few of these applications with the hopes that it might spark some ideas for application in your batch manufacturing process.

A manufacturer of sweeteners was having scheduling problems caused by the unpredictability of batch cycle times. End of batch could vary between six and twelve-plus hours. The operators could determine when end of batch was reached but not predict when this would occur. The APC consultants worked with this manufacturer to apply neural network technology as an inferential estimator to predict the end of batch time. The model can successfully predict the end of batch plus or minus ten minutes up to four hours before the completion of the batch. Scheduling downstream equipment is more manageable given these accurate predictions.

A second example Lou mentioned was again around batch cycle time, but in this case poor distillation control, which resulted in longer batches. Model Predictive Control was used in this pharmaceutical manufacturing process to control the batch distillation, specifically the reflux. Distillation time was reduced with the overall batch cycle time reduced by more than three hours per batch on average. The net effect of this improved control performance was a five-plus percent increase in production capacity. The quality of the product produced was also improved.

A third example is in a specialty chemical manufacturer's semi-continuous fluid bed hydrogenation reactor. In this process, cold solids are added to the top batch-wise based on level in the vertical reactor. Heated feedstock (gases) enters the bottom to provide the fluidizing medium and heat to drive the reaction. The reactor was a bottleneck, limited by temperature control and high temperature constraint. Adding model predictive control around the reactor provided more stable temperature control. The controller reduced temperature variability and allowed target to be moved closer to constraint limit with fewer high-temperature trips.

I thought these were great examples of advanced control technologies combined with people like Lou with process and APC application knowledge that are solving process problems and improving process efficiency. Perhaps these ideas will spark some ideas for improvement in your operations.

In the upcoming March issue of BioProcess International magazine, there is a great article by Emerson's Greg McMillan and Michael Boudreau, Broadley-James' Trish Benton, and the University of Texas at Austin's Yang Zang. The article, PAT Tools for Accelerated Process Development and Improvement, describes the collaborative effort between Emerson, Broadley-James, and UT, "...to examine and quantify the potential for faster optimization of batch operating points, process design, and cycle times." The specific objective of this collaboration:

...is to show that the impact of PAT can be maximized through the integration of dynamic simulation and multivariate analytics in a laboratory-optimized control system during product development.

Greg and Michael are putting many of the ideas they described in their book, New Directions in Bioprocess Modeling and Control: Maximizing Process Analytical Technology Benefits, into practice.

The authors outline the challenge for the 400 biotechnology medicines currently in development, which require overlapping and iterative stages for process development and commercialization. These stages include:

...cell line selection and development, media optimization, process conditions optimization and verification, scale-up, project definition, and plant design.

This team is working on beta tests using this new dynamic model and on-line data analytics and wants to make the results fully public to promote wide use and to advance these concepts and methodologies.

If you're like me and not in the biotechnology field, much of the article may get a little deep. I did glean a few tidbits you might find useful. By creating a dynamic model, one of the big benefits to the team is the ability to speed up the model by up to 1000 times real-time. Whether you're simulating the growth of mammalian cell lines or have another slow process, this can really help reduce trial and error time.

Another key is that the model, configuration, and tools can run in the "virtual plant" PC environment or can be downloaded to the automation system. With proper scale up factors:

...the embedded tools go readily from bench-top bioreactors to pilot plants and eventually industrial-scale bioreactors.

With the recognition by the FDA that quality cannot be tested into products, which led to the creation of the Process Analytical Technology (PAT) initiative, the authors discuss the role of analytics in their efforts.

Principal component analysis (PCA) and projection to latent structures (PLS) are two multivariate analysis techniques that can help analyze continuous and batch process operations. The authors' beta test is focusing on the on-line use of these analytical techniques where PLS detects deviations in quality parameters and PCA detects abnormal operations from measured and unmeasured disturbances.

Given the importance of new product development for pharmaceutical and biotechnology manufacturers, anything to reduce the overall development time and build in quality monitoring as prescribed in PAT should be a welcome addition.

While in Asia last week, I had the opportunity to catch a presentation by Bob Lenich, Director of Emerson's Data Management Services. With the announcement last year of Emerson's acquisition of Decision Management International and the Compliance Suite manufacturing execution system software, Bob has been busy integrating the organizations.

The Compliance Suite software is being used by many process manufacturers, especially in highly regulated industries such as Life Sciences--Pharmaceutical and Biotech manufacturers. The starting point for applying manufacturing execution system software is the data model defined by the ISA-95 (S95) standard. The S95 standard describes the architecture of information flow between the plant floor, the automation system, the manufacturing execution level and the enterprise resource planning levels. Getting these workflow activities and the flow of information between them right is what defines highly efficient, customer-responsive manufacturers.

Bob described the place to start as understand the challenges of improving quality, improving throughput and/or increasing process availability/uptime as a few examples of what can drive process manufacturers to look at improving the flow of information around the organization. You have to understand the problems and needs in order to improve things.

As an example, in the area of quality, typical issues are to reduce deviations. These can be caused by ensuring the right material is available to add at the right time or eliminating manual error in calculations. Also, much time and effort currently spent just doing all the paperwork and paper work tracking required to meet today's regulatory needs. Converting from paper to paperless systems can eliminate all of these problems

In addition to eliminating problems, reducing these deviations also improves throughput by reducing batch variability, reducing batch cycle time and reducing the overall batch release time as there aren't as many problems to address.

Solving these problems requires addressing a mixture of automated and manual processes. Bob noted that the best way to address these issues should begin with a look at the current workflow, to understand where efficiencies can be gained.

The workflow should look at equipment, people, materials, documents and existing information to develop the business justifications and information architecture to address the areas of inefficiencies. Once a good benchmark is established, improvements can be made and the results quantified.

There many opportunities to do this and Compliance Suite is a great tool to use for enforcing these changes. Bob stressed that these changes are typically strategic in nature for the process manufacturer and require the upfront planning and design work to focus the efforts to the areas of greatest efficiency gains and continuing to prioritize the areas of improved data management and flow over time.

As he announces yet another eBook now available, ModelingAndControl.com's Greg McMillan continues to share his control expertise with the world.

Greg describes the book Biochemical Measurement and Control:

When Monsanto was making the transition to a life science company, I had the opportunity to work on fermenter measurement and control for various genetically engineered products. Important opportunities identified then such as the application of mass spectrometers, dissolved carbon dioxide probes, and inferential measurements of metabolic processes have come to fruition today opening the door to more advanced process analysis and control techniques. Additionally the applications gave me a chance to apply my expertise in pH measurement and control in new ways and dig into the practical aspects of dissolved oxygen measurement and control.

As he goes on to mention, the progression of technology and new thinking prompted an updated version, New Directions in Bioprocess Modeling and Control: Maximizing Process Analytical Technology Benefits published by ISA in 2006. This book:

...provides an updated view and details on new tools for batch modeling, analysis, and control. This ISA book includes the development of neural network inferential measurements of dryer moisture by Washington University in Saint Louis and my first principle dynamic fermentor models for the National Corn to Ethanol Research Center. The book concludes with an excellent review of new technology for batch analytics by the University of Texas.

