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Vetter’s New RVS Facility Targets Outsized Growth in Aseptic Prefilled Administration Devices

Tue, 10/09/2007 - 11:11am
New plant maximizes automation while increasing both capacity and capability in manufacturing
Automation to the maximum was uppermost on the drawing boards at Vetter Pharma-Fertigung GmbH & Co. when it conceptualized, designed and built its new €100 million capacity and capability expanding state-of-the-art aseptic prefilling facility - Ravensberg Vetter South (RVS) - a venture that successfully enhanced the company's already formidable prowess in the rapidly expanding biotechnology contract manufacturing business.
Specialists In Aseptic Processes
Suppliers

Planners
• Architect  ...  Vetter planning team
•Technical Building Management  ...  LSMW GmbH, Nuremberg; Axima GmbH, Stuttgart
•Structural planning  ...  Schneider & Partner, Planungsgesellschaft mbH., Ravensburg
•SiGeKo (Health and Safety Coordinator)  ...  Ingenieurbüro Köberle, Nonnenhorn

Contractors – building services
• Skeleton construction  ...  Georg Reisch GmbH & Co. KG, Bad Saulgau
•Façade  ...  Friedrich Burk GmbH & Co. KG, Ravensburg
•Roof sealing  ...  Dieter Eitle GmbH, Ulm
•Screed  ...  Kirchhoff-Heine Straßenbau GmbH & Co. KG, Langenargen
•Dry lining  ...  Manfred Wucher GmbH, Ravensburg
•Floor coating  ...  Peter Wiedemann GmbH, Mochenwangen
•Floor finish  ...  Johann Engler GmbH, Bad Saulgau
•Paintwork  ...  Heinz Müller GmbH & Co. KG, Horgenzell

Contractors, Technical Building Equipment (TBE) services
• General technical contractor for all technical building equipment (TBE)  ...  Axima GmbH, Stuttgart

Subcontractors
• Steam generator  ...  Loos Deutschland GmbH
•PW generator  ...  Ondeo Industrial Solutions GmbH
•WFI still and pure steam generator  ...  Stilmas S.p.a
•Compressed air system  ...  Atlas Copco Kompressoren und Drucklufttechnik GmbH
•HVAC system  ...  Huber & Ranner GmbH
•UPS system  ...  GSA Euro-Diesel GmbH
•Electric systems  ...  Elektro Stotz GmbH & Co. KG
•Building automation  ...  Siemens AG / SSG Starkstrom Systeme GmbH
•Cooling system  ...  Axima Refrigeration GmbH

Process equipment suppliers
• Robotics  ...  Adept Technology Inc.
•Filling line 2 (vials/cartridges)  ...  Robert Bosch GmbH
•Filling vessels  ...  Binder GmbH
•Container washing machine  ...  BHT Hygienetechnik GmbH
•Multi-chamber washing machine, magazine washing machine  ...  Belimed GmbH
•Magazine handling (software)  ...  Fastec GmbH
•Tub handling  ...  Föratec GmbH & Co. KG
•Freeze dryers  ...  Hof Sonderanlagenbau GmbH
•Tub handling  ...  Inova Pharma Systems GmbH
•Magazine handling (hardware)  ...  Montech Deutschland GmbH
•Freeze dryer loading system, autoclave boxes, incl. frames  ...  Motus Engineering GmbH & Co. KG
•Vacuum dryer  ...  Pink GmbH
•CIP/SIP container  ...  Manfred Roth Edelstahl-Behälter und Apparatebau
•CIP/SIP unit  ...  Ruland Engineering & Consulting GmbH
•Autoclaves  ...  SBM Schoeller-Bleckmann Medizintechnik Ges.m.b.H
•Laminar flow benches  ...  Weiss GWE GmbH
•Filling line 1 (dual-chamber systems)  ...  Vetter Pharma-Fertigung GmbH & Co. KG
Founded in 1945 in Revensburg, Germany, contract manufacturer Vetter specializes in the aseptic filling of liquid and lyophilized drugs. "We don't only offer pre-filled syringes to our customers; we are a full service provider. Our contract manufacturing operations include development services, process development, regulatory support, quality assurance and quality control among other areas," says Thomas Otto, Managing Director, Vetter Pharma. Today, Vetter's customers include the top 20 pharmaceutical companies and the top ten biotech companies worldwide, according to Otto. Among its 1,700 employees are some 500 scientists and engineers. In addition to its German-based offices and manufacturing plants in Ravensberg and filling facilities in Langenargen, some 17 miles away, Vetter operates a United States-based subsidiary located in Yardley, Pennsylvania.
On The Fast Track From Design To Build To First Fill
The company finalized detailed design at the RVS facility in September 2003 and the first fills were initiated in October 2006 - 36 months from final design to validation. This is considered a benchmark in light of the facility's total size of about 172,000 ft2 and production area of about 31,500 ft2. Otto explains that the RVS site currently has two filling lines and that the availability of two reserve spaces (4,850 ft2 and 11,800 ft2) will facilitate expansion into four lines.

