CRADA Targets Drug Development Bottlenecks, Welcomes Participants

FDA and the California-based IT company, Conformia, have been at work for the past few years on a cooperative research and development agreement (CRADA) designed to analyze knowledge management within the drug industry and FDA, to pinpoint what is making drug development so costly.  Initial findings from the first phase of the CRADA, a blinded research study called “Challenges and Opportunities in Pharmaceutical Development,” will be released this Summer. Anjali Kataria, principal investigator on the CRADA and chief marketing officer for Conformia recently discussed some of the obstacles preventing industry and FDA from improving the overall drug development and approval process.

The fundamental problem is one of data transfer and knowledge management. Today, the most senior scientists at some pharma companies spend 30-40% of their time on mundane administrative tasks, and simply looking for data that already exist.  The same holds for FDA; at both organizations, a great deal of important information is still kept on paper, in scattered databases and in the heads of key staffers.

Information management must be improved, the research suggests.  But so must organizational thinking. In order for the industry to move to a true “Quality by Design” drug development model, FDA must improve the connection between review and inspector teams for small molecule drugs, while senior managers within the industry must get directly involved in  promoting the crossfunctional culture that QbD demands.

Both CRADA partners welcome and encourage more industry participation in this important research.  Pharma companies can take part in joint FDA/Industry workshops on QbD. So far, three of these workshops have been held in Washington,  involving over 200 participants in pharma biotech, and generics manufacturing, some of whom had not been exposed to QbD concepts and had never applied them to FDA submissions or their internal processes.

 These workshops, Ms. Katari says, allow top managers from very different companies to discuss crossfunctional implementation, and specific ways to apply ICH Q8 and 9; they also offer a neutral, open venue in which FDA and the industry can communicate issues and problems in the spirit of “continuous improvement.”

 Companies can also participate in case histories.  Currently, biopharma unit operation case histories are being developed, but the CRADA will establish a chemistry manufacturing and control information management (CMC -IM )working group to analyze real life mock submissions and apply quality systems management principles and knowledge management strategies.

Originally, nine pharma, biopharma and generics companies took part in this research, but Ms. Kataria expects the number to increase to 25 by this summer.

We will be covering this research in much greater depth in our magazine and web site, but for more information on the CRADA and how to participate in the conferences and case studies, visit crada@conformia.com, or contact Conformia at 408-625-3881.

-AMS 

Instilling Green Values in College Chemistry Courses: How St. Olaf’s is Doing It

College chemistry labs have changed a great deal since the 1980s, with most schools using “micro” quantities of reagents to ensure safety and minimize environmental impact.  It’s about time. There’s no reason to expose kids to unecessarily large amounts of potentially dangerous chemicals.

Analytical chemistry courses involved mostly benign materials.  Not so for organic. Istill recall when a lab partner managed to spill a substantial amount of carbon tet on fellow pre-med team mates during an Organic Chemistry I lab.  Was it accidental? I’ve often wondered.

Some spill or other mishap occurred almost daily in that lab, and there were few precautions taken, beyond the standard-issue safety glasses.

Using smaller quantities of reagents demands more skill on the part of the student, “weeding out” those, like me, who were not meant for lab work, or at least teaching them to be less klutzy.

It also prepares serious students for the ‘reality’ they’ll see if they move on to work in industry.

Recognizing that it’s never too early to think green, many universities have incorporated environmental stewardship into their chemistry courses.  A case in point is St. Olaf’s College in Minnesota, which has evaluated the safety and environmental impact of its advanced undergrad Analytical Chemistry course.  This poster, which was presented by Associate Professor Paul Jackson at February’s Pittcon in Chicago, explains how:  St Olaf’s Green Analytical Chemistry

How Good Are Your Manufacturing Operations? Take Our Survey and Find Out

Are Toyota tools and Six Sigma working for you; where do they fall short?  Is management empowering staff to make the best decision, or taking a top down approach? Are you going paperless, using new technology, or sticking with the status quo?   Take our benchmarking survey, learn what your peers are doing and compare results (to be interpreted in our next issue).