As I had mentioned in an earlier post, Greg has chosen to make many of his works available as free eBooks once the copyrights are returned to him. So, for the next many years, the Bioprocess book is available for purchase from the ISA folks or in the DeltaV Bookstore, along with many other great books we've discovered along the way.

We live in great times where many with expertise make it freely available. If this expertise happens to intersect with our interests and we have some bandwidth to absorb it, we're but a mere Google search (or whatever your favorite search engine happens to be) away. It just wasn't this easy way back when!

Pharmaceutical Technology magazine published an interesting article by Emerson's Bob Lenich and Christie Deitz. The article, A Look at 30 Years of Change in Pharmaceutical Automation, recounts the changes affecting Life Science manufacturers from the late 1970s though today. I joined the world of process automation in the early 80s as a summer systems engineering intern in offshore oil and gas production and this article brought back some memories of the amazing changes we've seen.

I'll highlight some items from the article to see if it generates any nostalgic thoughts for you.

Although the distributed control system came along in the mid-70s, Bob and Christie note that most life science companies used pneumatic and single-loop electronic controllers. Data was collected manually or with circular and strip charts.

With growing U.S. Food and Drug Administration (FDA) regulations through the late 70s and early 80s, the DCS began to be seen by life science manufacturers as a tool to help comply.

Batch-based automation systems, the first one being the PROVOX system, came out in the early-to-mid 80s to help with sequencing, failure handling, parallel unit operations, and the creation of recipes.

Just a few years before I recall a little collaborative effort between IBM and Microsoft being introduced to the market (wow a 4.77MHz CPU!) This would have some impact in our industry in the following decade as commercially available technologies (COTS) were incorporated.

Toward the later part of the 80s and into the 90s, standards began to play a larger role. ISA-88 (S88), a batch automation standard was important to life science manufacturers. The digital busses including Foundation fieldbus were developing, and Microsoft operating systems began to make their appearance in systems like the DeltaV system. For communications, the OLE for Process Control (OPC) standard became the way to connect Microsoft-based clients and servers--a big improvement over earlier generation DDE communications technologies.

Automation systems became increasingly modular with class-based configurations. These technologies would help the trend toward more modular construction techniques that brought production on-line quicker compared with prior construction and engineering methods.

Regulations continued to advance to try to address concerns around system, production and data management through the balance of the 90s. Efforts began on the ISA-95 (S95) standard to better define the integration of enterprise and control systems.

These regulations had a positive impact in building competency around data security, record security, lot tracking, and overall batch management. The downside was that it placed the focus of life science manufacturers on meeting regulations rather than continually improving their manufacturing operations compared with other industries.

The FDA's Process Analytical Technologies (PAT) initiative addressed this by changing the focus from meeting regulations to improving operation. The FDA's cGMPs for the 21^st Century added in using a risk-based approach to these improvements. As part of this initiative, they encouraged the use of innovative technologies. We've addressed a number of these innovations with respect to PAT in earlier posts.

Bob and Christie closed the article with a note of how flexibility and the integration of automation with the business-level systems is becoming increasingly important as life science manufacturers move from organic-based synthesis to biologics to continue to develop vaccines and medicines to address our health needs.

Update: Thank you Eric for pointing out the error of my ways! The link to the OPC Foundation has been corrected.

Standards play an important role in fostering technological progress--both in the willingness of consumers to adopt the technologies and suppliers in developing products to meet the standards.

In our world of process automation, standards have continued to advance from base-level digital communications protocols to higher-level data communications standards for process manufacturers. The ISA-95 (S95) or IEC/ISO 62264 family of standards as they are globally known are an example of a set of data standards for the interface between enterprise planning systems and automation systems.

I had a chance to get a preview of a whitepaper that Emerson's Shenling Yang is developing around S95 and the XML-based implementation of this standard called Business To Manufacturing Markup Language (B2MML). You may recall Shenling from an earlier post on project timelines. She is now a data integration specialist in the Life Sciences industry center.

As stated in an ISA press release this past January on B2MML improvements:

B2MML was developed by the WBF's XML Working Group to provide manufacturing companies with a freely available XML Schema implementation of the ISA-95 Enterprise - Control System Integration Standard.

You can get a sense for just how detailed and comprehensive these standards are by viewing some of the schema documents available on the World Batch Forum's B2MML web page. Beyond the common schema organized around the S95 data model, other schemas exist for equipment, extensions, maintenance, materials, personnel, process segments, product definitions, production capabilities, production performance, and production schedules. Warning, these schema documents are not light reading!

On projects requiring workflow improvements and/or paperless operations, Shenling and the team follow B2MML data definitions to be consistent with the S95 standard. Because leading enterprise resource planning (ERP) systems like SAP support B2MML, Shenling finds that it simplifies connectivity and reduces the overall engineering effort for integration between the ERP and manufacturing execution systems like Compliance Suite. Ongoing maintenance is also reduced since the information exchanged between applications follows well-defined data definitions.

An example is an order coming down from SAP in an XML-formatted document complying with the B2MML Production Performance schema. The project team used transaction templates, along with the Compliance Suite support component and the process order XML from SAP to generate the actual transaction documents to be passed from the ERP to Compliance Suite. The automated parts are handled by the DeltaV Batch system and other parts of the process like materials management, laboratory information, and proof of personnel training are sent to their respective workflow processes.

The results of these workflows and batch data from the automation system are consolidated in an electronic batch record, which is a critical piece in reducing the overall cycle time on the way to releasing the product for sale.

Update: Gary Mintchell reports on his Feed Forward blog today that the World Batch Forum has announced version 4 of the B2MML standard and some of the additions to this standard. Here's the announcement from the WBF.

At the recent Interphex Pharmaceutical Manufacturing Conference, Emerson's Todd Ham presented on the subject of automating fermentation. Todd acknowledged that Christie Deitz, whom we've featured in several other posts, had a large hand in the development of this presentation and work on the project discussed.

The presentation discussed a recent project done on a large-scale, multi-product biopharmaceutical complex. This project was so successful it recently won the Facility of the Year Award Winner in Project Execution. One of the keys to success was a clear design philosophy established up front. Elements of this philosophy included:

• Fully automated
• Paperless, dock-to-dock using electronic records, operator handheld devices, and barcode scanning
• Consistency for operators based on industry standards like ISA-88 (S88), ISA-95 (S95), and digital bus technologies
• Focus on fermentation as a key process area for the project

A key to success in the project was the close working relationship between the manufacturer and the Emerson Life Sciences project team on the up front requirements and design, and the subsequent module-level and integration-level testing.

The upfront design considered not only the fermentation and recovery processes, but also the full automation required for paperless operations. This design included recipe-level batch control, warehouse management, electronic signatures, and a complete electronic batch record, including the manual processes. These manufacturing processes included material management, container management, filter management and sampling.

The project team applied the S88 standard to control modules looking to identify the common modules and instances for things like motors and valves. At the S88 equipment module level, the team created project wide module templates, area specific module templates, and unique, one-time use equipment modules.

The sampling system and sparger control are examples of project-wide templates. Fermentation agitator control and dissolved oxygen control are examples of area-specific equipment modules. Transfer panels and valve assemblies are examples of unique equipment modules.

