Ever get stuck behind a loud bore on an airplane? I had that misfortune last week. Eventually tuned him out, but couldn’t help but pity his quiet seat-mate, who didn’t know a peptide from a Pepsi, as he got sucked deeper and deeper into a one-sided verbal black hole, a diatribe about the axis of evil: the pharmaceutical industry and its “ally,” the FDA.

This bore was well-read, but essential bits of knowledge were missing from everything he talked about, from his description of peptides and how cox-2 inhibitors work to his characterization of the evil FDA.

Everyone keeps talking about how the industry is on the brink of great change….it’s the death of the blockbuster….the birth of…what?  The niche-buster? Personalized medicine? 

Just keeping up and fire-fighting may be difficult enough so it is tempting to be like Scarlet O’Hara, as in “we’ll just deal with those issues tomorrow.” 

The talk was all about convergence and mashups at this week's annual Rockwell Automation Fair in Nashville. In case you haven't heard, a mashup is a web application that combines data from more than one source into a single integrated tool--at least that's how Wikipedia defines it.

After numerous travel delays and “customer service” by surly ground crew, I finally arrived to face the blazing heat of summertime in Phoenix, AZ. I like the laissez faire customer service of today’s airline industry just about as much as I enjoy 105 degree temperatures. However, I was excited to attend Honeywell’s 2008 User Group (HUG) to learn more about the technologies and advancements that Honeywell is making within the pharmaceutical industry.

There are a lot of active applications of Honeywell’s technologies within the pharmaceutical industry. An area that has particularly captured my attention is the advancements Honeywell is making and is helping to facilitate within the biopharmaceutical sector of the industry.

One of the significant challenges of manufacturing many biopharmaceutical products is the element of randomness or unpredictability within the production process. However, I think that it is fair to say that there is a difference between randomness, unpredictability and a lack of thorough understanding.

For the most part, the natural world, including living organisms, operates within a scope of order. It may be a complex order. An order we really don’t currently fully understand, but order none the less.

Advancements in biopharmaceutical technologies and understandings will help our industry determine the factors that must be controlled for more consistent production. Process automation vendors will be key assets to pharma and biopharma companies as they continue to develop process control technologies based on these understandings.

Pharmaceutical Manufacturing and our sister publications, Control, Control Design and Chemical Processing, will be delivering relevant information from HUG. In addition, I encourage you to read, if you have not already, the “Monitoring Bioprocess” article featured in the May issue of Pharmaceutical Manufacturing.

I am looking forward to exciting advancements in the biopharm industry and to our industry’s ability to better control its manufacturing processes. In addition, although I do enjoy Phoenix, I am looking forward to escaping the scorching Arizona heat as I head to BIO in San Diego.

- Tonia Becker, Publisher, Pharmaceutical Manufacturing magazine

That's how Control magazine's executive editor Jim Montague described the pharmaceutical industry in a recent and very memorable op-ed (read it here), in which he interviews experts including E-55 insider Gawayne Mahboubian-Jones. Jim brings to the the "so what" detachment of one who has covered PAT and process control as it has advanced in other industries over the years. We may appear to be a bit "gee wiz" on the subjects, if only to encourage the adoption of PAT and the open discussions of best practices, but Jim makes great points.

An accompanying review of pharmaceutical PAT asks whether it's a silver bullet for pharma?  (The bullet was used, in legend, to kill the devil or werewolves...in the case of pharma, it's killing a Frankenstein monster of pharma's own creation, paralyzed on the lab table ---although FDA played a major role in the vignette...which role....Igor? Remember Marty Feldman and Abbie Normal? Sniff. What was once a great Mel Brooks film is now another overblown Broadway musical).   Our own recent survey of pharma op ex practices found an uptick in pharma PAT adoption...although PAT is no longer the top motto (it's now Quality by Design, as enabled by PAT)

Noticed that a number of great blogs are blogging from BIO 2008.  Patent Baristas has entitled its blog "The Road to BIO".  I'm still on that road tonight, quite literally, having made the decision to take the younger children with me on a road trip that started last week...beautiful stretches in New Mexico, particularly....but long stretches. 