"We are already in discussions with a customer to expand the facility, which will mean the implementation of the next lines. We believe we can implement this very quickly because everything is already in place. That's what we see in the aseptic area, and we are already constructing a new building for secondary packaging, which will increase our capacity in that area as well," says Otto. "Having this additional capacity is very reassuring to our customers, because they can feel confident about adding new capacity in their operations if they need to," he says.

Of the two filling lines currently operational, one is dedicated to filling lyophilized/liquid or liquid/liquid drugs into dual chamber syringes and cartridges. Otto says that the other line handles single-chamber cartridges and vials for lyophilized and liquid substances.

Focusing on Vetter's foray into the vial business, Otto says, "We do not want to enter into the vial mass market. We see most biotech companies starting the life cycles of their products in vials. This means that when they do clinical studies, they start in vials.

"Customers have asked us what we can do to support them the entire way. If we are only able to offer pre-filled syringes, they will have to start with a different vial filler, and then return to us for syringes. This is inconvenient, so we decided to add that technology to our portfolio and be able to offer clients the full range of filling technology," says Otto.

"That is why we added the second line and we are now operating a combination of pre-filled syringe and vial technologies. So, we have included new technology and capabilities as well as additional capacity in the new plant," he says.

Otto says that the new facility expands Vetter's total capacity by some 30%. "This is a significant capacity improvement for us with much of the new capacity going into the biotech area."

"In addition to new capacity, we added a fully automated line - this means that we fill our syringe systems without any manual operations and as little human contact as possible," he says.

In February, 2007 Vetter obtained a manufacturing license for the new facility from the European regulatory authorities. "That means that as of the beginning of this year, we are fully operational from a regulatory standpoint. We expect our first US Food and Drug Administration (FDA) inspection in 2008," he says.

"For the time being we operate two shifts. There are roughly 150 people in the new plant right now," says Otto.
Market Research Key To Facility Expansion
Turning to Vetter's rationale for the capacity expansion, Otto says, "Our market studies indicated rapid growth in the pharmaceutical sector in the future. Vetter wanted to prepare itself. We recognized that a key way to accomplish this would be to increase our manufacturing capacity to meet the needs of our clients, and serve them better."

"Everybody knows that the pharmaceutical industry is growing very fast. If you want to keep your position in the market, you have only one option and that is to grow. Vetter has decided to grow not by buying other companies, as some of our competitors are doing. We have decided to grow organically and our investment planning for the future clearly shows that we are willing to take on the challenges to do this."

Otto is one of three managing directors at Vetter Pharma, who collectively manage all the high level planning, management and administrative functions of the company. In this group, Otto, a technical engineer by training, is responsible for technical operations as well as production and development activities. As a result, he had high level overall responsibility for the planning and execution of the new facility.

Vetter's strategists no doubt observed the ready adoption and use of prefilled administration devices in Europe since the 1970s. Even though prefilled systems gained traction somewhat more slowly in the United States, in the last several years the market showed a 10% annual expansion to hit sales of $16 billion in 2005.

The company's literature notes that prefilled systems including single- and dual-chamber syringes, cartridges and vials enjoy widespread application and market acceptance because of their practicality, safety record and user friendliness. They are used with an impressive number of medications ranging from vaccines to antithrombotics and increasingly with a large number of biologics.