At the S88 unit level, the team designed classes and instances based on physical similarity and phases that they use such as batch media, inoculate, ferment, etc. This led to various unit classes for fermentation vessels including seed fermenters, production fermenters, and feed vessels.

From a recipe standpoint, the design grouped phases into operations, then grouped operations into unit procedures, and finally grouped unit procedures into procedures, all again following the S88 standard.

Todd shared some lessons learned from the team. With regard to the modular design approach, the team learned to keep process units the same as much as possible. With similar units, it is also important to make sure the operations are also as uniform as possible. The team cautioned about the overuse of aliases, which reference pieces of physical equipment like valves and motors, in phase logic. By not overusing aliases, but rather relying on equipment modules to handle physical differences, the phase logic could be generically written to handle multiple pieces of similar equipment like process tanks.

Other lessons learned were to plan for the extra documentation required for high levels of modularity and dock-to-dock automation. Like other members of the Life Sciences team have counseled in earlier posts, time spent upfront in planning and testing saves a lot of project backend effort.

The benefits of a complete electronic batch record vs. a paper-based process in terms of faster release of products are pretty clear. It's important to assemble the project team and begin the planning and design early to prepare for the additional effort commensurate with the increased automation required for a successful project.

From my prior post with Greg McMillan and his thoughts on PAT and Advanced Control, I neglected to mention that he will be at the Interphex 2007 Conference & Exhibition next week presenting two seminars in the Emerson booth (#2354). The seminars will be held 1:30pm on Tuesday and 10am on Thursday. He'll also be around the booth demonstrating the Virtual Plant and DeltaV InSight.

In case you will be there at Interphex2007, I'd be remiss in not mentioning two other Emerson presenters featured here at the Emerson Process Experts blog.

Todd Ham is co-presenting with Genentech's Todd Edgington a session entitled Automating Fermentation on Tuesday from 9-10am.

Mark Coughran is presenting a session entitled Practical Control of Batch Reactors also on Tuesday from 3:15 to 4:15.

I'll work to get my hands on these presentations to recap them for you in future blog posts.

Recently I discovered in my PAT RSS persistent search feed an article in Pharmaceutical Processing magazine entitled, PAT Solutions-Eight advanced process control technologies worth considering. This article was written by Rick Rys, President, at R2 Controls, and Janice Abel, Director, Global Pharmaceutical and Biotech Industries, at Invensys.

Since ModelingAndControl.com's Greg McMillan recently co-authored a book New Directions in Bioprocess Modeling and Control-Maximizing Process Analytical Technology Benefits and recently had an article published entitled Maximizing PAT Benefits from Bioprocess Modeling and Control in the November 2006 issue of Pharmaceutical Technology IT Innovations, I had to ask for his thoughts.

Greg sent me a great email which I'll pass along with my edits to insert hyperlinks:

The DeltaV systems offers the advanced control technologies mentioned in the PAT article, such as synthetic analyzers, feedforward and predictive control, dead time compensation, and model predictive control in its standard integrated graphical configuration studio that uses Fieldbus function blocks. The synthetic analyzers not only include online regression models such as Neural Networks but also embedded first principal models. Furthermore, innovative analytics, control systems, and models can be prototyped faster than real time in a virtual plant on a desktop or laptop PC anywhere. The virtual plant uses an exact duplicate rather than an emulation or simulation of the control system in the control room. Advanced technologies in the virtual plant can be developed and tested from the high speed play back of historical data from existing systems used to automate bench top fermentors. This includes a new adaptive control technology that identifies process dynamics and indicates the relative improvement possible from better control. The high speed virtual experimentation capability of the virtual plant is a key feature and may be the only way to provide enough historical data particularly on "what if' scenarios since a fermentor batch for most new bioprocesses takes 14-17 days.

The same virtual plant can be used for education of operations and technical support by the dynamic restore and high speed playback of instructive periods of operation.

The technologies can be connected to the bench top system for evaluation, verification, and adaptation of models early on in the commercialization process.

The uses and advantages of the synergistic environment of the virtual plant are explored in the book New Directions in Bioprocess Modeling and Control, the article "Maximizing PAT Benefits from Bioprocess Modeling and Control" in the November 2006 issue of Pharmaceutical Technology IT Innovations, and in the lectures on the Modeling and Control.com blog. The important practical implications of the extremely slow one direction integrating response of biomass and product concentration on modeling and control are also discussed in the book, article, and website.

The integration and knowledge management of a diversity of technologies in DeltaV addresses the essence of the PAT initiative as expressed in the following statements by the FDA:

Process Analytical Technology:

• It is important to note that the term analytical in PAT is viewed broadly to include chemical, physical, microbiological, mathematical, and risk analysis conducted in an integrated manner.

Process Analytical Technology Tools:

• Multivariate data acquisition and analysis tools
• Process and endpoint monitoring and control tools
• Continuous improvement and knowledge management tools
• An appropriate combination of some, or all, of these tools may be applicable to a single-unit operation, or to an entire manufacturing process and its quality assurance.

In an earlier post, I mentioned seeing a draft article by Emerson's Terry Blevins and James Beall on performance monitoring and the Process Analytical Technologies (PAT) initiative.

The article, Monitoring and Control Tools for Implementing PAT, has now been published in Pharmaceutical Technology magazine.

Terry and James do a great job in summarizing the common problems process monitoring can detect. These include problems where the control is limited, information from the field transmitters is bad or uncertain, loop modes are incorrect, or there is high variability associate with the loop.

You can do process monitoring with an application that runs either on top of the existing automation system or embedded within it as I discussed in an earlier post on DeltaV InSight.

Here's a few tips gleaned from the article which I'll paraphrase:

• Make sure the performance monitoring application understands the operating states of the batch process avoid false indications or failed measurements
• Where you are using smart field devices like Foundation fieldbus, HART, or others include the status which accompanies the measurement so that performance calculations are based on valid information
• Check the operating modes of the loops versus their design as a basic measurement of control performance.
• Having a model to compare the actual running process against can help spot the largest areas of variability to focus improvement efforts.

Terry and James wrap up their article nicely pointing out that the Food and Drug Administration's PAT initiative has opened up the opportunity to use these performance monitoring tools to improve the operations of their processes. The timing is great with newer technologies coming along to simplify the performance monitoring process.

As reported in my DeltaV News RSS feed, Emerson's Michalle Adkins and Dawn Marruchella have written a great piece in the AIChE's Chemical Engineering Progress Magazine entitled, Ask the Experts - Avoiding the Pains of Systems Integration.

In it, they recognize some of the issues process manufacturers have faced with manufacturing execution system (MES) integration projects and they share their expertise about how to reduce concerns about integrating existing batch process and achievable business benefits.

Their initial guidance is to analyze the integration needs and current business processes and develop a solution weighing the costs and risks against the sought benefits.

Functionality can overlap in both the MES and control system. If your control system has well integrated batch capabilities, Michalle and Dawn recommend using it to manage recipe execution and historical data collection around the batch. This reduces the complexity of the integration between the MES and control system and helps simplify the requirements for the MES. Then ease of MES and DCS integration and specifically capturing the information required for the electronic batch record would be the focus of the integration efforts.