-AMS

Biotech Faces Acute Skills Shortage: Time for Another Sputnik?

Bloomberg just ran an article on the shortage of skilled biotech professionals, which has companies like Amgen and Genentech scrambling to find new talent.  Isn’t it time for a Sputnik-like approach to science education in the U.S?  Perhaps some of the billions being spent on certain tragic and fruitless activities abroad right now could be funneled into a radical revision of the educational system? To paraphrase Mr. Rumsfeld, as our contributor Emil Ciurczak recently did, if the nation doesn’t invest, it will be stuck with the workforce it has rather than the workforce it wants or needs.  Here is the article.

Interview with Six Sigma Rock Star Peter Pande and a Look at Six Sigma, The Rock Band

Will be interviewing Six Sigma expert Peter Pande today for his insights into six sigma in Pharma, and, in particular, how the concept fits with R&D.  Is it possible to take a more systematic “DMAIC” approach to innovation, or does that, by definition, destroy the essence of the creative process and lead to promising drugs abandoned too soon, or promising research labs carelessly sold, and valuable human assets—the talents and skills of highly trained and motivated researchers—wasted?

In the meantime, I’ve just discovered the Cincinnati based rock band, Six Sigma, who count The Police among their influences.  Here’s a video of theirs on YouTube, and a link to audio and video on their web site .

Lead guitarist’s Joe Beck’s philosophy sounds pretty good to me.

“It’s all about ideology and trying to be the best person you can be in what you do,” explains guitarist Joe Beck, “(and) how to eliminate your weaknesses to achieve a perfect performance.”While off-stage the band is lighthearted and friendly, it’s clear that they carry a strong message. They might sound pissed off but, upon careful dissection, you’ll notice that much of 6 Sigma is not about contempt and hatred, but more about the struggle to attain a perfect existence.“We try to keep it positive. That’s one thing I don’t see enough in Rock music. Things could always be worse. You can still have angry-sounding music and be angry in your music but, in all, it has to come back to finding your balance,” Reichert says sternly between bouts of cackling laughter.

From Bio by - Jacob Richardson, on YouTube.com

 With apologies to the hip among you and, in particular my teenaged daughter, who is fond of using the “L” word (for “lame”) to describe actions taken by 90% of those 40 and up, particularly those of her opera-nerd mother, I say, “Rock on, guys!”

You’ll find the interview with Mr. Pande in our next issue and on our web site.

-AMS

Improve Pharma R&D Profitability by 30% : GWU’s Jackson Nickerson Shows How (Video clip)

George Washington University’s management professor, Jackson Nickerson (of recent “Drug Manufacturing Wastes Over $50 Billion Per Year fame) and some colleagues have developed a new method for managing R&D that, they say, would improve profitability by 30%.

This process would eliminate pharma’s “desperate dater” syndrome, in which a company envisions a blockbuster, allows its pipeline to become paper thin, then licenses or buys a company to acquire some new technology, fast, and waits to see what happens.

Nickerson, his GWU colleague Tat Chan, and former GWU professor Hideo Owan, now at Aoyama Gakuin University in Japan, say that using this method could improve long-term profitability by 30% or more.

Using this approach, companies would partition their R&D porfolios, based on the specialized manufacturing, marketing and sales assets required.  They’d focus on keeping pipelines full, even if that meant they weren’t always focusing on blockbusters, but on drugs with smaller, targeted markets, until conditions favored setting their sights higher.

The professors will be publishing a paper on this new method, “ ”Strategic Management of R&D Pipelines with Co-Specialized Investments and Technology Markets” in the journal, Management Science.  But here is a summary article and a brief video clip explaining the concept.

A New Drug for Short-Sighted Pharma Managers, Brought to You By MarketingIsEverything

News of the latest pharmaceutical cureall for any pharma managers of the Chainsaw Al Dunlap variety: Deferred MaintenaXe.