Had hoped to be able to cover both Honeywell User's Group in Phoenix and BIO, but their schedules overlap completely....fortunately, our colleagues on Control have promised to help us provide coverage of HUG's extremely interesting pharma and biopharma track.  BTW, Control's   editor-in-chief, Walt Boyes, was very recently elected an ISA Fellow.

We love the progressive thinking that's going on in pharma. That's why I enjoy my job and what makes covering this side of the industry so much more interesting and positive than looking at the financial side and all the marketing scandals. As we do every year, we've covered this year's IFPAC process analytics conference, a hotbed for some of that thinking, and promoted it on our web site.

Only this year, thanks to our talented multimedia director Scott Babcock, we did some of this via video, and professionally edited video, not the "You Tube"-ish things that editors like me have thrown together in the past.

Thanks to Robert Zutkis and IFPAC for allowing access, and to everyone, especially FDA's Janet Woodcock, for being so gracious about doing impromptu interviews, and for not running away at the sight of a video camera, and to Emil Ciurczak and colleague Jack Carroll for being open to experimenting with new media. They are both developing an online video course on Quality by Design, PAT and Analytics that will soon be up on our web site.

You'll find the official report on IFPAC our web site. But here is a brief, unsanctioned one. Let's call it the PAT Gossip report. Please don't be offended, anyone, and remember. This is only a blog.

• Insiders say working conditions at FDA are much better, but budgets for travel to training conferences aren't expanding. "Travel is just for the big wigs, " said one.
• Ajaz Hussain is now working on transgenics at Philip Morris International, which is developing tobacco plant strains for cell culture for vaccine production.
• Martin Warman reports that there is life after Pfizer. He's now consulting and, given data management challenges facing most companies embarking on PAT, his work now takes him into the IT realm more often than instrumentation. Who knows? Perhaps he will return to Big Pharma
• Ron Miller reports that life after BMS is good. He is consulting and working on another book.
• Merck is looking for some PAT leaders, at the PhD, MS and BS levels. We hear that Wyeth is, too.
• Move over Tata Consultancy Services. Puerto Rico is considering a new export: PAT team leaders available on a contract basis. The island's universities are strong, and so are their training programs, one of which is taking an accredited PAT training course online to a Web format this year. Now for some extremely random thoughts, comments and questions, in no particular order.

  Why were some pharma PAT presentations this year almost completely identical to last year's?

  IFPAC offers access to some of the greatest minds in the industry. And some of the smaller ones, too. Like the person, who will remain nameless, who turned Scott and me away, literally at the door, at the opening night dinner.

  Thus, Scott had to lug very heavy, awkward video and lighting equipment all over the hotel and store it while grabbing a bite to eat. We didn’t have the electric power or Internet access we needed to cover the program at our booth either

  More revelations from this year’s conference?

  Don’t roll your eyes when your aunt complains that the generic version “just doesn’t feel the same” as old and expensive Brand Name X. She’s onto something. Don’t call her a hypochondriac. The fact is that the excipients used in formulation can show tremendous between-batch variability, even when they meet USP and other specs. At IFPAC, we heard no less an authority than Deputy FDA Commissioner Janet Woodcock suggest that there may be a connection between these complaints and measurable manufacturing issues" We just don’t know yet,” she said.

  One batch of excipient can meet basic USP specifications and yet perform completely differently, within the formulation, than another batch of the same material that meets specs.This is all part of the challenge of relating clinical outcomes to manufacturing issues, and a fundamental reason why pharma needs to use PAT.

  Want to Take Revenge on FDA Inspectors? Teach Them
  Instructors must have had fun designing the hands-on solid dosage training course for FDA’s Inspectorate last year.Using a lab featuring Emerson process control equipment and Optimal’s SynTQ, FDA students performed simple blending operations using lactose, but material from three different batches of lactose. If the blend was made with lactose from one batch, the reaction would be completed much faster than materials using the other batches. Huh? Isn’t lactose lactose? Not exactly. That’s just what prompted GSK’s Ray Scherzer to suggest that...