Also, as mentioned in prior posts, they recommend that the solution have:

Support for web services, a service-oriented architecture, and the use of XML schemas, such as ISA-S95's business-to-manufacturing markup language (B2MML)...

Their final recommendation is to review successful implementations to understand not only the software and integration, but also the experience of the project team who implemented the solution.

The benefits for these efforts must accomplish the highly sought after business objectives. If these objectives are to reduce the cycle time for product release, you can incorporate much of the current after-the-fact documentation into the running batch process. Examples cited include:

• Manual setup, cleaning, and maintenance activities
• Review and approval processes for master and batch documents
• On-line data validity checks, electronic signatures, and completed calculations
• Exception-based reporting tailored for intended audience

By executing these tasks during the production of the batch, process manufacturers can increase their right-first-time metrics and shorten the post-batch approval cycle time. The article cites other achievable benefits based on the identified business objectives such as reducing deviations, significantly decreasing manual data entries, and eliminating paper log books.

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.

In a recent Pharmaceutical Processing magazine article, PAT Searches for its Identity, author Bikash Chatterjee discusses the seemingly slow pace of Process Analytical Technology (PAT) implementations. The article states:

What the FDA has provided is a bold chance for our industry--long mired in historical inefficiencies and product failure--to reinvent and improve existing processes for superior cycle-time, consistency and yield.

Given the change in regulatory climate the article questions why we haven't seen a glut of PAT applications to help achieve better operational results. The author points to challenges in the details to implement. Also the traditional emphasis on product and compliance orientation needs to shift as the article states:

...toward an understanding of critical processes to achieve the significant PAT benefits that have worked so well in other sectors.

Given the complexity of this undertaking the author suggests going forward with an approach like Six Sigma as an operational excellence project management framework.

I caught up with Michalle Adkins, a consultant in Emerson's Life Sciences Industry Center, whom you may recall from an earlier post on five strategies for mitigating project risk. She agrees with the author that a PAT initiative should be managed as part of an overall Operational Excellence program. This is because more structure and process can be provided to the initiative.

Michalle believes that by using the Six Sigma methodology, the right tools can be applied at the right time for evaluating, managing, and implementing PAT projects. The Six Sigma structure of define, measure, analyze, improve, control provides the structure for managing the PAT initiative.

It's interesting to note that some of the same tools in the Six Sigma toolbox are already inherently part of PAT such as design of experiments (DOE), statistical process analysis, and methods development. These are all very much related in terms of the types of statistical tools that are used.

Given that the PAT guidelines are still relatively new, pharmaceutical and biotech manufacturers are recognizing that the proven Six Sigma tools along with the analytical tools already used for methods development can help organize the PAT process and move these initiatives forward. It will be interesting to see how these PAT implementations begin to accelerate in the coming years as structured methodologies are applied.

In an earlier post I discussed common transactions between enterprise, manufacturing execution, and control systems. At the heart of this exchange of information is Extensible Markup Language (XML) to pass types of data between systems in a standard, text-based way.

For instance, if you subscribe to this blog's RSS feed, it means you have an RSS reader which translates the XML data in the RSS feed and displays it in a readable format.

Another example is our Google search appliance that crawls the Emerson Process Management website to help you find things faster. The search results are in XML with eXtensible Stylesheet Language (XSL) to make the returned search results readable. Also, the latest version of Microsoft's Office (Office 2007) switched from saving data in a binary format to an XML format.

The uses for XML extend far beyond these examples and include the work being done with OPC Unified Architecture standard and many more.

I caught up with Dave Marschall who is an integration consultant in our Life Sciences industry center. He shared with me how he and his team were using the XSL/XSLT stylesheets in the process of creating custom electronic batch reports which contain information from the enterprise planning systems, manufacturing execution systems and control systems. XML is commonly used to store this batch report data from these various systems.

The XSL/XSLT stylesheets allowed the team to create different renditions or views of the same XML data. A production view might include process operations events and alarms, operator comments, equipment usage statistics etc. A quality assurance/quality control view might contain material usage, lot history, expirations, environmental data, laboratory data requests/results, etc.

Dave described a recent project where the addition of Quality Specifications data allowed the customer to add intelligence to these views of information. Instead of just displaying the data in a tabular format, the XSL/XLST stylesheets could perform comparisons between actual results versus the specifications, and change the color or highlighting of any discrepancies.

This change of colors was used to help the process manufacturer quickly scan dozens of pages of report data and identify areas of concern like out-of-spec conditions. The logic also triggered additional batch details where these abnormal conditions occurred to assist in the review process. The net effect of embedding this intelligence into the batch end report was quicker reviews of the batch which meant quicker release of the final product.

By using a text-based standard XML and XSL/XSLT approach, the solution can be well documented and more easily changed over time to meet the changing needs of the process manufacturer.

Update: Welcome readers of Gary Mintchell's Feed forward blog! Also, it was interesting timing to get a ControlGlobal.com email this morning discussing The ABCs of XML, Parts 1, 2 & 3.

My colleague, Deb Franke, who was instrumental in getting this Emerson Process Experts blog going nearly a year ago, pointed me to an excellent article in Biopharm International magazine.

The article, ON-LINE PROCESS CONTROL: Automating the Control of Process-Scale Purification Columns Using On-Line Liquid Chromatography describes how Lilly used liquid chromatography to measure product purity in near real-time. This is an example of how pharmaceutical and biotech manufacturers are using the guidance from the FDA's Process Analytical Technologies (PAT) initiative to improve their operations. I'll warn you that this article is pretty technical and suited best for those Chemical Engineers among us.

I ran this article by our Life Sciences industry experts to see if they were involved in this or any similar efforts. Lead engineer Brian Crandall, whom you may recall from an earlier post, sent me a note back how his team had recently completed a project for a biotech manufacturer. They wanted an integrated way for their operators to interact with the chromatography columns with the goal of achieving process repeatability and more quantifiable product quality.

Brian and his team developed a solution based upon the ISA S88 modular standard. The major pieces of equipment used on the chromatography skid including dilution control, feed pumps, columns and valve arrays were grouped into processing categories to provide the operators a way to efficiently operate this skid. They can start new operations, hold ones that are currently running, and respond to abnormal processing conditions to take corrective action before quality is impacted.

Also critical was collecting the data from the chromatographs to do analysis around product optical density trends and equipment performance metrics. The DeltaV Batch automation system was also integrated with manufacturing execution system (MES) software to provide material genealogy with the manual and automated process information. This genealogy record included the materials transferred into and out of the chromatography skid. The solution for this information integration was based upon the ISA S95 information standard between enterprise and control systems.

To tie this information back to the business objectives of repeatability and improved quality, Brian and the team created a final batch report that displays the complete product history through the chromatography process. As stated on the PAT site:

The goal of PAT is to understand and control the manufacturing process, which is consistent with our current drug quality system: quality cannot be tested into products; it should be built-in or should be by design.

This design, integration and implementation work by Brian and team sounds exactly like what this goal is meant to achieve.

Update: Welcome Wall Street Journal readers!

Pharmaceutical Technology Europe has a recent article entitled, Artificial intelligence the key to process understanding. It discusses the opportunity to enhance the FDA's Process Analytical Technologies (PAT) initiative using artificial intelligence based tools like neural networks, fuzzy logic and genetic algorithms. I shared this article with Greg McMillan who has been quite immersed with advanced control as it applies to bioprocesses.