Write in if you have worked with, or know, senior managers who have become addicted to this drug and need to reduce their dosage (or try rehab).

Here is a PPT that Joel Leonard and co. show, about Career Paths Not Taken, to promote their mission (which could easily be extended well beyond maintenance. )

I leave you with its a quote from its last page, very appropriate to drug manufacturing today (a reminder that not too many government officials (or their speechwriters) today are as eloquent as some of those in the past):

“The society that scorns excellence in plumbing because plumbing is a humble activity, and tolerates shoddiness in philosophy because philosophy is an exalted activity, will have neither good plumbing nor good philosophy, because neither its pipes nor its theories will hold water”

-John Gardner (former HEW secretary).

And now for a paraphrase for drug companies: “A drug company that scorns excellence in manufacturing because manufacturing is a humble activity and tolerates shoddiness in science and R&D because science and R&D are an exalted activity, may have great marketing but will have neither good science nor good manufacturing—its new R&D concepts won’t be manufacturable, and its products won’t be innovative…”

Enough preaching. “Say goodnight Gracie,” and so, good night.

“Find Me a Maintenance Woman” One Man’s Musical Response to Gen Y Skilled Workforce Training Issues and “American Idol Syndrome”

It’s certainly no secret that many of the most highly skilled people in manufacturing, including drug manufacturing, will be retiring soon. Leaving out the impacts of offshoring, we still hear from some HR departments that companies, including some drug companies, can’t easily find recent grads with the skill sets they need. 

Most kids would rather explore something “cool” (and impossibly competitive) to get into, like music or professional athletics, and, as a result, many of them end up stuck in low level service type jobs, while high paying gold collar jobs remain unfilled.

After noticing the thousands of kids lining up in cities across the U.S. to try out for American Idol, Plant Services columnist Joel Leonard asked why more of them weren’t pursuing training and positions in “gold collar” jobs. He writes about maintenance (Plant Services is an MRO oriented publication) but perhaps this could apply to many other technical fields, including some life sciences support functions.

Joel’s even written a few songs about this issue (for MRO), now available in mp3 and as ring tones in a number of different styles including Hip Hop , Skaa, Reggae, and even operatic style (downloads here)

Questions: Do kids do this because they saw their trained parents or their parents’ peers undervalued, given the layoffs of manufacturing and mid-level technical professionals in so many industries? 

Do they do this because employment in science (despite the handwringing about the need for more kids to study science) can be insecure or dead end, below that top echelon? 

Do they do this just because they’re kids?  (If so, why are kids in other countries pursuing training).

Do they do this because their education has been entirely inadequate?

Here’s Joel’s article.  But that’s not all.  Here’s the original song-with-powerpoint that started it all, recorded by a local blues band. To download, click here (you’ll find the button on the very low right hand corner of the home page). 

Of course,  maintenance folks are needed in drug plants, but please feel free to replace the word “maintenance” with “Sample Prep” “Bioinformatics Tech” or whatever you please.

Cook Pharmica, Genentech, Roche (Shanghai), Taiyo and Vetter named 2007 Facilities of the Year

 This just in from ISPE

2007 Facility of the Year Awards Winners Announced

Five pharmaceutical manufacturing facilities located in China, Germany, Japan, and the United States have been selected as Category Winners in the third annual Facility of the Year Awards competition sponsored by ISPE, INTERPHEX, and Pharmaceutical Processing magazine. New enhancements to this year’s awards program include naming winners in five specific categories. The companies and respective award categories include:
• Cook Pharmica, LLC, located in Bloomington, Indiana, USA, selected as winner of the Facility of the Year Award for Facility Integration
• Genentech located in Oceanside, California, USA, selected as winner of the Facility of the Year Award for Project Execution
• Shanghai Roche Pharmaceuticals, Ltd., located in Shanghai, China, selected as winner of the Facility of the Year Award for Project Execution Regional Excellence
• Taiyo Pharmaceutical Industry Co., Ltd., located in Takayama City, Japan, selected as winner of the Facility of the Year Award for Equipment Innovation
• Vetter Pharma-Fertigung GmbH & Co. KG located in Ravensburg, Germany, selected as winner of the Facility of the Year Award for Process Innovation