  Pharma needs more physicists and materials scientists (or, at least, industrial pharmacists with training in those areas----people who understand the mechanical and other physical properties of materials used in drug formulations

  Bored and want to see some intrigue unfold among PAT types? Start a conversation about dissolution test calibration or microbiological testing of pharma-grade water and watch otherwise reasonable people become unreasonable.Anti-USP sentiment appears to be on the rise in some quarters, with insiders of one camp accusing the organization of rank commercialism, conflicts of interest and impeding the interest of science.(But wait a minute: Does ASTM give its standards away for free

  Peter Rost is a favorite read among some folks we met.Said one insider, “He understands what pharma management is all about, because he worked alongside the guys who are so glued to Bloomberg and the stock results that they forget about what’s going on inside their plants. Too bad he doesn’t get into this side of the business. Consider that an open invitation, Peter… somehow, though, I think the subject matter might be a bit dry.

  One anonymous contrarian then posed a few interesting philosophical questions:

Is standards development by consensus, as with E-55, really a good thing for FDA to be promoting? Ditto for the idea of real time/parametric release of product. "Doesn’t this approach allow industry to write its own rules," this person asked. "I mean, it would be one thing if all of pharma’s senior management were universally on board and always put the public health first and foremost in their minds, but many of them are too busy watching Bloomberg.”

Is mechanical dissolution test calibration truly science based, since it eliminates the only baseline measurement now available? Would the FAA send planes out without mandating crash tests, using uniform testing methods, rather than tests developed by each vendor? One camp has argued convincingly that USP calibrating tablet quality can vary, leading to flawed results. The insider begs to differ. Using mechanical calibration does not provide any way to judge how the given drug will behave in the human bodyFurthermore, insider says, it forces each company or facility to develop its own internal standards, and FDA inspectors to master different internal standards at each facility. Isn’t that a waste of resources and money for an already cash-strapped Agency, and even for the companies themselves I don’t think anyone should worry too much about this. I hope that all drug companies the world over move to real-time product release, but I suspect they’ll still the USP tester tablets as a final check for a very long time to come. Will generics companies, in particular, suddenly throw out all their SOPs and go modern for the sake of trend setting

Please note: We are firm believers and supporters of PAT, Quality by Design, parametric release and continuous quality improvement.We have drunk deeply of the Kool-Aid and support E-55, USP and science-based standards, and we know that FDA has never mandated mechanical calibration. But it’s important to remember that PAT and all this is still fairly new to pharma and that certain scientific basics remain unknown. As this insider says, PAT is a great thing and critical to the future of pharma, but some of the underlying science isn’t there yet, and until it is, any radical changes in industry regulation may be premature, with the industry risking “slapping lipstick on a pig

Long story short, IFPAC is well worth a visit.

There is quite nothing like a trade show that provides complimentary lunch, snacks, and beverages to keep you charged as you plow the show floors. With an orange juice and muffin in hand I spent the morning at the Life Sciences Industry Forum of the Rockwell Automation Fair where manufacturing success was the topic of conversation.

Industry professionals spent the day discussing the ways in which integrating manufacturing and information systems can help achieve operational excellence in the life sciences.

Highlights:

Alan Thomas, vice president of Jacobs Engineering, began by addressing the recent global trends in life sciences manufacturing. He touched briefly on increased investment of manufacturing in particular India and China and the challenges the industry faces in terms of quality control with production handled in developing countries. Thomas also discussed the effect of fewer blockbuster drugs on the development and expansion of manufacturing facilities. Drug manufacturing facilities need to take an integrated approach to their new facilities and/or expansion of current plants, he said, and sustainability needs to be at the forefront of life science development.

Scott Sommer, automation technology manager at Jacobs Engineering followed with a presentation on automation trends that can optimize manufacturing. Sommer focused on measuring the value of each manufacturing application to determine its yield. Defining data requirements and utilizing "master data" in the initial production phases can help to assess an application's long-term value, he said. In regards to automation systems, Sommer discussed how maximization of value should bear far greater importance than minimization of cost. Value should be the factor by which all automation and manufacturing applications are measured for success.