I received this response which I'll share in total (I've inserted some context-sensitive hyperlinks to his work on Process Control Insights):

There are opportunities to improve plant performance in the front end of the process where most of the product qualities are set by the use of online process models, batch analytics, and Model Predictive Control (MPC). Online process models based on first principals offer a significant source of knowledge discovery for both the process and the control system. The models are part of a virtual plant that enables virtual experimentation for the exploration of "what if scenarios".

This is important for the next steps of implementing online batch analytics and MPC. Since fermentation batches take days to weeks to complete and the cost of wasted batches is considerable, the virtual plant can provide data on various degrees of adverse operating conditions that would be infeasible to obtain from the actual plant in terms of time and cost.

The virtual plant facilitates the development of techniques for the proper unfolding and alignment of batch data and more advanced analysis techniques such as super model based Principal Component Analysis. Neural networks can be employed to provide reaction rates when information on the kinetics is insufficient.

Fuzzy logic rules can be formularized and tested for a wide variety of scenarios. Inferential measurements can be developed for viable mass growth rates and product formation rates to fill in the blanks between lab measurements for MPC applications to improve batch consistency and yield and to reduce batch cycle time.

In summary, the virtual plant offers a synergistic environment for the application of online batch analytics, artificial intelligence, and advanced control. These opportunities and others are discussed in the book New Directions in Bioprocess Modeling and Control published and in the lectures on the Process Control Insights website.

I caught a sneak preview of draft article that ModelingAndControl.com's Terry Blevins who collaborated with James Beall whom you may recall from earlier posts.

The draft explores the initial steps Pharmaceutical and Biotech manufacturers should consider when preparing to implement the U.S. Food and Drug Administration's Process Analytical Technology (PAT) initiative. For those unfamiliar with the PAT guidelines, they were established to encourage innovation in development and implementation of manufacturing processes to improve product quality. The existing regulation designed to achieve quality through rigorous design and documentation actually served to discourage improvements due to the time-consuming nature of the revalidation of any changes.

Terry and James offer some guidance on some initial steps that Life Sciences manufacturers can take. Since most of their manufacturing processes are batch-based, it can be trickier to apply some of the advanced process control technologies more often found in continuous processes found in the chemical, petrochemical, and oil and gas industries. They recommend starting by looking at ongoing performance monitoring. This software has typically layered on top of the automation systems but has begun to become embedded in the automation system. DeltaV Insight is a good example of this type of performance monitoring software embedded in the DeltaV system. This performance monitoring can be keyed to the phases within the running batch to account for the changing process conditions. The dynamics of the process are learned as changes in the process are made.

Terry points out that these performance monitoring tools can help manufacturers spot issues like excessive process variability which can have direct impact on product quality. Other conditions this software can help detect include control-limited conditions, bad/unreliable data coming from intelligent field devices, and control loops operating in modes other than those intended. All of these conditions can contribute to quality issues in the final product.

He notes that the ability of intelligent field devices to provide status of the goodness of the data is a key part of performance monitoring so that the control strategies, history collection, and analytical tools have a clear picture of what is really happening in the process.

I look forward to seeing the finished article!

While thumbing through the November/December issue of Pharmaceutical Manufacturing magazine, I came across a great article, Getting the Most from Coriolis Flowmeters in Pharmaceutical Processes, co-written by Vince Salupo of Eli Lilly and Franki Parson of Emerson Process Management's Micro Motion division. It's a great article for discussing the advantages and disadvantages of bent-tube vs. straight-tube meters depending on the requirements of the application. If you are already well-versed in Coriolis flow technology, this may all be too basic for you. If you're like me and not as well-versed, the article is worth a read because it makes the complex understandable.

Coriolis meters provide mass flow and density measurements, and are available in both bent-tube and straight-tube design. The article discusses the two types of designs and their advantages specifically in Life Sciences applications. The bent-tube meters have better accuracy and turndown. The straight-tube meters offer improved drainability which is something critical for pharmaceutical and biotech manufacturing processes which have clean-in-place operations to clean and sterilize the process piping between batches. The choice for of Coriolis design most suitable really is based on the application. If accuracy and repeatability are the overriding concern, the bent-tube technology is recommended. If raw material contamination within a batch or between batches is the key concern, the straight-tube flowmeters are recommended.

Another reason for the popularity of Coriolis flowmeters in Life Sciences manufacturing applications is their non-intrusiveness into the process. There are no fluids or moving parts that can cause problems on failure. Only the inside of the flow tubes touch the process.

The article further explores specific challenges found in Life Science applications like API synthesis and purification, formulation, and high purity water and what you should consider in selecting bent-tube versus straight-tube Coriolis meters for these unique applications.

I hope others considering their options in these types of applications found the Pharmaceutical Manufacturing article as clear and succinct as I did.

Todd Ham and Dan Lorenzo from Emerson's Life Sciences Industry center presented a workshop entitled, Large Project Execution. The focus is on sharing best practices for successfully executing large projects.

They define a large project as 10 or more engineers with more that 5000 engineering hours. The project schedule is typically measured in years and tends to have high visibility with upper management.

Far and away the most important aspect to success is the team leadership. Team leaders should possess technical expertise, managerial competence, and the ability to attend to problems early. Many different styles of leader can be successful, but setting upfront expectations is critical. Dan cites a balanced leader that is knowledgeable, but non ego driven, is willing to make and stand behind tough decisions, knows when to defer to the team, and provides an environment for the team to explore new ideas. This leadership style gives the project its best chance of success.

The next important step is to create a common message to breakdown the project complexities, to provide a clear, cross-functional set of objectives, and to help everyone understand their roles in achieving these objectives. Todd made it clear this is not "rah-rah" motivational sayings on wall posters, but rather a clear vision such as a world-class biotech facility.

The makeup of the team is very important. Most teams have a mix of experience and inexperience and personalities. It's important the leadership be engaged, reinforce the common message and direction, and deal with people issues head-on and early. Build a team with a balance of skills and personality.

Project indicators that things are going well include new ideas being suggested, measured progress being made, and people on the project generally seem happy. On the flip side, indicators that things are not going well include people acting differently in the presence of team leadership, the leadership being unaware of major issues, and people hoarding information and knowledge. It boils down to reinforcing practices that are yielding good results.

Finally measure and monitor what makes sense for the project. Items that are measured will get better. Too many metrics can do more harm than good and not move the project forward toward the intended objectives.

At the recent conference, Implementing Manufacturing Execution Systems in the Pharmaceutical and Biotech Industry, Emerson Senior Vice President John Gardner presented with DMI International's Bob Schiros a paper on Integrated Recipe Authoring on the first day of the conference. John is the general manager for the Life Sciences, Food and Beverage, Pulp & Paper, Energy, Metals and Mining industry organizations.

The thrust of their presentation is that manufacturers need to integrate their existing "functional islands". Today people want to get information easier, but that's just the tip of the iceberg. Integrating and simplifying the management of documents, personnel qualifications, equipment and material, work activity, automation, various plant floor systems, etc. is where the real operational benefits occur.