The Facility of the Year Awards (FOYA) competition recognizes state-of-the-art pharmaceutical manufacturing projects that utilize new and innovative technologies to enhance the delivery of a quality project, as well as reduce the cost of producing high-quality medicines. Now in its third year, the Awards program effectively spotlights the accomplishments, shared commitment, and dedication of individuals in companies worldwide to innovate and advance pharmaceutical manufacturing technology for the benefit of all global consumers.

“There is something truly remarkable and innovative about every single submission,” said Scott Ludlum, ISPE’s Director of Business Initiatives. “The five Category Winners hail from four different countries.  This diversity demonstrates that the Awards program is a true reflection of the global nature of the pharmaceutical manufacturing industry,” said Ludlum.

Each of the submissions was reviewed by an independent, blue-ribbon judging panel of global representatives from the pharmaceutical design, construction, and manufacturing sectors.

“The addition of Category Winners to the 2007 Awards program significantly improved the competition and effectively enabled the judges to properly acknowledge those facilities that stood out and deserve special recognition,” stated Andy Skibo, 2007 Judging Panel Chair, and Vice President Corporate Engineering and Capital Projects for Amgen. Those Category Winners are:

Facility of the Year Award Winner in Facility Integration:
Cook Pharmica, LLC
The growing trend in cell culture-based therapeutics inspired Cook Group, Inc., to transform an abandoned factory into an innovative new contract manufacturing facility.  The result was Cook Pharmica’s Project Phoenix facility located in Bloomington, Indiana, USA.  Cook Pharmica is currently focused on mammalian cell culture-based production of Active Pharmaceutical Ingredients (API). In addition to its manufacturing train offering scale-up capabilities to 5,000L, Cook Pharmica also provides contract development and analytical services.

Project Phoenix (Phase 1) included the renovation and construction within the first of two buildings that were the former home of the world’s largest television assembly plant.  The renovation and construction of 124,000 square feet, includes office areas, a manufacturing train, a shell for a second manufacturing train, development laboratories, quality control laboratories, warehouse, and process utilities, designed to support up to two manufacturing trains. Construction on the abandoned television assembly plant was completed in 10 months. With the footprint available for future expansion already in place and a second, independent building of 450,000 square feet, Cook Pharmica’s facility is poised to expand with clients’ project needs.

Engineering Design Firm: CRB Consulting Engineers, Inc., St. Louis, Missouri, USA

Construction Manager: R.L. Turner Corporation, Zionsville, Indiana, USA

Manufacturing Facility Design/Build: AES Clean Technology, Inc., Montgomeryville, Pennsylvania, USA

Facility of the Year Award Winner in Project Execution:
Genentech

Genentech’s Oceanside Product Operations (NIMO) project is located in Oceanside, California, USA. Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes biotherapeutics for significant unmet medical needs. Upon U.S. Food and Drug Administration (FDA) licensure, which is expected in the first half of 2007, the facility will have 90,000 liters of capacity for the production of Avastin® (bevacizumab), a therapeutic antibody for the treatment of various forms of cancer.  The six-building, 500,000-square-foot, master-planned campus features manufacturing, laboratory/office space, a warehouse, central utilities, and a “spine” inter-connecting space.  The Oceanside Product Operations facility currently employs approximately 580 people.
 
