Cautionary tale for execs in pharma (or any industry) on the limits of "doing more with less," ignoring technical operations and focusing on financial balance sheets at the expense of quality and safety.   Frontline's documentary on the BP disaster and Texas City refinery tragedy.

AMS

Genzyme Corp. has had numerous regulatory problems at its Allston,  Mass. Facility of late—viral contamination issues last summer, and recently FDA warnings and production shutdowns related to metal and other contaminants found in products manufactured in Allston. The Agency has posted a redacted version of its inspectional observations chronicling specific violations.

At the American Chemical Society national conference last weekend, Rensselaer Polytechnic researcher Dr. Robert Linhart announced that his team may have built the first fully synthetic heparin. Whether or not you believe that the possibility of another contamination crisis of natural raw heparin exists, the potential for a heparin supply independent of the whims and worries of the global supply chain, not to mention the global pig population, is certainly welcome news.

Is synthetic heparin feasible on a large scale? Yes and no, says one of Linhart's collaborators, professor Jian Liu at the University of North Carolina. The science is there to produce synthetic heparin at the milligram level, and almost there to produce it at the kilo level, Liu told me this morning. But a lack of investment and low market incentive may collude to limit the short-term outlook for engineered heparin.

"We need someone who's willing to serve as partner to expedite production," Liu says. Right now, the researchers are talking with several smaller biotech firms about development for clinical trials. They have not yet been approached by larger pharma companies.

Synthesizing heparin involves introducing sulfa groups into polysaccharides derived from E. Coli bacteria, Liu says, in order to produce an key enzyme for heparin production. The cost of this process is 10 to 100 times less than making heparin from human enzyme, Liu says.

There are a couple technical issues to be worked out before synthetic heparin could be produced at greater rates, much less at a rate to satisfy the current market demand of 30 to 40 tons per year. The first, says Liu, would be improving the yield of the starting materials. The second would be scaling up the current lab procedures to an industrial level--an "engineering problem," says Liu.

And there are financial issues. Even though heparin prices have risen this year to more than $5,000 per kilo, the cost is not prohibitive to warrant a major push towards an alternative. The incentive is not there.

Unless another crisis occurred. While Liu and colleagues certainly don't wish for this, the impetus for their research, which began in 2005, was that the heparin supply is vulnerable. Three main factors are involved in control of the supply, Liu notes: the global pig supply, the heparin harvesting and purification process, and the analytical control. While measures by FDA, other regulatory bodies, and heparin suppliers and manufacturers to establish greater control have been "pretty impressive," according to Liu, the current way of making heparin will always be vulnerable to environmental (e.g., porcine disease) and human (e.g., purposeful adulteration) factors.

Liu likens maintaining control of the heparin supply to maintaining antidoping procedures for Olympic athletes. "You have to know what you're looking for," he says. But just as athletes find ways to circumvent drug tests, there may always be heparin contaminants that will fall outside of materials inspection parameters.

Synthetic heparin created in a GMP environment from fermentation to packaging would certainly eliminate these concerns. The best-case scenario, however, is that synthetic heparin could be ready for patient use within 4-5 years, Liu says. But this is only if there are investment dollars for development and production scale-up.

Pharmaceutical Manufacturing, PharmaManufacturing.com, and On Pharma have been covering, and analyzing, the heparin case since it began. In September, we'll take a closer look at the lessons learned from the heparin crisis, and what all manufacturers must do to ensure safe and efficient supply lines.

--Paul Thomas

Wyeth’s Pearl River, NY, facility recently earned an OSHA Voluntary Protection Program (VPP) “star”, designating excellence in workplace health and safety. It was the 2,000th site in the U.S. to earn such status.

The VPP program began in 1982 as a proactive effort to encourage safety and health management through collaboration between OSHA, corporate management, and facility workers. It has since become the gold standard for workplace safety.

Pearl River’s initiatives began nearly three years ago when "gap improvement" teams consisting of volunteers across the facility were set up to address safety deficiencies, says Susan Rera, the site's associate director of safety. The teams dealt with each issue one by one until the facility was ready for VPP consideration. Pearl River joins a number of other Wyeth facilities that have star quality. “Any site on the star list has gone well beyond what it is required to do,” says Ted Fitzgerald, an OSHA spokesperson. Other pharma facilities with VPP star designations:

Medicinal Chemicals and Botanical Products

DSM Nutrional Products, Inc., Freeport, TX

Noramco of Delaware, Wilmington, DE

Pfizer Global Kalamzaoo Operations, Kalamazoo, MI

Wyeth Biotech, Sanford, NC

Pharmaceutical Preparations

Baxter McGaw Park, Waukegan, IL

Bristol-Myers Squibb, Evansville, IN

Bristol-Myers Squibb, Mount Vernon, IN

Lilly Technology Center, Indianapolis, IN

Noramco of Athens, Athens, GA

Novartis Pharmaceuticals, East Hanover, NJ

Pfizer Global Manufacturing - Brooklyn Facility, Brooklyn, NY

Pfizer Pharmaceutical, Caguas, PR (Merit)*

Sandoz Pharmaceuticals, Broomfield, CO (Merit)*

Schering Plough - Miami Lakes Ops., Miami Lakes, FL

Schering Plough Healthcare Products, Cleveland, TN

Wyeth Chemical Development, Rouses Point, NY

Wyeth Pharmaceuticals, Rouses Point, NY

Wyeth Pharmaceuticals, Pearl River, NY

Wyeth Pharmaceuticals Plant B, Richmond, VA

Wyeth Research Drug Testing Facility, Chazy, NY

In Vitro and In Vivo Diagnostic Substances

Ortho Raritan Plant, Raritan, NJ

Ortho-Clinical Diagnostics Rochester Plant, Rochester, NY

Biological Products Except Diagnostic Substances

Monsanto Augusta Posilac Plant, Augusta, GA

Pfizer Global Manufacturing, White Hall, IL

Wyeth Biotech Andover-Wilimington, MA, Andover, MA

* “Merit” is one level below “star” designation

To some people, Process Analytical Technologies (PAT) and Quality by Design (QbD) might seem like the dullest topics imagineable. But they just might be the salvation of an industry dogged by recalls and adverse reaction reports, lawsuits, 483's and other compliance issues (and that's just on the GMP and non sales and marketing side!)