John stresses the place to begin is to analyze the causes of deviations in these areas. Eliminating these deviations provides the potential operational improvements at the heart of your business case for change. These areas of opportunities should be broken into manageable phases.

Gaining executive sponsorship for the changes is critical since people and processes are likely impacted, and organizational inertia tends to resist changes.

For pharmaceutical and biotech manufacturers, the opportunity comes in reducing the cost of goods manufactured. John stresses the place to begin is to analyze your current functional operations and the causes of deviations in these areas. This will lead to better inventory and yield management, lower regulatory compliance costs, and reduced product release times. John stresses the place to begin is to analyze your current functional operations and the causes of deviations in these areas. Focusing on eliminating these deviations is the most immediate potential improvement and that's at the heart of your business case for change. These areas should then be broken into manageable phases.

John believes the key is to start with the low hanging fruit which is to have a structured integrated recipe authoring process. The process starts by disassembling the recipe into its components: personnel, materials, equipment, data, and documents. These components are optimized and a database of reusable objects is created. Now the recipe can be reassembled with the optimized components and made available for execution of the batch with its associated electronic batch record.

The Emerson Life Sciences industry experts use the manufacturing execution system (MES) software product, Compliance Suite, as a platform to help manufacturers achieve this structured approach.

The presentation highlights measurable results which have been achieved including 40-70% reduction in batch record complexity, 30-50% reduction in product release cycle times, 20-40% reduction in documentation authoring and approval cycle times, and up to 40% reduction in errors, omissions and deviations of operational data.

Pharmaceutical Manufacturing magazine's On Pharma blog had an interesting post last week entitled Silencing Pharma's cGMP high priesthood. The post pointedly asks:

We all know that cGMPs are essential to safety. But has the industry gone too far with them? Has pharma, in effect, created a high priesthood of cGMP that stymies creativity, and even common sense?

This post references a Pharmaceutical Manufacturing editorial by Emil Ciurczak who makes the argument:

But, in some cases, cGMPs: have become laws to follow without question. Just as many religious people may not really know why they perform certain ceremonies, many scientists today don't know why they do many things. Ask them and you may hear an answer very close to "It is written!"

I ran this by Christie Deitz, a senior principal engineer in our Life Sciences organization that you may recall from an earlier post on executing S88 projects. Christie believes that this viewpoint has many subscribers and has some elements of truth to it.

She reminded me that this is on of the key drivers for the Process Analytical Technologies (PAT) initiative from the Food and Drug Administration. PAT, a risk-based regulatory framework, is one of the initiatives in the FDA's GMPs for the 21^st Century program.

The intent behind this initiative is to break down some of the barriers preventing pharmaceutical manufacturers from using current technologies to improve the quality of the products manufactured. An added benefit is that these technologies can also reduce the cost of manufacturing through improved cycle times and other process efficiencies. One example where this has happened is Baxter's use of model predictive control to improve solvent recovery.

Another example where today's technologies can help maintain high quality is Talecris Biotherapeutics' use of smart devices and digital bus technologies like Foundation Fieldbus to monitor on-line analyzers and generate "GMP critical alarms" in real-time for anything out of tolerance.

While there is some truth to the statement in the On Pharma blog, many in the industry, including the FDA, are working to change the "cGMP high priesthood" mentality. And, many Life Science manufacturers are beginning to take advantage of the risk-based regulatory framework and are using current technologies to improve their manufacturing quality and improve their overall operational performance.

An interesting paper was presented recently at the Honeywell User Group (HUG) meeting as captured by Pharmaceutical Manufacturing magazine's On Pharma blog. The post, Abbott dispels MES myths (Notes from HUG II) is interesting for the $1.3 Million USD estimated annual savings from applying Manufacturing Execution System (MES) software.

Why I make particular note of this project is that it was accomplished with the help of Emerson Life Sciences expertise in deliverying ANSI/ISA-95 (S95) solutions.

I caught up with Principal Engineer, Josh Gangl in our Life Sciences / Food and Beverage industry organization who was involved in this project. The selected MES software, POMSnet, was integrated by Josh and the team with the plant's DeltaV Batch system.

As the On Pharma post notes:

For Abbott, the MES was a critical aspect of its pursuit of an integrated and paperless environment.

As Abbott's David Kircher noted in the On Pharma post:

The customizations we did were related to integrations and custom reports, but everything else was out of the box.

Process manufacturers need better flows of information to make timely decisions to efficiently run their businesses. The ANSI/ISA-95 Manufacturing Enterprise Systems standard, commonly referred to as S95, is the international standard for the integration of enterprise and automation systems. This global standard consists of models and terminology for the exchange of information between systems for sales, finance and logistics and systems for production, maintenance and quality.

One key area of information flow is reading laboratory analysis results from the laboratory information management systems (LIMS) and coordinating this information with the running batch controlled between the batch automation system and the manufacturing execution system (MES). The MES normally maintains the complete electronic batch record of all automated and manual processes, including LIMS data.

I spoke with Steve Thorp, an Integration Consultant in our Life Sciences industry organization. He is currently working with a batch process manufacturer who is implementing extensive elements of the S95 model, including comprehensive LIMS integration. Some of the key objectives for this project included:

• Providing the MES system (Compliance Suite for this project) the ability to request the creation of new samples within the LIMS system based on the current status of the MES Electronic Work Instructions. The MES system would also read information from the process control system to determine when and what samples would be created.
• Providing the MES system the ability to monitor the status of specific samples within the LIMS system
• Providing the MES system the ability to read the analysis results for specific samples within the LIMS system after the samples status has been set to "completed"

Steve talked about the alternative of doing this process manually, the number of people who can be involved, and the delays this manual process can cause to the release of the batch. By analyzing this processes and architecting a solution to automate the manual pieces, big efficiencies can be gained.

For implementing this portion of the S95 model Steve offered the following guidance to process manufacturers. First, fully understand the current workflow including how and when the physical samples are taken, when the results are required, how these should be included into the electronic batch record, and what failure contingencies should be made in the MES and automation system if the results are not ready when expected. Second, when implementing the design, it critical to understand the underlying data structure within the LIMS system, and to understand the overall usage patterns to properly estimate server and storage requirement for the hardware design.

Given competitive pressures, process manufacturers put great pressure on project teams to bring projects on-time, on-budget to capture revenue and payback the outlay of capital sooner.

Engineering efficiency is one of the keys to success. This efficiency is measured in output per cost and in the ability to shrink task timelines on the project plan.

I spoke with lead engineer Brian Crandall in our Life Sciences industry organization to gain insight on what areas can help drive engineering efficiency. You may remember Brian from an earlier post.

Brian boiled it down to three areas: design & implementation standards, project execution methodology, and project design tools. I've addressed standards and projection execution methodology based on the S88 model in earlier posts so we've focused this post on project design tools.

Tools can help eliminate the repetitive and low-value tasks. They can also reduce risk and improve quality by eliminating errors associated with manual tasks.

