F. Hoffman La Roche’s BioIV Facility Wins The 2008 Facility of the Year Award For Project Execution

An ultra-fast track schedule in combination with a dedicated and highly experienced team of engineers has resulted in F.Hoffman L Roche’s BIO IV facility winning the 2008 Facility of the Year Award for Project Execution.

The Bio IV facility is located inPenzberg, Germany approximately40 km south of Munich.

The Facility of the Year Award (FOYA) is an annual competition sponsored by ISPE, INTERPHEX and Pharmaceutical Processing magazine. The program is designed to recognize state-of-the-art projects that use new and innovative technologies to improve the quality of products, reduce the costs of producing drugs and demonstrate advances in project delivery. Winners are selected in five distinct categories. The overall winner is announced during ISPE’s annual meeting.

A Leader In Pharmaceuticals And Diagnostics

Headquartered in Basel, Switzerland, Roche is one of the world’s leading research-focused healthcare groups in the fields of pharmaceuticals and diagnostics. As one of the world’s biggest biotech companies and an innovator of products and services for the early detection, prevention, diagnosis and treatment of diseases, the group contributes on a broad range of fronts to improving people’s health and quality of life. Roche is a leader in in-vitro diagnostics and drugs for cancer and transplantation, a market leader in virology and active in other major therapeutic areas such as autoimmune diseases, inflammation, metabolic disorders and diseases of the central nervous system.

In Penzberg, Germany where the BIO IV project was built, Roche operates one of Europe’s largest biotechnology sites. About 4400 people work in research, development and production for diagnostics and pharmaceuticals. Research and development is concentrated around diagnostic test systems and biological active ingredients for drugs. The Penzberg site is the Roche Center of Excellence for therapeutic proteins, including monoclonal antibodies.

Complex Projects? No Problem

According to Claus Herrmann, Project Manager for the BioIV facility, this is not the first time such a complex project has been undertaken, "As a company we have successfully completed several major projects in the past few years, BioIV being the most complex attempted to date. In that time our engineers have overcome many challenges. We have learned from those challenges and use the lessons learned to strengthen and shape our engineering organizations."

A Reason For Building

As with any facility of this size and complexity there has to be a reason – a market need - for such a facility. And indeed, in the case of the BIO IV facility there was, as

Facility operators were fully integrated into the team from day one and took part in every aspect of the project, resulting in them receiving a facility in which they were fully trained, leaving them free to focus on production.

Mr. Herrmann explains. "To make our innovative cancer drugs available as quickly as possible to an increasing number of patients, Roche initiated expansion of its Penzberg site, already one of the world’s largest biotechnology centers. The expansion increased production capacity for Trastuzumab, the Active Pharmaceutical Ingredient (API) for the anti-breast cancer drug Herceptin. Once running at full capacity, Biologics IV will enable the supply for 100,000 additional Herceptin patients per year."

The project scope included a production building finger with two independent production lines, an office/lab-building and the provision of a basement for a 2nd production finger extension. The main goal of the project was to enable product registration as quickly as possible. This project goal required the construction and start-up of the first of the two production units in the minimum time frame possible. This goal dominated the project execution strategy and was over achieved by the project team.

Forget Fast Track – How Does ULTRA Fast Track Sound?

While the project team at Roche had a reason for building the facility, they still needed to go out and do it. And do it as fast as possible. Mr Herrmann continues, "We knew we had a major challenge with the Bio IV project and addressed the challenge in a logical and ordered manner as engineers should. A team of experienced, high quality, and team-orientated Roche engineers who previously worked together on projects all over the world, was assembled.

The "Users", described as the people who would ultimately take over the operation of the facility, led by Dr. Juergen Wahl, head of Biotech Production Penzberg, were also key team members. The Users were fully integrated into the project team from day one and took part in every aspect of the project, resulting in them receiving a facility in which they were fully trained, leaving them free to focus on production.The complete Penzberg team developed a close cooperative relationship with their Roche colleagues who were simultaneously constructing a new biotech production facility in Basel, Switzerland. The exchange of knowledge and experience was highly valued by both teams. This led directly to cost and time savings when solutions to common problems were implemented on both projects."

Further detailing the projects organization, Mr. Herrmann explains some of the key initiatives that resulting in the final facility, "Starting in project initiation and continuing

The DCS system was developed with input from the plant operators eliminating a lot of changes, training and familiarization.

through qualification, we organized a series of workshops where the challenges, risks, and solutions were systematically identified, analyzed, and resolved. The critical series of workshops developed the highly successful and innovative execution strategies for design, procurement, construction, and commissioning. This project was teamwork at its best! Everybody was so passionate and committed to the project and proud to be part of it."