Signaling the expectation that demand will grow for the products from its new RVS and other facilities, the company's literature notes, "A further increase in sales of lyophilized drugs in particular is also expected, as growth in the overall pharmaceuticals market is due predominantly to new biotechnological products, which for the most part can only be stable in a lyophilized form."
High Technology Leads To Award
Zeroing in on what he believes swayed the judges in the third annual Facility of the Year Awards competition sponsored by ISPE, INTERPHEX, and Pharmaceutical Processing magazine to select Vetter as the winner of the 2007 Facility of the Year Award for Process Innovation, Otto says, "This is one of the most modern production facilities of its kind in the world. Regarding the filling of cartridges and vials, we have implemented the first combination line, which is able to handle both cartridges and vials on one line. This is the first combination line built in the world."

Otto says that some of the most important innovations in the facility are on the machine side. "The facility has fully automated lines that need no manual interaction from start to finish. It is operated fully by robotics, and this is the most important innovation from the filling point of view.

"From the process standpoint, we have designed the plant in a way that makes the interaction of people in crucial areas impossible. They cannot interfere in the different areas, so with respect to personnel and material flow, we have some of the highest standards in the world in this facility," says Otto. Vetter uses the Restricted Access Barrier System (RABS), which it has spent approximately a decade developing, to minimize human contact with the production lines, and so reduce opportunities for contamination.

"Another innovative area has to do with power supply, which is a major preoccupation in our technical support activities. We have implemented safety measures and uninterruptible power supplies (UPS) to make sure that the plant will have no power outages," says Otto.

The availability of back up power supply is crucial to mitigate the loss of large quantities of sensitive and expensive active materials in the event of power outage. The plant uses both electricity and gas. If one power system fails, a no-break power supply will kick in instantaneously. The back-up system is supported by two dynamic UPS units attached to a diesel powered generator. Should the gas supply fail, all the burners will immediately be switched to heating oil, which is stored in an underground double-walled oil tank.

"This is important because for many customers we are the sole supplier and if anything happens to their product flow this can cause serious problems downstream in their operations, and ours," says Otto.

Technologically, according to Otto, the facility incorporates the most advanced and modern systems available in the world today. Much of the technical systems of the new facility has been developed and perfected by Vetter and is considered proprietary and a key element of the company's competitive edge. For example, the filling line for its dual chamber Vetter Lyo-Ject syringe uses a patented system that permits in-process lyophilization.
Custom-Built And Planned In-House
In general, the facility is described as custom built with many unique features. It has incorporated all the needs and challenges that scientists and technicians face when dealing with the aseptic filling of syringes, cartridges and vials. Automated systems permeate the facility spanning from door openers to the new and innovative RABS system. The filling lines are arranged to allow for the greatest degree of modularity and flexibility.

Otto says that the whole facility was planned in-house by Vetter. The Vetter integrated project management team was also solely responsible for the execution of all aspects of the construction activities, which involved some 70 different outside contractors. The team was also responsible for the external management of all activities related to the supply of equipment and components from external suppliers, according to Otto.

"By and large, most of the equipment originated in Germany, in fact, from suppliers who are located relatively short distances from our facility," says Otto. He explains, "We are in a happy situation because in the pharmaceutical industry, some of the best known equipment makers and suppliers are located in the area where we operate."

Among the companies that supplied components were Adept Technology, which built the robotics, Binder GmbH supplied the filling vessels, BHT Hygienetechnik supplied the container washing machine, Belimed GmbH provided the multi-chamber washing machine and the magazine washing machine and Fastec GmbH supplied the magazine handling software.

"The first filling line was designed and constructed by Vetter because we wanted to keep that in our own hands. The next line for the filling of vials and cartridges was built by Robert Bosch GmbH, which is also well known in the United States."

Vetter took the decision early in the process to build most of the facility itself drawing from its extensive expertise and in-house capabilities. Otto explains that being a contract manufacturer entails handling a number of different product lines. As a result special expertise is needed to incorporate a number of elements that will need to be activated or switched off at different times depending on requirements for the product being handled.

"We are very happy that our endeavor to meet the requirements of tomorrow by means of today's innovative solution has met with the acknowledgement of facility of the year award judges," says Otto.

"We are really proud of this award. In our view, the award is one of the most important to be gained in the international pharmaceutical industry. In my eyes, it stands for innovation and quality and underlines the innovative prowess of Vetter and the region in which we live and operate," says Otto. "It validates our activities and our search at Vetter for innovative and sustainable solutions."
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