Unprecedented Integration Powered Pfizer’s NEWCON Facility to 2008 FOYA Award for Process Innovation
Blending of automation, process integration, IT and PAT applications at NEWCON unmatched in the global pharmaceutical industry
When the Pfizer team in Illertissen, Germany conceptualized their NEW CONtainment (NEWCON) facility in April 2004, the main, practical purpose was to create a manufacturing plant for oral solid dosage forms including high potent compounds with a high degree of integrated automation to produce the smoking cessation drug varenicline (Chantix®, Champix®).
Compelling Features Lead To Recognition
Upon completion, however, the US $48.8 million (US $59 million with soft costs), single floor, single containment module facility boasted such a compelling array of ground breaking features that it went on to capture the 2008 Process Innovation category in the annual Facility of the Year Awards (FOYA) competition, sponsored by the International Society for Pharmaceutical Engineering (ISPE), INTERPHEX, and Pharmaceutical Processing magazine.
Located in Germany's Bavarian region, the Illertissen facility has a total production floor area of 7,800 m2 that consists of 3,000 m2 of production space, including the currently idle areas for potential expansion. Construction ended in September 2007 and production began in October 2007, when the German inspection license (PIC) was granted to the facility. The plant currently uses a production area of 1,600 m2 and has a production capacity of 1 billion tablets per year.
Groundbreaking PAT Implementation
Holger Weyhers, Head of Production, points out that all unit operations at the Illertissen facility are within a single containment module, supported by automated systems without any manual handling. "What we have accomplished in terms of automation, process integration and process analytical technology (PAT) is groundbreaking - these are the features that really stand out," he says. The facility includes an automation layer for process sequencing, automated transport systems and a manufacturing execution system (MES) layer for electronic batch records (EBR) and data archiving.
Zeroing in on the accomplishments of the Illertissen team, Weyhers says, "This facility is unprecedented in the entire pharmaceutical industry. We have nothing like this in the Pfizer network, and I strongly believe at this stage that there is nothing comparable in the entire pharmaceutical industry when it comes to the manufacture of solid dosage forms and the containment philosophy."?"The PAT applications are front running and innovative," says George Bernhard, Director of Right First Time at Pfizer. Right First Time, which was launched in 2003, uses Six Sigma tools and includes PAT, which is included in the FDA framework for quality assurance (QA) in the pharmaceutical industry
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Bernhard explains that operationally, the instruments in the facility, which are quite sensitive, have already attained 95% robustness. "Our goal, however, is to get to 100% robustness, which will allow us to have full process control," he says. This is a part of the integrated process control strategy in which the process will be fully automated from beginning to end. "The vision is that you push a button and get tablets out at the end that won't need to be tested," he says.
"This is the first facility with such a high degree of integration with IT automation. You will not find another facility in the world with a similar technical approach," says Ernst Sander, Managing Director, PhC Pharma Consult, a Heidelberg-based engineering firm that provided design and engineering services at the facility, and which has a long-standing relationship with Pfizer, Illertissen.
Containment Issues Shape Facility Design
Weyhers holds responsibility for production at the facility and sets and manages output targets as well as ensures that all GMP requirements are satisfied. He says that the new plant is directly associated with the smoking cessation product varenicline (Chantix®, Champix®), which was launched in 2006.
"The issue with this product is that it falls into Pfizer's occupational exposure band (OEB) 4. This means that from an operator safety perspective, this product cannot be handled in a conventional, open manner. We were required to design and build a containment facility for this purpose," he says.
Weyhers explains that Pfizer Illertissen used its pilot facility, which has the capability to handle high potency drugs, to support the initial launch phase of Chantix in 2006. "But based on the demand forecast for Chantix, it became quite obvious that the capacity of the pilot facility would not be sufficient to support the demand. This, in essence, is the background for the design phase, the planning and the building of NEWCON.
"It is also the reason we moved the project forward by six months. Initially the plan was to have the facility fully commissioned and available for production during 2008, but we managed to have the plant ready by November 2007," says Weyhers.
A Company With A Long History Of Success
Based in New York City, Pfizer has been in continuous operation since its inception in 1849. The global drug giant has annual revenues estimated at some US $47.79 billion and an enterprise value as of May 2008 at some US $124.22 billion. It discovers, develops, manufactures, and markets a broad range of human and veterinary drugs throughout the world.
In 2007 Pfizer's Chantix® received the prestigious "Prix Galien USA Award" for Best Pharmaceutical Agent in 2007 based on its efficacy. Chantix represented one of the fastest product launches in the pharmaceutical industry in Europe - with launches in 16 European countries within a period of five months, according to a benchmark from IMS Health, which provides market intelligence to the pharmaceutical and healthcare industries.
In addition to Chantix, Pfizer's pharmaceutical product offerings include Lipitor, a blockbuster drug that helps to lower blood cholesterol, Norvasc for the management of high blood pressure, Caduet for cardiovascular issues, Lyrica for neuropathic pain, Aricept for Alzheimer's disease, Zoloft for the treatment of depression and anxiety, Celebrex for arthritis pain, inflammation and acute pain, Zyvox for bacterial infections, Selzentry/Celsentri for some forms of HIV, Viagra for erectile dysfunction, and Zyrtec for allergies and hives, among others.