Brian likes to think about these tools in distinct stages of the project. In the detailed design phase, documentation tools automate the system configuration work to come later. As an example, the Life Science project teams use DeltaV Control Studio as a design interface to generate textual and graphical description of how code should be implemented. This generates Visio diagrams for process visualization and Word documents to help detail further actions required. Documentation tools can also provide easily-readable summaries of the automation system configuration for use in project reviews, and in the case of non-GMP projects, provide the final documentation deliverables.

Coding tools are those that help in the implementation phase of the project. The project teams' see engineering efficiency gains in both batch and continuous elements of the project implementation including: units, phases, composite modules, recipes, equipment module sequence logic, module database elements, and I/O database elements. Using XML and SQL data standards helps move information between the external databases and the automation system configuration database. Tools like DeltaV Bulk Edit and other ones created by the Emerson project teams have increased efficiency during this implementation phase.

During the test phase of the project, execution tools can help the testers rapidly access and manipulate large amounts of parameter values to verify that proper the actual control matches the design. Excel spreadsheet templates connected to the system with an OPC-based Excel Add-in provide the ability to read and write large amounts of data and capture this data for historical viewing and analysis.

A final point Brian made is that these same tools can extend engineering efficiency beyond project commissioning. The combination of standards, methodology, and tools make ongoing changes and testing more streamlined and reduce the overall maintenance costs over the life of the plant operations.

Batch process manufacturers have long understood that applications which require both sequential and continuous control have been a challenge. A typical example is a centrifuge application commonly found in Biotech and Pharmaceutical manufacturing processes. A centrifuge separates solid and liquid material by spinning a sieve-like device at high rate of speed, and recovering the liquid, solid or both materials.

I caught up with Brian Crandall, a Life Sciences industry project engineer. He said that proper control was critical since centrifuges are quite expensive, and sensitive to a variety of failure conditions. These conditions need to be addressed within seconds to prevent equipment damage and possible injury to operations staff.

Brian summed up the control challenge as the centrifuge having various operational states. Moving between these states is best done using sequential operations. However, monitoring of the failure conditions, which change in severity and action depending upon the operational state, must be done in parallel with the sequencing.

If a failure condition occurs, the current sequence has to be stopped, and the specific failure sequence started within a minimum timeframe. The S88 Batch Model defines a sequential state driven approach, but it does not fit the requirements of this application. The big issue is the failure monitor does not offer continuous monitoring required for quick reaction to the failure condition.

Using a DeltaV system for this particular Biotech application, Brian designed, tested and implemented a modified S88 state model that had the ability to stop a sequence without waiting for a transition thus meeting the high-speed timing requirements of the equipment. Multiple sequences would be required for the main sequence, shutdown, and E-Stop to allow stopping one sequence and starting another at the same time. Also the code design needed to modular to fit the rest of the S88 modular design philosophy. Also, this design placed control at correct level in S88 batch model, at the equipment module level.

Some failure conditions the design addressed included: high vibration, VSD fault, low seal water pressure, and low instrument air pressure. Depending on the state of operation, the failure conditions required different actions per a failure condition matrix.

Other industries have applications requiring this mix of continuous and sequential control. Some examples include a refiner in the pulp and paper industry, extruders in the specialty chemicals industry, and other state-driven processes or equipment.

S88, short for ANSI/ISA-88 is a standard for addressing batch process control. This design philosophy for software, equipment and procedures provides a consistent set of standards and terminology for a batch automation project.

I spoke with Christie Deitz who coauthored a paper entitled, Writing a Functional Specification for an S88 Batch Project.

Christie believes that S88 provides many benefits for the project team and project stakeholders. It starts with establishing common structure and terminology for clear communications between the automation, quality control, manufacturing, and the management teams. The nature of the modular standard facilitates object-oriented, class-based designs. This helps minimize documentation by defining requirements only once for the entire class. It also helps improve the consistency of the design. By streamlining many instances into one class it means that design, implementation and testing efforts are reduced which help the project stay on schedule.

She stresses that the key is to use S88 early during the requirements definition. According to GAMP (Good Automation Manufacturing Practice), the functional specification defines the process automation requirements and becomes the basis for the design specifications. The functional specification may include a process description, piping and instrumentation diagrams (P&IDs), process flow diagrams (PFDs), and an instrument list.

Christie encourages process manufacturers to make sure automation or other S88 knowledgeable people are involved early in the process design to make sure the advantages of a modular approach are built into the project. It's also a good idea to include stakeholders from automation, process engineering, production and quality into the creation of the functional specification. This front end work will minimize changes due to misunderstandings by the project stakeholders. These changes become more expensive the later they occur in the project schedule and can delay the startup date.

Process manufacturers have many choices in how to organize the specifications. Christie's experience is that functional specifications should be created for each area, which allows classes to be described within a single document. There are typically five to ten process areas within a process. This allows for a limited number of documents to manage.

By taking this approach Christie and the experts in our Life Sciences organization have helped deliver projects ahead of schedule, which means faster payback on the project.

Highly regulated industries like those in which Life Sciences manufacturers operate need efficient solutions manage and properly document their production and use of materials in the manufacturing process.

The production process usually includes both manual and automated operations. The automated part is typically controlled with process control systems with batch software like the DeltaV system.

I spoke with Principal Engineer Todd Ham who coauthored a paper with Senior Technologist Dick Seemann, both in our Life Sciences industry organization. The paper, A Model for Integrating Material Management in a Production Environment, was presented at a past ISA Automation West Conference.

The paper generically describes a solution that Todd and our Life Sciences industry experts implemented at a biotech manufacturing facility. A manufacturing execution system managed the materials for manual parts of the operation.

Todd said the key to the solution was defining an integrated material management model which included support for the processes: batch campaign creation, raw material weigh-and-dispense, manual material charges, and automated material charges.

In their solution, the first step is campaign and batch creation. A unique campaign ID is established which all material information related to the campaign will connect. Also the batch report manager in the process control system can access this campaign ID, to bring in all the material information into a complete electronic batch record, needed for the release of final product. This information is included with the batch history, alarms, events, operator actions, and other data collected by the process control system.

Todd describes a manual weigh-and-dispense operation. An operator logs into a handheld personal data terminal/barcode reader. The system checks and verifies that he has authority and the up-to-date training to perform the weigh-and-dispense procedure. The operator selects the campaign, is presented with the appropriate and available weigh booths, and scans a weigh booth ID barcode. Next the operator selects an intermediate batch container which has been verified by the system as being the correct size, being clean, etc.

With everything properly validated the operator selects from a list of materials presented on the handheld device connected to the warehouse inventory system. Once the material has been retrieved and barcode scanned it is validated for expiration dates, lot numbers, and any other required quality measures. The operator dispenses and confirms the measured weight within the allowed tolerances.

A label containing all this information, as well as an electronic copy for the electronic batch record is available for the production environment. Similar integrated material management processes are available for manual material charging, automated material charging, and the creation of the batch report.

These integrated manufacturing procedures provide enforced compliance for the manual production activities. And overall cycle times can be reduced since the records captured from these procedures are available in the overall batch record instead of collecting and signing off papers after the fact.

Every capital project has it challenges, usually around tight budgets and tight schedules, not to mention team flexibility and changes in scope.

Recently at the Interphex conference, the big industry gathering for Life Science manufacturers and suppliers, Emerson's Michalle Adkins, Steve Murray, and Dawn Marruchella presented a paper entitled, "Optimizing Your Automation Investment By Mitigating Risk."