A team consisting of the owner, engineering company, architect, and general contractor was formed and developed an innovative project delivery approach that is best described as “Design-Build Hybrid.”  Civil, architectural, and structural work were executed design-bid-build, and mechanical, electrical, process, and instrumentation and controls (I&C) were completed design-build under the management of the general contractor. In order to achieve consistency in project standards and quality, the owner, architect and general contractor all unanimously selected an engineering company to oversee all engineering performed by the design-build subcontractors in the mechanical, electrical, process, and I&C engineering disciplines. Largely due to this Design-Build Hybrid approach and people -oriented execution focus, the team delivered the base project on time and under budget.
 
Architect/Designer: Ferguson Pape Baldwin Architects, San Diego, California, USA
 
Engineering: Clark, Richardson & Biskup Consulting Engineers, Inc., Carlsbad, California, USA
 
General Contractor: DPR Construction, Inc., San Diego, California, USA

Facility of the Year Award Winner in Project Execution Regional Excellence:
Shanghai Roche Pharmaceuticals Limited
Shanghai Roche Pharmaceuticals Limited is a successful joint venture together with Sunve Pharmaceuticals of Shanghai, China, and was started in 1994. The Shanghai High Potent Production Project (SHiP) was based on a modest budget and the entire project comprised construction of a new building for the production of highly active medicines with strict containment. The facility was created to manufacture tablets and capsules for the China market, and export of products for the prevention of organ rejection in transplant recipients and for the treatment of specific forms of cancer.

The focus of SHiP from conception to reality was about speed, innovation, and global teamwork. The result was achieved in a short timeframe – only two years from last approval of the funds to commercial production. The facility respects the highest standards for environmental safety. It was built using global and local resources that now manufactures key strategic products for the local market and for export. The rapid growth in production of Cellcept and Xeloda exemplify this success.

Project Management and Start-up: Shanghai Roche Pharmaceuticals Limited

Architect and Construction Manager: Meissnert & Wurst Zander (Shanghai) Limited
Facility of the Year Award Winner in Equipment Innovation:
Taiyo Pharmaceutical Industry Co., Ltd.
Taiyo Pharmaceutical Industry Co., Ltd., is located in Takayama City, Japan, and has its main business consisting of two major enterprises: contractual production for external parties, and the production of generic products. 

Consistent with its low cost strategy and in accordance with its mid- to long-term management strategy, Taiyo Pharmaceutical Industry Co., Ltd. began the in-house project of manufacturing pre-filled syringes (PFS) at its Unit Factory Building PFS Manufacturing facility. The project currently produces a total of six products, including four plastic syringe containers and two glass syringe containers.  In addition to the in-house syringe project, two other manufacturing lines have been successfully completed and produce pre-filled syringes equipped with high-speed type isolators.   

“The most important aspects of the services we provide to customers and markets are the provision of high quality products …and the stable supply of products. Our products are low in price, easy for nurses to use and create little burden on patients.” This includes pre-filled syringe preparations in various doses, which reduces the risk of contamination by foreign substances, and ease of use.

Designer – Production Facilities: Horiuchi Architectural Associates

Designer – Production Equipment: Taiyo Pharmaceutical Industry Co., Ltd.

Construction Management: Kashima Construction K.K.
Facility of the Year Award Winner in Process Innovation:
Vetter Pharma-Fertigung GmbH & Co. KG 
Vetter Pharma-Fertigung GmbH & Co. KG’s New Facility Ravensburg Vetter South (RVS) is located in Ravensburg, Germany.  Vetter is a contract manufacturer specializing in the aseptic filling of liquid and lyophilized drugs for international biotechnology and pharmaceutical companies.  

The New Facility Ravensburg Vetter South took 36 months from start of detailed design to complete validation. Vetter started operation of the facility in October 2006 and its production site currently has two filling lines, which will be expanded to four in the near future. The facility is the result of more than a quarter of a century of expertise in prefilling.  Automation was planned throughout the building, from door openers, to the use of the brand new Restricted Access Barrier System (RABS) on the filling lines.  It features maximum automation; high standards of sterility, safety, and quality; self-sufficient production site with its own utility and power supply; unique production lines; and a capacity of 90 million units per year.  RVS was designed to meet all of the challenges that technicians and scientists are faced with when aseptically filling syringes, cartridges, and vials. 