MES was later discussed by Jim Labonty, associate director for automation and systems engineering at Wyeth Biotech. He warned of the dangers of using an MES solution on all process areas as a 'one size fits all' mechanism. Numerous automation systems must have varying levels of MES integration in order for the system to be profitable at each level, he advised. "Different Horses for Different Courses," he stressed (fittingly also the title of his presentation).

These presentations in full will be posted to PhM.com in the upcoming weeks.

On the show floor, companies such as burkert, Cognex Corp., Hoffman, Matrikon, Stratus, and many more displayed their latest and greatest. For product information from the show, please visit our New Product section.

MV

Greetings from Las Vegas, all, where PackExpo is in full swing.  I haven't been able to see many booths yet, but I've heard presentations from David Ray at Parsec Automation and Bob Naegle at Videojet, each of which was exciting in its own way.

Ray gave a thorough explanation of how Parsec's real-time process management software can help manufacturers determine Overall Equipment Effectiveness (OEE). He provided enlightening examples of how seemingly minor problems in efficiency or availability can quickly lead to significant production losses, and conversely, how much extra money a small gain in OEE can generate over a one-year period. Ray is a Six Sigma Black Belt, so he isn't just selling a product.

Naegle detailed Videojet's new line of track-and-trace solutions, developed through the company's recent acquisition of Prism, a data management software provider. The Prism software leverages Videojet's marking and coding capabilities to create sets of unique codes with parent-child relationships between codes used at the package, case and pallet level for ultimate traceability. The flexible system allows pharma manufacturers to specify their preferences for alphanumeric code, serial 2-D codes or complex 2-D codes, to upload the software to their own or Videojet-provided computers, and to use internet-based programs to track when and where those codes are scanned. This system seems promising both for anti-counterfeiting and anti-diversion as well as for product recalls.

More to come; time to head to another meeting. 

-HP

As we found in developing articles for our August issue, pharma is embracing the Toyota Production System (TPS), but mainly one pillar of that system: Kan ban, or Just in Time.  Waiting to be developed is Jidoka, the other pillar of TPS.  People can't always agree on what it means says U.K. based ABB Robotics pharma industry segment manager, Bengt Stom.   We'd asked Bengt for his views on Jidoka and for pharma's readiness to embrace robotics.  Here's some of what he had to say.

PM Why isn't use of robotics gaining traction faster in pharma?

B.S. That pharmaceuticals companies have been reticent in addressing the use of robotics stems largely from the recent history of producing very large volumes of similar product 24/7 with no need for flexibility. Such production often lends itself to fixed automation whereby recipes never change.

However, as pharma companies [move away from the blockbuster drug model], the need for  flexibility in both volumes and packaging types will pressure manufacturers to [look for new ways to] introduce ever greater flexibility.This is where robotics technology always beats fixed automation systems.Of course, there is also the perfectly normal human prejudice of ignoring the unusual or unfamiliar because it challenges conventional thinking and experience.

PM How is Jidoka being incorporated into robotics products for pharma today?

B.S. There is widespread confusion over how to define Jidoka.Some interpret this as simply the ability to automatically stop a system if things go wrong. I prefer the more holistic concept that the automation system is intelligent enough to assess what is going on and act accordingly – rather as a human might.
What is needed is a combination of software and hardware.  By incorporating vision systems, weighing transducers and proximity sensors, the robots can be instructed to act in accordance with the performance of the overall system.  In other words, if a line slows, or product flow falters, the robots simply adjust their actions accordingly.  The key to the integration of this proven hardware lies in the ability of the software to integrate the robot controls with the senor data provided.  This software is also made simple to use in order to open up the possibility for increased machine intelligence to everybody.

PM How far is the industry from embracing the concept of artificial intelligence

BS Again, the question begged is “what constitutes artificial intelligence?�. If this simply infers the ability of a machine to make rudimentary “human like� assumptions and decisions, then many automation systems already have artificial intelligence.  However, if what is meant is the ability of machines to learn, then I think this is some way off yet.  The solution to true artificial intelligence lies with computer scientists, ancillary sensor designers and software developers