We think they need to be discussed openly and engagingly, and we've invited two experts whose erudition doesn't get in the way of their common sense, sense of humor and connection to broader culture...and yes, that includes (gasp) pop culture...to help lead an open discussion about this.

Jack Carroll and Emil Ciurczak, chemists and experts in spectroscopy and chemometrics, who teach courses on PAT, QbD and other topics around the world, are co-hosting a video and audio talk show, PAT Talk, to discuss issues.

Here's the first video pilot.

We're planning to feature this regularly in either audio or video format, and to open the discussion and, eventually, allow viewers or listeners to ask Emil and Jack questions about their implementation problems, much as Tom and Ray Magliozzi (better known as Click and Clak, the Tappet Brothers) do on the program, Car Talk. Eventually, guest experts will be invited and the program will also feature "puzzlers."

We hope that you enjoy the program, and welcome any comments, constructive criticism or questions. Especially comments! These subjects can't just be discussed by the elite but need to be talked about openly by everyone in the industry.

AMS

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.

Average OEE in pharma is still in the 30's.  At the Pack Expo last week, Heidi Parsons interviewed technical experts from Bosch and Parsec Automation for their insights. Among other topics, Europe's EN 954 was discussed in connection with downtime and safety problems. To watch, click here.

The International Facility Management Association's "World Workplace 2007" conference and Expo will be held in New Orleans on October 24-26.

More from IFMA's press release:

World Workplace brings industry leaders from the world’s top business and government organizations together with educators and exhibitors to focus on the future of facility management. Now in its 28th year, the conference will feature 78 educational sessions and new product demonstrations by hundreds of manufacturers from across the globe.

"World Workplace has transitioned over the years from one in a series of built environment events to the ultimate facility-focused opportunity for expanding learning horizons," said IFMA President and Chief Executive Officer David J. Brady. "IFMA’s decision to hold World Workplace 2007 in New Orleans reflects our belief that we can provide a positive economic impact while giving the city an opportunity to showcase how it has dealt with one of history’s greatest facility management challenges."

This year’s World Workplace will have an estimated 5,000 attendees seeing green. Because IFMA recognizes the continued importance of sustainability, World Workplace 2007 has received Cleaner & Greener certification from Leonardo Academy, a non-profit environmental consulting group. Organizations seeking Cleaner & Greener certification make a commitment to gather emission reductions, offsetting the emissions caused by events.

"We’re very excited about partnering with IFMA for World Workplace 2007 because of the key role that IFMA and its members play in advancing sustainability in buildings," said Michael Arny, president of Leonardo Academy. "Sustainability provides a great opportunity to advance the world’s understanding of the importance of high-quality facility management. Most organizations and companies have undervalued facility managers, but sustainability provides a way to explain to CEOs why good facility management is important to their company and their brand."

Following in the tradition of last year’s World Workplace, the conference will again feature the IFMA Green Zone, an exclusive section of the Expo floor reserved for those exhibitors offering environmentally friendly products and services.

Beyond going green, World Workplace is also going global. The new International Perspectives educational track is dedicated to industry trends and practices outside of North America. These sessions will help facility managers develop a global strategy for competing in the world marketplace, whether in a developing country or right next door.

This year’s event is also about giving back, not only to the city of New Orleans, but also to the brave men and women who serve as its first responders. One of the highlights of World Workplace 2007 will be the IFMA Foundation’s Volunteer Rebuild Project, which will help repair the lingering damage of Hurricane Katrina by rebuilding one or more of the 22 fire stations debilitated by the storm. The project, scheduled for Saturday, Oct. 27, has already recruited dozens of volunteers to stay a day after World Workplace ends and offer their time and talent to the people of New Orleans.

Conference attendees can add to their New Orleans experience by attending IFMA facility tours throughout the city. Among the facilities open for touring will be the Morial Convention Center, the Audubon Aquarium of the Americas and the largest rebuilding project in the history of U.S. stadiums, the Louisiana Superdome. These facilities, like the people who enjoy them, represent the strength, culture and resilience of New Orleans.

For the first time, World Workplace will feature a press room on the Expo floor, where exhibitors and sponsors reach out to members of the media to illustrate what’s hot in facility management. Other new offerings for 2007 include two Solutions Arenas, featuring problem-solving strategies from the best product and service providers in the industry, and the IFMA Foundation’s student E-Poster Competition, which gives students in facility management programs the opportunity to present their projects and research and gain international recognition.

The Expo will be open Wednesday, Oct. 24, from 2:30 to 5:30 p.m.; Thursday, Oct. 25, from 9:30 a.m. to 2:00 p.m.; and Friday, Oct. 26, from 9:30 a.m. to 2:00 p.m. For a complete list of exhibitors or more information, please visit

More from the "maintenance evangelist" Joel Leonard and his mission to show government officials the importance of new blue and gold collar training.