ImClone Systems Biopharmaceutical Plant, Branchburg, NJ, USA

ImClone Systems Incorporated was founded in 1986 and opened its first research laboratories in New York. In January 2000 it started the construction of a new 100,000ft² biopharmaceutical manufacturing facility in Branchburg, New Jersey (one of the up and coming biotech hubs).

The new facility (BB36) was constructed by Kvaerner at a cost of $53 million and was completed in early 2001. Kvaerner were also responsible for the engineering, procurement, construction and validation duties at the new facility.

ERBITUX (CETUXIMAB)

The facility was approved by the FDA (Food and Drug Administration) in July 2002 to produce investigational quantities of Erbitux (cetuximab).

Erbitux is a monoclonal antibody which was developed to treat patients with advanced colorectal cancer that has spread to other parts of the body. Erbitux is used as a combination treatment to be given intravenously with irinotecan or alone if patients cannot tolerate irinotecan.

The BB36 plant was able to produce clinical quantities of Erbitux for extensive Phase III clinical trials that were completed in 2004. Erbitux blocks a specific molecular target, the Epidermal Growth Factor receptor (EGFr). EGFr is associated with tumour cell growth and repair in a number of solid tumours.

The FDA approved Erbitux for advanced colorectal cancer in February 2004. In Europe the drug is licensed for use in combination with Irinotecan. It was shown that the combination of Erbitux and irinotecan, a chemotherapeutic agent, produced positive responses in patients who did not respond well, or at all, to treatment with irinotecan alone.

The drug was also shown to be of value in the treatment of patients with refractory advanced squamous cell head and neck carcinoma in combination with the chemotherapeutic agent, cisplatin. Erbitux in combination with gemcitabine was also shown to be effective in treating patients with pancreatic carcinoma.

SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK

At the end of 2005, Swiss authorities granted a marketing authorisation for Erbitux use in combination with radiotherapy as a treatment for locally advanced Squamous Cell Carcinoma of the Head and Neck (SCCHN) in untreated patients. ImClone Systems initially developed Erbitux for use in multiple cancer indications. This is the first approval for a new additional indication.

In April 2006 Merck KGAa announced that the EMEA (European Agency for the Evaluation of Medicinal Products) had approved the use of Erbitux as an adjunctive treatment for head and neck cancer. ImClone and Bristol-Myers Squibb have also filed a supplemental Biologics License Application (sBLA) with the FDA in the third quarter of 2005 to seek approval of Erbitux for use as a single agent and in combination with radiation in SCCHN. The outcome of these filings for SCCHN is awaited later in 2006.

IMCLONE, CONTRACT MANUFACTURING AND MARKETING PARTNERS

ImClone Systems has used Lonza Biologics as a contract manufacturer to produce Erbitux in the clinical phases to back up the supplies from their own plant. The FDA approved the Lonza Biologics manufacturing site and the Branchburg facility in letters of approval in February 2004. The supplies of Erbitux produced at the Lonza Biologics site have served as initial supplies for the commercial market.

The US marketing of Erbitux was carried out by Bristol Myers Squibb, who has now made payments to ImClone totalling $2 billion. The drug is marketed by Merck KGAa in Europe, who will also make royalty payments on the gross profit from sales. US sales of Erbitux are expected to top $1.2 billion by 2009 and worldwide sales could be more than $5 billion in the same time-scale.

THE OLD PLANT AND THE NEW

The Branchburg facility was a single product plant, with a capacity of 30,000 litres and a production volume of 250kg/year of Erbitux. It was given full commercial production clearance in June 2004.

The plant was renovated and extended by Silcon Inc (construction) and Lawton and Burns (mechanical and process engineers) in January 2003 to increase process efficiency and production capacity. But this was not enough; the demand for Erbitux was immediately more than the capacity of the small facility at Branchburg.

ImClone contracted Lonza Biologics to make up the shortfall and set out to expand the Branchburg facility to be the primary production site for Erbitux and other investigational compounds.

In mid 2004 an investment of $260 million was made to expand the plant to a multi-product facility, with three production suites, along with downstream facilities and a total of 110,000 litres of production capacity. The construction got underway in late 2004 and was completed and in full production following an FDA validation process by early 2006. Kvaerner were responsible for the engineering and project management along with Binskey and Snyder for the construction and Victaulic for the pipefitting and Midwest Mechanical Contractors of New Jersey for the process engineering.

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