I had a chance to catch up with Steve who is a consultant and project lead engineer in the Life Sciences industry organization to understand what experience they shared with those who attended their presentation.

Steve shared five strategies for helping to reduce risk in projects. These include:

1. Set Expectations
2. Prototype
3. Establish Project Guidelines
4. Use Global Standards
5. Leverage Testing

Set Expectations. Risks in miscommunication, budget, schedule, and overall project execution can be reduced by having the project team (both manufacturer and supplier(s)) align on the expectations for the project. The expectations include the deliverables, documentation, schedule, procedures and processes, tracking metrics, and the overall level of automation and integration between systems and processes. This helps aim everyone's efforts in the same direction and discovers efficiencies which can be gained as the project is implemented.

Prototype. Risks in budget, schedule, changes, and project execution can be reduced with a prototyping strategy. Prototyping helps incorporate operational philosophies into the upfront engineering, helps ensure consistent look and feel, and provides a visual medium to communicate designs to the project team, manufacturing, maintenance, and other interested parties. The prototype lays the foundation for the project guidelines and demonstrates methods for software testing, operator training, and process simulation. This strategy can reduce changes later in the project. There is much more to say on what and how to prototype which I'll save for a future post.

Establish Project Guidelines. Risks in budget, schedule, maintainability, and project execution can be reduced by establishing clear project guidelines. The agreement of established procedures, practices, and fundamental philosophies at the front of a project help avoid project-wide changes later in the project. These guidelines should cover execution methodology, change control, document control, testing and all the team member roles and responsibilities. It covers all aspects of the automation project including operator interface, batch architecture, continuous control, devices and I/O, and integration with external systems.

Use Global Standards. Risks in budget, schedule, maintainability, and training can be reduced by establishing or using already established global standards. Global standards in this context refer to standard, modular, pre-tested pieces of automation like control modules, equipment modules, phases, etc. These standards incorporate existing knowledge and best practices, help facilitate communication between team members, and shorten the learning curve for new members to the project team. Ongoing maintenance and support is easier for the 80-90% of the project configuration that typically can use global standards. These standards are often provided by automation suppliers since they see more projects and can more efficiently iterate towards an ideal standard. In addition, spreading the development costs across a broad project base can significantly reduce these costs.

Leverage Testing. Like using global standards, risks in budget, schedule, maintainability, and training can be reduced by leveraging good testing practices. For highly regulated Life Science manufacturers, everything needs to be tested and documented. The key is that each level of testing (supplier, acceptance, commissioning, IQ, OQ, PQ) should build on the previous layer and not repeat it. Testing is always a risk-based endeavor. There can never be so much as to eliminate every possible problem scenario. At some point the cost can drive a project cost more than anything else. It's better to spread testing cost for standard items as widely as possible, and load most of the testing into the front end of a project since testing gets progressively more expensive the further it is done in a project schedule. The key is a solid test plan which identifies the risk areas from all members of the project team and finding ways to combine some of the testing levels like commissioning and qualification.

Steve and other experienced Life Science Industry experts have shared their wisdom in many papers over the years including S88 batch project specs and S88 project requirements.

Automation World's Editor in Chief Gary Mintchell has an excellent recap of the Interphex show, a show targeted for pharmaceutical manufacturers. In that post Gary mentioned:

Another great learning experience resulted from dinner last night with Peter Dossing and Tom Diederich of Emerson Process...Now, pharma manufacturing is taking center stage--with a boost from the FDA--and they are ready to automate and study process improvement techniques.

Unfortunately getting things right the first time is extremely cumbersome and difficult with manual, paper-based operating procedures. Tom relayed an example of one pharmaceutical manufacturer getting things right the first time--less than 5% of the time. For this manufacturer, it meant spending 30,000 man-hours or 15 man-years annually checking, reviewing and recirculating documents before batches of the product could be released for sale.

A simple example - imagine an operator having to manually add 2 cc's of an additive to a running batch. Today, he does it, signs off on a paper saying he's done it, hands to his boss who signs off, who hands off to his boss to sign off according to the proscribed operating procedures, etc.

The questions this simple procedural example prompts are numerous: Was he trained properly to do this? Is his training current/expired? Was the measuring device calibrated? Did he add the correct additive? Did the additive have temp or light exposure limits/specs? Were those specs/limits exceeded? All these and much more must be checked, again to the standard operating procedures.

The Emerson Life Sciences industry team is working with pharmaceutical and biotech manufacturers and sharing their expertise in studying processes to see where they can be streamlined through work practice changes or through having automation and/or compliance management solutions applied. Many of these manual procedures and documentation steps like checking the training records, bar code scanning for equipment and material tracking, weighing, and dispensing additives, and electronic signatures, can be automated and collected as part of a complete batch record. This greatly speeds up the release of the manufactured product and significantly reduces the number of errors associated with manual data entry; both of which directly impact the bottom line.

The U.S. Food and Drug Administration's Process Analytical Technologies (PAT) initiative is a catalyst for Life Sciences manufacturers to re-examine their current practices and look at ways to build product quality and consistency into the processes and procedures instead of fixing it after the fact. Some of these operational excellence practices are now being adopted in partnership between manufacturers and Emerson Life Sciences experts with significant results.

As competitive pressures drive process manufacturers to run their processes more efficiently, a key area of focus is to improve the management of data from various sources. Better, more timely decisions come from better data.

I spoke with one of our Life Sciences/Food & Beverage industry senior manufacturing consultants and data management experts, Gary Silverman about this need to consolidate and migrate data. He cited several reasons for this:

• Updating a historian and/or operating system because it's no longer supported by the original supplier
• Needing to consolidate data from multiple process automation system platforms and other data sources into a single enterprise historian
• Changing business needs requiring broader dissemination of information from the manufacturing process to plant and corporate personnel with web browser-based technologies.

One example Gary cited was a DeltaV system upgrade project where an AIM/Bile Historian with 9 years of process data collected from a PROVOX system needed to move to an OSIsoft PI historian. The finished solution collected data from the new DeltaV system, PROVOX and utilities programmable controllers. Emerson is an OSIsoft Platinum Partner as a provider of data management and integration services.

The data management team had developed automated tools and methods to extract the AIM tag database, create the PI tag database and migrate this vast amount of data. The team also built a Process Module Database to streamline the implementation of the OSIsoft RtPortal/WebParts technology. The Portal allows operators, aupervisors or engineers to quickly spot problems and then use ProcessBook and/or DataLink to drill down for in-depth analysis. The Portal also provides a central repository for Shift Logs, Operator Logs, etc.

Another key need was being able to perform batch-to-batch analysis with data from over 70 reactors and make comparisons of critical process parameters to discover any deviations from the best or "Golden Batch." PI Batch configuration and the PI Batch Client Tools provided the customer with a means to do this. They were also able to monitor and improve cycle times as a result of this analysis. In the end the project achieved its objectives to modernize the existing technology disseminate information more broadly and provide critical data in Batch context for continuous improvement.

Given the high interest in having better information to help plants run more efficiently, I'll be checking back with Gary and other data management experts from time to time.