PDL Bioharma Biotech Manufacturing Facility, Brooklyn Park, Minnesota, USA

Protein Design Labs (now called PDL Biopharma), is an emerging biotechnology company that in late 2002 announced plans to build a new manufacturing facility on a 29-acre site in Brooklyn Park, Minnesota, US. The company had already established a much smaller pilot plant and manufacturing facility in Plymouth, Minnesota, in 1992, where it produced clinical trial material in the early stage of development for many of its products.

The company has now reached the stage of commercialisation of its first major product and requires a much larger manufacturing plant, hence the new facility. In 2005 the company acquired ESP Pharma in a $489m deal and changed the new company's name to PDL Biopharma.

The acquisition has helped PDL to gain an established sales team prior to commercialisation and also given three more licensed drugs to market prior to their own pipeline coming to fruition.

PROJECT CONSTRUCTION

The first phase of the facility in Brooklyn Park has 214,000ft² of floor space and required an investment of over $200m to construct and outfit. The building was structurally complete and opened during July 2004. However, fitting out, commissioning and validation of the facility has been an ongoing process and antibody production started in mid-2007.

The plant recruited over 100 specialist staff for the opening in 2004 to assist in commissioning, testing and validation. The final number of staff at the facility in 2007 is approaching 275.

Phase 2 of the facility is planned to add an additional 200,000ft² of floor space, drastically increase the manufacturing capacity of the plant, and take on a further 200 new staff. Phase 2 construction will not now start until at least 2008 following the establishment of the existing facility as a major production centre.

PROTEIN DESIGN LABS MAIN CONTRACTOR

The contractor for the project was Fluor Corporation who provided design, engineering and procurement services along with project management for the facility construction. Fluor was awarded the contract in the second half of 2002, and was paid $19.5m for its services.

The facility also has a unique IT infrastructure with a dual network; a corporate network for day to day activities and also a control network for manufacturing activity. Dell Comm was responsible for the system design and installation of the new IT system. Equipment for control system was provided by Ortronics and Berk-Tek.

BIOTECH MANUFACTURING FACILITY

The facility consists of five areas: manufacturing / operations, quality control / research laboratories, warehousing / dispatch, office / administration and a central utilities area. The manufacturing / operations area has four bioreactors for the manufacture of the same or multiple products depending on requirements.

The bioreactors are two 10,000l standard batch-fed type and two 1,000l continuous perfusion bioreactors, giving a total of 22,000l of capacity. The downstream processing facilities will include two purification suites including facilities for chromatography, filtration, centrifugation and freeze drying.

The plant also includes facilities for media preparation, storage and packaging / preparation of products prior to dispatch to a fill and finish facility. The central utilities area includes two 10,000l tanks for storage of high grade water for injection for media preparation. Central utilities will also supply high purity gases (oxygen, nitrogen, carbon dioxide) for use in fermentation processes.

The facility required 26,000t of structural steel, amounting to some 8,500 components and 11,000yd³ of concrete. The outfitting of the facility for deionized water, speciality gases, clean steam and waste required 40,000ft of high purity grade piping and 160,000ft of other piping.

Electrical outfitting required 1.5 million feet of cabling. Air handling for the facility is carried out by 15 units and 375,000ft of ducting. The air handling system is able to provide pressurisation to certain areas of the plant to assist in contamination control if required. It is estimated the plant will process and consume 1 million gallons of water per month.

PROTEIN DESIGN LABORATORY PRODUCTS AND PIPELINE

PDL's main area of interest is the technology of humanising monoclonal antibodies. This process uses structural information from selected useful mouse antibodies to capture the benefits of the antibodies without the limitations. Mouse antibodies in humans have only a short half-life as they would be neutralised by the immune system. PDL has developed methodology to fuse the useful portions of mouse antibodies (selected amino acid sequences) to human antibodies.

The resulting humanised antibody will retain the desired binding properties imparted by the mouse portion but will not elicit the same immune response in the human patient.

The process relies on the creation of mammalian cell-lines that will manufacture the desired hybrid antibody in a fermentation process and secrete it into the surrounding culture media ready for harvest.

Four antibody systems are currently in development for the treatment of autoimmune disease, such as Crohn's disease and ulcerative colitis, and also for the treatment of certain tumours. It is hoped that most or all of these products (visilizumab, fontolizumab, daclizumab and anti-a581 integrin antibody) will be manufactured in the new plant, starting in 2007.

Currently PDL markets seven licensed humanised antibody products (Zenapax, Mylotarg, Synagis, Herceptin, Xolair, Raptiva and Avastin) with partners that include Roche, Wyeth, Novartis and Genentech to treat a variety of conditions such as allergic asthma and psoriasis.