This dedication to the project and the team atmosphere led to some noteworthy achievements:
• First production batch was achieved 36 months after start of concept design.
• Total project final cost was 0.4% below the approved funding limit.
• 100% functionality of process equipment, the Distributed Control System (DCS), the Manufacturing Execution System (MES), the building and the associated infrastructure was fully available at hand over to the production team.
• Owner satisfaction is very high due to the high quality standards achieved, especially in process and process automation.
• Excellent two way communication was established between the end users and the project team.
• High motivation of the project team, the users, the prime contractors, the subcontractors and suppliers throughout the project.
• Avoidance of work overload and delays due to diligent resource planning which ensured adequate staffing levels especially on the user’s side. This was the key for a successful and smooth handover.
• Excellent sponsorship by senior management.
• Excellent senior management recognition within Roche (2 internal performance awards received).

First Of Its Kind Features

As with any facility of this complexity, innovation is the order of the day. Add into the mix the need for a speedy completion and you have a recipe for some truly ground-breaking concepts. Asked to comment on the "uniqueness" of the BIO IV facility Mr. Herrmann offered his opinions. "A schedule analysis showed that the equipment and piping installation and automation software development drove the critical path during construction. Building on experience of past projects, the team realized that skid mounted equipment reduced process equipment installation time from weeks to days."

A major review of the process and utility equipment was organized with the aim of using skid mounting as much as possible. This brought three immediate benefits:
1) The skids could be completed while the building construction was still in process, 2) The quality of the process equipment installation could be guaranteed as it was carried out under factory conditions, and 3) The field installation time for the process equipment was reduced from months to days.

View of the fermentation production area highlighting its glass facade.)

The skids were installed very quickly. It took only six weeks for the hook-ups and the first skid was commissioned before the last skid was installed. The project team also focused its attention on automation. Borrowing software techniques from the telecom industry, the huge volume of process automation software was broken down into small modules and additional programming resources were applied to compress the writing and testing time.

The natural extension of this was to use "copy/paste" as much as possible in the process design and the automation software production. To ensure the timely delivery of fit-for-purpose software, a large quality and progress control regime was set up. This delivered the software fully tested and ahead of schedule.

The final compression of the schedule was achieved by analyzing the commissioning and qualification steps required. Everything possible was commissioned and qualified in the factory. The actual field commissioning and qualification was managed using "Petrochem Shut Down" techniques. The work was subdivided into small tasks and two shifts a day, seven-days a week was employed to reduce the commissioning/qualification time to a minimum. An added benefit was that the skid mounted equipment allowed field commissioning to take place in close integration with the construction work. In practice, this meant field commissioning a skid while the building contractor was still working in the area. This called for careful co-ordination of the average 400 trade operatives and commissioning teams.

By involving the User's management and operatives from the start of the design, the final plant reflected their working practices. They were involved in the equipment layouts and advised on instrument positions and access stairs. The modular software was developed to their requirements which eliminated a lot of changes, training, and familiarization time required with a normal plant.

For the CIP and SIP, which was critical to the success of the facility, the operatives brought the practical knowledge from every day experience and the design engineers developed the system around the operative requirements. The resulting systems run efficiently.

The facility’s Manufacturing Execution System (MES), including Electronic Batch Recording, was developed in a similar manner. The MES delivered a reduction of labor cost and an increase of production process quality with the following built-in functionalities:

• Batch planning board for optimal sequencing of batches increasing equipment utilization
• Sample and filter management to enforce correct equipment and batch status in real-time assuring highest GMP standards
• Complete tracking of material movements allowing a full genealogy of use of raw materials vs. finished goods batches traceable from both ends
• Shuttle management tracks inventory and location of containers and controls transport orders to shuttle system leading to optimized use of transport and storage capacity.

While the facility’s main function is to efficiently produce the product it was designed for, it is also a workplace for 120 people. To meet the needs of the people employed there the project also delivered a high quality ergonomically designed workplace. The project represents the integration of high tech GMP process plants into a state of the art building. This is underlined by an impressive architecture which gives the building high transparency and which fosters communication.

It’s All About The Team

When asked what specific details and or features of the facility he’s most proud of Mr. Herrmann defers to the people on his team, "I was most proud of the team. It was most gratifying to watch them grow personally and as a team." As challenging and complex a projects as it was Dr. Wahl concurs with Mr. Herrmann. "This challenging project was terminated well in time and within budget. This could only have been achieved by excellent project teams and perfect coordination by the project management."

The Judges Have Spoken

Finally, when asked why he thought the Facility of the Year Award judges selected his facility Mr. Herrmann offers up these reasons. "I believe that Bio IV was an outstanding project in many aspects, specifically the manner in which the project team delivered a large, technically complex project ahead of time, under budget and to the complete satisfaction of the User; the innovative and effective execution strategies applied on the project and the truly integrated teamwork