Global Support Leads To Local Excellence
The Illertissen facility drew from both Pfizer's world class pharmaceutical and engineering capabilities and German industrial capabilities, which boasts some 75 years of experience in pharmaceutical manufacturing. "We had the support of Pfizer Global Engineering, which was kept in the loop and appraised of all progress. They did not come up with solutions for us - these were essentially formulated on site, and we managed to come up with our own solutions throughout the project," says Weyhers.
Tracing the early development of the project, Sander says, "Pfizer Illertissen has a very strong internal team, which has considerable knowledge of process technologies. The internal team was involved in the selection of engineering and design companies, and they picked PhC Pharma Consult, which has a strong relationship with Pfizer in Illertissen."?"We were involved in the pilot project plant before NEWCON. We worked on an integrated design, which integrated process, equipment specification, building services, architecture and automation of the facility as part of our general contract for engineering and design with Pfizer."
Weyhers noted that the Pfizer team, the PhC Pharma Consult team and all the suppliers and subcontractors worked very successfully together during the entire project - driven by a solid team spirit and a success oriented philosophy.
Sander explains, "This was one of the strongest teams we have ever put together. The team members were working closely together with a strong focus on being successful. The leaders of Pfizer Illertissen placed a great deal of trust in us, which allowed for the building of a team on a very friendly basis, and where everybody supported each other."
Current Site A Manufacturing Powerhouse
Today, the Illertissen site sits on 510,000 square meters of land, and the production and testing facilities occupy some 23,450 square meters. The site has a total of 598 employees and currently produces approximately 80 MM packs per year. The Illertissen plant supplies 82 countries worldwide, including the United States.
Illertissen has also served as a launch site for new products. In the last 10 years, 5 products with 13 strengths and 323 stock keeping units (SKUs) have been successfully launched without missing any launch date. Its track record of successful innovations include the ultrasonic fill weight control for bead filled capsules in 2003, capacity fill weight control for powder filled capsules (MG2 G100 world wide first prototype) in 2005, wallet packaging line in 2006, PAT applications for blend and tablets from 2003 and ongoing, NIR for raw material testing in 2006 and first regulatory filed NIR water content determination of film coated tablets in 2007, as a replacement for Karl Fischer.
The NEWCON facility is a single floor, single containment module ("cell concept layout"), which can house up to 3 productions trains. Currently, only 1 train is being used for the production of the high potent drug product Chantix®, according to Weyhers.
"The equipment train, however, could be used to accommodate various other products so that we could operate under a multipurpose mode if needed. We also have the flexibility and the space already available to expand the operation and add other unit operations if needed," says Weyhers. At the moment, PhC Pharma Consult is engaged in ongoing work in capacity enhancement at the facility, he adds.?Weyhers believes that the automation and process integration aspects may have been decisive factors that swayed the FOYA judges. He explains that the degree of automation in the facility is completely novel. The MES layer system triggers all process sequences from dispensing to coating, in the automation layer. Transporting of goods and materials is carried out automatically by automated laser-guided vehicles without any operator control. Processing is executed at the equipment level. The batch data are collected automatically into the MES and raw data are archived.
"This means that the automation layer takes care of the entire process flow, performs plausibility checks, and uses the results of the checks as a trigger for the initiation of the next unit operation. This degree of automation and process integration is unique and absolutely impressive," he says.
The Pfizer Illertissen teams points out that the facility incorporates all the elements of modern manufacturing. PAT applications are installed across the manufacturing process to support the vision of continuous quality verification. With respect to safety, no operator attendance is required, which substantially enhances workers' health and safety.
"Apart from the automation levels, we minimized the changeover times by using washing in place systems and cleaning in place systems, all of which helped to minimize the changeover times from one step to another. It is also integrated in the process and in the automation layer," says Sander.
Incorporated among the hazard control features at the facility are state-of-the-art containment techniques. HEPA filters were installed to protect the outside air. Production facilities were fully automated, and operators are able to work without personnel protective equipment (PPE).
Environmental Issues Given Priority
Cognizant of the need to observe green principles, the facility sought to minimize its environmental impact by using natural gas to produce steam, optimize waste separation and operate coolers with ground water in a separate loop - and assessing the impact of production waste water on water dwelling organisms.
With the need for the efficient use of energy, the project team implemented innovative technologies and concepts for saving energy. The heating, ventilation and air conditioning (HVAC) system use well water instead of conventional coolers. It also makes use of a heat recovery system for exchanges between supply air and exhaust air. The facility was outfitted with a central building control system for the regulation and optimization of HVAC energy consumption - complete with assessments to reduce air exchange rates in compliance with GMP and EHS requirements. The equipment in the facility were fitted with frequency controlled pumps and motors. The building was insulated to minimize heat loss, and energy fluxes are monitored.
Award Recognizes Innovative Thinking
Turning to the question of what the award means for his organization, Weyhers says, "It is a big honor to be the Facility of the Year category winner in Process Innovation. This is the first time that Pfizer has received an award for process innovation - and this is the result of our hard work and innovative thinking."
"From the PhC Pharma Consult perspective, this is great honor for us because this is the first time that one of our client's projects has received this award. I think that the biggest benefit for us is the knowledge and the know-how we have gained together with the Pfizer team for the next steps.
"We now have a high degree of knowledge in the world of OEB 4 and 5 products and we know how to design and build production facilities to handle them with the highest degree of automation," says Sander.
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