The judges have conferred and cast their ballots – Pfizer’s NEWCON (New Containment Facility for Oral Solid Dosage) facility in Illertissen, Germany has been named the 2008 Facility of the Year award winner.
The annual Facility of the Year Awards (FOYA) competition, sponsored by the International Society for Pharmaceutical Engineering (ISPE), INTERPHEX, and Pharmaceutical Processing magazine is designed to recognize and reward the facilities and people behind the industry’s most advanced manufacturing plants.
Looking back it’s apparent that Pfizer knew they had an award winning facility on their hands. By just reviewing the information they provided in their submission material you get a sense of the pride and accomplishment that they have in their new facility. Review their top five reasons why they thought their facility was worthy of the overall prize:
1. Facility Design
The new facility was built under an extremely aggressive timeline to support market demand. Equipment installations utilize containment technology. All such contained equipment are combined in a single High Containment Module with a high degree of automation and without manual operator intervention.
The degree of automation is completely novel: 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. The processing is executed at equipment level. The batch data are collected automatically into the MES. Raw data are archived in data historian.
3. Operational Excellence
From design of robust process (as part of FDA`s pilot program) from facility concept to ramp up of production, the project comprises all elements of modern manufacturing: Process robustness, facility design and throughput simulation for lean manufacturing was applied to accommodate synchronized operations to maximize capacity with “semi continuous flow”.
PAT applications are installed across the manufacturing process to support the vision of continuous quality verification. Raw material NIR identification and evaluation, online NIR blend monitoring, online NIR core testing and NIR testing of film coated tablets are in place to support the vision of adaptive process control and/or to replace conventional release testing. NIR water content is filed; filing of online NIR core testing is foreseen.
No operator attendance is required, substantially enhancing health and safety aspects for the employees.
In The Beginning
When the Pfizer team first conceptualized the NEWCON facility in April 2004, the main, practical purpose was to create a manufacturing plant for oral solid dosage forms including high potency compounds with a high degree of integrated automation to produce the smoking cessation drug varenicline (Chantix®, Champix®).
Upon completion, the US $48.8 million (US $59 million with soft costs), single floor, single containment module facility features 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.
PAT Leads The Way
“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,” says Holger Weyhers, Head of Production. He also points out that all unit operations at the Illertissen facility are within a single containment module, supported by automated systems without any manual handling.
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.
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.
Keeping It All Contained
“The issue with this product (varenicline ) 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,” Weyher stated.
Weyhers holds responsibility for production at the facility and sets and manages output targets as well as ensures that all GMP requirements are satisfied.
Weyhers continued by explaining 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.
NEWCON Benefits From Global Expertise
“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.”
High Capacity, Flexibility And Complete Control – All Under One Roof
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.
As mentioned earlier, 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.
One Facility – Two Awards – A Very Good Year
In addition to the overall Facility of the Year Award recognition, the NEWCON facility also snagged the Facility of the Year award for Process Innovation earlier this year.
Turning to the question of what the (Process Innovation) award meant 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.