Architect: Vetter planning team, Ravensburg, Germany

Technical Building Management: Axima GmbH, Cologne, Germany

Structural planning: Schneider & Partner Planungsgesellschaft mbH.,  Ravensburg, Germany

Facility of the Year Activities in 2007 include:

There will be several opportunities to meet the 2007 Facility of the Year Award Winners and learn first-hand about the facilities being honored as “best in their class.” These events include:
• INTERPHEX2007 – Meet the Category Award Winners 24-26 April at the Facility of the Year display area located in Hall 3D, Upper Level, Jacob K. Javits Convention Center.  This is the opportunity to meet personally with representatives from companies of the Category Winners to discuss the success stories associated with these pharmaceutical manufacturing facilities. To register, or for more information, visit www.interphex.com.
• ISPE Facilities Summit – Learn about case studies from 2007 Category Award winners during ISPE’s Facilities Summit taking place in Arlington, Virginia, from 4-7 June 2007. To register, or for more information, visit www.ispe.org.
• ISPE Annual Meeting – Learn first hand who the Overall Winner of the coveted 2007 Facility of the Year Award is during ISPE’s 2007 Annual Meeting taking place at Caesar’s Palace in Las Vegas, Nevada, USA, from 4-7 November. For more information, visit www.ispe.org.

At each event, a Facility of the Year Awards display will feature 2007 Category Award Winners.  Additionally, comprehensive coverage and publicity initiatives will be conducted by ISPE and Pharmaceutical Engineering, INTERPHEX, and Pharmaceutical Processing.

Shigeo Shingo Was Not a “Nice Guy”

The Shingo Prize will be awarded in Jacksonville, Florida in a few weeks, with a keynote from Dr. Sam Bahri, the world’s first “Lean Dentist” (a phrase that conjures up some rather frightening images).

We’re working on a cover story on Baxter, the first drug manufacturer to win a Shingo Prize twice.  We’ve interviewed team leadership at Cuernavaca and North Cove, but also got some perspective from the Shingo Prize director, Ross Robson and examiner Gwendolyn Galsworth, author of last year’s  Shingo Prize winning book, Visual Workplace, and director of the Lean-Visual Institute.

The application process is rigorous:  each facility must complete a 100-page application, for which data collection can take three months.  If selected, they must then agree to a two-day site visit (Baldrige prize site audits take 5 days, but “we’re Lean,” jokes Robson), during which examiners (each of whom signs a strict nondisclosure agreements) can take “deep dives,” and demand to see HR and other records, if they notice any disconnect between what they’re seeing on the shop floor and what’s in the application. 

The judges  (there is a pool of 300, with active group of less than 100) must review the applications or report on the site visits, a commitment of time, but also a learning experience for those who want to benchmark what their own companies are doing with Lean.

From his photos, I had imagined Dr. Shingo to be a very mild-mannered, quiet man.  I’m sure that he was a lovely person to family and friends,  but apparently he could be a bit of a firebrand, and didn’t hesitate to call a question “stupid” or a spade a spade.  At one U.S. facility he visited, the staff had reportedly hung a poster designed to inspire them and honor Shingo’s principles.  “Eliminate Waste,” the text on the poster read, which only provoked a tirade from the Doctor.  “It should say IDENTIFY waste,” he is reported to have replied, because you can’t eliminate what you can’t identify.

Apparently Dr. Deming suffered from the same “spade is a spade” syndrome.  Perhaps it’s because they were both engineers.

So much for quality guru hagiography….these were flesh and blood people, after all, and didn’t tolerate fools, or waste, gladly. 

For more, stay tuned for April’s report.  Perhaps pharma will get more involved in this worthwhile program, and there’ll be another drug manufacturing winner to talk about next year?