Lonza Biologics Plant Expansion, Portsmouth, NH, USA

Lonza Biologics completed the large-scale expansion of their facility in Portsmouth, New Hampshire, Pease International Tradeport, US in 2004. The project started in 2000 with the aim of expanding the production capacity of the New Hampshire plant by the installation of three 20,000l stirred tank batch bioreactors and supporting infrastructure such as purification facilities, warehousing and QC laboratories.

The investment for the expansion was estimated at some SFr330m ($207m). The workforce at the New Hampshire site is around 500 but this is set to rise by between 250 and 400 when the final phase of expansion is under full production.

The New Hampshire site has undergone many expansions since it was first opened in 1999. One of the first expansion projects was completed and opened in early April 2003. This was a two-storey office complex including a laboratory and office support utilities.

LONZA BIOLOGICS PLANT EXPANSION CONTRACTORS AND SUBCONTRACTORS

The 'Lonza Large-Scale Build-Out', an expansion of some 26,000m² (280,000ft²) floor space was managed by Parsons. This company was responsible for the management of engineering, procurement and construction in the overall project. The Lonza-Parsons project team started to work on the plant design late in 2000 with the design finalised in 2001.

Subcontractors working for Parsons included Phoenix Imperative, Grudeau, Appledore Engineering and Gilbane Construction. With the design finalised for a modular facility fully compliant with FDA cGMP requirements, construction of the main concrete superstructure started in 2002.

PRISM ENGINEERING PROJECT MANAGEMENT SOFTWARE

At the time of the 'Large-Scale Build-Out' Parsons and Lonza decided to use project administration and contract control software designed specifically for the engineering and construction industries as the platform for project communications. The PRISM and Livelink document management software was implemented in an attempt to save time on plan approval and decisions making as all design documents were fully electronic until construction began when paper plans were produced.

STIRRED TANK BATCH BIOREACTORS

The heart of the expansion, the three 20,000l stirred tank batch bioreactors, were designed and are being constructed by Kinetics Modular Systems (KMS). The automation and control systems in the plant were designed and installed by Emerson Process Management at a cost of $7m. Emerson also provided digital automation systems, instrumentation, valves and engineering services.

Emerson had 18 engineers working onsite alongside Lonza personnel. The programming work for the control systems was undertaken at Emerson's St Louis headquarters with some of the work being subcontracted to PROCONEX of Philadelphia, and New England Controls of Mansfield, Massachusetts.

MODULAR BIOLOGICS PLANT

Lonza favoured a modular design for the new expansion. A senior project engineer at Lonza, Steve Gravallese, and John Machulski, the project director, both explained the reasons for this decision at a 2003 meeting of the Boston chapter of the 'International Society of Pharmaceutical Engineers'. The modular approach reduces costs since off-site construction of a large plant can be carried out concurrently with other processes.

Some validation and most commissioning and testing can be carried out before the final installation with the end user. The modular approach does require designs to be finalised very early on and any problems to be flagged before proceeding. There is a size limitation imposed on the plant design because of the need to transport the equipment from the place of manufacture to the facility. Lonza adopted this approach to save time in this expansion project.

BIOLOGICS MANUFACTURING PLANT FACILITIES

The facilities at the new manufacturing plant then included some 60,000l of additional bioreactor capacity, which quadrupled the existing plant's manufacturing capability. The production target was to run up to 60 batches per year at full production. The facility was designed primarily for the production of therapeutic proteins produced from mammalian cell cultures using deep tank batch fermentation systems.

The new plant also incorporated new airlift fermentation technology (also stirred reactors and perfusion reactors). The purification train has ultra high speed centrifugal separation to remove the bulk of the cellular material followed by depth filtration and 0.22µm filtration. In addition there are four column stages with accompanying concentration and diafiltration. The train also includes two intermediate viral filtration stages before the final product is submitted for quality assurance/quality control.

The plant has extensive new cold room and clean room facilities along with the warehousing capacity necessary to store the manufactured products. The expansion of the production area was completed by August 2003 and operational following validation by March 2004. The bioreactor production volume after the expansion was 73,000l (including a number of 1,000l, 2,000l and 5,000l vessels and three 20,000l vessels).

BIOLOGICS PLANT CAPACITY UPTAKE

Alexion Pharmaceuticals signed a deal with Lonza Biologics in January 2003 for the long-term commercial manufacture of its C5 complement inhibitor antibody, eculizumab. Eculizumab is now used as treatment in membranous nephritis patients and patients with paroxysmal nocturnal hemoglobinuria (approved by the US FDA on 16 March 2007). Also a phase IIb clinical study has reported about the use of eculizumab in rheumatoid arthritis patients.

Additionally in May 2003 Lonza Biologics reached another agreement for large-scale product manufacture of new monoclonal antibodies with various indications. These two agreements have already claimed 90% of the capacity of the three new 20,000lreactors due to come on stream in March 2004.

FURTHER EXPANSION IN 2006-2007

In September 2004 plans were put forward for further expansion of the Portsmouth facility but due to the economic situation (market over capacity) at the time they were put on hold. Now with so many biopharmaceuticals nearing approval additional capacity is required.

In August 2006 the $300m (€220m) plan was revived. The three-storey, 330,000ft² expansion will bring up to 400 new jobs to the region (70% in operations and 30% in R&D) has already received approval from the City of Portsmouth Technical Advisory Committee (TAC) and the Pease Development Authority. The company is now building the 330,000ft² expansion at the original 17.7 acre site.

The addition includes 18 new parking spaces, according to the application submitted by Appledore Engineering on behalf of Lonza. The site currently has a 353,000ft² foot plant and a four-storey parking garage. There will be a new access road connecting to Goose Bay Drive. The expansion also includes a new 'mid-scale' plant with an additional six 5,000l bioreactors with airlift technology and high-titre purification capabilities. The facility has been designed for new, high-concentration production processes.

The concerns that have been raised over the expansion by TAC include traffic volume and the ability of the surrounding infrastructure to handle the additional waste water and sewerage requirements. Construction of the new expansion began in May 2007 and is expected to be completed by mid-2008. The expansion is using a temporary construction parking and staging area on a 24 acre site adjacent to the Lonza facility on Goose Bay Drive.

In mid-2006 a fourth 20,000l bioreactor was brought on-line at the facility. Bioreactor capacity following the completion of the 2006 expansion was 93,000l. A further 30,000l of mid-scale capacity will be added by 2008.

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